High-altitude haematology: Quechua-Aymara comparisons.

PubMed

Arnaud, J; Quilici, J C; Rivière, G

1981-01-01

Haematological studies have been carried out at various altitudes between 450 m and 4800 m, on two separate human groups (Quechuas and Aymaras) living in South America. Changes in the haematological parameters do not develop linearly in relation to the attitude. Th impact of chronic hypoxia on erythropoiesis is greater above 3000 m. The haemogram varies quantitatively and not qualitatively (mean corpuscular volume and mean haemoglobin concentration remain constant). The haematological study also reveals the greater adaptability to high altitude of the Aymaras, an adaptability characterized by an increase in red cell count and concentration and a decrease in red cell volume. The adaptative phenomena observed in the Quechuas are reversible, whereas they persist in the Aymaras when they migrate to the lowlands (450 m).

Automated haematology analysis to diagnose malaria

PubMed Central

2010-01-01

For more than a decade, flow cytometry-based automated haematology analysers have been studied for malaria diagnosis. Although current haematology analysers are not specifically designed to detect malaria-related abnormalities, most studies have found sensitivities that comply with WHO malaria-diagnostic guidelines, i.e. ≥ 95% in samples with > 100 parasites/μl. Establishing a correct and early malaria diagnosis is a prerequisite for an adequate treatment and to minimizing adverse outcomes. Expert light microscopy remains the 'gold standard' for malaria diagnosis in most clinical settings. However, it requires an explicit request from clinicians and has variable accuracy. Malaria diagnosis with flow cytometry-based haematology analysers could become an important adjuvant diagnostic tool in the routine laboratory work-up of febrile patients in or returning from malaria-endemic regions. Haematology analysers so far studied for malaria diagnosis are the Cell-Dyn®, Coulter® GEN·S and LH 750, and the Sysmex XE-2100® analysers. For Cell-Dyn analysers, abnormal depolarization events mainly in the lobularity/granularity and other scatter-plots, and various reticulocyte abnormalities have shown overall sensitivities and specificities of 49% to 97% and 61% to 100%, respectively. For the Coulter analysers, a 'malaria factor' using the monocyte and lymphocyte size standard deviations obtained by impedance detection has shown overall sensitivities and specificities of 82% to 98% and 72% to 94%, respectively. For the XE-2100, abnormal patterns in the DIFF, WBC/BASO, and RET-EXT scatter-plots, and pseudoeosinophilia and other abnormal haematological variables have been described, and multivariate diagnostic models have been designed with overall sensitivities and specificities of 86% to 97% and 81% to 98%, respectively. The accuracy for malaria diagnosis may vary according to species, parasite load, immunity and clinical context where the method is applied. Future

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis.

PubMed

Grigor, Emma J M; Fergusson, Dean A; Haggar, Fatima; Kekre, Natasha; Atkins, Harold; Shorr, Risa; Holt, Robert A; Hutton, Brian; Ramsay, Tim; Seftel, Matthew; Jonker, Derek; Daugaard, Mads; Thavorn, Kednapa; Presseau, Justin; Lalu, Manoj M

2017-12-29

Patients with relapsed or refractory malignancies have a poor prognosis. Immunotherapy with chimeric antigen receptor T (CAR-T) cells redirects a patient's immune cells against the tumour antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies, including acute B-cell lymphoblastic leukaemia and B-cell lymphomas. CAR-T cell therapy for patients with other solid tumours is also being tested. Safety is an important consideration in CAR-T cell therapy given the potential for serious adverse events, including death. Previous reviews on CAR-T cell therapy have been limited in scope and methodology. Herein, we present a protocol for a systematic review to identify CAR-T cell interventional studies and examine the safety and efficacy of this therapy in patients with haematology malignancies and solid tumours. We will search MEDLINE, including In-Process and Epub Ahead of Print, EMBASE and the Cochrane Central Register of Controlled Trials from 1946 to 22 February 2017. Studies will be screened by title, abstract and full text independently and in duplicate. Studies that report administering CAR-T cells of any chimeric antigen receptor construct targeting antigens in patients with haematological malignancies and solid tumours will be eligible for inclusion. Outcomes to be extracted will include complete response rate (primary outcome), overall response rate, overall survival, relapse and adverse events. A meta-analysis will be performed to synthesise the prevalence of outcomes reported as proportions with 95% CIs. The potential for bias within included studies will be assessed using a modified Institute of Health Economics tool. Heterogeneity of effect sizes will be determined using the Cochrane I 2 statistic. The review findings will be submitted for peer-reviewed journal publication and presented at relevant conferences and scientific meetings to promote knowledge transfer. CRD42017075331. © Article author(s) (or

Palliative care in patients with haematological neoplasms: An integrative systematic review.

PubMed

Moreno-Alonso, Deborah; Porta-Sales, Josep; Monforte-Royo, Cristina; Trelis-Navarro, Jordi; Sureda-Balarí, Anna; Fernández De Sevilla-Ribosa, Alberto

2018-01-01

Palliative care was originally intended for patients with non-haematological neoplasms and relatively few studies have assessed palliative care in patients with haematological malignancies. To assess palliative care interventions in managing haematological malignancies patients treated by onco-haematology departments. Integrative systematic review with data extraction and narrative synthesis (PROSPERO #: CRD42016036240). PubMed, CINAHL, Cochrane, Scopus and Web-of-Science were searched for articles published through 30 June 2015. Study inclusion criteria were as follows: (1) published in English or Spanish and (2) containing data on palliative care interventions in adults with haematological malignancies. The search yielded 418 articles; 99 met the inclusion criteria. Six themes were identified: (1) end-of-life care, (2) the relationship between onco-haematology and palliative care departments and referral characteristics, (3) clinical characteristics, (4) experience of patients/families, (5) home care and (6) other themes grouped together as 'miscellany'. Our findings indicate that palliative care is often limited to the end-of-life phase, with late referral to palliative care. The symptom burden in haematological malignancies patients is more than the burden in non-haematological neoplasms patients. Patients and families are generally satisfied with palliative care. Home care is seldom used. Tools to predict survival in this patient population are lacking. Despite a growing interest in palliative care for haematological malignancies patients, the evidence base needs to be strengthened to expand our knowledge about palliative care in this patient group. The results of this review support the need to develop closer cooperation and communication between the palliative care and onco-haematology departments to improve patient care.

[Safety profile of dolutegravir].

PubMed

Rivero, Antonio; Domingo, Pere

2015-03-01

Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Altitude training causes haematological fluctuations with relevance for the Athlete Biological Passport.

PubMed

Bonne, Thomas Christian; Lundby, Carsten; Lundby, Anne Kristine; Sander, Mikael; Bejder, Jacob; Nordsborg, Nikolai Baastrup

2015-08-01

The impact of altitude training on haematological parameters and the Athlete Biological Passport (ABP) was evaluated in international-level elite athletes. One group of swimmers lived high and trained high (LHTH, n = 10) for three to four weeks at 2130 m or higher whereas a control group (n = 10) completed a three-week training camp at sea-level. Haematological parameters were determined weekly three times before and four times after the training camps. ABP thresholds for haemoglobin concentration ([Hb]), reticulocyte percentage (RET%), OFF score and the abnormal blood profile score (ABPS) were calculated using the Bayesian model. After altitude training, six swimmers exceeded the 99% ABP thresholds: two swimmers exceeded the OFF score thresholds at day +7; one swimmer exceeded the OFF score threshold at day +28; one swimmer exceeded the threshold for RET% at day +14; and one swimmer surpassed the ABPS threshold at day +14. In the control group, no values exceeded the individual ABP reference range. In conclusion, LHTH induces haematological changes in Olympic-level elite athletes which can exceed the individually generated references in the ABP. Training at altitude should be considered a confounding factor for ABP interpretation for up to four weeks after altitude exposure but does not consistently cause abnormal values in the ABP. Copyright © 2014 John Wiley & Sons, Ltd.

Effects of probiotic supplementation over 5 months on routine haematology and clinical chemistry measures in healthy active adults.

PubMed

Cox, A J; West, N P; Horn, P L; Lehtinen, M J; Koerbin, G; Pyne, D B; Lahtinen, S J; Fricker, P A; Cripps, A W

2014-11-01

Use of probiotic-containing foods and probiotic supplements is increasing; however, few studies document safety and tolerability in conjunction with defined clinical end points. This paper reports the effects of 150 days of supplementation with either a single- (Bifidobacterium animalis subsp. lactis Bl-04) or a double-strain (Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07) probiotic on routine haematology and clinical chemistry measures in healthy active adults. Pre- to post-intervention changes in laboratory measures were determined and compared between supplement and placebo groups. Overall there were few differences in routine haematology and clinical chemistry measures between supplement and placebo groups post-intervention. Exceptions included plasma calcium (P=0.03) and urea (P=0.015); however, observed changes were small and within assay-specific laboratory reference ranges. These data provide evidence supporting the use of these probiotic supplements over a period of 5 months in healthy active adults without obvious safety or tolerability issues.

The hypoxia signalling pathway in haematological malignancies

PubMed Central

Irigoyen, Marta; García-Ruiz, Juan Carlos; Berra, Edurne

2017-01-01

Haematological malignancies are tumours that affect the haematopoietic and the lymphatic systems. Despite the huge efforts to eradicate these tumours, the percentage of patients suffering resistance to therapies and relapse still remains significant. The tumour environment favours drug resistance of cancer cells, and particularly of cancer stem/initiating cells. Hypoxia promotes aggressiveness, metastatic spread and relapse in most of the solid tumours. Furthermore, hypoxia is associated with worse prognosis and resistance to conventional treatments through activation of the hypoxia-inducible factors. Haematological malignancies are not considered solid tumours, and therefore, the role of hypoxia in these diseases was initially presumed to be inconsequential. However, hypoxia is a hallmark of the haematopoietic niche. Here, we will review the current understanding of the role of both hypoxia and hypoxia-inducible factors in different haematological tumours. PMID:28415662

Radionuclides in haematology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, S.M.; Bayly, R.J.

1986-01-01

This book contains the following chapters: Some prerequisites to the use of radionuclides in haematology; Instrumentation and counting techniques; In vitro techniques; Cell labelling; Protein labelling; Autoradiography; Imaging and quantitative scanning; Whole body counting; Absorption and excretion studies; Blood volume studies; Plasma clearance studies; and Radionuclide blood cell survival studies.

Haematological cancer and quality of life: a systematic literature review

PubMed Central

Allart-Vorelli, P; Porro, B; Baguet, F; Michel, A; Cousson-Gélie, F

2015-01-01

The aim of this study is to examine the impact of haematological cancers on quality of life (QoL). A review of the international literature was conducted from the databases ‘PsycInfo' and 'Medline' using the keywords: 'haematological cancer', 'quality of life', 'physical', 'psychological', 'social', 'vocational', 'professional', 'economic', 'cognitive', and 'sexual'. Twenty-one reliable studies were analysed. Among these studies, 12 showed that haematological cancer altered overall QoL, 8 papers found a deterioration of physical dimension, 8 papers reported on functional and role dimensions, 11 papers reported on the psychological component and 9 on the social component. Moreover, one study and two manuscripts, respectively, reported deteriorated sexual and cognitive dimensions. Our review demonstrates that the different dimensions of QoL are deteriorated by haematological malignancies and, probably, by the side effects of treatment. PMID:25909835

Alterations in cytokines and haematological parameters during the acute and convalescent phases of Plasmodium falciparum and Plasmodium vivax infections.

PubMed

Rodrigues-da-Silva, Rodrigo Nunes; Lima-Junior, Josué da Costa; Fonseca, Bruna de Paula Fonseca e; Antas, Paulo Renato Zuquim; Baldez, Arlete; Storer, Fabio Luiz; Santos, Fátima; Banic, Dalma Maria; Oliveira-Ferreira, Joseli de

2014-04-01

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.

Epidemiology, Clinico-Haematological Profile and Management of Aplastic Anaemia: AIIMS Experience.

PubMed

Mahapatra, M; Singh, P K; Agarwal, M; Prabhu, M; Mishra, P; Seth, T; Tyagi, S; Patil, H P; Saxena, R

2015-03-01

The incidence of aplastic anaemia (AA) is higher in Asia than in the West. The precise incidence of AA in India is not known due to lack of epidemiological study. 20-40% of pancytopenic patients in referral centres are of aplastic anaemia. This was an analysis of 1501 patients diagnosed with aplastic anaemia over a period of seven and half years (January 2007- June 2014) attending the Aplastic clinic of department of haematology of All India Institute of Medical Sciences, New Delhi. The details regarding medical history, physical examination, complete blood count, bone marrow aspirate and biopsy, treatment received, were retrieved. Inherited bone marrow failure was screened in patients below 35 years. Treatment response was analysed for various treatment modalities. 1501 patients of AA from 20 different states of India were analysed. The bulk of patients were from Uttar Pradesh (28.7%), Bihar (23.6%), Delhi/NCR (20%) and Haryana (7%).The average number of new aplastic anaemia patients enrolled per year 214 (range: 101 -263). The median age at presentation was 25 years (range 2-83),with M;F - 2.3:1. Severity of AA revealed: severe (SAA): 75%, very severe (VSAA): 15%, non-severe (NSAA): 10%. Inherited bone marrow failure syndromes constituted 5% (75 patients) of all aplastic anaemia patients. The most common clinical presentations were pallor (97%), bleeding manifestations (69.6%) and fever (54%). The haematological parameters showed: median level of haemoglobin level: 5.9 gm/dL, WBC: 2700/mm3, ANC: 380/mm3, platelet: 1 0000/mm3. PNH clone was present in 13.5% of patients. 107 patients (7%) were lost to follow up or expired before any treatment was initiated. Only 69 patients (4.5%) received treatment with HLA-matched sibling stem cell transplantation and another 232 (15.5%) patients received ATG plus cyclosporine as immunosuppressive therapy. Seven hundred thirteenpatients (47.5%) received cyclosporine. The overall response to various treatment modalities was: HLA

Meditation for adults with haematological malignancies.

PubMed

Salhofer, Ines; Will, Andrea; Monsef, Ina; Skoetz, Nicole

2016-02-03

Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and alternative treatment options such as meditation practice or yoga are becoming popular by treating all aspects of the disease including physical and psychological symptoms. However, there is still unclear evidence about meditation's effectiveness, and how its practice affects the lives of haematologically-diseased patients. This review aims to assess the benefits and harms of meditation practice as an additional treatment to standard care for adults with haematological malignancies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8, 2015), MEDLINE (1950 to August 2015), databases of ongoing trials, the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), conference proceedings of annual meetings of: the American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; European Congress for Integrative Medicine; and Global Advances in Health and Medicine (2010 to 2015). We included randomised controlled trials (RCTs) using meditation practice for adult patients with haematological malignancies. Two review authors independently extracted data from eligible studies and assessed the risk of bias according to predefined criteria. We evaluated quality of life and depression. The other outcomes of overall survival, anxiety, fatigue, quality of sleep and adverse events could not be evaluated, because they were not assessed in the included trial. We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no

Haematological, blood gas and acid-base values in the Galgo Español (Spanish greyhound).

PubMed

Mesa-Sanchez, I; Zaldivar-Lopez, S; Couto, C G; Gamito-Gomez, A; Granados-Machuca, M M; Lopez-Villalba, I; Galan-Rodriguez, A

2012-07-01

Haematologic profiles, electrolyte concentrations, blood gas values and acid-base balance have been studied and reported in healthy greyhounds; however, there is only one study published on blood gas values in Galgos Españoles. Because of their purported common origins with greyhounds (same group and class), it was hypothesised that Galgos Españoles also have differences in haematologic values, electrolyte concentrations, blood gas values and acid-base balance compared to other non-sporting breeds. Venous blood samples from 30 Galgos Españoles and 20 dogs from different breeds were collected, and complete blood counts, electrolyte concentrations, blood gas values and acid-base balance were measured. From the 24 parameters analysed, 5 had statistically significant differences (P<0·05). Galgos Españoles had higher haematocrit (P<0·001), haemoglobin concentration (P=0·003), erythrocyte count (P=0·016) and pH (P=0·03), and lower platelet count (P=0·005), than those in other-breed dogs. These results confirm that significant haematologic differences exist in Galgos Españoles when compared with other dogs, although these differences are not as striking as in greyhounds. Practitioners need to be aware of these breed-specific differences in order to make accurate diagnoses in Galgos Españoles. © 2012 British Small Animal Veterinary Association.

The role of CCN family genes in haematological malignancies.

PubMed

Wells, J E; Howlett, M; Cheung, L C; Kees, Ursula R

2015-09-01

Haematological malignancies, although a broad range of specific disease types, continue to show considerable overlap in classification, and patients are treated using similar chemotherapy regimes. In this review we look at the role of the CCN family of matricellular proteins and indicate their role in nine haematological malignancies including both myeloid and lymphoid neoplasms. The potential for further haematological neoplasms with CCN family associations is argued by summarising the demonstrated role of CCN family genes in the differentiation of haematopoietic stem cells (HSC) and mesenchymal stem cells. The expanding field of knowledge encompassing CCN family genes and cancers of the HSC-lineage highlights the importance of extracellular matrix-interactions in both normal physiology and tumorigenesis of the blood, bone marrow and lymph nodes.

Stability of haematological parameters and its relevance on the athlete's biological passport model.

PubMed

Lombardi, Giovanni; Lanteri, Patrizia; Colombini, Alessandra; Lippi, Giuseppe; Banfi, Giuseppe

2011-12-01

The stability of haematological parameters is crucial to guarantee accurate and reliable data for implementing and interpreting the athlete's biological passport (ABP). In this model, the values of haemoglobin, reticulocytes and out-of-doping period (OFF)-score (Hb-60√Ret) are used to monitor the possible variations of those parameters, and also to compare the thresholds developed by the statistical model for the single athlete on the basis of its personal values and the variance of parameters in the modal group. Nevertheless, a critical review of the current scientific literature dealing with the stability of the haematological parameters included in the ABP programme, and which are used for evaluating the probability of anomalies in the athlete's profile, is currently lacking. In addition, we collected information from published studies, in order to supply a useful, practical and updated review to sports physicians and haematologists. There are some parameters that are highly stable, such as haemoglobin and erythrocytes (red blood cells [RBCs]), whereas others, (e.g. reticulocytes, mean RBC volume and haematocrit) appear less stable. Regardless of the methodology, the stability of haematological parameters is improved by sample refrigeration. The stability of all parameters is highly affected from high storage temperatures, whereas the stability of RBCs and haematocrit is affected by initial freezing followed by refrigeration. Transport and rotation of tubes do not substantially influence any haematological parameter except for reticulocytes. In all the studies we reviewed that used Sysmex instrumentation, which is recommended for ABP measurements, stability was shown for 72 hours at 4 ° C for haemoglobin, RBCs and mean curpuscular haemoglobin concentration (MCHC); up to 48 hours for reticulocytes; and up to 24 hours for haematocrit. In one study, Sysmex instrumentation shows stability extended up to 72 hours at 4 ° C for all the parameters. There are

Laser safety at high profile projects

NASA Astrophysics Data System (ADS)

Barat, K.

2011-03-01

Laser Safety at high profile laser facilities tends to be more controlled than in the standard laser lab found at a research institution. The reason for this is the potential consequences for such facilities from incidents. This ranges from construction accidents, to equipment damage to personnel injuries. No laser user wants to sustain a laser eye injury. Unfortunately, many laser users, most commonly experienced researchers and inexperienced graduate students, do receive laser eye injuries during their careers. . More unforgiveable is the general acceptance of this scenario, as part of the research & development experience. How do senior researchers, safety personnel and management stop this trend? The answer lies in a cultural change that involves institutional training, user mentoring, hazard awareness by users and administrative controls. None of these would inhibit research activities. As a matter of fact, proper implementation of these controls would increase research productivity. This presentation will review and explain the steps needed to steer an institution, research division, group or individual lab towards a culture that should nearly eliminate laser accidents. As well as how high profile facilities try to avoid laser injuries. Using the definition of high profile facility as one who's funding in the million to billions of dollars or Euros and derives form government funding.

Population based haematology reference ranges for old people in rural South-West Uganda.

PubMed

Mugisha, Joseph O; Seeley, Janet; Kuper, Hannah

2016-09-07

Haematology reference values are needed to interpret haematology results and make clinical decisions, but these have not been established for old people in sub-Saharan Africa. The objective of this study was to establish haematology reference values for people aged 50 years and above in Uganda, to compare the haematology reference values for those aged 65 years and over with those less than 65 years and to compare these haematology reference values with established haematology reference values for old people from high income countries. A total of 1449 people aged 50 years and above were recruited from the Medical Research Council/Uganda Virus Research Institute general population cohort between January 2012 and January 2013 (response rate 72.3 %). From the blood samples collected, we did haematology, HIV testing and malaria tests. We also obtained stool samples and tested them for hookworm infection. Questionnaire data were obtained through interviews. In the analysis, we excluded those with HIV infection, malaria infection, hookworm infection and those not feeling well at the time of recruitment. Medians and reference ranges for 12 haematology parameters were determined, based on the Clinical Laboratory and Standards institute's guidelines. In total, 903 people aged 50 years and above were included in the analysis with the majority 545 (60.3 %) being female. Men had significant difference in median haemoglobin, haematocrit, erythrocytes counts and white blood cells counts, which were higher than those of women. Women had significant difference in mean platelet counts and neutrophil percentages which were higher than those of men. Comparing those aged 65+ and those aged less than 65 years, the following parameters were significantly lower in those aged above 65 years: haemoglobin, haematocrit, erythrocytes counts, platelets and mean corpuscular volume. Compared to the reference intervals from old people in high income countries, all the haematology

Strengthening medical education in haematology and blood transfusion: postgraduate programmes in Tanzania

PubMed Central

Makani, Julie; Lyimo, Magdalena; Magesa, Pius; Roberts, David J.

2017-01-01

Summary Haematology and blood transfusion, as a clinical and laboratory discipline, has a far-reaching impact on healthcare both through direct patient care as well as provision of laboratory and transfusion services. Improvement of haematology and blood transfusion may therefore be significant in achieving advances in health in Africa. In 2005, Tanzania had one of the lowest distributions of doctors in the world, estimated at 2·3 doctors per 100 000 of population, with only one haematologist, a medical doctor with postgraduate medical education in haematology and blood transfusion. Here, we describe the establishment and impact of a postgraduate programme centred on Master of Medicine and Master of Science programmes to build the capacity of postgraduate training in haematology and blood transfusion. The programme was delivered through Muhimbili University of Health and Allied Sciences (MUHAS) with partnership from visiting medical and laboratory staff from the UK and complemented by short-term visits of trainees from Tanzania to Haematology Departments in the UK. The programme had a significant impact on the development of human resources in haematology and blood transfusion, successfully training 17 specialists with a significant influence on delivery of health services and research. This experience shows how a self-sustaining, specialist medical education programme can be developed at low cost within Lower and Middle Income Countries (LMICs) to rapidly enhance delivery of capacity to provide specialist services. PMID:28369755

Temperature management in haematology patients with febrile neutropenia: a practice survey.

PubMed

Weinkove, Robert; Clay, Jennifer; Wood, Catherine

2013-04-19

To assess the attitudes of clinicians to temperature management in haematology patients with febrile neutropenia. An online scenario-based survey was circulated to consultant members of the New Zealand branch of the Haematology Society of Australia and New Zealand, to haematology advanced trainees, and to nursing representatives at each haematology department in New Zealand. Eighty-eight responses were obtained, from 34 doctors and 54 nurses. Most respondents would advise a neutropenic patient to take paracetamol as needed for pain. Median temperature intervention threshold for an asymptomatic patient with febrile neutropenia was higher for doctors than for nurses (38.5 versus 38.0 degrees Celcius), despite considerable heterogeneity. Both groups indicated they would intervene at a median 38.0 degrees Celcius for a patient with rigors. Paracetamol was the preferred first-line cooling measure, with physical methods second-line, and pethidine third-line. All respondents favoured oral over intravenous or rectal paracetamol. Most believed a clinical trial of antipyretic treatment for febrile neutropenia was warranted, and indicated willingness to enrol their patients in such a study. This survey documents clinicians' preferred temperature intervention thresholds and methods for haematology patients with neutropenic fever, and shows considerable variation in practice. Most respondents supported a trial of antipyretic management in febrile neutropenia.

Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems.

PubMed

Liptrott, Neill J; Giardiello, Marco; McDonald, Tom O; Rannard, Steve P; Owen, Andrew

2018-03-15

Recent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. Other SDN formulations are being studied for parenteral administration, either as intramuscular long-acting formulations, or for direct administration intravenously. The interaction of nanoparticles with the immunological and haematological systems can be a major barrier to successful translation but has been understudied for SDN formulations. Here we have conducted a preclinical evaluation of efavirenz SDN to assess their potential interaction with these systems. Platelet aggregation and activation, plasma coagulation, haemolysis, complement activation, T cell functionality and phenotype, monocyte derived macrophage functionality, and NK cell function were assessed in primary healthy volunteer samples treated with either aqueous efavirenz or efavirenz SDN. Efavirenz SDNs were shown not to interfere with any of the systems studied in terms of immunostimulation nor immunosuppression. Although efavirenz aqueous solution was shown to cause significant haemolysis ex vivo, efavirenz SDNs did not. No other interaction with haematological systems was observed. Efavirenz SDNs have been demonstrated to be immunologically and haematologically inert in the utilised assays. Taken collectively, along with the recent observation that lopinavir SDN formulations did not impact immunological responses, these data indicate that this type of nanoformulation does not elicit immunological consequences seen with other types of nanomaterial. The methodologies presented here provide a framework for pre-emptive preclinical characterisation of nanoparticle safety.

Strengthening medical education in haematology and blood transfusion: postgraduate programmes in Tanzania.

PubMed

Makani, Julie; Lyimo, Magdalena; Magesa, Pius; Roberts, David J

2017-06-01

Haematology and blood transfusion, as a clinical and laboratory discipline, has a far-reaching impact on healthcare both through direct patient care as well as provision of laboratory and transfusion services. Improvement of haematology and blood transfusion may therefore be significant in achieving advances in health in Africa. In 2005, Tanzania had one of the lowest distributions of doctors in the world, estimated at 2·3 doctors per 100 000 of population, with only one haematologist, a medical doctor with postgraduate medical education in haematology and blood transfusion. Here, we describe the establishment and impact of a postgraduate programme centred on Master of Medicine and Master of Science programmes to build the capacity of postgraduate training in haematology and blood transfusion. The programme was delivered through Muhimbili University of Health and Allied Sciences (MUHAS) with partnership from visiting medical and laboratory staff from the UK and complemented by short-term visits of trainees from Tanzania to Haematology Departments in the UK. The programme had a significant impact on the development of human resources in haematology and blood transfusion, successfully training 17 specialists with a significant influence on delivery of health services and research. This experience shows how a self-sustaining, specialist medical education programme can be developed at low cost within Lower and Middle Income Countries (LMICs) to rapidly enhance delivery of capacity to provide specialist services. © 2017 John Wiley & Sons Ltd.

The Potential Role of Aurora Kinase Inhibitors in Haematological Malignancies

PubMed Central

Farag, Sherif S.

2011-01-01

Summary Aurora kinases play an important role in the control of the cell cycle and have been implicated in tumourigenesis in a number of cancers. Among the haematological malignancies, overexpression of Aurora kinases has been reported in acute myeloid leukaemia, chronic myeloid leukaemia, acute lymphoblastic leukaemia, multiple myeloma, aggressive non-Hodgkin lymphoma and Hodgkin lymphoma. A large number of Aurora kinase inhibitors are currently in different stages of clinical development. In addition to varying in their selectivity for the different Aurora kinases, some also have activity directed at other cellular kinases involved in important molecular pathways in cancer cells. This review summarizes the biology of Aurora kinases and discusses why they may be good therapeutic targets in different haematological cancers. We describe preclinical data that has served as the rationale for investigating Aurora kinase inhibitors in different haematological malignancies, and summarize published results from early phase clinical trials. While the anti-tumour effects of Aurora kinase inhibitors appear promising, we highlight important issues for future clinical research and suggest that the optimal use of these inhibitors is likely to be in combination with cytotoxic agents already in use for the treatment of various haematological cancers. PMID:21980926

Estimating reliable paediatric reference intervals in clinical chemistry and haematology.

PubMed

Ridefelt, Peter; Hellberg, Dan; Aldrimer, Mattias; Gustafsson, Jan

2014-01-01

Very few high-quality studies on paediatric reference intervals for general clinical chemistry and haematology analytes have been performed. Three recent prospective community-based projects utilising blood samples from healthy children in Sweden, Denmark and Canada have substantially improved the situation. The present review summarises current reference interval studies for common clinical chemistry and haematology analyses. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Efficacy and safety profile of xanthines in COPD: a network meta-analysis.

PubMed

Cazzola, Mario; Calzetta, Luigino; Barnes, Peter J; Criner, Gerard J; Martinez, Fernando J; Papi, Alberto; Gabriella Matera, Maria

2018-06-30

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD. Copyright ©ERS 2018.

Coagulation profile, haematological and biochemical changes in kids naturally infected with peste des petits ruminants.

PubMed

Sahinduran, Sima; Albay, Metin Koray; Sezer, Kenan; Ozmen, Ozlem; Mamak, Nuri; Haligur, Mehmet; Karakurum, Cagri; Yildiz, Ramazan

2012-03-01

The aim of this study was to examine the coagulation profile in peste des petits ruminant (PPR) in kids. Five kids from a group of 150 animals (72 goats and 78 kids) were brought to the Veterinary Medical Teaching Hospital from a farm in Burdur province (Turkey) with nasal and ocular discharges and diarrhea. Fifteen goats and 41 kids had died due to diarrhea and three kids were presented to the Department of Pathology for diagnosis. Blood samples were taken from 12 ill animals (infected group) for haematological and biochemical analysis. In addition, five healthy kids were examined from another healthy flock (control group). Leukocyte and lymphocyte numbers of infected group showed significant declinations in comparison to control group (≤0.001). Haemorrhages in all organs of digestive system and small haemorrhagic areas in liver were caused to decrease in erythrocyte and haematocrit values (p ≤ 0.001) in infected group. Concentrations of blood urea nitrogen (BUN) (p ≤ 0.01) and creatinine (p ≤ 0.001) in infected group were significantly higher than control group. Compared to control group, significant increases were determined in serum concentrations of alkaline phosphatase (ALP) (p ≤ 0.01), aspartate aminotransferase (AST) (p ≤ 0.001) and alanine aminotransferase (ALT) (p ≤ 0.001) in the infected group. No significant differences were observed between the infected and control groups for serum gamma glutamyl-transferase (GGT) concentration value. In our study, thrombocytopenia (p ≤ 0.001) together with prolonged activated partial thromboplastin time (APTT; p ≤ 0.01) and prothrombin time (PT; p ≤ 0.001) may show that disseminated intravascular coagulopathy which can occur in kids with PPR.

Influenza vaccines: Evaluation of the safety profile

PubMed Central

Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

2018-01-01

ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

Effect of dietary alternative lipid sources on haematological parameters and serum constituents of Heterobranchus longifilis fingerlings.

PubMed

Babalola, T O O; Adebayo, M A; Apata, D F; Omotosho, J S

2009-03-01

The worldwide increase in aquaculture production and the decrease of wild fish stocks has made the replacement of fish oil (FO) in aquafeed industry a priority. Therefore, the use of terrestrial animal fats and vegetable oils, which has lower cost and larger supplies, may be good as substitute for FO. This study investigate the effects of total replacement of FO by two terrestrial animal fats (pork lard and poultry fat) and three vegetable oils (palm kernel oil, sheabutter oil and sunflower oil) on haematological and serum biochemical profile of Heterobranchus longifilis over 70 days. FO-diet was used as the control. The haematological parameters were significantly affected by dietary lipid sources. Serum total protein was not influenced by the dietary lipids. However, serum cholesterol was significantly higher in fish fed diet containing sunflower oil. Glucose and activities of liver enzymes in blood serum were significantly reduced in fish fed alternative lipids when compared with the control. These results indicate that FO can be replaced completely with alternative lipids without any serious negative health impacts.

Probiotic effect on calves infected with Salmonella Dublin: haematological parameters and serum biochemical profile.

PubMed

Soto, L P; Astesana, D M; Zbrun, M V; Blajman, J E; Salvetti, N R; Berisvil, A P; Rosmini, M R; Signorini, M L; Frizzo, L S

2016-02-01

The aim of this study was to evaluate the effect of a probiotic/lactose inoculum on haematological and immunological parameters and renal and hepatic biochemical profiles before and during a Salmonella Dublin DSPV 595T challenge in young calves. Twenty eight calves, divided into a control and probiotic group were used. The probiotic group was supplemented with 100 g lactose/calf/d and 10 10 cfu/calf/d of each strain of a probiotic inoculum composed of Lactobacillus casei DSPV318T, Lactobacillus salivarius DSPV315T and Pediococcus acidilactici DSPV006T throughout the experiment. The pathogen was administered on day 11 of the experiment, at an oral dose of 10 9 cfu/animal (LD 50 ). Aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), urea, red blood cells, haemoglobin, haematocrit, mean cell haemoglobin (MCH), mean corpuscular volume, mean corpuscular haemoglobin concentration (MCHC), white blood cells, lymphocytes, neutrophils, band neutrophils, monocytes, eosinophils, basophils and the neutrophils/lymphocytes ratio were measured on days 1, 10, 20 and 27 of the experiment. In addition, animals were necropsied to evaluate immunoglobulin A (IgA) production in the jejunal mucosa. The most significant differences caused by the administration of the inoculum/lactose were found during the acute phase of Salmonella challenge (9 days after challenge), when a difference between groups in neutrophils/lymphocytes ratio were detected. These results suggest that the probiotic/lactose inoculum administration increases the calf's ability to respond to the disease increasing the systemic immune response specific. No differences were found in haemoglobin, haematocrit, MCH, MCHC, AST, urea, GGT, band neutrophils, eosinophils, monocytes and IgA in the jejunum between the two groups of calves under the experimental conditions of this study. Further studies must be conducted to evaluate different probiotic/pathogens doses and different sampling times, to achieve a

Haematological profile of patients with mixed-phenotype acute leukaemia from a tertiary care centre of north India

PubMed Central

Sharma, Manupriya; Sachdeva, Man Updesh Singh; Bose, Parveen; Varma, Neelam; Varma, Subhash; Marwaha, R.K.; Malhotra, Pankaj

2017-01-01

Background & objectives: Mixed-phenotype acute leukaemia (MPAL) is a rare neoplasm with no definite treatment protocols and a distinctly poor outcome. Advancement in polychromatic flow cytometry has made its identification easier. This prospective study was designed to identify cases of MPAL and study their clinical presentation and haematological profile in a tertiary care hospital in north India. Methods: Ethylenediaminetetraacetic acid (EDTA)-anticoagulated bone marrow aspirate samples of patients diagnosed as acute leukaemia (AL) on the basis of morphology were utilized for immunophenotyping. A comprehensive panel of fluorochrome-labelled monoclonal antibodies targeting myeloid, B-cell, T-cell and immaturity markers was utilized. The patients diagnosed to have MPAL, on the basis of the World Health Organization 2008 classification, were selected for further analyses. Results: There were 15 (2.99%) patients with MPAL of the total 501 cases of AL. Seven were children, all males and mean age of 5.08±3.88 yr. Eight were adults, male:female=6:2 and mean age of 21.43±5.74 yr. Eight were diagnosed as B/myeloid and seven were T/myeloid. No association was observed between age and immunophenotype of MPAL. On morphology, 11 were diagnosed as AML and four as ALL, and no specific morphology of blasts was predictive of a MPAL. Interpretation & conclusions: MPAL appeared to be a rare neoplasm (2.99% of AL cases). A comprehensive primary panel of monoclonal antibodies should be used to identify this neoplasm known to have a poor outcome. PMID:28639598

Comparing changes in haematologic parameters occurring in patients included in randomized controlled trials of artesunate-amodiaquine vs single and combination treatments of uncomplicated falciparum in sub-Saharan Africa.

PubMed

Zwang, Julien; Ndiaye, Jean-Louis; Djimdé, Abdoulaye; Dorsey, Grant; Mårtensson, Andreas; Karema, Corine; Olliaro, Piero

2012-01-25

Artesunate-amodiaquine (AS&AQ) is a widely used artemisinin combination therapy (ACT) for falciparum malaria. A comprehensive appreciation of its effects on haematology vs other anti-malarials is needed in view of potential safety liabilities. Individual-patient data analysis conducted on a database from seven randomized controlled trials conducted in sub-Saharan African comparing AS&AQ to reference treatments in uncomplicated falciparum malaria patients of all ages. Haematologic values (white cells total and neutrophil counts, haemoglobin/haematocrit, platelets) were analysed as both continuous and categorical variables for their occurrence, (severity grade 1-4) and changes during follow-up. Risks and trends were calculated using multivariate logistic random effect models. 4,502 patients (72% < 5 years old), from 13 sites in nine countries with 28-day follow-up were treated with AS&AQ (45%) or a comparator (other forms of ACT accounted for 27%, other combination 12%, mono-therapies 16%). Pre-treatment leucopaenia (3%) and neutropaenia (6%) were infrequent; anaemia was common (39%). The treatment-emergent adverse events incidence (TEAE = condition not present or less severe pre-treatment) was 11% for neutropaenia, 6% for thrombocytopaenia with AS&AQ and not different from treatment groups; anaemia was higher with AS&AQ (20%) or other forms of ACT (22%) than in non-artemisinin groups (4%, p = 0.001). Multivariate analysis showed that the risk of anaemia, thrombocytopaenia, and leucopaenia decreased with follow-up time, while neutropaenia increased; the risk of anaemia and thrombocytopaenia increased with higher baseline parasitaemia and parasitological reappearance. White cells total count was not a good surrogate for neutropaenia. No systematic significant difference between treatments was detected. Older patients were at lower risks. The effects of AS&AQ on haematologic parameters were not different from those of other anti-malarial treatments used in sub

Determinants of hospital death in haematological cancers: findings from a qualitative study

PubMed Central

McCaughan, Dorothy; Roman, Eve; Smith, Alexandra G; Garry, Anne; Johnson, Miriam; Patmore, Russell; Howard, Martin

2018-01-01

Objectives Current UK health policy promotes enabling people to die in a place they choose, which for most is home. Despite this, patients with haematological malignancies (leukaemias, lymphomas and myeloma) are more likely to die in hospital than those with other cancers, and this is often considered a reflection of poor quality end-of-life care. This study aimed to explore the experiences of clinicians and relatives to determine why hospital deaths predominate in these diseases. Methods The study was set within the Haematological Malignancy Research Network (HMRN—www.hmrn.org), an ongoing population-based cohort that provides infrastructure for evidence-based research. Qualitative interviews were conducted with clinical staff in haematology, palliative care and general practice (n=45) and relatives of deceased HMRN patients (n=10). Data were analysed for thematic content and coding and classification was inductive. Interpretation involved seeking meaning, salience and connections within the data. Results Five themes were identified relating to: the characteristics and trajectory of haematological cancers, a mismatch between the expectations and reality of home death, preference for hospital death, barriers to home/hospice death and suggested changes to practice to support non-hospital death, when preferred. Conclusions Hospital deaths were largely determined by the characteristics of haematological malignancies, which included uncertain trajectories, indistinct transitions and difficulties predicting prognosis and identifying if or when to withdraw treatment. Advance planning (where possible) and better communication between primary and secondary care may facilitate non-hospital death. PMID:28663341

Where are we at with point-of-care testing in haematology?

PubMed

Briggs, Carol; Kimber, Simon; Green, Laura

2012-09-01

Point-of-care testing (POCT) in haematology has continued to grow in popularity and uptake throughout the world. The increasing demand to reduce the turnaround time of test results, coupled with rapid improvements in technology, have led to the development of several devices that are designed for use in different clinical settings, with the hope of improving patient care. The most used POCT in haematology is measurement of haemoglobin concentration. Other POCT devices (used primarily in developing countries) for malaria screening and CD4+ T-lymphocytes for quantification of human-immunodeficiency-virus are becoming the cornerstone for the diagnosis and management of these disorders. New devices are also available for red cell indices, white blood cell count and platelets. In this review clinical studies that validate the use of such devices will be discussed, as well as the advantages and disadvantages of POCT in haematology. A disadvantage of POCT is a lack of training, poor standardization in obtaining blood samples and insufficient internal/external quality assessment. As there is every reason to expect that POCT use will increase in all pathology disciplines, including haematology, it is imperative that systems are put in place to oversee these issues. © 2012 Blackwell Publishing Ltd.

Monoclonal antibody fluorescence for routine lymphocyte subpopulation analysis with the Abbott CELL-DYN Sapphire haematology analyser.

PubMed

Molero, T; Lemes, A; DE LA Iglesia, S; Scott, C S

2007-12-01

Using previously described procedures, this study quantified T-cell, T-cell subset, B-cell and NK-cell populations with the CD-Sapphire haematology analyser in a series of patients with mild to moderate lymphocytosis. Lymphocyte counts ranged from 6.0 to 14.9 x 10(9)/l, with 86/97 being <10.0 x 10(9)/l. Immunophenotyping (CD3/CD19/HLA-DR, CD4/CD8 and CD16/CD56 combinations) was performed using EDTA-anticoagulated blood, automated CD-Sapphire analysis and subsequent software processing. Of 35 samples from younger (<12 years) patients, 22 (63%) had nonspecific lymphocyte changes, 4 (11%) showed specific increases in nonreactive T-Helper or T-Suppressor cells, and five showed a reactive T-cell lymphocytosis. The remaining four were classified as 'Transient/Persistent NK-associated (NKa) Expansion' (n = 3) and specific B-cell lymphocytosis (n = 1). For older patients (n = 59), 15 (25%) had an increase (>1.5 x 10(9)/l) in B-cells, and seven investigated for surface immunoglobulin expression were all found to be clonal. The remaining samples were categorized as 'Transient/Persistent NK-associated (NKa) Expansion' (13/59), Reactive Lymphocytosis (5/59), 'Reactive Lymphocytosis or Transient/Persistent NKa Expansion' (8/59), specific T-Helper cell (n = 8) or T-Suppressor cell (n = 3) lymphocytosis, and 'Lymphocytosis of Undetermined Significance' (n = 7). This study has demonstrated the feasibility of applying limited immunophenotyping protocols to the investigation of patients with abnormal lymphocyte counts in routine haematology. By using commercially purchased liquid monoclonal reagents to determine lymphocyte subpopulation profiles, haematology laboratories can provide more definitive information of potential clinical importance.

Safety profile: fifteen years of clinical experience with ibuprofen.

PubMed

Royer, G L; Seckman, C E; Welshman, I R

1984-07-13

Since its introduction in the United States in 1974, ibuprofen (Motrin, Upjohn) has been shown to be safe and effective for the treatment of pain, dysmenorrhea, inflammation, and fever. A careful review of pre-registration and postmarketing data from both patients and normal subjects clearly indicates ibuprofen's remarkable safety profile compared with that of aspirin and other commonly prescribed nonsteroidal anti-inflammatory agents. Continued safety can be anticipated on the basis of the past 15 years of review experience.

Exploitation of molecular profiling techniques for GM food safety assessment.

PubMed

Kuiper, Harry A; Kok, Esther J; Engel, Karl-Heinz

2003-04-01

Several strategies have been developed to identify unintended alterations in the composition of genetically modified (GM) food crops that may occur as a result of the genetic modification process. These include comparative chemical analysis of single compounds in GM food crops and their conventional non-GM counterparts, and profiling methods such as DNA/RNA microarray technologies, proteomics and metabolite profiling. The potential of profiling methods is obvious, but further exploration of specificity, sensitivity and validation is needed. Moreover, the successful application of profiling techniques to the safety evaluation of GM foods will require linked databases to be built that contain information on variations in profiles associated with differences in developmental stages and environmental conditions.

Safety and efficacy of nelarabine in children and young adults with relapsed or refractory T-lineage acute lymphoblastic leukaemia or T-lineage lymphoblastic lymphoma: results of a phase 4 study.

PubMed

Zwaan, Christian Michel; Kowalczyk, Jerzy; Schmitt, Claudine; Bielorai, Bella; Russo, Mark W; Woessner, Mary; Ranganathan, Sulabha; Leverger, Guy

2017-10-01

Nelarabine is an antineoplastic agent approved for the treatment of relapsed/refractory T-lineage acute lymphoblastic leukaemia (T-ALL) or T-lineage acute lymphoblastic lymphoma (T-LBL). The purpose of this phase 4, multicentre, single-arm, observational, open-label trial was to provide additional data on the safety and efficacy of nelarabine under licensed conditions of use in children and young adults ≤21 years of age. Patients (N = 28) had a mean ± standard deviation age of 11·5 ± 4·6 years; 71% were male and 61% had a diagnosis of T-ALL. Adverse events (AEs) and treatment-related AEs were experienced by 46% and 21%, respectively, and included few haematological AEs and no haematological serious AEs. Neurological AEs from one of four predefined categories (peripheral and central nervous systems, mental status change and uncategorized) were reported in four patients. There were no AE-related treatment discontinuations/withdrawals. The overall response rate was 39.3%: complete response (CR), 35.7%; CR without full haematological recovery (CR*), 3.6%. Post-treatment stem cell transplantation was performed for 46% of the cohort. Median overall survival (OS) was 3·35 months for non-responders and not reached for responders (CR + CR*). The response rate, median OS, and safety profile of nelarabine in this disease setting and population were consistent with those reported previously. © 2017 John Wiley & Sons Ltd.

Determinants of hospital death in haematological cancers: findings from a qualitative study.

PubMed

McCaughan, Dorothy; Roman, Eve; Smith, Alexandra G; Garry, Anne; Johnson, Miriam; Patmore, Russell; Howard, Martin; Howell, Debra A

2018-03-01

Current UK health policy promotes enabling people to die in a place they choose, which for most is home. Despite this, patients with haematological malignancies (leukaemias, lymphomas and myeloma) are more likely to die in hospital than those with other cancers, and this is often considered a reflection of poor quality end-of-life care. This study aimed to explore the experiences of clinicians and relatives to determine why hospital deaths predominate in these diseases. The study was set within the Haematological Malignancy Research Network (HMRN-www.hmrn.org), an ongoing population-based cohort that provides infrastructure for evidence-based research. Qualitative interviews were conducted with clinical staff in haematology, palliative care and general practice (n=45) and relatives of deceased HMRN patients (n=10). Data were analysed for thematic content and coding and classification was inductive. Interpretation involved seeking meaning, salience and connections within the data. Five themes were identified relating to: the characteristics and trajectory of haematological cancers, a mismatch between the expectations and reality of home death, preference for hospital death, barriers to home/hospice death and suggested changes to practice to support non-hospital death, when preferred. Hospital deaths were largely determined by the characteristics of haematological malignancies, which included uncertain trajectories, indistinct transitions and difficulties predicting prognosis and identifying if or when to withdraw treatment. Advance planning (where possible) and better communication between primary and secondary care may facilitate non-hospital death. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Haematological alterations in the cardiac patient after use of an autotransfusion system.

PubMed

Luque-Oliveros, M

2018-02-01

There are studies that declare blood recovered with the autotransfusion system that is potentially heparinised and mixed with other drugs, can cause haematological alterations in the patient, according to existing evidence. The proposal was to compare the haematological values of the patients before reinfusing red blood cells from the cell saver and 12h after reinfusion. Observational analytical study of 479 patients who underwent cardiac surgery where the cell saver was used. Haematological variables were collected before reinfusion and 12h after reinfusion. Statistically significant haematological values before reinfusion and 12h after reinfusion were: haemoglobin (9.5 to 12.5g/dL), haematocrit (26 to 38%), platelets (214.2 to 164.210^3/μL), total proteins (7.6 to 5.1g/dL), PCR (8.5 to 22.1mg/L) and D-dimer (493.3 to 875.5μg/L) with P<.05. With the use of the cell saver an increase was observed of haemoglobin, haematocrit, PCR and D-dimer values together with a decrease in platelet and total protein numbers. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

PubMed

Albiti, Anisa H; Nsiah, Kwabena

2014-04-01

Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

The prevention and management of infections due to multidrug resistant organisms in haematology patients

PubMed Central

Trubiano, Jason A; Worth, Leon J; Thursky, Karin A; Slavin, Monica A

2015-01-01

Infections due to resistant and multidrug resistant (MDR) organisms in haematology patients and haematopoietic stem cell transplant recipients are an increasingly complex problem of global concern. We outline the burden of illness and epidemiology of resistant organisms such as gram-negative pathogens, vancomycin-resistant Enterococcus faecium (VRE), and Clostridium difficile in haematology cohorts. Intervention strategies aimed at reducing the impact of these organisms are reviewed: infection prevention programmes, screening and fluoroquinolone prophylaxis. The role of newer therapies (e.g. linezolid, daptomycin and tigecycline) for treatment of resistant and MDR organisms in haematology populations is evaluated, in addition to the mobilization of older agents (e.g. colistin, pristinamycin and fosfomycin) and the potential benefit of combination regimens. PMID:24341410

Preferred and actual place of death in haematological malignancy.

PubMed

Howell, D A; Wang, H I; Roman, E; Smith, A G; Patmore, R; Johnson, M J; Garry, A; Howard, M

2017-06-01

Home is considered the preferred place of death for many, but patients with haematological malignancies (leukaemias, lymphomas and myeloma) die in hospital more often than those with other cancers and the reasons for this are not wholly understood. We examined preferred and actual place of death among people with these diseases. The study is embedded within an established population-based cohort of patients with haematological malignancies. All patients diagnosed at two of the largest hospitals in the study area between May 2005 and April 2008 with acute myeloid leukaemia, diffuse large B-cell lymphoma or myeloma, who died before May 2010 were included. Data were obtained from medical records and routine linkage to national death records. 323 deceased patients were included. A total of 142 (44%) had discussed their preferred place of death; 45.8% wanted to die at home, 28.2% in hospital, 16.9% in a hospice, 5.6% in a nursing home and 3.5% were undecided; 63.4% of these died in their preferred place. Compared to patients with evidence of a discussion, those without were twice as likely to have died within a month of diagnosis (14.8% vs 29.8%). Overall, 240 patients died in hospital; those without a discussion were significantly more likely to die in hospital than those who had (p≤0.0001). Of those dying in hospital, 90% and 75.8% received haematology clinical input in the 30 and 7 days before death, respectively, and 40.8% died in haematology areas. Many patients discussed their preferred place of death, but a substantial proportion did not and hospital deaths were common in this latter group. There is scope to improve practice, particularly among those dying soon after diagnosis. We found evidence that some people opted to die in hospital; the extent to which this compares with other cancers is of interest. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Ask the eConsultant: Improving access to haematology expertise using an asynchronous eConsult system.

PubMed

Fogel, Adam; Khamisa, Karima; Afkham, Amir; Liddy, Clare; Keely, Erin

2017-04-01

Introduction The Champlain BASE (Building Access to Specialists through eConsultation) eConsultation service was designed to address the limited access to specialist care in Canada, which can lead to long waiting times and, subsequently, negative patient outcomes. Our primary objective was to perform an in-depth analysis of the use, content, and perceived value of haematology electronic consults (eConsults) submitted by primary care providers (PCPs) to the eConsult service. Methods We conducted a cross-sectional study using descriptive statistics to examine post-eConsult surveys for PCPs and other collected data including PCP designation, time for specialist to complete the eConsult, specialist response time, perceived value of the eConsult by the PCP, and the need for a face-to-face referral following the eConsult. A medically-trained author reviewed all haematology eConsults from April 2011 to January 2015, and categorized them by clinical topic and question type using validated taxonomies. Results Haematology accounted for 436 out of 5601 (7.8%) total eConsults, making it the third most popular service utilized. In 66% of haematology eConsults, a face-to-face consultation was not needed. Anaemia, neutropenia, and hyperferritinemia were the most common clinical queries. Most eConsult question types concerned the management of haematological disorders or the interpretation of laboratory tests. Most eConsults were answered within three days, using less than 15 minutes of the specialists' time. PCPs highly valued the service. Discussion This initiative increases access to haematology care and has the potential to reduce the long waiting times for non-urgent traditional consultation, along with the benefit of cost savings to the healthcare system.

Clinical and Haematological Manifestations of Typhoid Fever in Children in Eastern Turkey.

PubMed

Akbayram, S; Parlak, M; Dogan, M; Karasin, G; Akbayram, H T; Karaman, K

2016-01-12

Typhoid fever can involve various organs, leading to a wide range of presentations: from uncomplicated to complicated typhoid fever. The haematological changes are common in typhoid fever and include anaemia, leucopaenia, thrombocytopaenia and bleeding diathesis. This study was undertaken in order to determine the clinical and haematological presentation of typhoid fever in children. In this study, records of children and adolescents with typhoid fever aged under or equal to 16 years, admitted to Yuzuncu Yil University Hospital between 2010 and 2014, were analysed retrospectively. The cases (56%) were admitted to our hospital in July and October. Major symptoms of patients were abdominal pain (24%), arthralgia (21%) and fever (11%). In our study, decreased mean platelet volume (31%), eosinopaenia 20%), abnormal platelet count (19%), anaemia (16%), leucocytosis (16%) and eosinophilia (12%) were the most common haematological findings in the children. Typhoid fever is predominant in children at school age with a slight male predominance. Decreased mean platelet volume and abdominal pain might be useful as early diagnostic clues.

Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper.

PubMed

Sarmati, L; Andreoni, M; Antonelli, G; Arcese, W; Bruno, R; Coppola, N; Gaeta, G B; Galli, M; Girmenia, C; Mikulska, M; Pane, F; Perno, C F; Picardi, M; Puoti, M; Rambaldi, A; Svicher, V; Taliani, G; Gentile, G

2017-12-01

Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in patients with haematological disorders after chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Murphy, Michael F; Tinmouth, Alan

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in patients with haematological disorders after chemotherapy with or without stem cell transplantation. PMID:25722651

Effect of Ethanolic Leaf Extract of Senna Fistula on some Haematological Parameters, Lipid Profile and Oxidative Stress in Alloxan-induced Diabetic Rats.

PubMed

Ayinla, Tayo Maryam; Owoyele, Victor B; Yakubu, Toyin M

2015-12-20

Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. The disease is also known to adversely affect some haematological parameters and cause dyslipidemia. This study was designed to investigate the effect of chronic administration of ethanolic leave extract of Senna fistula on haematological values, oxidative stress and dyslipidemia in experimental diabetic rats. Twenty-four albino rats weighing 120-150 g were divided into 4 experimental groups of six rats each; control, diabetic untreated, diabetic treated with glibenclamide and diabetic treated with 100 mg/kg b.w of Senna fistula. Diabetes was induced by 100 mg/kg b.w. of alloxan monohydrates. The control and diabetic groups received normal saline while the diabetic treated groups were administered with 5mg/kg and 100mg/kg body weight of glibenclamide and ethanolic leaves extract of Senna fistula respectively for 28 days. At the end of experimental period blood samples were taken from the animals for the determination of Red blood cells (RBC), packed cell volume (PCV), Haemoglobin concentration (Hb), total cholesterol, triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and malondialdehyde (MDA), marker of lipid peroxidation. The result showed that in diabetic rats, PCV, RBC and Hb were decreased but the application of the extract increased the parameters. Similarly, the result showed a significant increase in total cholesterol, TG and LDL level of the diabetic group when compared with the control, glibenclamide and extract treated diabetic groups, however, there was no significant difference in HDL level in all the groups. The result also showed a significant decrease in elevated MDA of diabetic treated rats. These findings suggest that ethanolic leaves extract of Senna fistula might improve the diabetic induced disturbances of some haematological parameters, reduces

Pneumocystis jirovecii pneumonia: still a concern in patients with haematological malignancies and stem cell transplant recipients.

PubMed

Cordonnier, Catherine; Cesaro, Simone; Maschmeyer, Georg; Einsele, Hermann; Donnelly, J Peter; Alanio, Alexandre; Hauser, Philippe M; Lagrou, Katrien; Melchers, Willem J G; Helweg-Larsen, Jannik; Matos, Olga; Bretagne, Stéphane; Maertens, Johan

2016-09-01

Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%-60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence-based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Safety of tenofovir gel, a vaginal microbicide, in South African women: results of the CAPRISA 004 Trial.

PubMed

Sokal, David C; Karim, Quarraisha Abdool; Sibeko, Sengeziwe; Yende-Zuma, Nonhlanhla; Mansoor, Leila E; Baxter, Cheryl; Grobler, Anneke; Frolich, Janet; Kharsany, Ayesha Bm; Miya, Nomsa; Mlisana, Koleka; Maarshalk, Silvia; Karim, Salim S Abdool

2013-01-01

Tenofovir gel, used vaginally before and after coitus, reduced women's acquisition of HIV by 39%. This is a safety assessment of tenofovir gel, including renal, bone, gastrointestinal, genital and haematological parameters. In the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004, a double-blind, randomized placebo-controlled trial, 445 of the 889 eligibly enrolled women were assigned to tenofovir gel. All participants were advised to use the gel vaginally only, with one dose of gel within 12 h before and a second dose as soon as possible after sex, with no more than two doses in 24 h. Clinical and laboratory safety data were collected at monthly and quarterly visits, respectively. Genital assessments were undertaken at enrolment and quarterly thereafter, or as indicated. Women assigned to tenofovir gel were exposed to an average monthly vaginal dose of 240 mg of tenofovir (six applications). In total, six women, three in each group, had mild creatinine elevations, all of which occurred in July/August 2008. The incidence of anaemia was 3.5 and 3.8 per 100 women-years in tenofovir and placebo groups, respectively (P=0.80). Of the six women (four tenofovir and two placebo) experiencing bone fractures, none were associated with abnormal phosphate or calcium values. The proportion of women with diarrhoea was higher in the tenofovir gel group (17% versus 11%; P=0.026). There was no significant increase of any genital adverse event in the tenofovir group. No significant renal, haematological, genital or bone effects were associated with the use of tenofovir gel. Aside from a puzzling increase in diarrhoea, tenofovir gel has an excellent safety profile.

Excessive fluoride consumption increases haematological alteration in subjects with iron deficiency, thalassaemia, and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

PubMed

Pornprasert, Sakorn; Wanachantararak, Phenphichar; Kantawong, Fahsai; Chamnanprai, Supoj; Kongpan, Chatpat; Pienthai, Nattasit; Yanola, Jintana; Duangmano, Suwit; Prasannarong, Mujalin

2017-08-01

Excessive fluoride consumption leads to accelerated red blood cell death and anaemia. Whether that increases the haematological alteration in subjects with haematological disorders (iron deficiency, thalassaemia, and G-6-PD deficiency) is still unclear. The fluoride in serum and urine and haematological parameters of students at Mae Tuen School (fluoride endemic area) were analysed and compared to those of students at Baan Yang Poa and Baan Mai Schools (control areas). Iron deficiency, thalassaemia, and G-6-PD deficiency were also diagnosed in these students. The students at Mae Tuen School had significantly (P < 0.001) higher levels of mean fluoride in the serum and urine than those in control areas. In both control and fluoride endemic areas, students with haematological disorders had significantly lower levels of Hb, Hct, MCV, MCH, and MCHC than those without haematological disorders. Moreover, the lowest levels of Hb, MCH, and MCHC were observed in the students with haematological disorders who live in the fluoride endemic area. Thus, the excessive fluoride consumption increased haematological alteration in subjects with iron deficiency, thalassaemia, and G-6-PD deficiency and that may increase the risk of anaemia in these subjects.

Mixed donor chimerism in non-malignant haematological diseases after allogeneic bone marrow transplantation.

PubMed

Shamshad, Ghassan Umair; Ahmed, Suhaib; Bhatti, Farhat Abbas; Ali, Nadir

2012-12-01

To determine the frequency of mixed donor chimerism in patients of non-malignant haematological diseases after allogeneic bone marrow transplant. A cross-sectional, observational study. Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2010 to June 2011. Donor chimerism was assessed in patients of aplastic anaemia and beta-thalassaemia major who underwent allogeneic bone marrow transplantation (BMT). Peripheral blood samples were used to assess chimerism status by analysis of short tandem repeats (STR). In patients where pre-transplant blood sample was not available, swab of buccal mucosa was used for pre-transplant STR profile. A standard set of primers for STR markers were used and the amplified DNA was resolved by gel electrophoresis and stained with silver nitrate. The percentage of donor origin DNA was estimated by densitometer. Out of 84 patients, 52 (62%) were males, while 32 (38%) were females. In patients of beta-thalassaemia major, 31 (62%) developed mixed donor chimerism (MC), 13 (26%) developed complete donor chimerism (CC) and 6 (12%) had graft failure. In aplastic anaemia, 17 patients (50%) achieved MC, 13 (38.2%) had CC and 4 (11.8%) developed graft failure. The combined frequency of mixed donor chimerism for both the diseases was 58.3%. D3S1358 was the most informative STR marker in these patients. Majority of the studied patients developed mixed donor chimerism following bone marrow transplantation, whereas only a minor percentage of the patients had graft failure. Analysis of D3S1358 was the most informative in assessing donor chimerism in patients who underwent BMT.

Profiling contextual factors which influence safety in heavy vehicle industries.

PubMed

Edwards, Jason R D; Davey, Jeremy; Armstrong, Kerry A

2014-12-01

A significant proportion of worker fatalities within Australia result from truck-related incidents. Truck drivers face a number of health and safety concerns. Safety culture, viewed here as the beliefs, attitudes and values shared by an organisation's workers, which interact with their surrounding context to influence behaviour, may provide a valuable lens for exploring safety-related behaviours in heavy vehicle operations. To date no major research has examined safety culture within heavy vehicle industries. As safety culture provides a means to interpret experiences and generate behaviour, safety culture research should be conducted with an awareness of the context surrounding safety. The current research sought to examine previous health and safety research regarding heavy vehicle operations to profile contextual factors which influence health and safety. A review of 104 peer-reviewed papers was conducted. Findings of these papers were then thematically analysed. A number of behaviours and scenarios linked with crashes and non-crash injuries were identified, along with a selection of health outcomes. Contextual factors which were found to influence these outcomes were explored. These factors were found to originate from government departments, transport organisations, customers and the road and work environment. The identified factors may provide points of interaction, whereby culture may influence health and safety outcomes. Copyright © 2014. Published by Elsevier Ltd.

Long Non-Coding RNAs in Haematological Malignancies

PubMed Central

Garitano-Trojaola, Andoni; Agirre, Xabier; Prósper, Felipe; Fortes, Puri

2013-01-01

Long non-coding RNAs (lncRNAs) are functional RNAs longer than 200 nucleotides in length. LncRNAs are as diverse as mRNAs and they normally share the same biosynthetic machinery based on RNA polymerase II, splicing and polyadenylation. However, lncRNAs have low coding potential. Compared to mRNAs, lncRNAs are preferentially nuclear, more tissue specific and expressed at lower levels. Most of the lncRNAs described to date modulate the expression of specific genes by guiding chromatin remodelling factors; inducing chromosomal loopings; affecting transcription, splicing, translation or mRNA stability; or serving as scaffolds for the organization of cellular structures. They can function in cis, cotranscriptionally, or in trans, acting as decoys, scaffolds or guides. These functions seem essential to allow cell differentiation and growth. In fact, many lncRNAs have been shown to exert oncogenic or tumor suppressor properties in several cancers including haematological malignancies. In this review, we summarize what is known about lncRNAs, the mechanisms for their regulation in cancer and their role in leukemogenesis, lymphomagenesis and hematopoiesis. Furthermore, we discuss the potential of lncRNAs in diagnosis, prognosis and therapy in cancer, with special attention to haematological malignancies. PMID:23887658

Comparing diabetic with non-diabetic overweight subjects through assessing dietary intakes and key parameters of blood biochemistry and haematology.

PubMed

Gajda, Karolina; Sulich, Agnieszka; Hamułka, Jadwiga; Białkowska, Agnieszka

2014-01-01

An important way of preventing type 2 diabetes is by adopting a proper diet by which means appropriate control over blood glycaemia and lipids can be achieved. To assess selected biochemical and haematological markers in overweight subjects or those suffering from type 2 diabetes in relation to their estimated dietary intake. The study was conducted in 2012 on n = 86 overweight or obese subjects living in Warsaw or its environs, of whom n = 43 had type 2 diabetes. Dietary intakes were compared between non-diabetics (control group) and diabetics (test group) by 3 day records, whilst the relevant blood biochemistry and haematology results were obtained from medical records; with patient consent. Diabetic subjects had significantly higher serum glucose and CRP levels than controls, respectively; 190 vs 98 mg/ dl and 1.4 vs 1.1 mg/dl. Lipid profiles were however more significantly abnormal in controls, compared to diabetics with respectively; total cholesterol 220 vs 194 mg/dl, LDL-cholesterol 131 vs 107 mg/dl and triglycerides 206 vs 157 mg/dl. There were no significant differences in HDL-cholesterol; respectively 55 vs 51 mg/dl. In the diabetics, calorific intakes from carbohydrates, especially sugars, were significantly lower than controls i.e. 9% vs 13%. The proportional share of calories derived from dietary fats did not differ between groups, nevertheless a positive correlation was observed between dietary fat content with blood cholesterol concentrations in diabetics. Disorders of carbohydrate metabolism were confirmed in both overweight and diabetic (type 2) subjects. In addition, both groups demonstrated untoward lipid profiles that correlated with their improper nutrition.

Destined to die in hospital? Systematic review and meta-analysis of place of death in haematological malignancy

PubMed Central

2010-01-01

Background Haematological malignancies are a common, heterogeneous and complex group of diseases that are often associated with poor outcomes despite intensive treatment. Research surrounding end-of-life issues, and particularly place of death, is therefore of paramount importance, yet place of death has not been formally reviewed in these patients. Methods A systematic literature review and meta-analysis was undertaken using PubMed to identify all studies published between 1966 and 2010. Studies examining place of death in adult haematology patients, using routinely compiled morbidity and mortality data and providing results specific to this disease were included. 21 studies were identified with descriptive and/or risk-estimate data; 17 were included in a meta-analysis. Results Compared to other cancer deaths, haematology patients were more than twice as likely to die in hospital (Odds Ratio 2.25 [95% Confidence Intervals, 2.07-2.44]). Conclusion Home is generally considered the preferred place of death but haematology patients usually die in hospital. This has implications for patients who may not be dying where they wish, and also health commissioners who may be funding costly end-of-life care in inappropriate acute hospital settings. More research is needed about preferred place of care for haematology patients, reasons for hospital deaths, and how these can be avoided if home death is preferred. PMID:20515452

The Perspectives of Haematological Cancer Patients on Tissue Banking.

PubMed

Turon, Heidi; Waller, Amy; Clinton-McHarg, Tara; Boyes, Allison; Fleming, Jennifer; Marlton, Paula; Harrison, Simon J; Sanson-Fisher, Rob

2016-01-01

A high level of support for tissue banking has been identified amongst both the general public and patients. However, much debate remains about the regulatory framework of tissue banks. This study explored the views of haematological cancer patients regarding tissue banking and how tissue banks should operate. Haematological cancer patients from three outpatient clinics in Australia completed a questionnaire examining their preferences for tissue banking as well as items about their sociodemographic characteristics, disease and treatment history. The majority of participants (95%) reported being willing to allow their leftover tissue to be used for medical research. Three quarters (76%) supported the idea of their medical record being linked to their tissue sample, and 77% preferred a blanket (one-off) consent model for future research use of their tissue sample. Only 57 (27%) participants had been asked to give a tissue sample for research, 98% of whom gave permission. The majority of haematological cancer patients are willing to donate their leftover tissue to a tissue bank and have their medical records linked to tissue samples and prefer a one-off consent process. These novel data from potential donors inform the debate about how tissue banks might operate. Strategic Research Partnership Grant from the Cancer Council NSW to the Newcastle Cancer Control Collaborative (New-3C) and infrastructure funding from the Hunter Medical Research Institute (HMRI). A.W. is supported by an Australian Research Council DECRA fellowship (DE150101262). T.C.M. was supported by a Leukaemia Foundation of Queensland Post-Doctoral Fellowship. A.B. is supported by National Health and Medical Research Council (APP1073317) and Cancer Institute NSW (13/ECF/1-37) Early Career Fellowships.

Screening haematology patients for carbapenem-resistant Klebsiella pneumoniae

PubMed Central

Kilgour, Elizabeth; Dunn, Caroline; Thomas, Linda; Fox, Richard; Mitchell, Lindsay; Paterson, Pamela

2013-01-01

Following a cluster of haematology patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) septicaemia, we initiated screening for rectal carriage of CRKP and multidrug-resistant K. pneumoniae (MDRKP) in this patient group. Haematology inpatients submit a rectal swab once weekly. When plated onto chromogenic Brilliance™ UTI Agar (Oxoid), and incubated overnight with a 10 µg ertapenem disc (Oxoid), K. pneumoniae is identified and semi-automated antibiotic susceptibility testing is performed using the Vitek 2 analyser (Biomerieux). When no zone of inhibition occurs, immediate intervention through patient isolation and enhanced environmental cleaning can be instigated to control further spread while empirical antibiotic prescribing is adapted to take account of identified resistances. Over 2 years, six patients with CRKP and 20 patients with MDRKP were identified. These isolates were resistant to first-line empirical treatment choices for neutropenic sepsis and presented a clinical risk of treatment failure for sepsis post cytotoxic chemotherapy. We describe how this rectal screening methodology was developed and how the results influenced appropriate antibiotic prescribing, patient placement in single rooms and the cleaning of the ward environment to prevent person-to-person transmission of MDRKP and CRKP. PMID:28989355

Bloodstream infections in haematology: risks and new challenges for prevention.

PubMed

Worth, Leon J; Slavin, Monica A

2009-05-01

Bloodstream infections are an important cause of morbidity and mortality in the haematology population, and may contribute to delayed administration of chemotherapy, increased length of hospitalisation, and increased healthcare expenditure. For gram-positive, gram-negative, anaerobic and fungal infections, specific risk factors are recognised. Unique host and environmental factors contributing to pathogenesis are acknowledged in this population. Trends in spectrum and antimicrobial susceptibility of pathogens are examined, and potential contributing factors are discussed. These include the widespread use of empiric antimicrobial therapy, increasingly intensive chemotherapeutic regimens, frequent use of central venous catheters, and local infection control practices. In addition, the risks and benefits of prophylaxis, and spectrum of endemic flora are identified as relevant factors within individual centres. Finally, challenges are presented regarding prevention, early detection, surveillance and prophylaxis. To reduce the rate and impact of bloodstream infections multifaceted and customised strategies are required within individual haematology units.

Molecular diagnosis of bloodstream infections in onco-haematology patients with PCR/ESI-MS technology.

PubMed

Jordana-Lluch, Elena; Rivaya, Belén; Marcó, Clara; Giménez, Montserrat; Quesada, Mª Dolores; Escobedo, Agustín; Batlle, Montserrat; Martró, Elisa; Ausina, Vicente

2017-02-01

Onco-haematological patients are prone to develop infections, and antibiotic prophylaxis may lead to negative blood cultures. Thus, the microbiological diagnosis and subsequent administration of a targeted antimicrobial therapy is often difficult. The goal of this study was to evaluate the usefulness of IRIDICA (PCR/ESI-MS technology) for the molecular diagnosis of bloodstream infections in this patient group. A total of 463 whole blood specimens from different sepsis episodes in 429 patients were analysed using the PCR/ESI-MS platform, comparing the results with those of blood culture and other clinically relevant information. The sensitivity of PCR/ESI-MS by specimen (excluding polymicrobial infections, n = 25) in comparison with blood culture was 64.3% overall, 69.0% in oncological patients, and 59.3% in haematological patients. When comparing with a clinical infection criterion, overall sensitivity rose to 74.7%, being higher in oncological patients (80.0%) than in haematological patients (67.7%). Thirty-one microorganisms isolated by culture were not detected by IRIDICA, whereas 42 clinically relevant pathogens not isolated by culture were detected moleculary. PCR/ESI-MS offers a reliable identification of pathogens directly from whole blood. While additional studies are needed to confirm our findings, the system showed a lower sensitivity in onco-haematological patients in comparison with previously reported results in patients from the Intensive Care Unit. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Haematological and biochemical reference intervals for free-ranging brown bears (Ursus arctos) in Sweden

PubMed Central

2014-01-01

Background Establishment of haematological and biochemical reference intervals is important to assess health of animals on individual and population level. Reference intervals for 13 haematological and 34 biochemical variables were established based on 88 apparently healthy free-ranging brown bears (39 males and 49 females) in Sweden. The animals were chemically immobilised by darting from a helicopter with a combination of medetomidine, tiletamine and zolazepam in April and May 2006–2012 in the county of Dalarna, Sweden. Venous blood samples were collected during anaesthesia for radio collaring and marking for ecological studies. For each of the variables, the reference interval was described based on the 95% confidence interval, and differences due to host characteristics sex and age were included if detected. To our knowledge, this is the first report of reference intervals for free-ranging brown bears in Sweden. Results The following variables were not affected by host characteristics: red blood cell, white blood cell, monocyte and platelet count, alanine transaminase, amylase, bilirubin, free fatty acids, glucose, calcium, chloride, potassium, and cortisol. Age differences were seen for the majority of the haematological variables, whereas sex influenced only mean corpuscular haemoglobin concentration, aspartate aminotransferase, lipase, lactate dehydrogenase, β-globulin, bile acids, triglycerides and sodium. Conclusions The biochemical and haematological reference intervals provided and the differences due to host factors age and gender can be useful for evaluation of health status in free-ranging European brown bears. PMID:25139149

Internet use for health information among haematology outpatients: a cross-sectional survey.

PubMed

Laurent, Michaël R; Cremers, Saskia; Verhoef, Gregor; Dierickx, Daan

2012-03-01

Patients are increasingly seeking health information on the Internet, but to the best of our knowledge, this has not been previously studied in haematology. We aimed to characterise online health information use and associated variables among adult outpatients in our tertiary-care centre in Flanders, Belgium. During a 6-week period, we distributed 477 anonymous self-administered questionnaires and received 451 (response rate 94.5%), of which 444 (93.1% of total) contained information on Internet use for health information, the primary outcome. Two hundred and thirty-two respondents (52.3%) had ever sought any health information online, and 187 (33.1%) conducted searches pertaining to their haematological disease in the past year. The latter was independently associated with younger age and a higher level of education in multivariate analysis. Internet users ranked the Internet higher and other resources lower as health information resources. Among Internet users, 196 (89.5%) would be interested in a list of reliable websites about their disease. Patients reported positive and negative aspects of online health information-seeking; it increased anxiety in some while it stimulated coping in others. We conclude that haematological patients commonly use the Internet for health information and report both positive and negative aspects of using this medium.

Atorvastatin calcium encapsulated eudragit nanoparticles with enhanced oral bioavailability, safety and efficacy profile.

PubMed

Kumar, Nagendra; Chaurasia, Sundeep; Patel, Ravi R; Khan, Gayasuddin; Kumar, Vikas; Mishra, Brahmeshwar

2017-03-01

Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.

Assessment of depression and anxiety in haematological cancer patients and their relationship with quality of life.

PubMed

Priscilla, Das; Hamidin, Awang; Azhar, M Zain; Noorjan, Khin Ohnmar Naing; Salmiah, M Said; Bahariah, Khalid

2011-09-01

To determine the relationship between major depressive disorder, anxiety disorders and the quality of life of haematological cancer patients. This cross-sectional study was conducted at Ampang Hospital Kuala Lumpur, Malaysia, a tertiary referral centre hospital for haematological cancer. The Mini-International Neuropsychiatric Interview was used for the diagnosis of major depressive disorder and anxiety disorders. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire was utilised to measure patients' quality of life. A total of 105 haematological cancer patients were included in the study with response rate of 100%. Major depressive disorder correlated with almost all domains of the quality of life, except the pain scores. Logistic regression showed that insomnia and financial difficulties were related to major depressive disorder. Different anxiety disorders also correlated with quality of life in specific domains. The leading anxiety disorders that correlated mostly with quality-of-life scales were generalised anxiety disorder, followed by obsessive-compulsive disorder, social anxiety disorder, as well as post-traumatic stress disorder and panic disorder with agoraphobia (p<0.05). Psychological treatment along with medication and intervention should be implemented to improve the overall quality of life and psychiatric disorder symptoms among the haematological cancer patients.

Standardization of haematology critical results management in adults: an International Council for Standardization in Haematology, ICSH, survey and recommendations.

PubMed

Keng, T B; De La Salle, B; Bourner, G; Merino, A; Han, J-Y; Kawai, Y; Peng, M T; McCafferty, R

2016-10-01

These recommendations are intended to develop a consensus in the previously published papers as to which parameters and what values should be considered critical. A practical guide on the standardization of critical results management in haematology laboratories would be beneficial as part of good laboratory and clinical practice and for use by laboratory-accrediting agencies. A working group with members from Europe, America, Australasia and Asia was formed by International Council for Standardization in Haematology. A pattern of practice survey of 21 questions was distributed in 2014, and the data were collected electronically by Survey Monkey. The mode, or most commonly occurring value, was selected as the threshold for the upper and lower alert limits for critical results reporting. A total of 666 laboratories submitted data to this study and, of these, 499 submitted complete responses. Full blood count critical results alert thresholds, morphology findings that trigger critical result notification, critical results alert list, notification process and maintenance of critical results management protocol are described. This international survey provided a snapshot of the current practice worldwide and has identified the existence of considerable heterogeneity of critical results management. The recommendations in this study represent a consensus of good laboratory practice. They are intended to encourage the implementation of a standardized critical results management protocol in the laboratory. © 2016 John Wiley & Sons Ltd.

What are the barriers of quality survivorship care for haematology cancer patients? Qualitative insights from cancer nurses.

PubMed

Langbecker, Danette; Ekberg, Stuart; Yates, Patsy; Chan, Alexandre; Chan, Raymond Javan

2016-02-01

Many haematological cancer survivors report long-term physiological and psychosocial effects beyond treatment completion. These survivors continue to experience impaired quality of life (QoL) as a result of their disease and aggressive treatment. As key members of the multidisciplinary team, the purpose of this study is to examine the insights of cancer nurses to inform future developments in survivorship care provision. Open text qualitative responses from two prospective Australian cross-sectional surveys of nurses (n = 136) caring for patients with haematological cancer. Data were analysed thematically, using an inductive approach to identify themes. This study has identified a number of issues that nurses perceive as barriers to quality survivorship care provision. Two main themes were identified: the first relating to the challenges nurses face in providing care ('care challenges') and the second relating to the challenges of providing survivorship care within contemporary health care systems ('system challenges'). Cancer nurses perceive the nature of haematological cancer and its treatment and of the health care system itself, as barriers to the provision of quality survivorship care. Care challenges such as the lack of a standard treatment path and the relapsing or remitting nature of haematological cancers may be somewhat intractable, but system challenges relating to clearly defining and delineating professional responsibilities and exchanging information with other clinicians are not. Addressing the issues identified will facilitate cancer nurses' provision of survivorship care and help address haematological survivors' needs with regard to the physical and psychosocial consequences of their cancer and treatment.

Some haematological parameters in human immunodeficiency virus (HIV) infected Africans: the Nigerian perspective.

PubMed

Erhabor, O; Ejele, O A; Nwauche, C A; Buseri, F I

2005-01-01

Haematologic abnormalities are among the most common manifestations of advanced human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). A specific diagnosis of cause, severity and mechanism of cytopenia should be sought because of specific treatments or intervention may be indicated for its correction. This study was to determine some haematological parameters in HIV/AIDS infected Nigerians. One hundred HIV/AIDS infected previously antiretroviral naïve adult Nigerians, aged 18-58 year (males 47 and females 53) consisting of 88 symptomatic and 12 asymptomatic patients recruited into the antiretroviral pilot project in the Haematology department of the University of Port Harcourt Teaching Hospital between June 2002 to July 2003 were studied. Haematological parameters of hemoglobin, white cell count, platelet count, erythrocyte sedimentation rate and differential leucocyte count were determined. Data was analyzed using a multipurpose statistical package version 9 SPSS. The mean haemoglobin was 10.25 +/- 1.97 g/dl (range 6.31-14.2 g/dl), severe anaemia occurred in 80% of subjects while 20% were non-anaemic. Haemoglobin values was found positively correlated to lymphocyte count (r = .319, P = 0.01) and inversely correlated to ESR (r = -.343, P = 0.01) and neutrophil count (r = -.343, P = 0.01). Red cell morphology was variable with majority normochromic and normocytic (64%) and 36% showing hypochromia and anisopoikilocytosis. The mean total WBC count was 4.51 +/- 1.82 x 10(9)/l (range 0.9-8.2 x 10(9)/l). Leucopaenia occurred in 10/100 (10%) of study population. Total white cell count showed a significant inverse correlation to lymphocyte count (r = -.326, P = 0.01). The mean neutrophil count was 2.32 +/- 1.58 x 10(9)/l (range 0.00-5.48). Neutropaenia occurred in 24% of subjects. Neutrophil count showed a significant positive correlation with total white cell count (r = .314, P = 0.01) and a negative correlation with lymphocyte count

Curriculum Design of a Flipped Classroom to Enhance Haematology Learning

ERIC Educational Resources Information Center

Porcaro, Pauline A.; Jackson, Denise E.; McLaughlin, Patricia M.; O'Malley, Cindy J.

2016-01-01

A common trend in higher education is the "flipped" classroom, which facilitates active learning during class. The flipped approach to teaching was instituted in a haematology "major" class and the students' attitudes and preferences for the teaching materials were surveyed. The curriculum design was explicit and involved four…

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes.

PubMed

Kullenberg, Torbjörn; Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

2016-08-01

Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. ClincialTrials.gov, clinicaltrials.gov, NCT00069329. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes

PubMed Central

Löfqvist, Malin; Leinonen, Mika; Goldbach-Mansky, Raphaela; Olivecrona, Hans

2016-01-01

Objective. Anakinra is approved for the treatment of RA and cryopyrin-associated periodic syndromes (CAPS). While the anakinra safety profile is well established in RA, the long-term safety profile in severe CAPS is less well documented and will therefore be discussed in this report. Methods. A prospective, open-label, single centre, clinical cohort study was conducted at the National Institutes of Health in the USA, from 2003 to 2010, investigating the efficacy and safety of anakinra treatment for up to 5 years in 43 patients with CAPS. Safety was evaluated using adverse event (AE) reports, laboratory assessments, vital signs and diary reports. Results. In total, 1233 AEs were reported during the study, with a yearly rate of 7.7 AEs per patient. The event rate decreased over time, and dose escalation during the study did not affect AE frequency. Anakinra had similar safety profiles in adults and children. The most frequently reported AEs were typical CAPS disease symptoms such as headache and arthralgia. Injection site reactions occurred mainly during the first month of anakinra treatment. In total, 14 patients experienced 24 serious AEs (SAEs), all of which resolved during the study period. The most common types of SAEs were infections such as pneumonia and gastroenteritis. There were no permanent discontinuations of treatment due to AEs. Conclusion. In this study anakinra treatment of patients with severe CAPS for up to 5 years was safe and well tolerated both in paediatric and adult patients, with most AEs emerging during the first months after treatment initiation. Trial registration: ClincialTrials.gov, clinicaltrials.gov, NCT00069329 PMID:27143789

Who are the support persons of haematological cancer survivors and how is their performance perceived?

PubMed

Hall, Alix; Lynagh, Marita; Carey, Mariko; Sanson-Fisher, Rob; Mansfield, Elise

2017-12-01

To explore: (1) how haematological cancer survivors and their support persons perceive the overall performance of the support person; (2) disagreement between survivor and support person ratings; and (3) characteristics associated with support persons rating their performance poorly. This is a substudy of a larger project of Australian haematological cancer survivors and their support persons. For this substudy, haematological cancer survivors were recruited from 4 Australian population-based cancer registries and asked to pass on a questionnaire package to their support persons. Survivors who passed on a questionnaire package to their support person were asked to answer questions about the support person and how they perceived the support person's performance. Similarly, support persons answered questions on their own performance as a support person. A total of 924 haematological cancer survivors and 821 support persons were eligible for this study. Most survivors rated their support person as performing very well (84%) while less than half (48%) of support persons rated their own performance as very well. There was significant disagreement between survivor and their support person (dyad) ratings of the support person's performance. Support persons with above normal levels of depression (vs those with normal levels) had significantly higher odds of rating their own performance as "not well/somewhat well." Health care providers should consider providing additional education and skills-based interventions to support persons who experience increased symptoms of depression. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of pretreatment with chromium picolinate on haematological parameters during dengue virus infection in mice.

PubMed

Shrivastava, Richa; Nagar, R; Ravishankar, G A; Upreti, R K; Chaturvedi, U C

2007-11-01

Dengue virus (DV) has caused severe epidemics of dengue fever (DF) and dengue haemorrhagic fever (DHF) and is endemic all over India. We have earlier reported that exposure of mice to hexavalent chromium [Cr(VI)] compounds increased the severity of dengue virus infection. Trivalent chromium picolinate (CrP) is used worldwide as micronutrient and nutritional supplement. The present study was therefore, carried out to investigate the effects of CrP on various haematological parameters during DV infection of mice. The Swiss Albino smice were inoculated with dengue virus (1000 LD50, intracerebrally) and fed with chromium picolinate (CrP) in drinking water (100 and 250 mg/l) for 24 wk. Peripheral blood leucocytes and other haematological parameters, and spleens were studied on days 4 and 8 after virus inoculations and the findings were compared with those given only CrP and the normal control age matched mice. CrP in drinking water for 24 wk had no significant effects on peripheral blood cells of mice. On the other hand, there was significant decrease in different haematological parameters following inoculation of normal mice with DV. In CrP fed mice the effects of DV infection were abolished on most of the haematological parameters. The findings of present study showed that the adverse effects of DV infection, specially on platelets and leucocytes, were abrogated by pretreatment of mice with CrP. The therapeutic utility of CrP in viral infections including dengue needs to be studied in depth.

Audit of clinical-laboratory practices in haematology and blood transfusion at Muhimbili National Hospital in Tanzania.

PubMed

Makubi, Abel N; Meda, Collins; Magesa, Alex; Minja, Peter; Mlalasi, Juliana; Salum, Zubeda; Kweka, Rumisha E; Rwehabura, James; Quaresh, Amrana; Magesa, Pius M; Robert, David; Makani, Julie; Kaaya, Ephata

2012-10-01

In Tanzania, there is paucity of data for monitoring laboratory medicine including haematology. This therefore calls for audits of practices in haematology and blood transfusion in order to provide appraise practice and devise strategies that would result in improved quality of health care services. This descriptive cross-sectional study which audited laboratory practice in haematology and blood transfusion at Muhimbili National Hospital (MNH) aimed at assessing the pre-analytical stage of laboratory investigations including laboratory request forms and handling specimen processing in the haematology laboratory and assessing the chain from donor selection, blood component processing to administration of blood during transfusion. A national standard checklist was used to audit the laboratory request forms (LRF), phlebotomists' practices on handling and assessing the from donor selection to administration 6f blood during transfusion. Both interview and observations were used. A total of 195 LRF were audited and 100% of had incomplete information such as patients' identification numbers, time sample ordered, reason for request, summary of clinical assessment and differential diagnoses. The labelling of specimens was poorly done by phlebotomists/clinicians in 82% of the specimens. Also 65% (132/202) of the blood samples delivered in the haematology laboratory did not contain the recommended volume of blood. There was no laboratory request form specific for ordering blood and there were no guidelines for indication of blood transfusion in the wards/ clinics. The blood transfusion laboratory section was not participating in external quality assessment and the hospital transfusion committee was not in operation. It is recommended that a referral hospital like MNH should have a transfusion committee to provide an active forum to facilitate communication between those involved with transfusion, monitor, coordinate and audit blood transfusion practices as per national

Effects of bedrest 1: cardiovascular, respiratory and haematological systems.

PubMed

Knight, John; Nigam, Yamni; Jones, Aled

This is the first in a three-part series on the physiological effects of bedrest. It discusses what happens to the cardiovascular, respiratory and haematological systems when a person is bedridden. Other articles in the series will cover the effects of immobility on the digestive, endocrine, renal, nervous, immune and musculoskeletal systems and will examine the effects of bedrest on the skin.

Wage-subsidised employment as a result of permanently reduced work capacity in a nationwide cohort of patients diagnosed with haematological malignancies.

PubMed

Horsboel, Trine A; Nielsen, Claus V; Nielsen, Bendt; Andersen, Niels T; De Thurah, Annette

2015-05-01

Patients with haematological malignancies have a poorer labour market prognosis than the general population. We have previously found that they have low rates of return to work, and a higher risk of being granted disability pension, than individuals without a history of these diseases. The aim of this study was to further investigate the labour market prognosis for these patients, by comparing the risk of being granted wage-subsidised (WS) employment as a result of permanently reduced work capacity among patients diagnosed with haematological malignancies to a reference cohort, and to determine if relative risks differ between subtypes of haematological malignancies. We combined data from national registers on Danish patients diagnosed with haematological malignancies between 2000 and 2007 and a reference cohort without a history of these diseases. A total of 3194 patients and 28 627 reference individuals were followed until they were granted WS employment, disability pension, anticipatory pension, old age pension, emigration, death or until 26 February 2012, whichever came first. A total of 310 (10%) patients and 795 (3%) reference individuals had their work capacity permanently reduced to an extent that they were granted WS employment during the follow-up period. Age- and gender-adjusted relative risks differed significantly between the subgroups of haematological malignancies, and four years after diagnosis they ranged from 2.47 (95% CI 1.46-4.16) for patients with Hodgkin lymphoma to 10.83 (95% CI 7.15-16.40) for patients with chronic myeloid leukaemia. All eight subtypes of haematological malignancies were associated with an increased risk of being granted WS employment due to permanently reduced work capacity compared to the reference cohort. The relative risks differed according to haematological malignancy subtype, and the highest was found for patients with chronic myeloid leukaemia.

A molecular and haematological study of Theileria equi in Balkan donkeys.

PubMed

Davitkov, Dajana; Davitkov, Darko; Vucicevic, Milos; Stanisic, Ljubodrag; Radakovic, Milena; Glavinic, Uros; Stanimirovic, Zoran

2017-06-01

Equine piroplasmosis in donkeys has been recognised as a serious problem of major economic importance. The present molecular study is the first investigation of the presence of Theileria equi and Babesia caballi in Balkan donkeys and of the possible haematological alterations related to it. A total of 70 apparently healthy donkeys from Serbia were included in this study. The overall prevalence of T. equi infection in donkeys tested with multiplex PCR was 50%. There was no B. caballi-positive sample. Infections in donkeys included in this study seem to be associated with decreased red blood cell count, haemoglobin concentration, haematocrit and platelet count, and with increased white blood cell count, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. Altered haematological parameters in donkeys can lead to a decrease in working capacity and production performance. Further molecular research and long-term monitoring of equine piroplasmosis is needed in Serbia and throughout Europe.

Food caregivers influence on nutritional intake among admitted haematological cancer patients - a prospective study.

PubMed

Lindman, Astrid; Rasmussen, Helle Brygger; Andersen, Niels Frost

2013-12-01

Haematological cancer patients have an increased risk of undernourishment due to their malignancy, treatment toxicity and severe infections. This study examines whether kitchen assistants working as food caregivers increase nutritional intake and knowledge among haematological cancer patients. Comparison of two cross-sectional studies with dietary assessment of patients with haematological malignancies before (N = 42) and after (N = 45) implementation of food caregivers. Secondly, a questionnaire concerning dietary counselling performed before (N = 74) and after (N = 78) the implementation. The energy requirements were fulfilled with 76.2% (CI 95% 64.6-87.9) and 93.3% (CI 95% 82.3-104.3) of the calculated need in the before-group and the after-group, respectively (p = 0.03). The improvement was mainly due to increased energy intake through between meal snacks served by the food caregivers. There was no difference in protein intake between the two groups. The study showed that more than two-thirds of the patients in both groups had side effects like fatigue, loss of appetite, vomiting, xerostomia or taste disorder to a degree that affected nutritional intake. When adjusted for side effects, patients in the after-group increased energy intake by 22% (CI 95% 6.1-38.0) (p = 0.007). After implementation of food caregivers significantly more patients stated that they were informed about their nutritional needs, 41% in the before-group and 67% in the after-group (p = 0.001). Educated and trained food caregivers working at the wards increase nutritional intake and knowledge among haematological cancer patients and play an important role in the multi professional nutritional management. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of haematology, coagulation and clinical chemistry parameters in blood samples from the sublingual vein and vena cava in Sprague-Dawley rats.

PubMed

Seibel, J; Bodié, K; Weber, S; Bury, D; Kron, M; Blaich, G

2010-10-01

The investigation of clinical pathology parameters (haematology, clinical chemistry and coagulation) is an important part of the preclinical evaluation of drug safety. However, the blood sampling method employed should avoid or minimize stress and injury in laboratory animals. In the present study, we compared the clinical pathology results from blood samples collected terminally from the vena cava (VC) immediately before necropsy with samples taken from the sublingual vein (VS) also prior to necropsy in order to determine whether the sampling method has an influence on clinical pathology parameters. Forty-six 12-week-old male Sprague-Dawley rats were assigned to two groups (VC or VS; n = 23 each). All rats were anaesthetized with isoflurane prior to sampling. In the VC group, blood was withdrawn from the inferior VC. For VS sampling, the tongue was gently pulled out and the VS was punctured. The haematology, coagulation and clinical chemistry parameters were compared. Equivalence was established for 13 parameters, such as mean corpuscular volume, white blood cells and calcium. No equivalence was found for the remaining 26 parameters, although they were considered to be similar when compared with the historical data and normal ranges. The most conspicuous finding was that activated prothrombin time was 30.3% less in blood taken from the VC (16.6 ± 0.89 s) than that in the VS samples (23.8 ± 1.58 s). Summing up, blood sampling from the inferior VC prior to necropsy appears to be a suitable and reliable method for terminal blood sampling that reduces stress and injury to laboratory rats in preclinical drug safety studies.

The Efficacy of Nardostachys Jatamansi Against The Radiation Induced Haematological Damage In Rats

PubMed Central

Gowda, Damodara K M; Shetty, Lathika; A P, Krishna; Kumari, Suchetha N; Sanjeev, Ganesh; P, Naveen

2013-01-01

Introduction: Radiation is increasingly being used for medical purposes and it is an established weapon in the diagnosis and the therapy of cancer. An exposure to 1-2 Gys causes the NVD (Nausea, vomiting, diarrhoea) syndrome, whereas an exposure to 2-6 Gys causes the haematopoietic syndrome. The aim of the present study was to investigate the protective effect of the Nardostachys jatamansi root extract (NJE) on the radiation induced haematological damage in rats. Materials and Methods: EBR was performed at the Microtron Centre, Mangalore University, India. Rats were treated with NJE once daily for 15 days before and after the irradiation. After the irradiation, blood was collected for determining the peripheral blood counts (RBC and WBC), haemoglobin, the platelet count and the packed cell volume (PCV) at 6 hours, 12 hours, 24 hours, 48 hours and 5, 10 and 15 days post irradiation. The data was analyzed by one way ANOVA, followed by the Tukey’s test for multiple comparisons. Result: NJE provided protection against the radiation induced haematological disorders. The rats treated with NJE exhibited a time dependent significant elevation in all the haematological parameters which were studied and its modulation upto the near normal level was recorded. Conclusion: From this study, we concluded that, NJE provides protection by modulating the radiation induced damage on the haematopoietic system. PMID:23905085

Effect of Sweet Orange Fruit Waste Diets and Acidifier on Haematology and Serum Chemistry of Weanling Rabbits

PubMed Central

Daudu, Oluremi Martha; Sani, Rahamatu Usman; Adedibu, Iyetunde Ifeyori; Ademu, Lawrence Anebi; Bawa, Gideon Shaibu; Olugbemi, Taiye Sunday

2014-01-01

A total of thirty-five mixed breed (35) rabbits of average weight of 700 g aged 5-6 weeks were allocated to seven treatments in a completely randomised design to investigate the effect of sweet orange fruit waste (SOFW) and acidomix acidifier on haematology and serum chemistry. The diets were 0% SOFW, 10% SOFW with 0.5% acidomix, 10% SOFW with 0.7 acidomix, 15% SOFW with 0.5% acidifier, 15% SOFW with 0.7% acidifier, 20% SOFW with 0.5% acidifier, and 20% SOFW with 0.7% acidifier. Blood samples were analyzed for haemoglobin (hb) concentration, white blood cells (WBC), red blood cells (RBC), differential WBC count (lymphocyte, basophil, eosinophil, monocyte, and neutrophil), alanine amino transferase (ALT), alkaline phosphatase (ALP), aspartate amino transferase (AST), total protein, albumin, and globulin. There was no interaction between SOFW and acidifier for the haematological and most of the serum chemistry parameters but significant difference was observed in ALT; however the values were within the normal range. SOFW had no significant effect on all haematological and serum chemistry parameters. Acidomix had significant effect (P < 0.05) on haemoglobin concentration; rabbits fed 0.5% acidomix diets had higher values which were within the normal range. It is therefore concluded that SOFW with acidifier up to 20% had no detrimental effect on serum chemistry and haematology. PMID:26464931

[Effectiveness of palifermin in the prevention of oral mucositis in patients with haematological cancers].

PubMed

Ayago Flores, D; Ferriols Lisart, R

2010-01-01

To assess the effectiveness of palifermin for the prevention of oral mucositis in patients with haematological cancers. Retrospective observational study of cohorts of patients with haematological cancer undergoing cytotoxic therapy causing hematopoietic ablation. The main variable assessed was the duration of the oral mucositis. Secondary variables assessed were incidence of mucositis, febrile or septic neutropenia and the administration of opioids and parenteral nutrition. We included 36 patients in this study, 11 in the group that received palifermin and 25 in the control group. The duration of oral mucositis was 4.6+/-3.1 days (median: 5 days) in the patients treated with palifermin in comparison with 7.4+/-4.0 days (median: 6 days) in patients treated with conventional prophylactic therapy (p<0.05). However, no significant differences were seen in the incidence of mucositis, febrile or septic neutropenia, opioid administration of the use of parenteral nutrition. Prophylactic treatment with palifermin reduces the duration of oral mucosities in patients with haematological cancer. Further studies are necessary with larger samples to be able to assess palifermin and its influence on other variables, such as incidence of mucositis, sepsis, febrile neutropenia, etc. Copyright © 2009 SEFH. Published by Elsevier Espana. All rights reserved.

Communication during haematological consultations; patients' preferences and professionals' performances.

PubMed

van Bruinessen, Inge R; van der Hout, Lotte E; van Weel-Baumgarten, Evelyn M; Gouw, Hans; Zijlstra, Josée M; van Dulmen, Sandra

2016-06-01

Many patients with haematological malignancies experience barriers in clinical communication. Reaching effective communication is of great importance as it has been linked to a range of improved patient outcomes such as satisfaction, compliance to treatment, perceived quality of life and physical and mental health. To get a better understanding how communication in haematological consultations can be improved, the current study focussed on patients' preferences and perceived performances regarding the communicative behaviour of their health care professional. Secondly, the mediation of an online communication tool for patients was analysed. Within a controlled pre- post-test design, 78 datasets of clinical consultations could be analysed. Patients considered both affective and instrumental communication aspects important. The affective communication behaviour of the health care professional met the patients' pre-visit preferences well. In the information exchange, more variability and discrepancies were found. Overall, the online intervention did not seem to influence the patients' perceived communication performance of their health care professional much. To further improve the communication during clinical consultations, health care professionals should inquire about patients' expectations, especially during the exchange of information and advices. At the same time, patients should be supported to express their preferences at the start of the consultation. The study was registered in the Netherlands Trial Register, number 3779.

Haematology and erythrocyte metabolism in man at high altitude: an Aymara-Quechua comparison.

PubMed

Arnaud, J; Gutierrez, N; Tellez, W; Vergnes, H

1985-07-01

In the course of haematological and biological investigations among Aymara and Quechua populations in Bolivia, an anthropological study of the erythrocytary respiratory function was carried out on the two groups at two altitudes: 3,600 m and 450 m. A difference in the intensity of the biological variations of the two populations is observed at high altitude. In the Quechuas, as in any lowland native, the adaptative phenomena are totally and quickly reversible. In the Aymaras, we detected the existence of more marked haematological and biochemical characters: moderate polycythemia, hyperhaemoglobinemia, microcytosis, metabolical hyperactivity with accumulation of 2-3 di-phosphoglycerate and ATP, and methaemoglobinemia with a drop in the activity of the methaemoglobin reductases. The Aymaras preserve some of those characters (methaemoglobinemia excepted) when they settle in lowlands.

Effect of dietary supplementation with carnosic acid or vitamin E on animal performance, haematological and immunological characteristics of artificially reared suckling lambs before and after road transport.

PubMed

Morán, Lara; Andrés, Sonia; Blanco, Carolina; Benavides, Julio; Martínez-Valladares, María; Moloney, Aidan P; Giráldez, F Javier

2017-08-01

To elucidate the influence of dietary carnosic acid (CA) and vitamin E on animal performance, immune response indicators and haematological parameters before and after transport stress, 24 lambs were individually fed ad libitum with milk replacer (MR) using an auto-feeder. Once daily the lambs received MR alone (Group CON, n = 8), MR + 0.096 g CA/kg live weight (LW) (Group CARN, n = 8) or MR + 0.024 g of α-tocopheryl acetate per kg LW (Group VitE, n = 8). After reaching the target slaughter weight (12 ± 0.5 kg), blood samples were collected to measure haematological and immunological parameters. Then, lambs were subjected to 4-h road transport and blood samples were collected again for haematological assessment. The animals were subsequently slaughtered. Before road transport, dietary CA supplementation promoted a descent of circulating white blood cells (WBC), red blood cells (RBC), haematocrit and haemoglobin concentration when compared with Groups CON and VitE (p < 0.05), but it did not affect production of cytokines by blood mononuclear cells. Road transport did not affect either RBC or haematocrit significantly. Nevertheless, transport affected leucocyte profile similarly in all the treatments, increasing granulocytes and monocytes proportions and decreasing lymphocytes. In contrast, after transport, WBC was increased in Group CARN, reaching similar values than Groups CON and VitE. However, under conditions of the present study, those modifications did not influence animal performance or immunity parameters of artificially reared suckling lambs.

Safety profile of methotrexate in inflammatory bowel disease.

PubMed

Gabbani, Tommaso; Deiana, Simona; Lunardi, Sarah; Manetti, Natalia; Annese, Vito

2016-10-01

Methotrexate, which was initially developed in 1948 for the treatment of leukemia, is known to be an immunomodulatory and anti-inflammatory drug. It has been widely used for over 60 years as both a low and high-dose therapy in chronic inflammatory diseases. The aim of this review was to analyze and summarize the available data specifically on the safety of this drug in the management of inflammatory bowel diseases. A structured search of articles was conducted using the PubMed database up to April 2016. All articles in English with isolated or combined keywords were included according to their relevance to the aims of this study. Numerous of studies have established the efficacy of parenteral methotrexate in the management of steroid-dependent and steroid-resistant Crohn's disease, either for inducing or maintaining remission. However, its efficacy in ulcerative colitis has not been properly investigated. Additionally, methotrexate has been shown to reduce the effect of immunization with anti-TNF agents when combined. The drug has potential advantages over thiopurines such as its weekly administration, a possible shorter time of action, low cost, decreased risk for malignancy and overall a comparable safety profile.

Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care.

PubMed

Lachenmayr, Sarah J; Berking, Sophie; Horns, Heidi; Strobach, Dorothea; Ostermann, Helmut; Berger, Karin

2018-03-25

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified. © 2018 Blackwell Verlag GmbH.

Establishment of baseline haematology and biochemistry parameters in wild adult African penguins (Spheniscus demersus).

PubMed

Parsons, Nola J; Schaefer, Adam M; van der Spuy, Stephen D; Gous, Tertius A

2015-03-25

There are few publications on the clinical haematology and biochemistry of African penguins (Spheniscus demersus) and these are based on captive populations. Baseline haematology and serum biochemistry parameters were analysed from 108 blood samples from wild, adult African penguins. Samples were collected from the breeding range of the African penguin in South Africa and the results were compared between breeding region and sex. The haematological parameters that were measured were: haematocrit, haemoglobin, red cell count and white cell count. The biochemical parameters that were measured were: sodium, potassium, chloride, calcium, inorganic phosphate, creatinine, cholesterol, serum glucose, uric acid, bile acid, total serum protein, albumin, aspartate transaminase and creatine kinase. All samples were serologically negative for selected avian diseases and no blood parasites were detected. No haemolysis was present in any of the analysed samples. Male African penguins were larger and heavier than females, with higher haematocrit, haemoglobin and red cell count values, but lower calcium and phosphate values. African penguins in the Eastern Cape were heavier than those in the Western Cape, with lower white cell count and globulin values and a higher albumin/globulin ratio, possibly indicating that birds are in a poorer condition in the Western Cape. Results were also compared between multiple penguin species and with African penguins in captivity. These values for healthy, wild, adult penguins can be used for future health and disease assessments.

Modeling for influenza vaccines and adjuvants profile for safety prediction system using gene expression profiling and statistical tools

PubMed Central

Sasaki, Eita; Momose, Haruka; Hiradate, Yuki; Furuhata, Keiko; Takai, Mamiko; Asanuma, Hideki; Ishii, Ken J.

2018-01-01

Historically, vaccine safety assessments have been conducted by animal testing (e.g., quality control tests and adjuvant development). However, classical evaluation methods do not provide sufficient information to make treatment decisions. We previously identified biomarker genes as novel safety markers. Here, we developed a practical safety assessment system used to evaluate the intramuscular, intraperitoneal, and nasal inoculation routes to provide robust and comprehensive safety data. Influenza vaccines were used as model vaccines. A toxicity reference vaccine (RE) and poly I:C-adjuvanted hemagglutinin split vaccine were used as toxicity controls, while a non-adjuvanted hemagglutinin split vaccine and AddaVax (squalene-based oil-in-water nano-emulsion with a formulation similar to MF59)-adjuvanted hemagglutinin split vaccine were used as safety controls. Body weight changes, number of white blood cells, and lung biomarker gene expression profiles were determined in mice. In addition, vaccines were inoculated into mice by three different administration routes. Logistic regression analyses were carried out to determine the expression changes of each biomarker. The results showed that the regression equations clearly classified each vaccine according to its toxic potential and inoculation amount by biomarker expression levels. Interestingly, lung biomarker expression was nearly equivalent for the various inoculation routes. The results of the present safety evaluation were confirmed by the approximation rate for the toxicity control. This method may contribute to toxicity evaluation such as quality control tests and adjuvant development. PMID:29408882

Establishment of a New Quality Control and Vaccine Safety Test for Influenza Vaccines and Adjuvants Using Gene Expression Profiling

PubMed Central

Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

2015-01-01

We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. PMID:25909814

The effect of safety factor profile on transport in steady-state, high-performance scenarios

DOE PAGES

Holcomb, C. T.; Ferron, J. R.; Luce, T. C.; ...

2012-03-09

In this study, an analysis of the dependence of transport on the safety factor profile in high-performance, steady-state scenario discharges is presented. This is based on experimental scans of q 95 and q min taken with fixed β N, toroidal field, double-null plasma shape, divertor pumping, and electron cyclotron current drive input. The temperature and thermal diffusivity profiles were found to vary considerably with the q-profile, and these variations were significantly different for electrons and ions. With fixed q 95, both temperature profiles increase and broaden as q min is increased and the magnetic shear becomes low or negative inmore » the inner half radius, but these temperature profile changes are stronger for the electrons. Power balance calculations show the peak in the ion thermal diffusivity (χ i) at ρ – 0.6 – 0.8 increases with q 95 or q min.« less

Comparison of haemoglobin assessments by HemoCue and two automated haematology analysers in young Laotian children.

PubMed

Hinnouho, Guy-Marino; Barffour, Maxwell A; Wessells, K Ryan; Brown, Kenneth H; Kounnavong, Sengchanh; Chanhthavong, Bigphone; Ratsavong, Kethmany; Kewcharoenwong, Chidchamai; Hess, Sonja Y

2017-12-02

Haemoglobin (Hb) assessment by Hemocue is used widely for anaemia screening in both adults and children. However, few studies have compared the diagnostic accuracy of Hemocue with an automated haematology analyser in young children. To compare Hb concentrations by Hemocue Hb301 and two automated haematology analysers in young children in rural communities of Lao PDR. Capillary blood was collected from 6-month-old to 23-month-old children (n=1487) for determination of Hb concentration by Hemocue Hb301. On the same day, venous blood was collected for complete blood count using one of two haematology analysers (XT-1800i, Sysmex, and BC-3000Plus, Mindray Medical International). In a subsample of children (n=129), venous Hb was also measured by HemoCue Hb301. Agreement between the two methods was estimated using Bland-Altman plots. Mean capillary Hb by Hemocue was significantly higher than mean venous Hb by haematology analysers combined (108.4±10.3 g/L vs 102.3±13.1 g/L; P<0.001), resulting in a significantly lower anaemia prevalence (Hb <110 g/L) by Hemocue (53.7% vs 73.9%; P<0.001). The Bland-Altman assessment of agreement showed a bias of 6.1 g/L and limits of agreement were -11.5 g/L to 23.7 g/L. Mean venous Hb concentration by Hemocue Hb301 (113.6±14.0 g/L) was significantly higher than mean capillary Hb concentration by Hemocue Hb301 (110.0±10.7; P=0.03 g/L), which in turn was significantly higher than mean venous Hb concentration by the Mindray BC-3000Plus (102.3±17.4 g/L). Capillary and venous Hb concentrations assessed by Hemocue Hb301 showed poor agreement compared with venous Hb by automated haematology analysers, resulting in significantly different anaemia prevalences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effect of azadirachtin on haematological and biochemical parameters of Argulus-infested goldfish Carassius auratus (Linn. 1758).

PubMed

Kumar, Saurav; Raman, R P; Kumar, Kundan; Pandey, P K; Kumar, Neeraj; Mallesh, B; Mohanty, Snatashree; Kumar, Abhay

2013-08-01

Argulosis hampers aquaculture production and alters the host physiology and growth. Azadirachtin is recognized as a potential antiparasitic agent against Argulus sp. The present study aimed to investigate the effect of different concentration of azadirachtin solution on haematological and serum biochemical parameters of Argulus-infested goldfish Carassius auratus. Ninety Argulus-infested goldfish were randomly divided into six equal groups. Fish of group 1-5 were treated with azadirachtin solution through bath of 1, 5, 10, 15 and 20 mg L(-1) as T1, T2, T3, T4 and T5, respectively, and group 6 was exposed to 2% DMSO solution without azadirachtin and considered as negative control T0(-). Along with six treatment groups, a positive control T0(+) of healthy goldfish free from Argulus infestation was also maintained. Parasitic mortality was evaluated after 3 days of consecutive bath treatment. After 7 days of post-treatment, the blood and serum were drawn from each of the treatment groups and haematological and serum biochemical parameters were evaluated. Total leucocyte count (TLC), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), blood glucose, total protein (TP), globulin, serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) were significantly (p < 0.05) high in negative control group when compared with positive control group. It could be concluded that Argulus infestation altered marked haematological and serum biochemical parameters. However, in treated groups complete elimination of Argulus was found in T4 and T5 groups. Also significant (p < 0.05) reduction in haematological and serum biochemical parameters of all the treatment groups were recorded in comparison with negative control group. In addition, T4 and T5 groups showed significantly (p < 0.05) high superoxide dismutase (SOD), catalase, total erythrocyte count (TEC) and haemoglobin (Hb). However, higher mean corpuscular haemoglobin

Immunophenotyping of posttraumatic neutrophils on a routine haematology analyser.

PubMed

Groeneveld, Kathelijne Maaike; Heeres, Marjolein; Leenen, Loek Petrus Hendrikus; Huisman, Albert; Koenderman, Leo

2012-01-01

Flow cytometry markers have been proposed as useful predictors for the occurrence of posttraumatic inflammatory complications. However, currently the need for a dedicated laboratory and the labour-intensive analytical procedures make these markers less suitable for clinical practice. We tested an approach to overcome these limitations. Neutrophils of healthy donors were incubated with antibodies commonly used in trauma research: CD11b (MAC-1), L-selectin (CD62L), FcγRIII (CD16), and FcγRII (CD32) in active form (MoPhab A27). Flow cytometric analysis was performed both on a FACSCalibur, a standard flow cytometer, and on a Cell-Dyn Sapphire, a routine haematology analyser. There was a high level of agreement between the two types of analysers, with 41% for FcγRIII, 80% for L-selectin, 98% for CD11b, and even a 100% agreement for active FcγRII. Moreover, analysis on the routine haematology analyser was possible in less than a quarter of the time in comparison to the flow cytometer. Analysis of neutrophil phenotype on the Cell-Dyn Sapphire leads to the same conclusion compared to a standard flow cytometer. The markedly reduced time necessary for analysis and reduced labour intensity constitutes a step forward in implementation of this type of analysis in clinical diagnostics in trauma research. Copyright © 2012 Kathelijne Maaike Groeneveld et al.

Assessment of haematological parameters in HIV-infected and uninfected Rwandan women: a cross-sectional study

PubMed Central

Munyazesa, Elisaphane; Emile, Ivan; Mutimura, Eugene; Hoover, Donald R; Shi, Qiuhu; McGinn, Aileen P; Musiime, Stephenson; Muhairwe, Fred; Rutagengwa, Alfred; Dusingize, Jean Claude; Anastos, Kathryn

2012-01-01

Objectives Although haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women. Study design Cross-sectional analysis of a longitudinal cohort. Setting Community-based women's associations. Participants 710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV−) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit. Results Prevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200–349 (16%) and <200 cells/mm3 (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV− women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm3 (8.4%). The HIV+ were more likely than HIV− women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×103 cells/mm3 and 8.4% of HIV+ women with CD4 <200 cells/mm3 had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m2, 95% CI 0.82 to 0.93; p<0.001), CD4 200–350 vs HIV− (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm3 vs HIV− (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm3 vs HIV− (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia. Conclusions Anaemia was more common than neutropenia or

Effects of ginseng extract on various haematological parameters during aerobic exercise in the rat.

PubMed

Ferrando, A; Vila, L; Voces, J A; Cabral, A C; Alvarez, A I; Prieto, J G

1999-04-01

The effects of the Ginseng extract on various biochemical and haematological parameters in male Wistar rats subjected to a treadmill exercise protocol were studied for 12 weeks. The results showed increases in the haematological parameters, these increases being greatest for the animals treated with the extract during the third month of the study. The exercise also led to increases in these parameters, while the combination of both exercise and extract produced smaller increases. This study shows a clear physiological response due to the ginseng extract administration that reproduces many of the effects obtained after long-term exercise. The combination of exercise and treatments seems to support the theory that there is no clear synergic effect when the advantages associated with the ingestion of ginseng are compared with the performance of exercise.

Anorectal complications in patients with haematological malignancies.

PubMed

Loureiro, Rafaela V; Borges, Verónica P; Tomé, Ana L; Bernardes, Carlos F; Silva, Mário J; Bettencourt, Maria J

2018-04-13

Anorectal complications are common in patients with haematological malignancies. The objectives are to characterize anorectal complications in these patients, identify risk factors and shed light on treatment, morbidity and mortality rates. A retrospective, observational study that included 83 inpatients with haematological malignancies and proctological symptoms from January 2010 to September 2015 was conducted. Clinical outcomes were obtained through a detailed review of medical records. The median age was 56 years, and 52 (62.7%) patients were men. Fifty-six (67.5%) patients had nonseptic anorectal complications and 27 (32.5%) patients had septic anorectal complications. Patients with septic anorectal complications were more commonly male, older, and had lower absolute neutrophil counts, but the differences were not statistically significant (P=0.79, 0.67 and 0.89, respectively). In positive blood cultures [23/70 (32.9%)], Enterococcus faecium, Klebsiella pneumonia, and Escherichia coli were the most common isolated agents. In nonseptic anorectal complications, conservative treatments/minor proctological procedures were adopted, and patients with septic anorectal complications were treated with antibiotics±major proctological procedures and/or surgical drainage/debridement. Forty-eight (85.7%) patients in the nonseptic complications group improved compared with 23 (85.2%) patients in the septic complications group. The overall mortality rate was 2.4% (n=2), with one (1.2%) death related to perianal sepsis. Enterococcus spp. were more commonly identified in this study and can be increasing in this specific population. In contrast to other reports, we did not identify an association between septic anorectal complications and possible risk factors such as male sex, younger age or a low absolute neutrophil count. Most patients had nonseptic anorectal complications. A major proctological procedure/surgical debridement should always be applied in septic complications

[A new method for safety monitoring of natural dietary supplements--quality profile].

PubMed

Wang, Juan; Wang, Li-Ping; Yang, Da-Jin; Chen, Bo

2008-07-01

A new method for safety monitoring of natural dietary supplements--quality profile was proposed. It would convert passive monitoring of synthetic drug to active, and guarantee the security of natural dietary supplements. Preliminary research on quality profile was completed by high performance liquid chromatography (HPLC) and mass spectrometry (MS). HPLC was employed to analyze chemical constituent profiles of natural dietary supplements. The separation was completed on C18 column with acetonitrile and water (0.05% H3PO4) as mobile phase, the detection wavelength was 223 nm. Based on HPLC, stability of quality profile had been studied, and abnormal compounds in quality profile had been analyzed after addition of phenolphthalein, sibutramine, rosiglitazone, glibenclamide and gliclazide. And by MS, detector worked with ESI +, capillary voltage: 3.5 kV, cone voltage: 30 V, extractor voltage: 4 V, RF lens voltage: 0.5 V, source temperature: 105 degrees C, desolvation temperature: 300 degrees C, desolvation gas flow rate: 260 L/h, cone gas flow rate: 50 L/h, full scan mass spectra: m/z 100-600. Abnormal compound in quality profile had been analyzed after addition of N-mono-desmethyl sibutramine. Quality profile based on HPLC had good stability (Similarity > 0.877). Addition of phenolphthalein, sibutramine, rosiglitazone, glibenclamide and gliclazide in natural dietary supplements could be reflected by HPLC, and addition of N-mono-desmethyl sibutramine in natural dietary supplements could be reflected by MS. Quality profile might monitor adulteration of natural dietary supplements, and prevent addition of synthetic drug after "approval".

Safety Profile of Biologic Drugs in the Therapy of Ulcerative Colitis: A Systematic Review and Network Meta-Analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-08-01

We compared the safety profile of biologic drugs in patients with moderately to severely active ulcerative colitis (UC). A systematic literature search was performed using Medline (PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases through February 9, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, golimumab, and vedolizumab) with one another or with placebo in patients with UC. Two reviewers independently conducted the search and selection of studies and rated the risk of bias in each trial. The network meta-analysis (NMA) was conducted for an induction phase (6-8 weeks) and maintenance phase (52-54 weeks) with a Bayesian hierarchical random effects model in Aggregate Data Drug Information System (ADDIS) software. The PROSPERO registration number was CRD42016032607. Seven RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, golimumab, and vedolizumab, and in the case of the maintenance phase of infliximab, adalimumab, golimumab, and vedolizumab. The methodological quality of the included RCTs was evaluated as low risk of bias, but high risk of bias in the case of attrition bias (incomplete outcome data) according to the Cochrane criteria. No significant differences were found in the rate of adverse events in patients treated with the reviewed biologics. Vedolizumab was most likely to have the most favorable safety profile in the induction phase as was infliximab for the maintenance phase. The assessment of the relative safety profile revealed no significant differences between the biologic drugs. Further studies are needed to confirm our findings including head-to-head comparisons between the analyzed biologics. © 2016 Pharmacotherapy Publications, Inc.

Pulmonary aspergillosis in immunosuppressed patients with haematological malignancies.

PubMed

Spearing, R L; Pamphilon, D H; Prentice, A G

1986-06-01

Invasive pulmonary aspergillosis as a cause of mortality and morbidity in patients with haematological malignancies is becoming more common. Predisposing factors are powerful immunosuppressive chemotherapy, neutropenia and synergistic combinations of antibiotics of great potency and wide spectrum of activity. Clinical and radiological signs are heterogeneous, sometimes misleading and often absent. Treatment is often empirical on suspicion alone. Amphotericin B is the only effective drug but it has marked toxicity, mainly renal. Infection is usually fatal without adequate treatment. This paper describes eight cases of invasive pulmonary aspergillosis seen in one centre in two years, reviews the literature and assesses associated problems.

Safety and Antioxidant Efficacy Profiles of Rutin-Loaded Ethosomes for Topical Application.

PubMed

Cândido, Thalita Marcílio; De Oliveira, Camila Areias; Ariede, Maíra Bueno; Velasco, Maria Valéria Robles; Rosado, Catarina; Baby, André Rolim

2018-05-01

Topical application of dermocosmetics containing antioxidant and/or the intake of antioxidants through diet or supplementation are remarkable tools in an attempt to slow down some of the harmful effects of free radicals. Rutin is a strong antioxidant compound used in food and pharmaceutical industries. It was established that rutin presents a low skin permeation rate, a property that could be considered an inconvenience to the satisfactory action for a dermocosmetic formulation to perform its antioxidant activity onto the skin. Therefore, it is indispensable to improve its delivery, aiming at increasing its antioxidant capacity in deeper layers of the epidermis, being a possibility to associate the rutin to liposomal vesicles, such as ethosomes. Thus, in this work, the pre-clinical safety of rutin-loaded ethosomes was investigated employing an in vitro method, and the clinical safety and efficacy were also assessed. Rutin-loaded ethosomes were efficaciously obtained in a nanoscale dimension with a relevant bioactive compound loading (80.2%) and provided antioxidant in vitro activity in comparison with the blank sample. Pre-clinical and clinical safety assays assured the innocuous profile of the rutin-loaded ethosomes. The ethosomes containing the bioactive compound accomplished a more functional delivery system profile, since in the tape stripping assay, the deeper layers presented higher rutin amounts than the active delivered in its free state. However, the ex vivo antioxidant efficacy test detected no positive antioxidant activity from the rutin-loaded ethosomes, even though the in vitro assay demonstrated an affirmative antioxidant action.

Endocrine Profiles, Haematology and Pregnancy Outcomes of Late Pregnant Holstein Dairy Heifers Sired by Bulls Giving a High or Low Incidence of Stillbirth

PubMed Central

Kornmatitsuk, B; Dahl, E; Ropstad, E; Beckers, JF; Gustafsson, H; Kindahl, H

2004-01-01

The high incidence of stillbirth in Swedish Holstein heifers has increased continuously during the last 15 years to an average of 11% today. The pathological reasons behind the increased incidence of stillbirth are unknown. The present experiment was undertaken to investigate possible causes of stillbirth and to study possible physiological markers for predicting stillbirth. Twenty Swedish Holstein dairy heifers sired by bulls with breeding values for a high risk of stillbirth (n = 12) (experimental group) and a low risk of stillbirth (n = 8) (control group, group B) were selected based on information in the Swedish AI-data base. The experimental group consisted of 2 subgroups of heifers (groups A1 and A2) inseminated with 2 different bulls with 3.5% and 9% higher stillbirth rates than the average, and the control group consisted of heifers pregnant with 5 different bulls with 0%–6% lower stillbirth rates than the average. The bull used for group A1 had also calving difficulties due to large calves as compared to the bull in group A2 showing no calving difficulties. The heifers were supervised from 6–7 months of pregnancy up to birth, and the pregnancies and parturitions were compared between groups regarding hormonal levels, haematology, placental characteristics and calf viability. In group A1, 1 stillborn, 1 weak and 4 normal calves were recorded. In group A2, 2 stillborn and 4 normal calves were registered. All animals in the control group gave birth to a normal living calf without any assistance. The weak calf showed deviating profiles of body temperature, saturated oxygen and heart rates, compared with the normal living calves. No differences of the placentome thickness, measured in vivo by ultrasonography were seen between the groups. The number of leukocytes and differential cell counts in groups A1 and A2 followed the profiles found in the control group. In group A1, a slight decrease of oestrone sulphate (E1SO4) levels was found in the animal

[Healthcare-associated infections in a paediatric haematology/oncology unit in Morocco].

PubMed

Cherkaoui, Siham; Lamchahab, Mouna; Samira, Hassoun; Zerouali, Khalid; Madani, Abdallah; Benchekroun, Said; Quessar, Asmaa

2014-01-01

HAI cause considerable morbidity and mortality and are associated with prolonged hospital stay and increased health care costs. To describe the incidence of HAI in paediatric cancer patients as the first step towards improving infection control policies. A prospective surveillance study was performed in the Casablanca university hospital paediatric haematology/oncology unit over an 8-month period from January to August 2011. Data including extrinsic risk factors associated with HAI were recorded. The incidence of HAI was 28 per 1000 patient-days. The median age was 9.6 years and the most frequent diagnosis was acute myeloid leukaemia (32%). Neutropenia at diagnosis was significantly correlated with the risk of HAI. 55.7% of HAls were nosocomial fever of unknown origin. Gram-negative bacteria were the main pathogens (60%), gram-positive cocci were responsible for 26% of HAI and Candida for 14% of HAI. The length of hospital stay for patients with and without infection were 16.5 and 5 days, respectively (P < 0.001). Six of the 11 deaths were related to HAI. These findings suggest the need to evaluate infection control measures in order to reduce morbidity and mortality in paediatric haematology/oncology units.

The dynamics of health in wild field vole populations: a haematological perspective

PubMed Central

Beldomenico, Pablo M.; Telfer, Sandra; Gebert, Stephanie; Lukomski, Lukasz; Bennett, Malcolm; Begon, Michael

2010-01-01

Summary Pathogens have been proposed as potentially important drivers of population dynamics, but while a few studies have investigated the impact of specific pathogens, the wealth of information provided by general indices of health has hardly been exploited. By evaluating haematological parameters in wild populations, our knowledge of the dynamics of health and infection may be better understood. Here, haematological dynamics in natural populations of field voles are investigated to determine environmental and host factors associated with indicators of inflammatory response (counts of monocytes and neutrophils) and of condition: measures of immunological investment (lymphocyte counts) and aerobic capacity (red blood cell counts). Individuals from three field vole populations were sampled monthly for 2 years. Comparisons with individuals kept under controlled conditions facilitated interpretation of field data. Mixed effects models were developed for each cell type to evaluate separately the effects of various factors on post-juvenile voles and mature breeding females. There were three well-characterized ‘physiological’ seasons. The immunological investment appeared lowest in winter (lowest lymphocyte counts), but red blood cells were at their highest levels and indices of inflammatory response at their lowest. Spring was characterized by a fall in red blood cell counts and peaks in indicators of inflammatory response. During the course of summer—autumn, red blood cell counts recovered, the immunological investment increased and the indicators of inflammatory response decreased. Poor body condition appeared to affect the inflammatory response (lower neutrophil and monocyte peaks) and the immunological investment (lower lymphocyte counts), providing evidence that the capacity to fight infection is dependent upon host condition. Breeding early in the year was most likely in females in better condition (high lymphocyte and red blood cell counts). All the

Boston City Hospital and the Thorndike Memorial Laboratory: the birth of modern haematology.

PubMed

Elrod, Jeffrey M; Karnad, Anand B

2003-05-01

Established in 1923, the Thorndike Memorial Laboratory at Boston City Hospital was the first clinical research laboratory in a municipal hospital in the United States of America. Minot and Castle, who were the second and third directors of the Laboratory, were pioneer haematologists and clinical investigators of the highest calibre who created an atmosphere at the Laboratory that would foster patient-centred research and attract the best physician-scientists to work and train there. The haematology research division of the Laboratory made important original contributions to the understanding of the pathophysiology of anaemia, the mechanisms of red cell and platelet destruction and the phagocytic role of the spleen, the nature of haemoglobin (normal and sickle cell), the nature of haemophilia and its therapy and the early classification of lymphoma. It contributed to the Thorndike Memorial Laboratory's worldwide reputation as a model research laboratory and established its reputation as the birthplace of modern haematology.

Potential risk factors for haematological cancers in semiconductor workers.

PubMed

Lee, K; Kim, S-G; Kim, D

2015-10-01

There has recently been increased interest in cancer incidence in electronics workers. To determine the cancer incidence ratio in electronics workers and the potential factors affecting the risk for development of cancer. Epidemiological study performed in electronics workers who were employed between 1999 and 2008 in South Korea. Cancer incidence ratio was analysed with respect to departments, divisions, job titles, gender, age, hepatitis B and C virus infection and work duration. We compared the incidence of haematological cancer in this cohort with that expected in the general population. The study population was 56283. Overall, the standardized incidence ratio (SIR) for haematological cancer was 0.85. In particular, the SIR for leukaemia was 0.86 and for non-Hodgkin lymphoma (NHL) was 0.93, which were not statistically significant. The SIR for NHL was significantly increased [SIR 5.23, 95% confidence interval (CI) 1.31-20.95] in female office workers. We also found that the SIR for NHL was significantly increased in female workers who tested positive for hepatitis virus infection (SIR 7.69, 95% CI 1.08-54.60). The raised SIR for NHL among female workers was due to potential risk factors such as hepatitis virus infection although additional research and an ongoing, long-term, prospective epidemiological cohort study is needed. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Short-term effect of levetiracetam monotherapy on haematological parameters in children with epilepsy: a prospective study.

PubMed

Dinopoulos, Argiris; Attilakos, Achilleas; Paschalidou, Maria; Tsirouda, Maria; Garoufi, Anastasia; Moustaki, Maria; Siafakas, Nikos; Papaevangelou, Vassiliki

2014-05-01

Studies evaluating the effect of levetiracetam (LEV) on haematological parameters in patients with epilepsy are very limited. Clinical trials have also reported an unexplained increased incidence of pharyngitis and rhinitis in LEV-treated patients. The objective of this study was to evaluate prospectively the changes in haematological parameters in children treated with LEV monotherapy. White blood cell, neutrophils, lymphocytes, monocytes, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration and platelets were measured in 22 children (13 females, mean age 6.70±4.23 years) with epilepsy, before and after 2 and 6 months of LEV monotherapy. Lymphocyte count was significantly decreased at 6 months (p=0.019) of treatment and this effect was not dose dependent. One child (4.5%) at 2 months and four children (18%) at 6 months of treatment had lymphocyte count below 10th percentile for age. There were no significant alterations in the other parameters evaluated during the study. LEV monotherapy may significantly decrease lymphocyte count at six months of treatment in children with epilepsy. Further prospective studies are needed to investigate the effect of LEV on haematological parameters and the possible association with the higher incidence of infections reported in children receiving LEV. Copyright © 2014 Elsevier B.V. All rights reserved.

Dyadic interdependence of psychosocial outcomes among haematological cancer survivors and their support persons.

PubMed

Paul, Christine; Hall, Alix; Oldmeadow, Christopher; Lynagh, Marita; Campbell, Sharon; Bradstock, Ken; Williamson, Anna; Carey, Mariko; Sanson-Fisher, Rob

2017-11-01

This study aimed to explore the dyadic relationships between unmet need, depression, and anxiety in people diagnosed with haematological cancer and their support persons. Adult survivors (18 years+) who had been diagnosed with a haematological cancer were recruited to a cross-sectional mailed survey via five state cancer registries in Australia. Participating survivors invited a support person to also complete a survey. Structural equation modelling was used to explore the relationships among survivor and support person self-reported depression, anxiety, and unmet needs. Of the 4299 eligible haematological cancer survivors contacted by the registries, 1511 (35%) returned a completed survey as did 1004 support persons. There were 787 dyads with complete data. After adjusting for age, gender, rurality, cancer type, and whether the support person was a relative, positive correlations were found between survivor and support person scores for depression (p = 0.0029) and unmet needs (p < 0.001), but not anxiety scores (p = 0.075). Survivor unmet needs were significantly related to support person depression (p = 0.0036). Support person unmet needs were significantly related to a higher depression score for survivors (p = 0.0067). Greater support person unmet needs were significantly related to a higher anxiety score for survivors (p = 0.0083). Survivor unmet needs did not have a significant relationship to support person anxiety (p = 0.78). Unmet needs may mediate the interdependence of psychosocial experiences for survivors and support persons, although a longitudinal study is required to confirm causality. Addressing unmet needs may be a potential target for improving outcomes for both groups.

Haematological and electrophoretic characterisation of β-thalassaemia in Yunnan province of Southwestern China

PubMed Central

Zhang, Jie; He, Jing; Mao, Xiaoqin; Zeng, Xiaohong; Chen, Hong; Su, Jie; Zhu, Baosheng

2017-01-01

Objectives β-Thalassaemia is widely found in Southwestern China. Characterisation of β-thalassaemia can improve screening and prenatal diagnosis for at-risk populations. Design A retrospective study. Methods In this study, the levels of haemoglobin alpha 2 (HbA2) and haemoglobin alpha (HbA) were analysed by gender for a total of 15 067 subjects screened by capillary electrophoresis. The cut-off value with the highest accuracy was established to identify β-thalassaemia in 723 patients suspected to have this disease. Haematological and electrophoretic characterisation of eight common types of β-thalassaemia were analysed in 486 β-thalassaemia subjects. Results HbA levels were significantly higher in men than in women, but there was no significant difference on HbA2 levels. A new cut-off value for the diagnosis of β-thalassaemia (HbA2≥4.0%) with the highest accuracy was proposed for the studied populations. Haemoglobin (Hb) was significantly higher in men compared with women (p<0.05), whereas no statistically significant differences were found for mean cell volume (MCV), mean cell haemoglobin (MCH), HbA and HbA2. The haemoglobin E (HbE) group showed comparatively higher values for haematological indices (Hb, MCV and MCH) than the other genotypes in heterozygous β-thalassaemia groups (p<0.05), and −28 (A>G) (HBB (β-globin):c.−78A>C) had significantly higher HbA2 values compared with other β-thalassaemia. Conclusions Ethnic groups have diversified β-globin gene mutations and considerable haematological variations. Our study will lay the foundation for screening programmes and clinical management of thalassaemia in Southwestern China. PMID:28143837

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

PubMed

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

PubMed Central

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

Aerobic physical exercise for adult patients with haematological malignancies.

PubMed

Bergenthal, Nils; Will, Andrea; Streckmann, Fiona; Wolkewitz, Klaus-Dieter; Monsef, Ina; Engert, Andreas; Elter, Thomas; Skoetz, Nicole

2014-11-11

Although people with haematological malignancies have to endure long phases of therapy and immobility which is known to diminish their physical performance level, the advice to rest and avoid intensive exercises is still common practice. This recommendation is partly due to the severe anaemia and thrombocytopenia from which many patients suffer. The inability to perform activities of daily living restricts them, diminishes their quality of life and can influence medical therapy. To evaluate the efficacy, safety and feasibility of aerobic physical exercise for adults suffering from haematological malignancies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2014, Issue 1) and MEDLINE (1950 to January 2014) as well as conference proceedings for randomised controlled trials (RCTs). We included RCTs comparing an aerobic physical exercise intervention, intending to improve the oxygen system, in addition to standard care with standard care only for adults suffering from haematological malignancies. We also included studies that evaluated aerobic exercise in addition to strength training. We excluded studies that investigated the effect of training programmes that were composed of yoga, tai chi chuan, qigong or similar types of exercise. We also excluded studies exploring the influence of strength training without additive aerobic exercise. Additionally, we excluded studies assessing outcomes without any clinical impact. Two review authors independently screened search results, extracted data and assessed the quality of trials. We used risk ratios (RRs) for adverse events and 100-day survival, standardised mean differences for quality of life (QoL), fatigue, and physical performance, and mean differences for anthropometric measurements. Our search strategies identified 1518 potentially relevant references. Of these, we included nine RCTs involving 818 participants. The potential risk of bias in these trials is unclear, due

New geometric design consistency model based on operating speed profiles for road safety evaluation.

PubMed

Camacho-Torregrosa, Francisco J; Pérez-Zuriaga, Ana M; Campoy-Ungría, J Manuel; García-García, Alfredo

2013-12-01

To assist in the on-going effort to reduce road fatalities as much as possible, this paper presents a new methodology to evaluate road safety in both the design and redesign stages of two-lane rural highways. This methodology is based on the analysis of road geometric design consistency, a value which will be a surrogate measure of the safety level of the two-lane rural road segment. The consistency model presented in this paper is based on the consideration of continuous operating speed profiles. The models used for their construction were obtained by using an innovative GPS-data collection method that is based on continuous operating speed profiles recorded from individual drivers. This new methodology allowed the researchers to observe the actual behavior of drivers and to develop more accurate operating speed models than was previously possible with spot-speed data collection, thereby enabling a more accurate approximation to the real phenomenon and thus a better consistency measurement. Operating speed profiles were built for 33 Spanish two-lane rural road segments, and several consistency measurements based on the global and local operating speed were checked. The final consistency model takes into account not only the global dispersion of the operating speed, but also some indexes that consider both local speed decelerations and speeds over posted speeds as well. For the development of the consistency model, the crash frequency for each study site was considered, which allowed estimating the number of crashes on a road segment by means of the calculation of its geometric design consistency. Consequently, the presented consistency evaluation method is a promising innovative tool that can be used as a surrogate measure to estimate the safety of a road segment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Recommendations of the SFH (French Society of Haematology) for the diagnosis, treatment and follow-up of hairy cell leukaemia.

PubMed

Cornet, Edouard; Delmer, Alain; Feugier, Pierre; Garnache-Ottou, Francine; Ghez, David; Leblond, Véronique; Levy, Vincent; Maloisel, Frédéric; Re, Daniel; Zini, Jean-Marc; Troussard, Xavier

2014-12-01

Hairy cell leukaemia (HCL) is a rare haematological malignancy, with approximately 175 new incident cases in France. Diagnosis is based on a careful examination of the blood smear and immunophenotyping of the tumour cells, with a panel of four markers being used specifically to screen for hairy cells (CD11c, CD25, CD103 and CD123). In 2011, the V600E mutation of the BRAF gene in exon 15 was identified in HCL; being present in HCL, it is absent in the variant form of HCL (HCL-v) and in splenic red pulp lymphoma (SRPL), two entities related to HCL. The management of patients with HCL has changed in recent years. A poorer response to purine nucleoside analogues (PNAs) is observed in patients with more marked leukocytosis, bulky splenomegaly, an unmutated immunoglobulin variable heavy chain (IgVH) gene profile, use of VH4-34 or with TP53 mutations. We present the recommendations of a group of 11 experts belonging to a number of French hospitals. This group met in November 2013 to examine the criteria for managing patients with HCL. The ideas and proposals of the group are based on a critical analysis of the recommendations already published in the literature and on an analysis of the practices of clinical haematology departments with experience in managing these patients. The first-line treatment uses purine analogues: cladribine or pentostatin. The role of BRAF inhibitors, whether or not combined with MEK inhibitors, is discussed. The panel of French experts proposed recommendations to manage patients with HCL, which can be used in a daily practice.

Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

PubMed Central

2016-01-01

Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

Impact of external haematology proficiency testing programme on quality of laboratories.

PubMed

Saxena, Renu; Katoch, S C; Srinivas, Upendra; Rao, Seema; Anand, Hema

2007-11-01

A reliable and reproducible report from a laboratory needs internal quality control within the laboratory and participation in external proficiency testing programmes (EPTP). This study conducted at the Department of Haematology, All India Institute of Medical Sciences (AIIMS), New Delhi, which has been conducting an EPTP since 1992, was undertaken to assess the efficacy of this programme in improving the performance of participating laboratories in reporting test samples sent for Hb, total leucocyte count (TLC), reticulocyte count and assessment of peripheral blood smear (PBS). The samples were prepared in our laboratory according to the International Standards Organization (ISO) guidelines. The performance of individual laboratories was assessed using robust Z score, which is an indicator of acceptability of the test result. An improvement in the overall percentage of laboratories with acceptable reports was seen during the study period. It has increased from 38,40,40 per cent in 1992 to 85, 90,94.7 per cent in 2006 for Hb, TLC, reticulocyte count, respectively. However, the results for peripheral smear assessment improved only marginally. The external haematology proficiency testing programme run by our department for Hb, TLC, reticulocyte count, and peripheral blood smear assessment, has helped in improving the reporting standards of these parameters in Indian laboratories.

Age-associated and breed-associated variations in haematological and biochemical variables in young labrador retriever and miniature schnauzer dogs

PubMed Central

Brenten, Thomas; Morris, Penelope J.; Salt, Carina; Raila, Jens; Kohn, Barbara; Schweigert, Florian J.; Zentek, Jürgen

2016-01-01

Breed, sex and age effects on haematological and biochemical variables were investigated in 24 labrador retriever and 25 miniature schnauzer dogs during the first year of life. Blood samples were taken regularly between weeks 8 and 52. White blood cell and red blood cell counts, haemoglobin concentration, haematocrit, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, platelet count as well as total protein, albumin, calcium, phosphate, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, total cholesterol, triglycerides, creatine and urea were evaluated. For all haematological and biochemical parameters, there were significant effects of age on test results. Statistically significant effects for breed and the breed×age interaction on test results were observed for most of the parameters with the exception of haemoglobin. Variations in test results illustrate growth related alterations in body tissue and metabolism leading to dynamic and marked changes in haematological and biochemical parameters, which have to be considered for the interpretation of clinical data obtained from dogs in the first year of life. PMID:27252875

Age-associated and breed-associated variations in haematological and biochemical variables in young labrador retriever and miniature schnauzer dogs.

PubMed

Brenten, Thomas; Morris, Penelope J; Salt, Carina; Raila, Jens; Kohn, Barbara; Schweigert, Florian J; Zentek, Jürgen

2016-01-01

Breed, sex and age effects on haematological and biochemical variables were investigated in 24 labrador retriever and 25 miniature schnauzer dogs during the first year of life. Blood samples were taken regularly between weeks 8 and 52. White blood cell and red blood cell counts, haemoglobin concentration, haematocrit, mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration, platelet count as well as total protein, albumin, calcium, phosphate, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, total cholesterol, triglycerides, creatine and urea were evaluated. For all haematological and biochemical parameters, there were significant effects of age on test results. Statistically significant effects for breed and the breed×age interaction on test results were observed for most of the parameters with the exception of haemoglobin. Variations in test results illustrate growth related alterations in body tissue and metabolism leading to dynamic and marked changes in haematological and biochemical parameters, which have to be considered for the interpretation of clinical data obtained from dogs in the first year of life.

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

PubMed

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

A retrospective series of gut aspergillosis in haematology patients.

PubMed

Kazan, E; Maertens, J; Herbrecht, R; Weisser, M; Gachot, B; Vekhoff, A; Caillot, D; Raffoux, E; Fagot, T; Reman, O; Isnard, F; Thiebaut, A; Bretagne, S; Cordonnier, C

2011-04-01

Gut invasive aspergillosis is an extremely rare infection in immunocompromised patients. The goal of this retrospective multicentre study is to report on cases of gut aspergillosis in haematology patients, including clinical presentation, risk factors, and outcome. Twenty-one patients from nine centres were identified. Eight had isolated gut aspergillosis, with no evidence of other infected sites, and 13 had disseminated aspergillosis. Thirteen patients had acute leukaemia. Nine were allogeneic stem cell transplant recipients. Clinical symptoms and imaging were poorly specific. The galactomannan antigenaemia test result was positive in 16/25 (64%) patients, including in four of the eight cases of isolated gut aspergillosis. Five of 21 patients had a dietary regimen rich in spices, suggesting that, in these cases, food could have been the source of gut colonization, and then of a primary gut Aspergillus lesion. The diagnosis was made post-mortem in six patients. The mortality rate in the remaining patients at 12 weeks was 7/15 (47%). Gut aspergillosis is probably misdiagnosed and underestimated in haematology patients, owing to the poor specificity of symptoms and imaging. Patients with a persistently positive galactomannan antigenaemia finding that is unexplained by respiratory lesions should be suspected of having gut aspergillosis in the presence of abdominal symptoms, and be quickly investigated. In the absence of severe abdominal complications leading to surgery and resection of the lesions, the optimal treatment is not yet defined. Clinical Microbiology and Infection © 2010 European Society of Clinical Microbiology and Infectious Diseases. No claim to original US government works.

Evolving prevalence of haematological malignancies in orphan designation procedures in the European Union.

PubMed

Polsinelli, Benedetta; Tsigkos, Stelios; Naumann-Winter, Frauke; Mariz, Segundo; Sepodes, Bruno

2017-01-21

The Committee for Orphan Medicinal Products (COMP) evaluates prevalence of rare conditions as one of the criteria for granting an orphan designation with a prevalence threshold of 5 in 10.000. At the time of Marketing Authorisation (MA) these criteria are reassessed to ensure they are still met. The COMP has noted discordance between the prevalence of certain haematological malignancies at the time of Orphan Designation and at the time of Marketing Authorisation. Consequently, we conducted a retrospective assessment of Chronic Lymphocytic Lymphoma and Multiple Myeloma/Plasma cell Myeloma as well as several other haematological rare aetiologies frequently subject of orphan designation. These were: Diffuse large B-Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Cutaneous T-Cell Lymphoma (CTCL), Mantle Cell Lymphoma (MCL) and Chronic Myeloid Leukaemia (CML). The review used submissions as well as recent publications and results from external and EMA databases. As a first step in the analysis, an increase over time in the number of people affected was evident for four conditions in the COMP designation documents, whereas for DLBCL, FL, CTCL and MCL there had been no significant change, since the introduction of the Regulation in 2000. Specifically, the prevalence estimates increased from 1.2 to 3.6 per 10,000 for multiple myeloma, from 0.4 to 1.7 in acute lymphoblastic leukaemia, and from 2.7 to 4.85 for chronic lymphocytic leukaemia/small lymphocytic leukaemia and 1 to 2 in 10,000 for chronic myeloid leukaemia. The reasons for the changes in the prevalence of these four haematological conditions over the last 15 years were not assessed but recent publications have alluded to better outcomes due to new treatments being made available. In addition, many orphan diseases have a median age of onset over 60 years so that also the aging of the population may be a relevant contributing factor.

Haematological and electrophoretic characterisation of β-thalassaemia in Yunnan province of Southwestern China.

PubMed

Zhang, Jie; He, Jing; Mao, Xiaoqin; Zeng, Xiaohong; Chen, Hong; Su, Jie; Zhu, Baosheng

2017-01-31

β-Thalassaemia is widely found in Southwestern China. Characterisation of β-thalassaemia can improve screening and prenatal diagnosis for at-risk populations. A retrospective study. In this study, the levels of haemoglobin alpha 2 (HbA 2 ) and haemoglobin alpha (HbA) were analysed by gender for a total of 15 067 subjects screened by capillary electrophoresis. The cut-off value with the highest accuracy was established to identify β-thalassaemia in 723 patients suspected to have this disease. Haematological and electrophoretic characterisation of eight common types of β-thalassaemia were analysed in 486 β-thalassaemia subjects. HbA levels were significantly higher in men than in women, but there was no significant difference on HbA 2 levels. A new cut-off value for the diagnosis of β-thalassaemia (HbA 2 ≥4.0%) with the highest accuracy was proposed for the studied populations. Haemoglobin (Hb) was significantly higher in men compared with women (p<0.05), whereas no statistically significant differences were found for mean cell volume (MCV), mean cell haemoglobin (MCH), HbA and HbA 2 . The haemoglobin E (HbE) group showed comparatively higher values for haematological indices (Hb, MCV and MCH) than the other genotypes in heterozygous β-thalassaemia groups (p<0.05), and -28 (A>G) (HBB (β-globin):c.-78A>C) had significantly higher HbA 2 values compared with other β-thalassaemia. Ethnic groups have diversified β-globin gene mutations and considerable haematological variations. Our study will lay the foundation for screening programmes and clinical management of thalassaemia in Southwestern China. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Health assessment of free-ranging endangered Australian sea lion (Neophoca cinerea) pups: effect of haematophagous parasites on haematological parameters.

PubMed

Marcus, Alan D; Higgins, Damien P; Gray, Rachael

2015-06-01

Evaluation of the health status of free-ranging populations is important for understanding the impact of disease on individuals and on population demography and viability. In this study, haematological reference intervals were developed for free-ranging endangered Australian sea lion (Neophoca cinerea) pups within the context of endemic hookworm (Uncinaria sanguinis) infection and the effects of pathogen, host, and environment factors on the variability of haematological parameters were investigated. Uncinaria sanguinis was identified as an important agent of disease, with infection causing regenerative anaemia, hypoproteinaemia, and a predominantly lymphocytic-eosinophilic systemic inflammatory response. Conversely, the effects of sucking lice (Antarctophthirus microchir) were less apparent and infestation in pups appears unlikely to cause clinical impact. Overall, the effects of U. sanguinis, A. microchir, host factors (standard length, body condition, pup sex, moult status, and presence of lesions), and environment factors (capture-type and year of sampling) accounted for 26-65% of the total variance observed in haematological parameters. Importantly, this study demonstrated that anaemia in neonatal Australian sea lion pups is not solely a benign physiological response to host-environment changes, but largely reflects a significant pathological process. This impact of hookworm infection on pup health has potential implications for the development of foraging and diving behaviour, which would subsequently influence the independent survival of juveniles following weaning. The haematological reference intervals developed in this study can facilitate long-term health surveillance, which is critical for the early recognition of changes in disease impact and to inform conservation management. Copyright © 2015 Elsevier Inc. All rights reserved.

Recent RF Experiments and Application of RF Waves to Real-Time Control of Safety Factor Profile in JT-60U

NASA Astrophysics Data System (ADS)

Suzuki, T.; Isayama, A.; Ide, S.; Fujita, T.; Oikawa, T.; Sakata, S.; Sueoka, M.; Hosoyama, H.; JT-60 Team

2005-09-01

Two topics of applications of RF waves to current profile control in JT-60U are presented; application of lower-hybrid (LH) waves to safety factor profile control and electron cyclotron (EC) waves to neo-classical tearing mode (NTM) control. A real-time control system of safety factor (q) profile was developed. This system, for the first time, enables 1) real time evaluation of q profile using local magnetic pitch angle measurement by motional Stark effect (MSE) diagnostic and 2) control of current drive (CD) location (ρCD) by controlling the parallel refractive index N∥ of LH waves through control of phase difference (Δφ) of LH waves between multi-junction launcher modules. The method for real-time q profile evaluation was newly developed, without time-consuming reconstruction of equilibrium, so that the method requires less computational time. Safety factor profile by the real-time calculation agrees well with that by equilibrium reconstruction with MSE. The control system controls ρCD through Δφ in such a way to decrease the largest residual between the real-time evaluated q profile q(r) and its reference profile qref(r). The real-time control system was applied to a positive shear plasma (q(0)˜1). The reference q profile was set to monotonic positive shear profile having qref(0)=1.3. The real-time q profile approached to the qref(r) during application of real-time control, and was sustained for 3s, which was limited by the duration of the injected LH power. Temporal evolution of current profile was consistent with relaxation of inductive electric field induced by theoretical LH driven current. An m/n=3/2 NTM that appeared at βN˜3 was completely stabilized by ECCD applied to a fully-developed NTM. Precise ECCD at NTM island was essential for the stabilization. ECCD that was applied to resonant rational surface (q=3/2) before an NTM onset suppressed appearance of NTM. In order to keep NTM intensity below a level, ECCD before the mode onset was more

Normal haematology and blood biochemistry of wild Nile crocodiles (Crocodylus niloticus) in the Okavango Delta, Botswana.

PubMed

Lovely, C J; Pittman, J M; Leslie, A J

2007-09-01

Wild Nile crocodiles (Crocodylus niloticus) of various size classes were captured in the Okavango Delta, Botswana. Blood was collected from the post occipital sinus and used for the determination of a wide range of haematological and biochemical parameters. These values were compared between the sexes and between 3 size classes. The values were also compared with the limited data available from farmed Nile crocodiles, as well as from other wild Nile crocodiles. The Okavango crocodiles were comparatively anaemic, and had comparatively low total protein and blood glucose levels. There was a high prevalence of Hepatozoon pettiti infection, however, there was no significant difference in haematological values between the infected and uninfected crocodiles. The values reported here will be useful in diagnostic investigations in both zoo and farmed Nile crocodiles.

Evaluation of haematological, hepatic and renal functions of petroleum tanker drivers in Lagos, Nigeria.

PubMed

Awodele, Olufunsho; Sulayman, Ademola A; Akintonwa, Alade

2014-03-01

Hydrocarbons which are among the major components of petroleum products are considered toxic and have been implicated in a number of human diseases. Tanker drivers are continuously exposed to hydrocarbons by inhalation and most of these drivers do not use protective devices to prevent inhalation of petroleum products; nor do they visit hospital regularly for routine check-up. In view of this occupational hazard, we investigated the haematological, renal and hepatic functions of workers of petroleum tankers drivers in Lagos, Nigeria. Twenty-five tanker drivers' and fifteen control subjects were randomly selected based on the selection criteria of not smoking and working for minimum of 5 years as petroleum tanker driver. The liver, renal and haematological parameters were analyzed using automated clinical and haematological analyzers while the lipid peroxidation and antioxidant level tests were assayed using standard methods. There were significant (p ≤ 0.05) increases in the levels of serum alanine amino transferase (31.14±13.72; 22.38±9.89), albumin (42.50±4.69; 45.36±1.74) and alkaline phosphatase (84.04±21.89; 62.04±23.33) of petroleum tanker drivers compared with the controls. A significant (p≤0.05) increase in the levels of creatinine, urea and white blood cells of the tanker drivers, compared with the controls, were also obtained. The results have enormous health implications of continuous exposure to petroleum products reflected hepatic and renal damage of petroleum tanker drivers. Therefore, there is need for this group of workers to be sensitized on the importance of protective devises, regular medical checkup and management.

Oncology/haematology nurses: a study of job satisfaction, burnout, and intention to leave the specialty.

PubMed

Barrett, Linda; Yates, Patsy

2002-01-01

The impact of the current nursing shortage on the health care system is receiving attention by both state and federal governments. This study, using a convenience sample of 243 oncology/haematology nurses working in 11 Queensland health care facilities, explored factors that influence the quality of nurses' working lives. Although nurses reported high levels of personal satisfaction and personal accomplishment, results indicated that nearly 40% of registered nurses (RNs) are dealing with workloads they perceive excessive, 48% are dissatisfied regarding pay, and professional support is an issue. Furthermore, emotional exhaustion is a very real concern: over 70% of the sample experienced moderate to high levels. Over 48% of the sample could not commit to remaining in the specialty for a further 12 months. Health care managers and governments should implement strategies that can increase nurses' job satisfaction and reduce burnout, thereby enhancing the retention of oncology/haematology nurses.

Haematological considerations in patients with cyanotic congenital heart disease: a review.

PubMed

Auluck, Ajit; Manohar, Chetan

2006-12-01

In patients with cyanotic congenital heart disease (CCHD), the need for prior antibiotic prophylaxis for infective endocarditis is well known to dentists, but not many dentists are aware of the associated haemorrhagic tendencies in such patients. Haemostatic abnormalities associated with CCHD are an important aspect that is often overlooked by both physicians and dentists. We briefly review the literature to highlight the importance of more elaborate haematological evaluation in patients with CCHD, prior to any oral surgical procedures.

The effect of in-vivo intravenous administration of sodium meglumine diatrizoate on some haematological parameters.

PubMed

Agwu, K K; Mgbor, S; Ogbu, S O I; Okeji, M

2007-01-01

To investigate the in-vivo effects of intravenous administration of sodium meglumine diatrizoate on some haematological parameters in a Nigerian population. Blood samples were collected before and one hour after intravenous injection of sodium-meglumine diatrizoate from 50 subjects undergoing intravenous urography examinations who had no history of and laboratory confirmed diseases that may affect haematological parameters. Standard laboratory methods were used to assay the haemoglobin concentration (Hb), packed cell volume (PCV), total white blood cell (WBC) count and differentials and blood film for any morphological changes in the red blood cells (RBC). Comparisons were made between the mean values of these haematological parameters before and one hour post injection using paired t-test for any statistically significant differences. There were statistically significant reductions in the mean values of Hb concentration and the neutrophil count one hour post injection compared with their pretest values (p < 0.05). The lymphocytes were also significantly increased post injection compared to the pretest values whereas 70% of the erythrocytes were morphologically altered from their approximately 100% normocytic shape at pre-test. Intravenous administration of sodium-meglumine diatrizoate causes in-vivo reduction in Hb concentration and neutrophil count in humans as well as poikilocytosis of the erythrocytes. Some of these effects have the potential of triggering or exacerbating crisis in a sickle cell anaemia subject which is endemic in our locality. Caution should therefore be exercised in the choice and administration of radiological contrast agents to sickle cell subjects. Preparations that are iso-osmolar with plasma and have less probability in precipitating crises should be preferred instead.

[Incidence of haematological neoplasms in Castilla y León, Spain].

PubMed

Rodríguez-García, José Antonio; Vázquez, Lourdes; Ramos, Fernando; Cuevas, Beatriz; Martín, Alejandro; Smucler, Alicia; Guerola, Dulce Nombre; Cantalapiedra, Alberto; Alonso, José María; Fernández, Silvia; Díez, Eva; Rodríguez, María Jesús; Calmuntia, María José; Aguilar, Carlos; Sierra, Magdalena; Gracia, José Antonio; Cebeira, María José; Cantalejo, Rosa

2015-06-08

We aimed to assess the incidence of haematological neoplasms (HNs) in Castilla y León (2,5 million inhabitants) and its distribution by age, gender and histological type. The epidemiological profile based on the described variables of the 10,943 HNs diagnosed during a 10-years period was analyzed, compared with other studies. The overall age-adjusted incidence was 29.4 cases/10(5) inhabitants-year, with some geographical differences. The mean age was 67.3 years, with a turning point between the 6th-7th decades of life from which there was a very significant increase of incidence. Two relevant facts where simultaneous with advancing age: decreased lymphoid neoplasms incidence and increased low degree neoplasms incidence. Lymphoid low degree neoplasms accounted for half of the registered processes, showed the greatest preference for male and reached the mode before the rest of neoplasms. Myeloid neoplasms incidence (9.5) was higher than that reported in other European registries, specially compared to southern European countries, opposite to lymphoid neoplasms incidence (20.0). A higher myeloid neoplasms incidence and lower lymphoid one than expected was observed. The turning point of incidence is between the 6th-7th decades of life, with a preference for male that decreases with age. There is an increased incidence of HNs in the area where a higher density of potentially polluting facilities is concentrated. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Human NK cells activated by EBV+ lymphoblastoid cells overcome anti-apoptotic mechanisms of drug resistance in haematological cancer cells

PubMed Central

Sánchez-Martínez, Diego; Azaceta, Gemma; Muntasell, Aura; Aguiló, Nacho; Núñez, David; Gálvez, Eva M; Naval, Javier; Anel, Alberto; Palomera, Luis; Vilches, Carlos; Marzo, Isabel; Villalba, Martín; Pardo, Julián

2015-01-01

Natural killer (NK) cells recognize and eliminate transformed or infected cells that have downregulated MHC class-I and express specific activating ligands. Recent evidence indicates that allogeneic NK cells are useful to eliminate haematological cancer cells independently of MHC-I expression. However, it is unclear if transformed cells expressing mutations that confer anti-apoptotic properties and chemoresistance will be susceptible to NK cells. Allogeneic primary human NK cells were activated using different protocols and prospectively tested for their ability to eliminate diverse mutant haematological and apoptotic-resistant cancer cell lines as well as patient-derived B-cell chronic lymphocytic leukemia cells with chemotherapy multiresistance. Here, we show that human NK cells from healthy donors activated in vitro with Epstein Barr virus positive (EBV+)-lymphoblastoid cells display an enhanced cytotoxic and proliferative potential in comparison to other protocols of activation such a K562 cells plus interleukin (IL)2. This enhancement enables them to kill more efficiently a variety of haematological cancer cell lines, including a panel of transfectants that mimic natural mutations leading to oncogenic transformation and chemoresistance (e.g., overexpression of Bcl-2, Bcl-XL and Mcl-1 or downregulation of p53, Bak/Bax or caspase activity). The effect was also observed against blasts from B-cell chronic lymphocytic leukemia patients showing multi-resistance to chemotherapy. Our findings demonstrate that particular in vitro activated NK cells may overcome anti-apoptotic mechanisms and oncogenic alterations frequently occurring in transformed cells, pointing toward the use of EBV+-lymphoblastoid cells as a desirable strategy to activate NK cells in vitro for the purpose of treating haematological neoplasia with poor prognosis. PMID:25949911

Protective Isolation for Patients with Haematological Malignancies: A Pilot Study Investigating Patients' Distress and Use of Time.

PubMed

Annibali, O; Pensieri, C; Tomarchio, V; Biagioli, V; Pennacchini, M; Tendas, A; Tambone, V; Tirindelli, M C

2017-10-01

Background: Patients with haematological malignancies are often hospitalized in protective isolation until full neutrophil recovery in order to prevent infections. This descriptive pilot study evaluate the level of isolation-related distress and the use of free time in a sample of Italian onco-haematological patients who were hospitalized in protective isolation. Materials and Methods: Participants were 18 patients hospitalized in hematologic ward to receive induction therapy (n=12) or autologous stem cell transplant (n=6). They completed a self-report questionnaire before discharge. Results: Participants reported a moderate level of isolation-related distress, anxiety, and boredom: the more the anxiety and the boredom, the more the distress (r=.77; P<.001), (r=.79; P<.001), respectively. The activities performed during isolation were: watching TV (72.2%), reading (55.6%), thinking (33.3%), surfing in Internet or using PC (33.3%), and playing games or making cross-words (16.7%). Participants who reported pessimistic thinking had higher isolation-related distress (P=.004) as well as anxiety (P<.001) and boredom (P=.001). Conclusion: Haematology Units should support isolated patients in spending their time in recreational activities, allowing more contacts with immediate relatives and friends, providing free TV and Wi-Fi connection inside the room. In addition, patients should have to keep themselves physically active. Isolation-related distress could also be reduced by providing psychological support.

Protective Isolation for Patients with Haematological Malignancies: A Pilot Study Investigating Patients’ Distress and Use of Time

PubMed Central

Annibali, O.; Pensieri, C.; Tomarchio, V.; Biagioli, V.; Pennacchini, M.; Tendas, A.; Tambone, V.; Tirindelli, M.C.

2017-01-01

Background: Patients with haematological malignancies are often hospitalized in protective isolation until full neutrophil recovery in order to prevent infections. This descriptive pilot study evaluate the level of isolation-related distress and the use of free time in a sample of Italian onco-haematological patients who were hospitalized in protective isolation. Materials and Methods: Participants were 18 patients hospitalized in hematologic ward to receive induction therapy (n=12) or autologous stem cell transplant (n=6). They completed a self-report questionnaire before discharge. Results: Participants reported a moderate level of isolation-related distress, anxiety, and boredom: the more the anxiety and the boredom, the more the distress (r=.77; P<.001), (r=.79; P<.001), respectively. The activities performed during isolation were: watching TV (72.2%), reading (55.6%), thinking (33.3%), surfing in Internet or using PC (33.3%), and playing games or making cross-words (16.7%). Participants who reported pessimistic thinking had higher isolation-related distress (P=.004) as well as anxiety (P<.001) and boredom (P=.001). Conclusion: Haematology Units should support isolated patients in spending their time in recreational activities, allowing more contacts with immediate relatives and friends, providing free TV and Wi-Fi connection inside the room. In addition, patients should have to keep themselves physically active. Isolation-related distress could also be reduced by providing psychological support. PMID:29340129

Safety and bleeding profile of continuous levonorgestrel 90 mcg/ethinyl estradiol 20 mcg based on 2 years of clinical trial data in Canada.

PubMed

Reid, Robert L; Fortier, Michel P; Smith, Lynne; Mirkin, Sebastian; Grubb, Gary S; Constantine, Ginger D

2010-12-01

The study was conducted to evaluate bleeding profile and safety of continuous oral contraceptive (OC) containing levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg. Healthy women who participated at seven Canadian sites in 1-year open-label study of LNG 90 mcg/EE 20 mcg daily were eligible for this second-year extension study. Primary end points included bleeding profile and adverse events. Seventy-nine women enrolled without interrupting pill taking; 62 (78.5%) completed. Adverse events were comparable to cyclic OC regimens, except unscheduled vaginal bleeding. Amenorrhea and absence of bleeding increased to about 80% and 90%, respectively, by Pill Pack 18. Mean (median) number of bleeding days for the last two 90-day intervals was 1.1 (0) and 0.7 (0) days, respectively. Continuous LNG 90 mcg/EE 20 mcg had a safety profile similar to low-dose cyclic OCs. Short-term safety profile remained excellent, with increasing rates of amenorrhea and decreasing incidence of unscheduled bleeding and/or spotting. Copyright © 2010 Elsevier Inc. All rights reserved.

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic review and network meta-analysis.

PubMed

Moćko, Paweł; Kawalec, Paweł; Pilc, Andrzej

2016-12-01

Crohn disease (CD) is an inflammatory bowel disease which occurs especially in developed countries of Western Europe and North America. The aim of the study was to compare the safety profile of biologic drugs in patients with CD. A systematic literature search was performed using PubMed, Embase, and CENTRAL databases, until April 27, 2016. We included randomized controlled trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab, vedolizumab, certolizumab pegol, and ustekinumab) with one another or with placebo in patients with CD. The network meta-analysis (NMA) was conducted for an induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian hierarchical random effects model in the ADDIS ® software. The PROSPERO registration number was CRD42016032606. Ten RCTs were included in the systematic review with NMA. In the case of the induction phase, the NMA could be conducted for the assessment of the relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab, and vedolizumab. There were no significant differences in the rate of adverse events in patients treated with biologics. Statistical analysis revealed that vedolizumab had the greatest probability of being the safest treatment in most endpoints in the induction phase and adalimumab-in the maintenance phase. No significant differences between the biologics in the relative safety profile analysis were observed. Further studies are needed to confirm our findings, including head-to-head comparisons between the analyzed biologics. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Primary prophylaxis of invasive fungal infections in patients with haematological malignancies: 2017 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society for Haematology and Medical Oncology (DGHO).

PubMed

Mellinghoff, Sibylle C; Panse, Jens; Alakel, Nael; Behre, Gerhard; Buchheidt, Dieter; Christopeit, Maximilian; Hasenkamp, Justin; Kiehl, Michael; Koldehoff, Michael; Krause, Stefan W; Lehners, Nicola; von Lilienfeld-Toal, Marie; Löhnert, Annika Y; Maschmeyer, Georg; Teschner, Daniel; Ullmann, Andrew J; Penack, Olaf; Ruhnke, Markus; Mayer, Karin; Ostermann, Helmut; Wolf, Hans-H; Cornely, Oliver A

2018-02-01

Immunocompromised patients are at high risk of invasive fungal infections (IFI), in particular those with haematological malignancies undergoing remission-induction chemotherapy for acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) and recipients of allogeneic haematopoietic stem cell transplants (HSCT). Despite the development of new treatment options in the past decades, IFI remains a concern due to substantial morbidity and mortality in these patient populations. In addition, the increasing use of new immune modulating drugs in cancer therapy has opened an entirely new spectrum of at risk periods. Since the last edition of antifungal prophylaxis recommendations of the German Society for Haematology and Medical Oncology in 2014, seven clinical trials regarding antifungal prophylaxis in patients with haematological malignancies have been published, comprising 1227 patients. This update assesses the impact of this additional evidence and effective revisions. Our key recommendations are the following: prophylaxis should be performed with posaconazole delayed release tablets during remission induction chemotherapy for AML and MDS (AI). Posaconazole iv can be used when the oral route is contraindicated or not feasible. Intravenous liposomal amphotericin B did not significantly decrease IFI rates in acute lymphoblastic leukaemia (ALL) patients during induction chemotherapy, and there is poor evidence to recommend it for prophylaxis in these patients (CI). Despite substantial risk of IFI, we cannot provide a stronger recommendation for these patients. There is poor evidence regarding voriconazole prophylaxis in patients with neutropenia (CII). Therapeutic drug monitoring TDM should be performed within 2 to 5 days of initiating voriconazole prophylaxis and should be repeated in case of suspicious adverse events or of dose changes of interacting drugs (BIItu). General TDM during posaconazole prophylaxis is not recommended (CIItu), but may be helpful in

Evaluating the Safety Profile of Non-Active Implantable Medical Devices Compared with Medicines.

PubMed

Pane, Josep; Coloma, Preciosa M; Verhamme, Katia M C; Sturkenboom, Miriam C J M; Rebollo, Irene

2017-01-01

Recent safety issues involving non-active implantable medical devices (NAIMDs) have highlighted the need for better pre-market and post-market evaluation. Some stakeholders have argued that certain features of medicine safety evaluation should also be applied to medical devices. Our objectives were to compare the current processes and methodologies for the assessment of NAIMD safety profiles with those for medicines, identify potential gaps, and make recommendations for the adoption of new methodologies for the ongoing benefit-risk monitoring of these devices throughout their entire life cycle. A literature review served to examine the current tools for the safety evaluation of NAIMDs and those for medicines. We searched MEDLINE using these two categories. We supplemented this search with Google searches using the same key terms used in the MEDLINE search. Using a comparative approach, we summarized the new product design, development cycle (preclinical and clinical phases), and post-market phases for NAIMDs and drugs. We also evaluated and compared the respective processes to integrate and assess safety data during the life cycle of the products, including signal detection, signal management, and subsequent potential regulatory actions. The search identified a gap in NAIMD safety signal generation: no global program exists that collects and analyzes adverse events and product quality issues. Data sources in real-world settings, such as electronic health records, need to be effectively identified and explored as additional sources of safety information, particularly in some areas such as the EU and USA where there are plans to implement the unique device identifier (UDI). The UDI and other initiatives will enable more robust follow-up and assessment of long-term patient outcomes. The safety evaluation system for NAIMDs differs in many ways from those for drugs, but both systems face analogous challenges with respect to monitoring real-world usage. Certain features

Effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers.

PubMed

Saleh-Gohari, Nasrollah; Khademi Bami, Maryam; Nikbakht, Roya; Karimi-Maleh, Hassan

2015-07-01

Thalassaemia is a haemoglobin disorder caused by a reduction in, or a complete absence of, the production of α- or β-globin genes. Detection of β-thalassaemia carriers is the first step in the prenatal diagnosis of the disease and is based primarily on the differences between levels of blood cell indices. Since co-inheritance of β- and α-thalassaemia mutations modulates the haematological parameters of heterozygote β-thalassaemia indices, understanding the influence of this interaction is helpful for identification of disease carriers. To determine the effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers. We used gap-PCR and amplification refractory mutation system techniques to find any α- and/or β-thalassaemia mutations in 270 subjects who were suspected to be thalassaemia carriers. The mean values of the haematological parameters in α, β-thalassaemia and β-thalassaemia carriers were compared. Significant differences in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and HbA2 were found between the two groups. Patients who were α, β-thalassaemia carriers had higher mean values of MCV and MCH, whereas HbA2 levels were higher in simple β-thalassaemia. No marked differences were found in mean cell haemoglobin (Hb) concentration and Hb blood cell indices. The value of MCV, MCH and HbA2 were significantly different between α,β-thalassaemia and simple β-thalassaemia in men and women, but the mean values of Hb in the two groups differed markedly only in men. We conclude that co-inheritance of α- and β-thalassaemia mutations may result in misdiagnosis of β-thalassaemia carriers. Therefore, in genetic counselling of patients with a near-normal range of blood cell indices the possibility that they may carry α, β-thalassaemia mutations must be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Haematological toxicity of Valproic acid compared to Levetiracetam in patients with glioblastoma multiforme undergoing concomitant radio-chemotherapy: a retrospective cohort study.

PubMed

Tinchon, Alexander; Oberndorfer, Stefan; Marosi, Christine; Gleiss, Andreas; Geroldinger, Angelika; Sax, Cornelia; Sherif, Camillo; Moser, Walter; Grisold, Wolfgang

2015-01-01

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

Brentuximab vedotin, an antibody–drug conjugate, in patients with CD30‐positive haematologic malignancies and hepatic or renal impairment

PubMed Central

Chen, Robert; O'Connor, Owen A.; Gopal, Ajay K.; Ramchandren, Radhakrishnan; Goy, Andre; Matous, Jeffrey V.; Fasanmade, Adedigbo A.; Manley, Thomas J.; Han, Tae H.

2016-01-01

Abstract Aims Brentuximab vedotin, an antibody–drug conjugate (ADC), selectively delivers the microtubule‐disrupting agent monomethyl auristatin E (MMAE) into CD30‐expressing cells. The pharmacokinetics of brentuximab vedotin have been characterized in patients with CD30‐positive haematologic malignancies. The primary objective of this phase 1 open label evaluation was to assess the pharmacokinetics of brentuximab vedotin in patients with hepatic or renal impairment. Methods Systemic exposures were evaluated following intravenous administration of 1.2 mg kg–1 brentuximab vedotin in patients with CD30‐positive haematologic malignancies and hepatic (n = 7) or renal (n = 10) impairment and compared with those of unimpaired patients (n = 8) who received 1.2 mg kg–1 brentuximab vedotin in another arm of the study. Results For any hepatic impairment, the ratios of geometric means (90% confidence interval) for AUC(0,∞) were 0.67 (0.48, 0.93) for ADC and 2.29 (1.27, 4.12) for MMAE. Mild or moderate renal impairment caused no apparent change in ADC or MMAE exposures. Severe renal impairment (creatinine clearance <30 ml min–1; n = 3) decreased ADC exposures (0.71 [0.54, 0.94]) and increased MMAE exposures (1.90 [0.85, 4.21]). No consistent pattern of specific adverse events was evident, but analysis of the safety data was confounded by the patients' poor baseline conditions. Five patients died due to adverse events considered unrelated to brentuximab vedotin. All had substantial comorbidities and most had poor baseline performance status. Conclusions Hepatic impairment and severe renal impairment may cause decreases in brentuximab vedotin ADC exposures and increases in MMAE exposures. PMID:27115790

Haematological effects of 2-phenoxyethanol and etomidate in carp (Cyprinus carpio L.).

PubMed

Witeska, Malgorzata; Dudyk, Joanna; Jarkiewicz, Natalia

2015-09-01

To evaluate the effects of handling alone versus handling under anaesthesia with 2-phenoxyethanol or etomidate on haematological parameters in carp. Prospective, randomized, laboratory experiment. Seventy-two juvenile carp (Cyprinus carpio) weighing 35.9 ± 10.4 g were divided into six groups of 12 fish. Either 2-phenoxyethanol or 2% etomidate were administered to induce deep anaesthesia (0.3 mL L(-1) and 0.6 mL L(-1) , respectively) or deep sedation (0.15 mL L(-1) and 0.3 mL L(-1) , respectively). Fish were handled with and without sedation. Blood was sampled at 1 hour and 1 week post-treatment. Phagocyte oxidative activity [nitrotetrazolium blue reduction test (NBT)] and differential erythrocyte [red blood cell (RBC)] and leukocyte (white blood cell) counts were evaluated. At 1 hour after the induction of anaesthesia, haematocrit (Ht) and haemoglobin (Hb) were increased in fish anaesthetized with 2-phenoxyethanol, and mean corpuscular haemoglobin (MCH) was increased in fish anaesthetized with etomidate. At 1 week, an increase in RBC, erythroblastosis, erythrocyte damage, lymphopenia, neutrophilia, monocytosis and thrombocytosis occurred in both groups. Red blood parameters did not change 1 hour after handling alone, but after 1 week Ht, Hb and mean cell volume decreased, whereas MCH concentration (MCHC) and abnormal erythrocytes increased. Lymphopenia, neutrophilia, monocytosis, thrombocytosis and a decrease in NBT occurred. Fish handled under sedation showed an increase in Hb and MCHC followed by a decrease at 1 week in Ht, Hb and MCH, erythroblastosis and increased abnormal erythrocytes. Lymphopenia and neutrophilia were less pronounced than in fish handled without sedation, but a decrease in NBT was noted at 1 week post-treatment. Deep anaesthesia with 2-phenoxyethanol or etomidate induced significant haematological alterations in juvenile carp. Deep sedation reduced the immediate immunosuppressive effects of handling but did not eliminate

The Effect of Cement Dust Exposure on Haematological Parameters of Cement Factory workers in Nalagonda, Andhra Pradesh.

NASA Astrophysics Data System (ADS)

Guguloth, Mohan Rao.; Sambanaik, A.; srinivasnaik, L.; Mude, Jagadishnaik.

2012-10-01

This study was measured on haematological parameters in workers exposed to cement dust in order to test the the hypothesis and to identify a simple, readily available, cost effective screening test that could help in identifying the presence of disease, its severity, that Cement dust exposure may perturb these functions related to their workplace.Assesment of haematological parameters were performed in 100exposed workers occupationally exposed to cement dust and 50 matched unexposed controls with ages ranging from 20-35, 35-50, 50-65 years. The blood samples were taken from them and percentage of hemoglobin, Lymphocytes / monocytes count were analysed.The hemoglobin percentage of exposed workers were significantly lower(P<0.05).Lymphocytes/Monocytes counts of exposed workers was insignificant (P<0.05).These results suggest that long term occupational exposure to cement dust may perturb haemopoietic function.

Safety profile and gender specific differences of a methanol extract of Eriosema laurentii (Leguminosae) in acute and subchronic (28 days) oral toxicity studies in Wistar rats.

PubMed

Ateba, Sylvin Benjamin; Simo, Rudy Valdès; Mbanya, Jean Claude; Krenn, Liselotte; Njamen, Dieudonné

2014-03-01

Despite widespread use of Eriosema laurentii De Wild (Leguminosae) in West and Central Africa as herbal medicine and food additive the toxicity of this plant is unknown. Therefore, we performed the safety evaluation of a methanol extract (AEL). In acute toxicity, single oral administration of 2000mg/kg AEL caused neither toxicological symptoms nor mortality and the LD50 was estimated >5000mg/kg. In the subchronic oral toxicity, AEL induced no phenotypical signs of toxicity during and after treatment. Only a delayed decrease of relative spleen weight in males at the highest dose of 400mg/kg occurred. High density lipoprotein (HDL) increased significantly in females at 200 and 400mg/kg. Non-persistent increases in alanine aminotransferase activity within normal ranges were noted at 200mg/kg in males and at all doses in females. In males, AEL induced a decrease of white blood cell count at 400mg/kg, whereas lymphocytes increased at 200 and 400mg/kg and granulocytes at 400mg/kg. In females, no differences in haematological parameters occurred. Neither differences in bilirubin, creatinine and total protein levels were observed nor histological alterations in organs. The results indicate a broad safety margin for AEL. Copyright © 2013 Elsevier Ltd. All rights reserved.

Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen. Working Party of the British Committee for Standards in Haematology Clinical Haematology Task Force.

PubMed Central

1996-01-01

Overwhelming postsplenectomy infection should be preventable if simple precautions are taken. An ad hoc working party of the British Committee for Standards in Haematology has reviewed recommendations for patients without a spleen and drawn up a consensus. Members of the working party were selected for their personal expertise and to represent relevant professional bodies. The guidelines, which are set out below, include and extend the chief medical officer's 1994 update. PMID:8601117

Epidemiology of invasive fungal diseases among patients with haematological disorders in the Asia-Pacific: a prospective observational study.

PubMed

Hsu, L Y; Lee, D G; Yeh, S P; Bhurani, D; Khanh, B Q; Low, C Y; Norasetthada, L; Chan, T; Kwong, Y L; Vaid, A K; Alejandria, I; Mendoza, M; Chen, C Y; Johnson, A; Tan, T Y

2015-06-01

We conducted a 2-year multicentre prospective observational study to determine the epidemiology of and mortality associated with invasive fungal diseases (IFDs) among patients with haematological disorders in Asia. Eleven institutions from 8 countries/regions participated, with 412 subjects (28.2% possible, 38.3% probable and 33.5% proven IFDs) recruited. The epidemiology of IFDs in participating institutions was similar to Western centres, with Aspergillus spp. (65.9%) or Candida spp. (26.7%) causing the majority of probable and proven IFDs. The overall 30-day mortality was 22.1%. Progressive haematological disorder (odds ratio [OR] 5.192), invasive candidiasis (OR 3.679), and chronic renal disease (OR 6.677) were independently associated with mortality. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Safety and efficacy of azacitidine in Belgian patients with high-risk myelodysplastic syndromes, acute myeloid leukaemia, or chronic myelomonocytic leukaemia: results of a real-life, non-interventional post-marketing survey.

PubMed

Beguin, Y; Selleslag, D; Meers, S; Graux, C; Bries, G; Deeren, D; Vrelust, I; Ravoet, C; Theunissen, K; Voelter, V; Potier, H; Trullemans, F; Noens, L; Mineur, P

2015-02-01

We evaluated azacitidine (Vidaza(®)) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. The median age of patients was 74·7 (range: 43·9-87·8) years; 69·4% had MDS, 26·5% had primary or secondary AML, and 4·1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67·3%, 28·6%, and 18·4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (n = 29), 41·4% had CR, PR, or HI, 41·4% had SD, and 17·2% had TF. Among AML patients (n = 9), 44·4% had CR or PR, 33·3% had SD, and 22·2% had TF. TI was observed in 14/32 (43·8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0·571 (0·422-0·696). Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.

Safety of a weekly high dose of liposomal amphotericin B for prophylaxis of invasive fungal infection in immunocompromised patients: PROPHYSOME Study.

PubMed

Cordonnier, Catherine; Mohty, Mohamad; Faucher, Catherine; Pautas, Cécile; Robin, Marie; Vey, Norbert; Monchecourt, Françoise; Mahi, Lamine; Ribaud, Patricia

2008-02-01

With its broad spectrum of activity and better tolerability profile than conventional amphotericin B, liposomal amphotericin B (L-AmB) may be the drug of choice for antifungal prophylaxis in haematological patients. An open-label, multicentre, prospective, pilot study was conducted in adult patients receiving chemotherapy for acute leukaemia (AL) or myeloablative allogeneic stem cell transplantation (SCT). Patients received weekly 10mg/kg infusions of L-AmB for 4 weeks for AL and 8 weeks for SCT. The primary objective was safety, with particular attention to infusion-related reactions and nephrotoxicity. Twenty-nine adult patients were included: 21 AL (median age 52 years) and 8 SCT (median age 37 years). The most frequent adverse events (AEs) related to study drug were infusion-related reactions, 12 of which (from a total of 76 infusions) led to increased infusion duration for better tolerance. No AE related to the study drug led to discontinuation of prophylactic treatment in AL patients. In SCT patients, eight AEs (in six patients) reported to be related to study treatment led to treatment discontinuation. Enrolment was discontinued in the SCT group as recommended by the independent data review committee in accordance with the 10% limit of AEs (CTC grade 3-4) fixed by the protocol. The appropriate timing of high-dose prophylactic L-AmB remains to be determined in the SCT setting to optimise the safety profile of this regimen. For AL, a 10mg/kg weekly dose appears to be well tolerated during chemotherapy and may represent an important tool towards improving AL patient outcome.

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria.

PubMed

Varo, Rosauro; Crowley, Valerie M; Sitoe, Antonio; Madrid, Lola; Serghides, Lena; Bila, Rubao; Mucavele, Helio; Mayor, Alfredo; Bassat, Quique; Kain, Kevin C

2017-05-23

Despite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention. In this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem ® ) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations. Thirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters. Adjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria. The trial is registered with Clinicaltrials.gov, NCT02694874.

Alfalfa dodder (Cuscuta campestris) toxicity in horses: clinical, haematological and serum biochemical findings.

PubMed

Abutarbush, S M

2013-07-27

The objective of this observational study is to describe clinical, haematological and serum biochemical findings of horses affected with alfalfa dodder (Cuscuta campestris) toxicity. Twenty horses naturally exposed to alfalfa dodder toxicity were examined and information was collected on history and clinical signs. Physical examination was done on horses in the premises (n=20), and venous blood samples of 12 horses were submitted for haematology and serum biochemical examination for each horse. Abnormal clinical signs started around 36 hours after horses were fed the contaminated alfalfa. Abnormal signs were seen in 11 horses and those included diarrhoea (n=8), decreased appetite (n=7), neurological signs (n=4) and abdominal pain (n=1). Some horses had multiple clinical signs of the above. The results of complete blood cell count revealed leukocytopenia, neutropenia and thrombocytopenia. Serum biochemical analysis revealed decreased ALP, AST and CPK levels and increased direct bilirubin level. The used alfalfa was stopped immediately and a different alfalfa from a new container that did not contain any weeds was fed. Horses on the premises were observed closely, and the abnormal clinical signs resolved within three days. No treatment was implemented. Knowledge about toxicity of horses by Cuscuta species is scarce in the English veterinary literature and very limited.

A national study of the unmet needs of support persons of haematological cancer survivors in rural and urban areas of Australia.

PubMed

Lynagh, Marita C; Williamson, A; Bradstock, K; Campbell, S; Carey, M; Paul, C; Tzelepis, F; Sanson-Fisher, R

2018-06-01

This study aimed to compare support persons of haematological cancer survivors living in rural and urban areas in regard to the type, prevalence and factors associated with reporting unmet needs. One thousand and four (792 urban and 193 rural) support persons of adults diagnosed with haematological cancer were recruited from five Australian state population-based cancer registries. Participants completed the Support Person Unmet Needs Survey (SPUNS) that assessed the level of unmet needs experienced over the past month across six domains. Overall, 66% of support persons had at least one 'moderate, high or very high' unmet need and 24% (n = 182) reported having multiple (i.e. 6 or more) 'high/very high' unmet needs in the past month. There were no significant differences between rural and urban support persons in the prevalence of multiple unmet needs or mean total unmet needs scores. There were however significant differences in the types of 'high/very high' unmet needs with support persons living in rural areas more likely to report finance-related unmet needs. Support persons who indicated they had difficulty paying bills had significantly higher odds of reporting multiple 'high/very high' unmet needs. This is the first large, population-based study to compare the unmet needs of support persons of haematological cancer survivors living in rural and urban areas. Findings confirm previous evidence that supporting a person diagnosed with haematological cancer correlates with a high level of unmet needs and highlight the importance of developing systemic strategies for assisting support persons, especially in regard to making financial assistance and travel subsidies known and readily accessible to those living in rural areas.

Exchange transfusion as a life-saving intervention in three patients with different haematological malignancies with severe hyperleukocytosis where leukapheresis was not available.

PubMed

Barrett, Claire L; Louw, Vernon J; Webb, Michael J

2013-12-01

Hyperleukocytosis is a rare but potentially serious complication of haematological malignancies. It is usually treated with rehydration, prevention of tumour lysis syndrome and the administration of cytotoxic therapy. Leukapheresis may be life-saving in emergency cases. In this article we describe how, in a resource-limited setting where leukapheresis was not available, manual exchange transfusion was utilised as a life-saving intervention in three patients with different haematological malignancies complicated by hyperleukocytosis. Further we outline the procedure that was carried out and evaluated possible complications associated with this rarely used practice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Training-induced annual changes in red blood cell profile in highly-trained endurance and speed-power athletes.

PubMed

Ciekot-Sołtysiak, Monika; Kusy, Krzysztof; Podgórski, Tomasz; Zieliński, Jacek

2017-10-24

An extensive body of literature exists on the effects of training on haematological parameters, but the previous studies have not reported how hematological parameters respond to changes in training loads within consecutive phases of the training cycle in highly-trained athletes in extremely different sport disciplines. The aim of this study was to identify changes in red blood cell (RBC) profile in response to training loads in consecutive phases of the annual training cycle in highly-trained sprinters (8 men, aged 24 ± 3 years) and triathletes (6 men, aged 24 ± 4 years) who competed at the national and international level. Maximal oxygen uptake (VO2max), RBC, haemoglobin (Hb), haematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and RBC distribution width (RDW) were determined in four characteristic training phases (transition, general subphase of the preparation phase, specific subphase of the preparation phase and competition phase). Our main findings are that (1) Hb, MCH and MCHC in triathletes and MCV in both triathletes and sprinters changed significantly over the annual training cycle, (2) triathletes had significantly higher values than sprinters only in case of MCH and MCHC after the transition and general preparation phases but not after the competition phase when MCH and MCHC were higher in sprinters and (3) in triathletes, Hb, MCH and MCHC substantially decreased after the competition phase, which was not observed in sprinters. The athletes maintained normal ranges of all haematological parameters in four characteristic training phases. Although highly-trained sprinters and triathletes do not significantly differ in their levels of most haematological parameters, these groups are characterized by different patterns of changes during the annual training cycle. Our results suggest that when interpreting the values of haematological parameters in speed-power and endurance

[Safety profile of zolpidem: two studies of 3805 patients by Swiss practitioners].

PubMed

Ganzoni, E; Gugger, M

1999-06-24

Evaluation and treatment of insomnia are frequent procedures in the physician's everyday practice, since many patients seek medical treatment for this condition. Knowledge of pharmacological therapeutical alternatives is therefore decisive, in order to identify the most efficaceous and safe therapy for the patient among the available hypnotics. The short-acting hypnotic zolpidem has been investigated in Switzerland in two multicenter safety studies in ambulatory practice. In the first study 8.9% (n = 125 of 1,972 treated patients), and in the second 7.2% of the patients (n = 175 of 1,833 treated patients) reported an adverse event. The most frequent events were related to the central nervous system (CNS) (somnolence, headache, confusion, vertigo); gastrointestinal and cutaneous symptoms were the most frequent non CNS-dependent effects. New, unknown or serious adverse events were not found and no specific risk factor or population at risk was identified. The safety profile of zolpidem is consistent with its known pharmacological properties, the results of previous clinical trials and the international experience obtained in large patients groups.

Can Disproportionality Analysis of Post-marketing Case Reports be Used for Comparison of Drug Safety Profiles?

PubMed

Michel, Christiane; Scosyrev, Emil; Petrin, Michael; Schmouder, Robert

2017-05-01

Clinical trials usually do not have the power to detect rare adverse drug reactions. Spontaneous adverse reaction reports as for example available in post-marketing safety databases such as the FDA Adverse Event Reporting System (FAERS) are therefore a valuable source of information to detect new safety signals early. To screen such large data-volumes for safety signals, data-mining algorithms based on the concept of disproportionality have been developed. Because disproportionality analysis is based on spontaneous reports submitted for a large number of drugs and adverse event types, one might consider using these data to compare safety profiles across drugs. In fact, recent publications have promoted this practice, claiming to provide guidance on treatment decisions to healthcare decision makers. In this article we investigate the validity of this approach. We argue that disproportionality cannot be used for comparative drug safety analysis beyond basic hypothesis generation because measures of disproportionality are: (1) missing the incidence denominators, (2) subject to severe reporting bias, and (3) not adjusted for confounding. Hypotheses generated by disproportionality analyses must be investigated by more robust methods before they can be allowed to influence clinical decisions.

Evaluation of the in-service safety performance of safety-shape and vertical concrete barriers.

DOT National Transportation Integrated Search

2011-12-16

Roadside concrete barriers have been widely used to protect errant motorists from hitting : roadside hazards or obstacles. Two concrete barrier profiles, vertical and safety-shape, have been used : for this purpose. The safety-shape profile has been ...

Protocol of a multi-centre randomised controlled trial of a web-based information intervention with nurse-delivered telephone support for haematological cancer patients and their support persons.

PubMed

Bryant, Jamie; Sanson-Fisher, Rob; Stevenson, William; Smits, Rochelle; Henskens, Frans; Wei, Andrew; Tzelepis, Flora; D'Este, Catherine; Paul, Christine; Carey, Mariko

2015-04-17

High rates of anxiety, depression and unmet needs are evident amongst haematological cancer patients undergoing treatment and their Support Persons. Psychosocial distress may be minimised by ensuring that patients are sufficiently involved in decision making, provided with tailored information and adequate preparation for potentially threatening procedures. To date, there are no published studies evaluating interventions designed to reduce psychosocial distress and unmet needs specifically in patients with haematological cancers and their Support Persons. This study will examine whether access to a web-based information tool and nurse-delivered telephone support reduces depression, anxiety and unmet information needs for haematological cancer patients and their Support Persons. A non-blinded, parallel-group, multi-centre randomised controlled trial will be conducted to compare the effectiveness of a web-based information tool and nurse-delivered telephone support with usual care. Participants will be recruited from the haematology inpatient wards of five hospitals in New South Wales, Australia. Patients diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, Burkitt's lymphoma, Lymphoblastic lymphoma (B or T cell), or Diffuse Large B-Cell lymphoma and their Support Persons will be eligible to participate. Patients and their Support Persons will be randomised as dyads. Participants allocated to the intervention will receive access to a tailored web-based tool that provides accurate, up-to-date and personalised information about: cancer and its causes; treatment options including treatment procedures information; complementary and alternative medicine; and available support. Patients and Support Persons will complete self-report measures of anxiety, depression and unmet needs at 2, 4, 8 and 12 weeks post-recruitment. Patient and Support Person outcomes will be assessed independently. This study will assess whether providing information and support

EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies.

PubMed

Traeger-Synodinos, Joanne; Harteveld, Cornelis L; Old, John M; Petrou, Mary; Galanello, Renzo; Giordano, Piero; Angastioniotis, Michael; De la Salle, Barbara; Henderson, Shirley; May, Alison

2015-04-01

Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially 'atypical' cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis.

EMQN Best Practice Guidelines for molecular and haematology methods for carrier identification and prenatal diagnosis of the haemoglobinopathies

PubMed Central

Traeger-Synodinos, Joanne; Harteveld, Cornelis L; Old, John M; Petrou, Mary; Galanello, Renzo; Giordano, Piero; Angastioniotis, Michael; De la Salle, Barbara; Henderson, Shirley; May, Alison

2015-01-01

Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially ‘atypical' cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis. PMID:25052315

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

PubMed

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

PubMed Central

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications. PMID:27536103

Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

PubMed

Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2015-02-01

The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Haematological validation of a computer-based bone marrow reporting system.

PubMed Central

Nguyen, D T; Diamond, L W; Cavenagh, J D; Parameswaran, R; Amess, J A

1997-01-01

AIMS: To prove the safety and effectiveness of "Professor Belmonte", a knowledge-based system for bone marrow reporting, a formal evaluation of the reports generated by the system was performed. METHODS: Three haematologists (a consultant, a senior registrar, and a junior registrar), none of whom were involved in the development of the software, compared the unedited reports generated by Professor Belmonte with the original bone marrow reports in 785 unselected cases. Each haematologist independently graded the quality of Belmonte's reports using one of four categories: (a) better than the original report (more informative, containing useful information missing in the original report); (b) equivalent to the original report; (c) satisfactory, but missing information that should have been included; and (d) unsatisfactory. RESULTS: The consultant graded 64 reports as more informative than the original, 687 as equivalent to the original, 32 as satisfactory, and two as unsatisfactory. The senior registrar considered 29 reports to be better than the original, 739 to be equivalent to the original, 15 to be satisfactory, and two to be unsatisfactory. The junior registrar found that 88 reports were better than the original, 681 were equivalent to the original, 14 were satisfactory, and two were unsatisfactory. Each judge found two different reports to be unsatisfactory according to their criteria. All 785 reports generated by the computer system received at least two scores of satisfactory or better. CONCLUSIONS: In this representative study, Professor Belmonte generated bone marrow reports that proved to be as accurate as the original reports in a large university hospital. The haematology knowledge contained within the system, the reasoning process, and the function of the software are safe and effective for assisting haematologists in generating high quality bone marrow reports. PMID:9215118

Pulmonary complications in patients with haematological malignancies treated at a respiratory ICU.

PubMed

Ewig, S; Torres, A; Riquelme, R; El-Ebiary, M; Rovira, M; Carreras, E; Raño, A; Xaubet, A

1998-07-01

Patients with haematological malignancies developing severe pulmonary complications have a poor outcome, especially after bone-marrow transplantation (BMT). We studied the aetiology, the yield of different diagnostic tools, as well as the outcome and prognostic factors in the corresponding population admitted to our respiratory intensive care unit (RICU). Overall, 89 patients with haematological malignancies and pulmonary complications treated within a 10 yr period were included. The underlying malignancies were predominantly acute leukaemia and chronic myeloid leukaemia (66/89, 74%). Fifty-two of 89 (58%) patients were bone marrow recipients. An aetiological diagnosis could be obtained in 61/89 (69%) of cases. The aetiology was infectious in 37/89 (42%) and noninfectious in 24/89 (27%). Blood cultures and cytological examinations of bronchoalveolar lavage fluid were the diagnostic tools with the highest yield (13/43 (30%) and 13/45 (29%) positive results, respectively). Necropsy results were coincident with results obtained during the lifetime in 43% of cases with infectious and 60% with noninfectious aetiologies. Overall mortality was 70/89 (79%), and 47/52 (90%) in transplant recipients. The requirement of mechanical ventilation, BMT, and an interval <90 days of BMT prior to ICU admission were independent adverse prognostic factors. The outcome in this patient population was uniformly poor. It was worst in bone marrow recipients developing pulmonary complications <90 days after transplantation and requiring mechanical ventilation. Decisions about intensive care unit admission and mech-anical ventilation should seriously consider the dismal prognosis of these patients.

Direct measurements of safety factor profiles with motional Stark effect for KSTAR tokamak discharges with internal transport barriers

NASA Astrophysics Data System (ADS)

Ko, J.; Chung, J.

2017-06-01

The safety factor profile evolutions have been measured from the plasma discharges with the external current drive mechanism such as the multi-ion-source neutral beam injection for the Korea Superconducting Tokamak Advanced Research (KSTAR) for the first time. This measurement has been possible by the newly installed motional Stark effect (MSE) diagnostic system that utilizes the polarized Balmer-alpha emission from the energetic neutral deuterium atoms induced by the Stark effect under the Lorentz electric field. The 25-channel KSTAR MSE diagnostic is based on the conventional photoelastic modulator approach with the spatial and temporal resolutions less than 2 cm (for the most of the channels except 2 to 3 channels inside the magnetic axis) and about 10 ms, respectively. The strong Faraday rotation imposed on the optical elements in the diagnostic system is calibrated out from a separate and well-designed polarization measurement procedure using an in-vessel reference polarizer during the toroidal-field ramp-up phase before the plasma experiment starts. The combination of the non-inductive current drive during the ramp-up and shape control enables the formation of the internal transport barrier where the pitch angle profiles indicate flat or slightly hollow profiles in the safety factor.

Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516.

PubMed

Lagu, Bharat; Kluge, Arthur F; Goddeeris, Matthew M; Tozzo, Effie; Fredenburg, Ross A; Chellur, Shekar; Senaiar, Ramesh S; Jaleel, Mahaboobi; Babu, D Ravi Krishna; Tiwari, Nirbhay K; Takahashi, Taisuke; Patane, Michael A

2017-11-04

Compound 1 regulates significantly fewer genes than the PPARδ modulator, GW501516. Both compounds are efficacious in a thermal injury model of muscle regeneration. The restricted gene profile of 1 relative to GW501516 suggests that 1 may be pharmacoequivalent to GW501516 with fewer PPAR-related safety concerns. Copyright © 2017 Elsevier Ltd. All rights reserved.

Invasive infections caused by Saprochaete capitata in patients with haematological malignancies: report of five cases and review of the antifungal therapy.

PubMed

García-Ruiz, Juan Carlos; López-Soria, Leyre; Olazábal, Iñigo; Amutio, Elena; Arrieta-Aguirre, Inés; Velasco-Benito, Verónica; Pontón, Jose; Moragues, Maria-Dolores

2013-01-01

Saprochaete capitata (formerly known as Geotrichum capitatum and Blastoschizomyces capitatus) is a ubiquitous fungus found in soil, water, air, plants and dairy products. It colonizes the skin, and bronchial and intestinal tract of healthy people producing serious opportunistic infections in patients with haematological malignancies, especially in those with acute leukaemia. Since 1960s its presence is being increasingly recognized in this group of patients. The clinical spectrum of S. capitata disseminated infections is very similar to that produced by Candida, being easily misinterpreted. The associated high mortality and low susceptibility to fluconazole and echinocandins of S. capitata require the acknowledgement of this emergent infection so that it can be properly treated. We report 5 new cases of S. capitata disseminated infection in patients with advanced haematological malignancies observed in the haematology unit between the years 2004 and 2010, and review the state-of-the-art for diagnosis and treatment of this infection. Based on our experience, the prophylactic use of or the empirical antifungal treatment with fluconazole and/or echinocandins would not be adequate for oncohaematological patients in those hospitals where S. capitata infection may be highly prevalent. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

PubMed

Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

2016-06-22

Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.

Patient safety climate profiles across time: Strength and level of safety climate associated with a quality improvement program in Switzerland-A cross-sectional survey study.

PubMed

Mascherek, Anna C; Schwappach, David L B

2017-01-01

Safety Climate has been acknowledged as an unspecific factor influencing patient safety. However, studies rarely provide in-depth analysis of climate data. As a helpful approach, the concept of "climate strength" has been proposed. In the present study we tested the hypotheses that even if safety climate remains stable on mean-level across time, differences might be evident in strength or shape. The data of two hospitals participating in a large national quality improvement program were analysed for differences in climate profiles at two measurement occasions. We analysed differences on mean-level, differences in percent problematic response, agreement within groups, and frequency histograms in two large hospitals in Switzerland at two measurement occasions (2013 and 2015) applying the Safety Climate Survey. In total, survey responses of 1193 individuals were included in the analyses. Overall, small but significant differences on mean-level of safety climate emerged for some subgroups. Also, although agreement was strong at both time-points within groups, tendencies of divergence or consensus were present in both hospitals. Depending on subgroup and analyses chosen, differences were more or less pronounced. The present study illustrated that taking several measures into account and describing safety climate from different perspectives is necessary in order to fully understand differences and trends within groups and to develop interventions addressing the needs of different groups more precisely.

Patient safety climate profiles across time: Strength and level of safety climate associated with a quality improvement program in Switzerland—A cross-sectional survey study

PubMed Central

Mascherek, Anna C.

2017-01-01

Safety Climate has been acknowledged as an unspecific factor influencing patient safety. However, studies rarely provide in-depth analysis of climate data. As a helpful approach, the concept of “climate strength” has been proposed. In the present study we tested the hypotheses that even if safety climate remains stable on mean-level across time, differences might be evident in strength or shape. The data of two hospitals participating in a large national quality improvement program were analysed for differences in climate profiles at two measurement occasions. We analysed differences on mean-level, differences in percent problematic response, agreement within groups, and frequency histograms in two large hospitals in Switzerland at two measurement occasions (2013 and 2015) applying the Safety Climate Survey. In total, survey responses of 1193 individuals were included in the analyses. Overall, small but significant differences on mean-level of safety climate emerged for some subgroups. Also, although agreement was strong at both time-points within groups, tendencies of divergence or consensus were present in both hospitals. Depending on subgroup and analyses chosen, differences were more or less pronounced. The present study illustrated that taking several measures into account and describing safety climate from different perspectives is necessary in order to fully understand differences and trends within groups and to develop interventions addressing the needs of different groups more precisely. PMID:28753633

The effects of the non-contingent presentation of safety signals on the elimination of safety behaviors: An experimental comparison between individuals with low and high obsessive-compulsive profiles.

PubMed

Angelakis, Ioannis; Austin, Jennifer L

2018-06-01

Safety behaviors, defined as engagement in avoidance within safe environments, are a key symptom of obsessive-compulsive and related disorders. They may interfere with daily functioning and as such their emission should be reduced. The purpose of the current study is to investigate the effects of the non-contingent presentation of safety signals (cues produced by safety behaviors) on reducing safety behaviors in participants self-reporting low and high OCD profiles. In total, 32 participants were asked to play a game to gain points and avoid their loss. After having developed avoidance behavior, evidenced by maintaining all of their earned points, they were exposed to safe environments where no point loss was programmed. In Test 1, safety cues (blue bar) were produced contingent on performing safety behaviors. In Test 2, safety cues were presented continuously without any response requirement. Findings demonstrated that high OCD group displayed higher rates of safety behaviors than low OCD group. However, exposure to the non-contingent presentation of safety signals eliminated their emission in both groups. Future studies need to evaluate the effects of different non-contingent schedules on the suppression of safety behaviors. These findings contribute to the literature by demonstrating that non-contingent introduction of safety signals eliminated safety behaviors completely, even in high OCD participants, who performed safety behavior at higher rates. Such a treatment protocol may ameliorate exposure therapy in which response prevention constitutes a key element and is generally associated with increased drop-out rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unmet supportive care needs of haematological cancer survivors: rural versus urban residents.

PubMed

Tzelepis, Flora; Paul, Christine L; Sanson-Fisher, Robert W; Campbell, H Sharon; Bradstock, Kenneth; Carey, Mariko L; Williamson, Anna

2018-07-01

Due to fewer cancer services in rural locations, rural survivors may have unique unmet needs compared to urban survivors. This study compared among rural and urban haematological cancer survivors the most common "high/very high" unmet supportive care needs and the unmet need scores for five domains (information, financial concerns, access and continuity of care, relationships and emotional health). Survivors' socio-demographics, rurality, cancer history and psychological factors associated with each unmet need domain were also explored. A total of 1511 haematological cancer survivors were recruited from five Australian state cancer registries and 1417 (1145 urban, 272 rural) allowed extraction of their residential postcode from registry records. A questionnaire that contained the Survivor Unmet Needs Survey was mailed to survivors. Dealing with feeling tired was the most common "high/very high" unmet need for rural (15.2%) and urban (15.5%) survivors. The emotional health domain had the highest mean unmet need score for rural and urban survivors. Rurality was associated with a decreased unmet emotional health domain score whereas travelling for more than 1 h to treatment was associated with increased unmet financial concerns and unmet access and continuity of care. Depression, anxiety and stress were associated with increased unmet need scores for all five domains. Unmet need domain scores generally did not differ by rurality. Travelling for more than 1 h to treatment was associated with increased unmet need scores on two domains. Telemedicine and increased financial assistance with travel and accommodation may help those travelling long distances for treatment.

Effect of Aripiprazole Lauroxil on Metabolic and Endocrine Profiles and Related Safety Considerations Among Patients With Acute Schizophrenia.

PubMed

Nasrallah, Henry A; Newcomer, John W; Risinger, Robert; Du, Yangchun; Zummo, Jacqueline; Bose, Anjana; Stankovic, Srdjan; Silverman, Bernard L; Ehrich, Elliot W

2016-11-01

Aripiprazole lauroxil, a long-acting injectable antipsychotic, demonstrated safety and efficacy in treating symptoms of schizophrenia in a double-blind, placebo-controlled trial. Because the metabolic profile of antipsychotics is an important safety feature, the effects of aripiprazole lauroxil on body weight, endocrine and metabolic profiles, and safety were examined in a secondary analysis. Patients with schizophrenia (DSM-IV-TR criteria) were randomly assigned to aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, or placebo intramuscularly once monthly between December 2011 and March 2014. Changes in body weight, body mass index, fasting blood glucose and serum lipids, glycosylated hemoglobin (HbA1c), and prolactin over 12 weeks were assessed. The incidence of treatment-emergent adverse events (AEs) was evaluated. Among 622 randomized patients, no clinically relevant changes from baseline to week 12 were observed for any serum lipid, lipoprotein, plasma glucose, or HbA1c value with placebo or either dose of aripiprazole lauroxil. Both doses of aripiprazole lauroxil were associated with reductions in mean prolactin levels, whereas placebo treatment was not. The mean (standard deviation) change from baseline for body weight was 0.74 (3.9) kg, 0.86 (3.7) kg, and 0.01 (3.6) kg for aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. AEs related to metabolic parameters were reported in 2.4%, 1.4%, and 2.4% of patients in the aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg, and placebo groups, respectively. Aripiprazole lauroxil was well tolerated, with a low-risk metabolic profile relative to published data for other antipsychotics. Changes similar to those observed with placebo were observed in the aripiprazole lauroxil groups for metabolic parameters, with modest weight gain in the active treatment groups over the 12-week course. ClinicalTrials.gov identifier: NCT01469039. © Copyright 2016 Physicians

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

PubMed

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-03-01

Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

Motor carrier safety performance profile.

DOT National Transportation Integrated Search

2004-02-01

This report provides a summary of the safety performance of carriers across all the individual segments in the industry. It includes summaries for both for-hire and private carriers in each segment and is drawn from measures that are collected as par...

Differences in incidence and trends of haematological malignancies in Japan and the United States

PubMed Central

Chihara, Dai; Ito, Hidemi; Matsuda, Tomohiro; Shibata, Akiko; Katsumi, Akira; Nakamura, Shigeo; Tomotaka, Sobue; Morton, Lindsay M; Weisenburger, Dennis D; Matsuo, Keitaro

2014-01-01

The incidence of a malignant disease reflects the genetic and cumulative exposure to the environment of a population. Therefore, evaluation of the incidence and trends of a disease in different populations may provide insights into its aetiology and pathogenesis. To evaluate the incidence of haematological malignancies according to specific subtypes, we used population-based registry data in Japan (N = 125 148) and the United States (US; N = 172 925) from 1993 to 2008. The age-adjusted incidence of haematological malignancies in Japan was approximately one-half that in the US but has been increasing significantly, whereas no significant change was seen in the US [annual percent change (95% C confidence interval): Japan, +2·4% (1·7, 3·1); US, +0·1% (−0·1, 0·2)]. Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) showed the largest differences in incidence, with the most remarkable differences observed for chronic lymphocytic leukaemia, HL-nodular sclerosis, mycosis fungoides and cutaneous T-cell lymphoma. HL and NHL are increasing substantially in Japan but not in the US, suggesting that environmental exposures, such as Westernization of the life style may be causing this increase. Differences in the incidence and trends for specific subtypes also showed a marked contrast across subtypes, which, in turn, may provide significant new insights into disease aetiology in the future. PMID:24245986

Haematology and plasma chemistry of the red top ice blue mbuna cichlid (Metriaclima greshakei).

PubMed

Snellgrove, Donna L; Alexander, Lucille G

2011-10-01

Clinical haematology and blood plasma chemistry can be used as a valuable tool to provide substantial diagnostic information for fish. A wide range of parameters can be used to assess nutritional status, digestive function, disease identification, routine metabolic levels, general physiological status and even the assessment and management of wild fish populations. However to evaluate such data accurately, baseline reference intervals for each measurable parameter must be established for the species of fish in question. Baseline data for ornamental fish species are limited, as research is more commonly conducted using commercially cultured fish. Blood samples were collected from sixteen red top ice blue cichlids (Metriaclima greshakei), an ornamental freshwater fish, to describe a range of haematology and plasma chemistry parameters. Since this cichlid is fairly large in comparison with most tropical ornamental fish, two independent blood samples were taken to assess a large range of parameters. No significant differences were noted between sample periods for any parameter. Values obtained for a large number of parameters were similar to those established for other closely related fish species such as tilapia (Oreochromis spp.). In addition to reporting the first set of blood values for M. Greshakei, to our knowledge, this study highlights the possibility of using previously established data for cultured cichlid species in studies with ornamental cichlid fish.

Reporting unit size and measurement uncertainty: current Australian practice in clinical chemistry and haematology.

PubMed

Hawkins, Robert C; Badrick, Tony

2015-08-01

In this study we aimed to compare the reporting unit size used by Australian laboratories for routine chemistry and haematology tests to the unit size used by learned authorities and in standard laboratory textbooks and to the justified unit size based on measurement uncertainty (MU) estimates from quality assurance program data. MU was determined from Royal College of Pathologists of Australasia (RCPA) - Australasian Association of Clinical Biochemists (AACB) and RCPA Haematology Quality Assurance Program survey reports. The reporting unit size implicitly suggested in authoritative textbooks, the RCPA Manual, and the General Serum Chemistry program itself was noted. We also used published data on Australian laboratory practices.The best performing laboratories could justify their chemistry unit size for 55% of analytes while comparable figures for the 50% and 90% laboratories were 14% and 8%, respectively. Reporting unit size was justifiable for all laboratories for red cell count, >50% for haemoglobin but only the top 10% for haematocrit. Few, if any, could justify their mean cell volume (MCV) and mean cell haemoglobin concentration (MCHC) reporting unit sizes.The reporting unit size used by many laboratories is not justified by present analytical performance. Using MU estimates to determine the reporting interval for quantitative laboratory results ensures reporting practices match local analytical performance and recognises the inherent error of the measurement process.

Carbendazim-induced haematological, biochemical and histopathological changes to the liver and kidney of male rats.

PubMed

Selmanoglu, G; Barlas, N; Songür, S; Koçkaya, E A

2001-12-01

Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.

Safety of multiple repeated cycles of 177Lu-octreotate in patients with recurrent neuroendocrine tumour.

PubMed

Yordanova, Anna; Mayer, Karin; Brossart, Peter; Gonzalez-Carmona, Maria A; Strassburg, Christian P; Essler, Markus; Ahmadzadehfar, Hojjat

2017-07-01

Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of 177 Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET. We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles. We observed no life-threatening adverse events (CTC-4) during 177 Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001). Therapy with eight or more cycles of 177 Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET.

Haematological manifestations of lupus

PubMed Central

Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

2015-01-01

Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

Genetic variation in aryl N-acetyltransferase results in significant differences in the pharmacokinetic and safety profiles of amifampridine (3,4-diaminopyridine) phosphate.

PubMed

Haroldsen, Peter E; Garovoy, Marvin R; Musson, Donald G; Zhou, Huiyu; Tsuruda, Laurie; Hanson, Boyd; O'Neill, Charles A

2015-02-01

The clinical use of amifampridine phosphate for neuromuscular junction disorders is increasing. The metabolism of amifampridine occurs via polymorphic aryl N-acetyltransferase (NAT), yet its pharmacokinetic (PK) and safety profiles, as influenced by this enzyme system, have not been investigated. The objective of this study was to assess the effect of NAT phenotype and genotype on the PK and safety profiles of amifampridine in healthy volunteers (N = 26). A caffeine challenge test and NAT2 genotyping were used to delineate subjects into slow and fast acetylators for PK and tolerability assessment of single, escalating doses of amifampridine (up to 30 mg) and in multiple daily doses (20 mg QID) of amifampridine. The results showed that fast acetylator phenotypes displayed significantly lower C max, AUC, and shorter t 1/2 for amifampridine than slow acetylators. Plasma concentrations of the N-acetyl metabolite were approximately twofold higher in fast acetylators. Gender differences were not observed. Single doses of amifampridine demonstrated dose linear PKs. Amifampridine achieved steady state plasma levels within 1 day of dosing four times daily. No accumulation or time-dependent changes in amifampridine PK parameters occurred. Overall, slow acetylators reported 73 drug-related treatment-emergent adverse events versus 6 in fast acetylators. Variations in polymorphic NAT corresponding with fast and slow acetylator phenotypes significantly affects the PK and safety profiles of amifampridine.

Integration Profile and Safety of an Adenovirus Hybrid-Vector Utilizing Hyperactive Sleeping Beauty Transposase for Somatic Integration

PubMed Central

Zhang, Wenli; Muck-Hausl, Martin; Wang, Jichang; Sun, Chuanbo; Gebbing, Maren; Miskey, Csaba; Ivics, Zoltan; Izsvak, Zsuzsanna; Ehrhardt, Anja

2013-01-01

We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB) transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR) and linear amplification-mediated PCR (LAM-PCR). Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models. PMID:24124483

Safety profile and protocol prevention of adverse reactions to uroangiographic contrast media in diagnostic imaging.

PubMed

Rossi, C; Reginelli, A; D'Amora, M; Di Grezia, G; Mandato, Y; D'Andrea, A; Brunese, L; Grassi, R; Rotondi, A

2014-01-01

The purpose of the study is to examine the incidence of adverse reactions caused by non-ionic contrast media in selected patients after desensitization treatment and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a multistep prevention protocol. In a population of 2000 patients that had received a CT scan, 100 patients with moderate/high risk for adverse reactions against iodinated contrast agents followed a premedication protocol and all adverse reactions are reported and classified as mild, moderate or severe. 1.7 percent of the pre-treated patients reported a mild, immediate type reaction to iodine contrast; of these five patients with allergy 0.71 percent had received iomeprol, 0.35 percent received ioversol and 0.71 percent received iopromide. The incidence of adverse reactions was reported to be higher (4 out of 5 patients) among those that referred a history of hypersensitivity against iodinated i.c.m. Although intravenous contrast materials have greatly improved, especially in terms of their safety profile, they should not be administered if there isn't a clear or justified indication. In conclusion, even if we know that the majority of these reactions are idiosyncratic and unpredictable we propose, with the aim of improving our knowledge on this subject, a multicenter study, based on skin allergy tests (prick test, patch test, intradermal reaction) in selected patients that have had previous experiences of hypersensitivity against parenteral organ iodine contrast media.

The safety profile of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY).

PubMed

Rinderknecht, Stephen; Bryant, Kristina; Nolan, Terry; Pavia-Ruz, Noris; Doniz, Carlos Aranza; Weber, Miguel Angel Rodriguez; Cohen, Christopher; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M

2012-03-01

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12-15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens. These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies).

Primary immunodeficiencies predisposed to Epstein-Barr virus-driven haematological diseases.

PubMed

Parvaneh, Nima; Filipovich, Alexandra H; Borkhardt, Arndt

2013-09-01

Epstein-Barr virus (EBV), a ubiquitous human herpesvirus, maintains lifelong subclinical persistent infections in humans. In the circulation, EBV primarily infects the B cells, and protective immunity is mediated by EBV-specific cytotoxic T cells (CTLs) and natural killer (NK) cells. However, EBV has been linked to several devastating diseases, such as haemophagocytic lymphohistiocytosis (HLH) and lymphoproliferative diseases in the immunocompromised host. Some types of primary immunodeficiencies (PIDs) are characterized by the development of EBV-associated complications as their predominant clinical feature. The study of such genetic diseases presents an ideal opportunity for a better understanding of the biology of the immune responses against EBV. Here, we summarize the range of PIDs that are predisposed to EBV-associated haematological diseases, describing their clinical picture and pathogenetic mechanisms. © 2013 John Wiley & Sons Ltd.

Comparison on the Effects and Safety of Tualang Honey and Tribestan in Sperm Parameters, Erectile Function, and Hormonal Profiles among Oligospermic Males

PubMed Central

Ismail, Shaiful Bahari; Bakar, Mohd. Bustamanizan; Nik Hussain, Nik Hazlina; Sulaiman, Siti Amrah; Jaafar, Hasnan; Draman, Samsul; Ramli, Roszaman; Wan Yusoff, Wan Zahanim

2014-01-01

Introduction. This study aims to evaluate the effectiveness of Tualang honey on sperm parameters, erectile function, and hormonal and safety profiles. Methodology. A randomized control trial was done using Tualang honey (20 grams) and Tribestan (750 mg) over a period of 12 weeks. Sperm parameters including sperm concentration, motility, and morphology were analyzed and erectile function was assessed using IIEF-5 questionnaire. Hormonal profiles of testosterone, FSH, and LH were studied. The volunteers were randomized into two groups and the outcomes were analyzed using SPSS version 18. Results. A total of 66 participants were involved. A significant increment of mean sperm concentration (P < 0.001), motility (P = 0.015) and morphology (P = 0.008) was seen in Tualang honey group. In Tribestan group, a significant increment of mean sperm concentration (P = 0.007), and morphology (P = 0.009) was seen. No significant differences of sperm concentration, motility, and morphology were seen between Tualang honey and Tribestan group and similar results were also seen in erectile function and hormonal profile. All safety profiles were normal and no adverse event was reported. Conclusion. Tualang honey effect among oligospermic males was comparable with Tribestan in improving sperm concentration, motility, and morphology. The usage of Tualang honey was also safe with no reported adverse event. PMID:25505918

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

PubMed

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pre-analytical effects of pneumatic tube system transport on routine haematology and coagulation tests, global coagulation assays and platelet function assays.

PubMed

Le Quellec, Sandra; Paris, Mickaël; Nougier, Christophe; Sobas, Frédéric; Rugeri, Lucia; Girard, Sandrine; Bordet, Jean-Claude; Négrier, Claude; Dargaud, Yesim

2017-05-01

Pneumatic tube system (PTS) in hospitals is commonly used for the transport of blood samples to clinical laboratories, as it is rapid and cost-effective. The aim was to compare the effects on haematology samples of a newly acquired ~2km-long PTS that links 2 hospitals with usual transport (non-pneumatic tube system, NPTS). Complete blood cell count, routine coagulation assays, platelet function tests (PFT) with light-transmission aggregometry and global coagulation assays including ROTEM® and thrombin generation assay (TGA) were performed on blood samples from 30 healthy volunteers and 9 healthy volunteers who agreed to take aspirin prior to blood sampling. The turnaround time was reduced by 31% (p<0.001) with the use of PTS. No statistically significant difference was observed for most routine haematology assays including PFT, and ROTEM® analysis. A statistically significant, but not clinically relevant, shortening of the APTT after sample transport by PTS was found (mean±SD: 30s±1.8 vs. 29.5s±2.1 for NPTS). D-dimer levels were 7.4% higher after transport through PTS but were not discordant. A statistically significant increase of thrombin generation was found in both platelet poor- and platelet rich- plasma samples after PTS transport compared to NPTS transport. PTS is suitable for the transport of samples prior to routine haematology assays including PFT, but should not be used for samples intended for thrombin generation measurement. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety Profile of Cough and Cold Medication Use in Pediatrics.

PubMed

Green, Jody L; Wang, George Sam; Reynolds, Kate M; Banner, William; Bond, G Randall; Kauffman, Ralph E; Palmer, Robert B; Paul, Ian M; Dart, Richard C

2017-06-01

The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children <12 years of age from a multisystem surveillance program. Cases with adverse events (AEs) after ingestion of at least 1 index CCM ingredient (brompheniramine, chlorpheniramine, dextromethorphan, diphenhydramine, doxylamine, guaifenesin, phenylephrine, and pseudoephedrine) in children <12 years of age were collected from 5 data sources. An expert panel determined relatedness, dose, intent, and risk factors. Case characteristics and AEs are described. Of the 4202 cases reviewed, 3251 (77.4%) were determined to be at least potentially related to a CCM, with accidental unsupervised ingestions (67.1%) and medication errors (13.0%) the most common exposure types. Liquid (67.3%), pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children <2 years of age (70.0%) and none involved a therapeutic dose. The overall reported AE rate was 0.573 cases per 1 million units (ie, tablets, gelatin capsules, or liquid equivalent) sold (95% confidence interval, 0.553-0.593) or 1 case per 1.75 million units. The rate of AEs associated with CCMs in children was low. Fatalities occurred even less frequently. No fatality involved a therapeutic dose. Accidental unsupervised ingestions were the most common exposure types and single-ingredient, pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts. Copyright © 2017 by the American Academy of Pediatrics.

Determining research priorities for young people with haematological cancer: a value-weighting approach.

PubMed

Clinton-McHarg, Tara; Paul, Christine; Sanson-Fisher, Rob; D'Este, Catherine; Williamson, Anna

2010-12-01

Haematological malignancies account for a third of all cancers affecting adolescents and young adults (AYAs). Funding agencies are regularly faced with the dilemma of how to deploy resources in order to provide the greatest possible benefit to this patient group. This study used a value-weighting approach to quantify the stakeholders' perceptions about how resources should be allocated to best improve outcomes for AYA patients and their families. One hundred and fifty seven participants (112 health care providers, researchers and other professionals and 45 patients and carers) were invited to complete a web-based value-weighting questionnaire and indicate how they would allocate 100 units of funding among various research approaches, areas and populations. Eighty participants (51%) completed the questionnaire. Strategic research was allocated a significantly higher proportion of funding than investigator-driven research. For research areas, clinical medicine and psychosocial research were allocated the highest proportion of funding. Within research populations, AYAs who were newly diagnosed, relapsed or finished treatment were allocated the largest proportion of funds. Psychosocial research which focussed on identifying risk and resilience, developing psychosocial measures, translating research into practice and improving the treatment centre was allocated funding slightly above other items, however the difference was not significant. To improve potential congruence between the views of stakeholders and funding agencies, research funding for AYA haematological cancer patients and their families could be targeted towards newly diagnosed patients and those who have relapsed. Research in the areas of clinical medicine and psychosocial care is perceived to be of utmost value. Copyright © 2010 Elsevier Ltd. All rights reserved.

In utero exposure to radiation and haematological malignancies: pooled analysis of Southern Urals cohorts

PubMed Central

Schüz, Joachim; Deltour, Isabelle; Krestinina, Lyudmila Y; Tsareva, Yulia V; Tolstykh, Evgenia I; Sokolnikov, Mikhail E; Akleyev, Alexander V

2017-01-01

Background: It is scientifically uncertain whether in utero exposure to low-dose ionising radiation increases the lifetime risk of haematological malignancies. Methods: We pooled two cohorts from the Southern Urals comprising offspring of female workers of a large nuclear facility (the Mayak Production Association) and of women living in areas along the Techa River contaminated by nuclear accidents/waste from the same facility, with detailed dosimetry. Results: The combined cohort totalled 19 536 subjects with 700 504 person-years at risk over the period of incidence follow-up, and slightly more over the period of mortality follow-up, yielding 58 incident cases and 36 deaths up to age 61 years. Risk was increased in subjects who received in utero doses of ⩾80 mGy (excess relative risk (ERR): 1.27; 95% confidence interval (CI): −0.20 to 4.71), and the risk increased consistently per 100 mGy of continuous exposure in utero (ERR: 0.77; CI: 0.02 to 2.56). No association was apparent in mortality-based analyses. Results for leukaemia and lymphoma were similar. A very weak positive association was observed between incidence and postnatal exposure. Conclusions: In summary, the results suggest a positive association between in utero exposure to ionising radiation and risk of haematological malignancies, but the small number of outcomes and inconsistent incidence and mortality findings preclude firm conclusions. PMID:27855443

Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions.

PubMed

Monaco, Luca; Biagi, Chiara; Conti, Valentino; Melis, Mauro; Donati, Monia; Venegoni, Mauro; Vaccheri, Alberto; Motola, Domenico

2017-07-01

Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P ≤ 0.05 were statistically significant. We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P ≤ 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47-1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28-0.34)]. We identified other potential signals that have not been associated with DOACs previously. As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred. © 2017 The British Pharmacological Society.

Cavernosal arterial insufficiency is a major component of erectile dysfunction in some recipients of high-dose chemotherapy/chemo-radiotherapy for haematological malignancies.

PubMed

Chatterjee, R; Andrews, H O; McGarrigle, H H; Kottaridis, P D; Lees, W R; Mackinnon, S; Ralph, D J; Goldstone, A H

2000-06-01

We studied 24 male patients aged 26-62 years (median 41) prospectively presenting over a 5 year period with clinical features of hypogonadism and erectile dysfunction (ED), who had been treated with autologous or allogeneic bone marrow/stem cell transplant for a variety of haematological malignancies and had received either high-dose chemotherapy or high-dose chemotherapy combined with total body irradiation (TBI). Ten healthy adult controls (aged 35-50 years) were also studied. Erectile dysfunction (ED) was assessed clinically and by colour flow Doppler studies of the cavernosal vessels. Testicular function was assessed by testicular volume including orchidometry, FSH, LH and testosterone measurements. Libido and ejaculatory function were also recorded. Patients had severe hypogonadism as evidenced by low mean testicular volume (7.0 +/- 2.4 ml vs 20 +/- 2.0 ml; P < 0.001), elevated gonadotrophins (FSH = 18.54 +/- 7.61 vs 5 IU/l (P < 0.001); LH = 8.02 +/- 2.89 vs 3. 9 IU/l (P < 0.001)) and low normal mean testosterone levels (16.4 nmol/l +/- 9.1 vs 22.4 nmol/l (P < 0.5)). Cavernosal arterial insufficiency was found in 11/14 of TBI-treated and in 3/10 HDC-treated patients, indicative of vasculogenic damage to corpora cavernosal vessels. Patients were given a therapeutic trial with testosterone replacement therapy (TRT). Those who had diminished libido had a marked improvement in their symptoms but the effect of TRT on ED was equivocal. In conclusion, this is the first report to show vasculogenic insufficiency in patients with haematological malignancies treated by BMT. Although hypogonadism can account for diminished libido, arteriogenic insufficiency is likely to be an important factor accounting for ED in these patients, especially those treated by TBI. We recommend a comprehensive assessment including endocrine profile and colour flow Doppler study in formulating the best management plan in recipients of high-dose therapy presenting after transplant with ED.

The effect of Iron Supplying on VO2 MAX and Haematology Parameter on Menstrual Woman

NASA Astrophysics Data System (ADS)

Nailuvar Sinaga, Rika; Sari Harahap, Novita; Mediyana Sari, Rima

2018-03-01

One of the supporting factors to have good aerobic endurance requires high VO2 max levels supported by good quality and quantity level of Haematology parameter especially such as erythrocytes, hematocrit and hemoglobin. One of the components in hemoglobin is iron which functions as theoxygen transport to parts of all body required in the process of metabolism. The objective of this research was to find out the difference between VO2 Max and Haematology parameter between iron supplying and no iron supplyingonmenstrual woman. The type of this research is quasi experimental research with non-randomized control group Pretest-Postest Design. The subjectsarethe studentsat faculty of Sports Sciences, Medan State University with the criteria of female gender, monthly regular menstrual cycle, having the level of health and the level of training, willing to be a sample by filling out informed consent. The total number of research subjectsis twenty students, divided into two groups namely the treatment group and the control group. The hematology parameter was measuredby Haemotology analyzer and VO2 Max was measured by multi-stage run. The result showed that there was a significant effect of iron supplyingon the increase of erythrocyte level on menstrual women, hemotocrit, haemoglobin and an increase in VO2 Max. Iron supplying on menstrual woman has the effect on the increase of erythrocyte, hematocrit, hemoglobin level and VO2 Max

Safety Profile of Stromal Hydration of Clear Corneal Incisions with Cefuroxime in the Mouse Model.

PubMed

Moosajee, Mariya; Tracey-White, Dhani; Harbottle, Richard P; Ferguson, Veronica

2016-09-01

The use of sutureless clear corneal incisions (CCIs) for phacoemulsification is an established surgical technique, but the dynamic morphology of the wound and poor construction can lead to an increased risk of postoperative endophthalmitis. Stromal hydration with balanced salt solution (BSS) can improve the self-sealing status. Intracameral cefuroxime has reduced endophthalmitis rates. This study investigates the safety profile of stromal hydration with cefuroxime, as sequestering antibiotic at the wound may potentially provide added protection against infection. MF-1 mice underwent bilateral CCI, followed by stromal hydration with 5 μL of 10 mg/mL cefuroxime, cefuroxime-texas red conjugate (for detection using confocal microscopy), or BSS. Corneas were harvested from 1 h to 12 weeks postoperatively; gross morphology, histology, and apoptotic cell death levels were investigated to determine the safety profile. Bactericidal activity of cefuroxime was assayed using homogenized whole cornea following stromal hydration at 1 h, 24 h, and day 7 against gram-negative Escherichia coli. Cefuroxime stromal hydration did not alter corneal morphology, with no evidence of corneal scarring or vascularization. Corneal histology and levels of apoptosis were minimal and comparable to the BSS groups up to 12 weeks. Confocal microscopy detected cefuroxime-texas red up to 1 week surrounding the corneal wound. Whole corneal tissue homogenates displayed bactericidal activity up to 24 h postoperatively. Stromal hydration of CCI with cefuroxime is safe in mouse corneas. A reservoir of antibiotic at the wound can potentially act as a barrier of defense against infection following cataract and associated ocular surgery.

Low muscle mass is associated with chemotherapy-induced haematological toxicity in advanced non-small cell lung cancer.

PubMed

Sjøblom, Bjørg; Grønberg, Bjørn H; Benth, Jūratė Šaltytė; Baracos, Vickie E; Fløtten, Øystein; Hjermstad, Marianne J; Aass, Nina; Jordhøy, Marit

2015-10-01

Recent research suggests a significant relationship between lean body mass (LBM) and toxicity from chemotherapeutic agents. We investigated if higher drug doses per kg LBM were associated with increased toxicity in stage IIIB/IV non-small cell lung cancer (NSCLC) patients receiving a first-line chemotherapy regimen dosed according to body surface area (BSA). Data from patients randomised to receive intravenous gemcitabine 1000 mg/m(2) plus orally vinorelbine 60 mg/m(2) days 1 and 8 in a phase III trial comparing two chemotherapy regimens were analysed. LBM was estimated from assessment of the cross-sectional muscle area at the third lumbar level (L3) on computed tomography images obtained before chemotherapy commenced. Common terminology criteria for adverse events (CTCAE) grade 3-4 haematological toxicity and dose reduction and/or stop of treatment after the first course of chemotherapy were defined as primary and secondary toxicity outcomes. The study sample included 153 patients, mean age was 66 years, 55% were men, 87% had disease stage IV and 75% had performance status (PS) 0-1. Gemcitabine doses per kg LBM varied from 23.2 to 53.1 mg/kg LBM, and vinorelbine doses from 1.5 to 3.3 mg/kg LBM. Higher doses of gemcitabine per kg LBM were significantly associated with grade 3-4 haematological toxicity in bivariate (OR=1.12, 95% CI 1.03-1.23, p=0.008) and multivariate analyses (OR=1.15, 95% CI 1.01-1.29, p=0.018), as were also higher doses of vinorelbine per kg LBM. No significant association was found between drug doses per kg LBM and dose reduction and/or stop of treatment. The study showed that dose estimates according to BSA lead to a substantial variation in drug dose per kg LBM, and higher doses per kg LBM are a significant predictor for chemotherapy-induced haematological toxicity. The results indicate that taking LBM into account may lead to a better dose individualisation of chemotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Perceived need for information of patients with haematological malignancies: a literature review.

PubMed

Rood, Janneke A J; Eeltink, Corien M; van Zuuren, Florence J; Verdonck-de Leeuw, Irma M; Huijgens, Peter C

2015-02-01

To provide insight into the perceived need for information of patients with haematological malignancies. Providing timely and accurate information to patients diagnosed with a haematological malignancy is a challenge in clinical practice; treatment often has to start promptly, with little time to inform patients. Literature review. A comprehensive literature search was conducted from all available literature to May 2013 in the databases: Cumulative Index to Nursing and Allied Health Literature, PsycINFO and PubMed (Medline). Relevant studies were reviewed regarding the perceived need for information on various topics, sources of information and satisfaction with information provided. The initial search revealed 215 articles, fourteen of which were relevant. Patients need basic information on the disease (diagnosis and diagnostics), treatment (various treatment options, side effects and duration), prognosis (curability and prolonging life) and all other topics (recovery, self-care and psychosocial functioning). Need for detailed information varied between studies. Patients expressed a higher need for medical than for psychosocial information. Patients preferred to receive information from their doctors the most, followed by nurses. Most studies described patients' satisfaction with the information provided. Based on the limited number of data available, medical information is for patients of higher priority compared to psychosocial information. Patients need basic information on diagnosis, treatment, prognosis and all other topics. Need for detailed information varied between studies. Patients were satisfied with the provided information, preferably offered by doctors and nurses. The perceived need for information and satisfaction with the information provided differs strongly between patients. In clinical practice, more attention is needed for information tailored to the patient, taking into account important moderating factors such as age, type of cancer, time

An investigation into between-meal food desires among hospitalised haematological cancer patients.

PubMed

Okkels, S L; Bredie, W L P; Klausen, T W; Beck, A M

2016-04-01

Hospitalised haematological cancer patients often suffer from reduced appetite and food intake, which negatively influences the patients' well-being and nutritional status. The aim of this study was to identify specific between-meal food desires in a patient group, in order to increase food intake. The study was conducted using a picture-aided questionnaire, and relating the preferences to factors that could easily be implemented in the hospital menu, such as time of the day and texture. Moreover, the results of the questionnaire were verified by acceptance tests on six selected food items. A structured 42 items food questionnaire was developed and used to quantify appetitive food desires in patients during morning (11 am) and afternoon (3 pm) sessions. Food items were scored according to patients' preferences and immediate desire to eat. A total of 112 hospitalised haematological cancer patients, screened for nutrition-related symptoms, participated. Univariate statistical models were used to investigate the influence of time-of-day and food texture on between-meal desires. Fresh fruit, ice cream, cheese and mashed potatoes with bacon were the most desired food items. Patients showed significant higher desire to eat in the morning as opposed to the afternoon. Moreover, texture had an influence on food desire, where liquid food was more desired than food with soft or coarse texture. Ranking of food desires among hospitalised cancer patients showed inclination for fresh fruit, ice cream, mashed potatoes with bacon, and cheese. Time of the day (morning) and texture (liquid) had the greatest and most positive impact on food desires. The findings may be easily implemented in hospital food service routines for cancer patients, and might positively contribute to patients' well-being and nutrition. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Thermophysiological, haematological, biochemical and behavioural stress responses of sheep transported on road.

PubMed

Pascual-Alonso, M; Miranda-de la Lama, G C; Aguayo-Ulloa, L; Villarroel, M; Mitchell, M; María, G A

2017-06-01

The study was conducted to evaluate the thermophysiological, haematological, biochemical and behavioural stress responses of sheep transported on road. A total of 44 Chamarita breed adult ewes were randomly allotted to one of two groups, one control group (untransported) and transported group (journey of 4 h), and blood stress indicators were measured 1 day before transport and at four time points post-transport (0, 4 and 24 h). Thermophysiological profiles of ewes were measured by temperature buttons (iButton Thermochron ® ) and placed in intravaginal sponges. Direct observations, with a combination of scan and behaviour sampling, were carried out to collect information on individual behaviour and the time it took the ewes to drink water, eat and rest after returning to their pen respectively. Transported ewes lost approximately 1 kg live weight compared to controls and had higher body temperatures until 12 h post-transport. Cortisol, glucose, non-esterified fatty acid (NEFA) concentrations as well as the neutrophil-lymphocyte ratio (N/L) and other physiological indicators were higher immediately after unloading in transported ewes but mostly returned to normal after 4 h, with complete recovery after 24 h. Behavioural analysis post-transport demonstrated that transported ewes chose to eat before drinking and spent less time resting than controls in the first 3 h after unloading. The study demonstrates that transportation even under short-journey conditions induced behavioural, physiological and thermophysiological responses indicative of the induction of significant stress, leading to live weight shrinkage that may jeopardize farmer's incomes. Finally, results of this study validated the use of iButton Thermochron ® data loggers for monitoring the stress response during transport. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Knowledge, attitude and practice of aspects of laboratory safety in Pathology Laboratories at the University of Port Harcourt Teaching Hospital, Nigeria.

PubMed

Ejilemele, A A; Ojule, A C

2005-12-01

To assess current knowledge, attitudes and practice of aspects of laboratory safety in pathology laboratories at the University of Port Harcourt Teaching Hospital in view of perceived inadequacies in safety practices in clinical laboratories in developing countries. Sixty (60) self- administered questionnaires were distributed to all cadres of staff in four (4) different laboratories (Chemical Pathology, Haematology, Blood bank and Medical Microbiology) at the Hospital. Gross deficiencies were found in the knowledge, attitudes and practice of laboratory safety by laboratory staff in areas of use of personal protective equipment, specimen collection and processing, centrifuge--related hazards, infective hazards waste disposal and provision and use of First Aid Kits. Issues pertaining to laboratory safety are not yet given adequate attention by both employers and employees in developing countries in this ear of resurgence of diseases such as HIV/AIDS and Hepatitis Band C, is emphasized.

Guidelines for point-of-care testing: haematology.

PubMed

Briggs, Carol; Guthrie, David; Hyde, Keith; Mackie, Ian; Parker, Norman; Popek, Mary; Porter, Neil; Stephens, Clare

2008-09-01

This guideline provides a framework for the arrangement of point-of-care testing (POCT) services, previously known as near patient testing (patient self-testing not covered). POCT is defined as any analytical test performed outside the laboratory. Primary users are often non-laboratory healthcare workers. The guidance applies to units within hospitals as well as general practioner surgeries, community clinics and pharmacies. The head of the haematology laboratory or a point of care coordinator must take responsibility for all aspects of the POCT service, including quality and training. Depending on the size and nature of the POCT practice, a local POCT manager may also be required. Equipment selected should have received a successful independent performance evaluation. If an independent evaluation has not been performed the purchaser should assess the device according to the protocol in this document. POCT devices should generate results that are comparable to those of the local laboratory. An accredited external quality assessment programme and internal quality control system must be established. Manufacturers promoting POCT devices designed for non-laboratory sites, e.g. pharmacies, should undertake training and annual competency assessment, perhaps using a web-based system. A diagram to illustrate the stages for the implementation of a POCT service is illustrated.

Effects of supplementation of threshed sorghum top with selected browse plant foliage on haematology and serum biochemical parameters of Red Sokoto goats.

PubMed

Okunade, Sunday Adewale; Isah, Olubukola Ajike; Oyekunle, Mufutau Atanda; Olafadehan, Olurotimi Ayobami; Makinde, Olayinka John

2016-06-01

The haematological and biochemical parameters of 24 growing Red Sokoto bucks (9.00 ± 0.25 kg body weight) fed threshed sorghum top (TST) with or without five different browse plant foliage Afzelia africana (AA), Daniellia oliveri (DO), Piliostigma thonningii (PT), Pterocarpus erinaceus (PE) and Annona senegalensis (AS) supplements were studied using a completely randomized design. All haematological parameters were (P < 0.05) lower in TST-fed goats compared with TST-supplemented goats, except for mean corpuscular haemoglobin concentration (MCHC), lymphocytes and monocytes which did not follow a particular pattern. Packed cell volume, haemoglobin and monocytes were higher for AA-supplemented goats while MCHC was reduced relative to other supplements (P < 0.05). White blood cell counts were increased in DO lambs compared to other supplements (P < 0.05). Serum proteins, creatinine, alanine transaminase and alkaline phosphate were reduced in TST compared with the supplements (P < 0.05). Cholesterol was higher for PT and AA than other diets (P < 0.05). Aspartate transaminase was reduced in TST goats relative to the supplements (P < 0.05). Except for potassium which was reduced in AS (P < 0.05), all serum major minerals were similar among diets. Results indicate that the entire browse fodder are good supplements to low-quality TST, though A. africana appears to have a better supplementary effect on haematological and biochemical parameters of the goats.

Haematological and histopathological effects of apigenin, phloretin and myricetin based on uterotrophic assay in immature Wistar female albino rats.

PubMed

Barlas, N; Karabulut, G

2015-07-01

In this study, it is aimed to determine the histopathological and haematological effects of apigenin, phloretin and myricetin on Wistar immature female rats using Tier 2 of the uterotrophic assay. The female rats were divided into 17 groups with 6 rats in each group. There was a negative control group and positive control dose groups that contained 0.07 µg/kg/day, 0.7 µg/kg/day and 7 µg/kg/day of ethinyl estradiol (EE), 0.7 µg/kg/day 17α-ethinyl estradiol + 1 mg/kg/day tamoxifen and genistein. The other dose groups contain 1 mg/kg/day, 10 mg/kg/day and 100 mg/kg/day of apigenin, myricetin and phloretin. All chemicals had been given to Wistar immature female rats with oral gavage for three consecutive days. At the end of the study, blood samples were analysed for haematological parameters. Tissue samples that were taken from the liver, kidney, spleen and thyroid were histopathologically and histomorphometrically examined. There were no significant differences between oil control and other dose groups for glomerular histomorphometry. However, there were significant differences for thyroid histomorphometry. Especially, 10 and 100 mg/kg/day of phloretin dose groups had a significant increase in colloid surface area in thyroid compared with the 1 mg/kg/day of phloretin and oil control groups. Significant histopathological changes (congestion, degeneration, fibrosis and mononuclear cell infiltration) were noted in the tissue specimens obtained from the treatment groups compared with the control group. According to the results of the haematological analysis of the groups, especially the values of erythrocytes and haematocrit were increased significantly in most of the dose groups according to the oil control group. © The Author(s) 2014.

The challenge of compiling data profiles to stimulate local preventive health action: a European case study from child safety.

PubMed

Alexander, Denise; Rigby, Michael; Gissler, Mika; Köhler, Lennart; MacKay, Morag

2015-05-01

Positive recent experience of presenting comparative child safety data at national level has instigated policy action in Europe. It was hoped a Child Safety Index could quantify how safe a community, region or locality is for its children in comparison with similar areas within Europe, as a focus for local targeted action. Validated indicators proposed by previous European projects identified from areas of child injury prevention, such as road safety, burns or poisoning, were selected to give a balanced profile, and populated from available published data. An index using a sub-score for each specific injury topic was proposed. The indicators' presentation, sensitivity and appropriateness were considered, as well as data availability. Satisfactory indicators were not identified for all areas and very few local area data were available. This forced the researchers to conclude that at present, constructing a reliable Child Safety Index for use at the local level is not feasible. There is a worrying lack of data available at the sub-national level to support injury prevention, evaluate interventions, and enable informed local decision making.

[Safety profile of heterologous serum produced by the Butantan Institute, in São Paulo-SP, Brazil, from 2012 to 2015].

PubMed

Gattás, Vera Lúcia; Braga, Patrícia Emília; Koike, Marcelo Eiji; Lucchesi, Maria Beatriz; Precioso, Alexander Roberto

2017-01-01

to describe the safety profile of the heterologous serum produced by the Butantan Institute (BI) of São Paulo-SP, Brazil. a descriptive study of adverse events (AEs) post-exposure to serum produced by the BI, encoded in the medical terminology of the Medical Dictionary for Regulatory Activities (MedDRA), and spontaneously reported to BI from 2012 to 2015. 52 individuals reported AEs, mainly related to Bothrops antivenom (n=11), diphtheria antitoxin (n=9) and unspecified snakebite serum (n=9); a mean of 3.2 AEs per individual was observed; among the total of 173 AEs, 63.0% were expected considering that they were described in the package insert; most of them were classified as skin and subcutaneous tissue disorders (30.6%); there were six deaths temporally related to the use of serum, but this association was discarded. in the studied period, the serum produced by the BI had no changes in their safety profiles, considering that the AEs were expected, according to the information previously described in the package insert.

50th Annual Scientific Meeting of the British Society for Haematology.

PubMed

Thomas, Angela E

2010-08-01

The 50th Annual Scientific Meeting of the British Society for Haematology was notable, not only for its golden anniversary, but also because it coincided with the eruption of the Icelandic volcano, Eyjafjallajökull, and the ensuing travel chaos. In total, 28 speakers from overseas were unable to reach Edinburgh, including a significant number of British speakers who were stranded. However, owing to the superb efforts of the conference organisers and Edinburgh International Conference Centre staff, teleconferencing equipment was installed and all speakers were contacted and able to give their talks on time. The program, consisting of simultaneous sessions and plenary lectures, covered not only recent advances in clinical and laboratory hematology, but also reflected on the contribution of British hematology to the international arena over the past 50 years.

Safety profile of bilastine: 2nd generation H1-antihistamines.

PubMed

Scaglione, F

2012-12-01

Bilastine is a new H1 antagonist with no sedative side effects, no cardiotoxic effects, and no hepatic metabolism. In addition, bilastine has proved to be effective for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Pharmacological studies have shown that bilastine is highly selective for the H1 receptor in both in vivo and in vitro studies, and with no apparent affinity for other receptors. The absorption of bilastine is fast, linear and dose-proportional; it appears to be safe and well tolerated at all doses levels in healthy population. Multiple administration of bilastine has confirmed the linearity of the kinetic parameters. The distribution in the brain is undetectable. The safety profile in terms of adverse effects is very similar to placebo in all Phase I, II and III clinical trials. Bilastine (20 mg), unlike cetirizine, does not increase alcohol effects on the CNS. Bilastine 20 mg does not increase the CNS depressant effect of lorazepam. Bilastine 20 mg is similar to placebo in the driving test. Therefore, it meets the current criteria for medication used in the treatment of allergic rhinitis and urticaria.

Evaluation of request forms submitted to the haematology laboratory in a Ghanaian tertiary hospital.

PubMed

Olayemi, Edeghonghon; Asiamah-Broni, Rebecca

2011-01-01

Laboratory request forms provide information about the laboratory test being requested for. They carry demographic data and other information such as location of patient, laboratory number, doctor's name, signature of the doctor, telephone number of the requesting doctor. Omission of information on the forms may lead to laboratory errors. The aim of this study was to evaluate the level of completion of laboratory request forms at the haematology department of a Ghanaian tertiary hospital. Three thousand request forms submitted to the haematology department between January and April 2010 were retrieved and studied. The information provided on each request form was recorded in a spread sheet and analyzed. The patient's age and sex were missing in 25.6% and 32.7% of the forms respectively. About half of the request forms did not have the patient's location. No clinical detail was provided on 22.7% of the forms. Doctors were more likely to sign their request forms and provide a name but they all failed to provide an address or a contact telephone number. This study demonstrates that, the standard of completion of request forms was poor. Essential information required on the forms was often missing. This can lead to limited advice given by laboratory physicians and may increase the potential for errors. Conversely, provision of all the information needed on the forms will aid laboratory diagnosis and enhance patient care and save time and resources. There should be closer interaction between clinicians and laboratory personnel to improve quality of services.

Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders

PubMed Central

Estcourt, Lise J; Desborough, Michael; Brunskill, Susan J; Doree, Carolyn; Hopewell, Sally; Murphy, Michael F; Stanworth, Simon J

2016-01-01

Background People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. Selection criteria We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration’s ‘Risk of bias’ tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data

Ethnic Variation in Inflammatory Profile in Tuberculosis

PubMed Central

Coussens, Anna K.; Wilkinson, Robert J.; Nikolayevskyy, Vladyslav; Elkington, Paul T.; Hanifa, Yasmeen; Islam, Kamrul; Timms, Peter M.; Bothamley, Graham H.; Claxton, Alleyna P.; Packe, Geoffrey E.; Darmalingam, Mathina; Davidson, Robert N.; Milburn, Heather J.; Baker, Lucy V.; Barker, Richard D.; Drobniewski, Francis A.; Mein, Charles A.; Bhaw-Rosun, Leena; Nuamah, Rosamond A.; Griffiths, Christopher J.; Martineau, Adrian R.

2013-01-01

Distinct phylogenetic lineages of Mycobacterium tuberculosis (MTB) cause disease in patients of particular genetic ancestry, and elicit different patterns of cytokine and chemokine secretion when cultured with human macrophages in vitro. Circulating and antigen-stimulated concentrations of these inflammatory mediators might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. Studies to characterise such variation, and to determine whether it relates to host or bacillary factors, have not been conducted. We therefore compared circulating and antigen-stimulated concentrations of 43 inflammatory mediators and 14 haematological parameters (inflammatory profile) in 45 pulmonary tuberculosis patients of African ancestry vs. 83 patients of Eurasian ancestry in London, UK, and investigated the influence of bacillary and host genotype on these profiles. Despite having similar demographic and clinical characteristics, patients of differing ancestry exhibited distinct inflammatory profiles at presentation: those of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP) but higher serum CCL5 concentrations and higher antigen-stimulated IL-1 receptor antagonist and IL-12 secretion. These differences associated with ethnic variation in host DBP genotype, but not with ethnic variation in MTB strain. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum differed between patients of African vs. Eurasian ancestry. Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients that associates primarily with ethnic variation in host, rather than bacillary, genotype. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should be derived

Cytogenetic profile of aplastic anaemia in Indian children

PubMed Central

Gupta, Vineeta; Kumar, Akash; Saini, Isha; Saxena, Ajit Kumar

2013-01-01

Background & objectives: Aplastic anaemia is a rare haematological disorder characterized by pancytopenia with a hypocellular bone marrow. It may be inherited/genetic or acquired. Acquired aplastic anaemia has been linked to many drugs, chemicals and viruses. Cytogenetic abnormalities have been reported infrequently with acquired aplastic anaemia. Majority of the studies are in adult patients from the West. We report here cytogenetic studies on paediatric patients with acquired aplastic anaemia seen in a tertiary care hospital in north India. Methods: Patients (n=71, age 4-14 yr) were diagnosed according to the guidelines of International Agranulocytosis and Aplastic Anaemia Study. Conventional cytogenetics with Giemsa Trypsin Giemsa (GTG) banding was performed. Karyotyping was done according to the International System for Human Cytogenetics Nomenclature (ISCN). Results: Of the 71 patients, 42 had successful karyotyping where median age was 9 yr; of these 42, 27 (64.3%) patients had severe, nine (21.4%) had very severe and six (14.3%) had non severe aplastic anaemia. Five patients had karyotypic abnormalities with trisomy 12 (1), trisomy 8 (1) and monosomy 7 (1). Two patients had non numerical abnormalities with del 7 q - and t (5:12) in one each. Twenty nine patients had uninformative results. There was no difference in the clinical and haematological profile of patients with normal versus abnormal cytogenetics although the number of patients was small in the two groups. Interpretation & conclusions: Five (11.9%) patients with acquired aplastic anaemia had chromosomal abnormalities. Trisomy was found to be the commonest abnormality. Cytogenetic abnormalities may be significant in acquired aplastic anaemia although further studies on a large sample are required to confirm the findings. PMID:23640556

Cytogenetic profile of aplastic anaemia in Indian children.

PubMed

Gupta, Vineeta; Kumar, Akash; Saini, Isha; Saxena, Ajit Kumar

2013-03-01

Aplastic anaemia is a rare haematological disorder characterized by pancytopenia with a hypocellular bone marrow. It may be inherited/genetic or acquired. Acquired aplastic anaemia has been linked to many drugs, chemicals and viruses. Cytogenetic abnormalities have been reported infrequently with acquired aplastic anaemia. Majority of the studies are in adult patients from the West. We report here cytogenetic studies on paediatric patients with acquired aplastic anaemia seen in a tertiary care hospital in north India. Patients (n=71, age 4-14 yr) were diagnosed according to the guidelines of International Agranulocytosis and Aplastic Anaemia Study. Conventional cytogenetics with Giemsa Trypsin Giemsa (GTG) banding was performed. Karyotyping was done according to the International System for Human Cytogenetics Nomenclature (ISCN). Of the 71 patients, 42 had successful karyotyping where median age was 9 yr; of these 42, 27 (64.3%) patients had severe, nine (21.4%) had very severe and six (14.3%) had non severe aplastic anaemia. Five patients had karyotypic abnormalities with trisomy 12 (1), trisomy 8 (1) and monosomy 7 (1). Two patients had non numerical abnormalities with del 7 q - and t (5:12) in one each. Twenty nine patients had uninformative results. There was no difference in the clinical and haematological profile of patients with normal versus abnormal cytogenetics although the number of patients was small in the two groups. Five (11.9%) patients with acquired aplastic anaemia had chromosomal abnormalities. Trisomy was found to be the commonest abnormality. Cytogenetic abnormalities may be significant in acquired aplastic anaemia although further studies on a large sample are required to confirm the findings.

Ibrutinib alone or with dexamethasone for relapsed or relapsed and refractory multiple myeloma: phase 2 trial results.

PubMed

Richardson, Paul G; Bensinger, William I; Huff, Carol Ann; Costello, Caitlin L; Lendvai, Nikoletta; Berdeja, Jesus G; Anderson, Larry D; Siegel, David S; Lebovic, Daniel; Jagannath, Sundar; Laubach, Jacob P; Stockerl-Goldstein, Keith E; Kwei, Long; Clow, Fong; Elias, Laurence; Salman, Zeena; Graef, Thorsten; Bilotti, Elizabeth; Vij, Ravi

2018-03-01

Novel therapies with unique new targets are needed for patients who are relapsed/refractory to current treatments for multiple myeloma. Ibrutinib is a first-in-class, once-daily, oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in the myeloma stem cell population. This study examined various doses of ibrutinib ± low-dose dexamethasone in patients who received ≥2 prior lines of therapy, including an immunomodulatory agent. Daily ibrutinib ± weekly dexamethasone 40 mg was assessed in 4 cohorts using a Simon 2-stage design. The primary objective was clinical benefit rate (CBR; ≥minimal response); secondary objectives included safety. Patients (n = 92) received a median of 4 prior regimens. Ibrutinib + dexamethasone produced the highest CBR (28%) in Cohort 4 (840 mg + dexamethasone; n = 43), with median duration of 9·2 months (range, 3·0-14·7). Progression-free survival was 4·6 months (range, 0·4-17·3). Grade 3-4 haematological adverse events included anaemia (16%), thrombocytopenia (11%), and neutropenia (2%); grade 3-4 non-haematological adverse events included pneumonia (7%), syncope (3%) and urinary tract infection (3%). Ibrutinib + dexamethasone produced notable responses in this heavily pre-treated population. The encouraging efficacy, coupled with the favourable safety and tolerability profile of ibrutinib, supports its further evaluation as part of combination treatment. © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Effect of high wavelengths low intensity light during dark period on physical exercise performance, biochemical and haematological parameters of swimming rats.

PubMed

Beck, W; Gobatto, C

2016-03-01

Nocturnal rodents should be assessed at an appropriate time of day, which leads to a challenge in identifying an adequate environmental light which allows animal visualisation without perturbing physiological homeostasis. Thus, we analysed the influence of high wavelength and low intensity light during dark period on physical exercise and biochemical and haematological parameters of nocturnal rats. We submitted 80 animals to an exhaustive exercise at individualised intensity under two different illuminations during dark period. Red light (> 600 nm; < 15lux) was applied constantly during dark period (EI; for experimental illumination groups) or only for handling and assessments (SI; for standard illumination groups). EI led to worse haematological and biochemical conditions, demonstrating that EI alone can influence physiological parameters and jeopardise result interpretation. SI promotes normal physiological conditions and greater aerobic tolerance than EI, showing the importance of a correct illumination pattern for all researchers that employ nocturnal rats for health/disease or sports performance experiments.

Understanding the information needs of people with haematological cancers. A meta-ethnography of quantitative and qualitative research.

PubMed

Atherton, K; Young, B; Salmon, P

2017-11-01

Clinical practice in haematological oncology often involves difficult diagnostic and treatment decisions. In this context, understanding patients' information needs and the functions that information serves for them is particularly important. We systematically reviewed qualitative and quantitative evidence on haematological oncology patients' information needs to inform how these needs can best be addressed in clinical practice. PsycINFO, Medline and CINAHL Plus electronic databases were searched for relevant empirical papers published from January 2003 to July 2016. Synthesis of the findings drew on meta-ethnography and meta-study. Most quantitative studies used a survey design and indicated that patients are largely content with the information they receive from physicians, however much or little they actually receive, although a minority of patients are not content with information. Qualitative studies suggest that a sense of being in a caring relationship with a physician allows patients to feel content with the information they have been given, whereas patients who lack such a relationship want more information. The qualitative evidence can help explain the lack of association between the amount of information received and contentment with it in the quantitative research. Trusting relationships are integral to helping patients feel that their information needs have been met. © 2017 John Wiley & Sons Ltd.

Recommendations for reference method for haemoglobinometry in human blood (ICSH standard 1986) and specifications for international haemiglobincyanide reference preparation (3rd edition). International Committee for Standardization in Haematology; Expert Panel on Haemoglobinometry.

PubMed

1987-01-01

Scientific symposia on haemoglobinometry were held at the 9th Congress of the European Society of Haematology, Lisbon, 1963 (ESH 1964) and the 10th Congress of the International Society of Haematology (ISH), Stockholm, 1964 (ISH 1965). The International Committee for Standardization in Haematology (ICSH) made recommendations endorsed by the General Assembly of ICSH in Sydney on 23 August 1966 (ICSH 1967), for a reference method for haemoglobinometry and for the manufacture and distribution of an international reference preparation. Further symposia were held at the 12th Congress of the ISH, New York, 1968 (Astaldi, Sirtori & Vanzetti 1979) and at the 13th Congress of ISH, Munich, 1970 (Izak & Lewis 1972). The recommendations were reissued in 1978 (ISH 1978). On the basis of continuing experimental studies, the reference method and the specifications for the international reference preparation have been modified. The revised recommendations are described in this document.

Safety assessment of widely used fermented virgin coconut oil (Cocos nucifera) in Malaysia: Chronic toxicity studies and SAR analysis of the active components.

PubMed

Ibrahim, Ahmad H; Khan, Md Shamsuddin Sultan; Al-Rawi, Sawsan S; Ahamed, Mohamed B Khadeer; Majid, Aman Shah Bin Abdul; Al-Suede, Fouad Saleih R; Ji, Dan; Majid, Amin Malik Shah Abdul

2016-11-01

Fermented Virgin Coconut Oil (FVCO) is widely used in the Southeast Asia as food and traditional medicine. The objective of the present study is the evaluation of chronic safety of the commercialized FVCO of Malaysia and other Southeast Asian countries. A single dose of 5000 mg/kg of FVCO was administered orally in rats (each group, n = 5) for the acute toxicity study and 175, 550 and 2000 mg/kg for sub-chronic and chronic studies (each group, n = 10), respectively. The behavior, mortality, and body weight of the rats were assessed to determine the toxic effects of FVCO. The haematology, biochemistry and histopathology of the treated rats were evaluated. The treated rats were safe with the dose of 5000 mg/kg in acute, sub-chronic and chronic indication. Abnormal clinical signs and morphology (gross necroscopy), changes of organ weight, anomalous haematology and biochemistry indexes were not found in comparison with the control (p > 0.05). In general, food and water intake were higher in the treated rats related to control. It was concluded that the presence of the antioxidant active compounds of FVCO might be the reason of safety. The structure activity relationship (SAR) provides a comprehensive mechanism to determine the safety that is the presence of the electron donating phenolic groups, carbonyl groups, and carboxylic acid in the ortho and meta position of the aromatic rings. The SAR showed the antioxidant properties of myristic acid and lauric acid determined by GC-MS analysis. This result suggests the safety of FVCO for chronic use, nutritional activity that FVCO formulation complies the requirements of regulatory agencies. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

PubMed Central

2013-01-01

Background Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. Methods Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. Results Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. Conclusion Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However

Performance evaluation of the Abbott CELL-DYN Ruby and the Sysmex XT-2000i haematology analysers.

PubMed

Leers, M P G; Goertz, H; Feller, A; Hoffmann, J J M L

2011-02-01

Two mid-range haematology analysers (Abbott CELL-DYN Ruby and Sysmex XT-2000i) were evaluated to determine their analytical performance and workflow efficiency in the haematology laboratory. In total 418 samples were processed for determining equivalence of complete blood count (CBC) measurements, and 100 for reticulocyte comparison. Blood smears served for assessing the agreement of the differential counts. Inter-instrument agreement for most parameters was good although small numbers of discrepancies were observed. Systematic biases were found for mean cell volume, reticulocytes, platelets and mean platelet volume. CELL-DYN Ruby WBC differentials were obtained with all samples while the XT-2000i suppressed differentials partially or completely in 13 samples (3.1%). WBC subpopulation counts were otherwise in good agreement with no major outliers. Following first-pass CBC/differential analysis, 88 (21%) of XT-2000i samples required further analyser processing compared to 18 (4.3%) for the CELL-DYN Ruby. Smear referrals for suspected WBC/nucleated red blood cells and platelet abnormalities were indicated for 106 (25.4%) and 95 (22.7%) of the XT-2000i and CELL-DYN Ruby samples respectively. Flagging efficiencies for both analysers were found to be similar. The Sysmex XT-2000i and Abbott CELL-DYN Ruby analysers have broadly comparable analytical performance, but the CELL-DYN Ruby showed superior first-pass efficiency. © 2010 Blackwell Publishing Ltd.

Specific Safety Profile of Bevacizumab in Asian Patients With Advanced NSCLC

PubMed Central

Chen, Zhenguang; Zhong, Beilong; Lun, Xueping; Lai, Yingrong; Bella, Amos Ela; Yang, Weilin; Wu, Jiabin

2015-01-01

Abstract Randomized studies have obtained varying findings regarding the benefits and toxicities of bevacizumab in the treatment of nonsmall cell lung cancer (NSCLC). It is unclear whether the discrepancies among trials are due to ethnic/racial differences. We therefore performed a meta-analysis of all published, randomized, controlled clinical trials involving bevacizumab in patients with NSCLC to assess its effectiveness and safety in Asian and non-Asian populations. Results from the phase II JO19907 trial, the phase III AVAiL and ECOG 4599 trials, and the phase IV SAiL trials were used to calculate the benefits and toxicities of bevacizumab in Asian and non-Asian patients. Combined statistical estimates, including hazard ratios and odds ratios, were calculated using fixed-effects and random-effects models. A total of 4308 patients were evaluated. Combining bevacizumab with different chemotherapy regimens resulted in similar objective response rates, overall survival, and progression-free survival in Asian and non-Asian populations. Disease control rates, however, were only reported in Asian populations. The rates of severe bleeding (relative risk [RR], 2.17; P = 0.02) and thromboembolism (RR, 3.65; P < 0.0001) were significantly higher, while the rate of severe proteinuria was significantly lower (RR, 0.43; P < 0.0001), in non-Asian than in Asian populations. The rates of severe hypertension (P = 0.71) and hemoptysis (P = 0.66) were similar in Asian and non-Asian populations. Bevacizumab combined with chemotherapy for first-line NSCLC treatment showed similar benefits in Asian and non-Asian populations, but had specific safety profiles in each. PMID:26091469

Cognitive coping style (monitoring and blunting) and the need for information, information satisfaction and shared decision making among patients with haematological malignancies.

PubMed

Rood, Janneke A J; Van Zuuren, Florence J; Stam, Frank; van der Ploeg, Tjeerd; Huijgens, Peter C; Verdonck-de Leeuw, Irma M

2015-05-01

A haematological malignancy is a serious, life-altering disease and may be characterised as an uncontrollable and unpredictable stress situation. In dealing with potentially threatening information, individuals generally utilise two main cognitive coping styles: monitoring (the tendency to seek threat-relevant information) and blunting (avoiding threatening information and seeking distraction). The aim of this study was to obtain insight into the association between cognitive coping style and (a) need for information, (b) satisfaction with information, (c) involvement in decision making, and (d) quality of life (QoL). In this cross-sectional study, coping style was assessed among adult patients diagnosed with a haematological malignancy, using an adapted version of the Threatening Medical Situations Inventory. Information need, information satisfaction, decision-making preference and QoL were measured with validated questionnaires. In total, 458 patients returned the questionnaire (66%). A monitoring coping style was positively related to need for both general and specific information. Blunting was positively and QoL was negatively related to need for information. Monitoring was positively related to involvement in decision-making and negatively to information satisfaction. Using multivariate analysis, this relation between monitoring and information satisfaction disappeared, and for blunting, we found a negatively significant relation. QoL was not related to coping style. Among patients with haematological malignancies, coping style is related to a need for information, information satisfaction, and involvement in treatment decision-making. Therefore, it is important for health care professionals to be aware of individual differences in cognitive coping style. Copyright © 2014 John Wiley & Sons, Ltd.

Implementing evidence in an onco-haematology nursing unit: a process of change using participatory action research.

PubMed

Abad-Corpa, Eva; Delgado-Hito, Pilar; Cabrero-García, Julio; Meseguer-Liza, Cristobal; Zárate-Riscal, Carmen Lourdes; Carrillo-Alcaraz, Andrés; Martínez-Corbalán, José Tomás; Caravaca-Hernández, Amor

2013-03-01

To implement evidence in a nursing unit and to gain a better understanding of the experience of change within a participatory action research. Study design of a participatory action research type was use from the constructivist paradigm. The analytical-methodological decisions were inspired by Checkland Flexible Systems for evidence implementation in the nursing unit. The study was carried out between March and November 2007 in the isolation unit section for onco-haematological patients in a tertiary level general university hospital in Spain. Accidental sampling was carried out with the participation of six nurses. Data were collected using five group meetings and individual reflections in participants' dairies. The participant observation technique was also carried out by researchers. Data analysis was carried out by content analysis. The rigorous criteria were used: credibility, confirmability, dependence, transferability and reflexivity. A lack of use of evidence in clinical practice is the main problem. The factors involved were identified (training, values, beliefs, resources and professional autonomy). Their daily practice (complexity in taking decisions, variability, lack of professional autonomy and safety) was compared with an ideal situation (using evidence it will be possible to normalise practice and to work more effectively in teams by increasing safety and professional recognition). It was decided to create five working areas about several clinical topics (mucositis, pain, anxiety, satisfaction, nutritional assessment, nauseas and vomiting, pressure ulcers and catheter-related problems) and seven changes in clinical practice were agreed upon together with 11 implementation strategies. Some reflections were made about the features of the study: the changes produced; the strategies used and how to improve them; the nursing 'subculture'; attitudes towards innovation; and the commitment as participants in the study and as healthcare professionals. The

Haematological profile of rats (Rattus norvegicus) induced BCG and provided leaf extract of Plectranthus amboinicus Lour Spreng)

NASA Astrophysics Data System (ADS)

Silitonga, Melva; Silitonga, Pasar M.

2017-08-01

Plectranthus amboinicus Lour Spreng is a medicinal plant that has many benefits, such as an antioxidant, hepatoprotective and immunostimulan. Immune status can be seen from hematological profile. This study aims to investigate hematology profile on rats induced BCG and leaf extract of Plectranthus amboinicus. 24 male rats aged 3 months and weighing between 140-200 grams divided equally into six groups, P0, P1, P2, P3, P4 and P5. P0 as controle was given aquadest. The P1, P2, P3, P4 and P5 treatment groups were given 19 g / kg AEP + BCG, 31.5 g / kg AEP + BCG, 19g / kg AEP, 31.5 g / kg AEP and BCG consecutively. The BCG were used as antigen. The AEP was administered orally for 30 days and 100 µl BCG were intramusculary administered on day 14 th and day 21. On day 31st, the rats we decapitated and their blood were collected for hematology (leucocyte (WBC), Erythrocyte (RBC), thrombocyte (PLT) count, Haemoglobin (Hb), erythrocyte sedimentation rate (ESR), MCV, MHC, and MHCH analysis. Data were analyzed with ANOVA. WBC increased significantly in treatment AEP 31.5 g / kg bw, 31.5 g AEP / kg bw + BCG and so were only given BCG. RBC tend to increase in all AEP treatment but tends to increase again when given a BCG. Hb increased in treatment P1, P2, T3 and P4, but the improvement was significant only in treatment P1. While PLT increase significantly in all treatments compared to the controls. HCT did not show significant differences but all of them were in the normal range. EAP without BCG and with the addition of BCG lowered ESR significantly, whereas BCG alone increased the ESR significantly. MCV increased significantly only in the treatment of P1 and show the same pattern with the MHC and MHCH. The conclusion that Plectranthus amboinicus Lour a positive impact on blood profiles with and without BCG. Plectranthus amboinicus Lour managed blood profile when administered together with BCG

States Respond to School Safety Concerns with 2013 Legislation. School Safety: 2013 Legislative Session

ERIC Educational Resources Information Center

Wixom, Micah Ann

2014-01-01

School safety policies are constantly evolving, often in response to fatal events. After several high-profile and tragic shootings over the past 15 years, school safety has become a major focus for parents, school officials, policymakers and the public nationwide. ECS [Education Commission of the States] conducted a scan of school safety-related…

[Application and usefulness of flowcytometry in the haematology laboratory].

PubMed

Kubota, K; Makino, M

1991-02-01

Recent technological advances, in both hardware and software, and availability of various monoclonal antibodies (MoAb) for membrane antigens of blood cells have expanded the application of flow cytometry (FCM) in medicine. In the haematology laboratory, FCM has been used mainly for assessment of leukemia and lymphoma and for determination of lymphocyte subsets. In acute leukemia, FCM is useful to classify ALL accurately, particularly for bi phenotypic or mixed lineage leukemia. In lymphocyte subset determination, we found that the use of magnetic beads to remove contaminating monocytes and some granulocytes to purify the lymphocyte-population is helpful in clarify the subsets. We present data describing the age dependent variation in lymphocyte subsets in the pediatric population. In early life (up to 2 years old), CD4 (+) 2H4 (+) lymphocyte overwhelmed CD4 (+) 2H4 (-) cells, implying predominance of suppressor-inducer activity. We also presented some cases of markedly increased double negative T cells (gamma/delta TCR) and a rare case of double positive (CD4+, CD8+) T cells.

Assessment of yeast as a dietary additive on haematology and water quality of common carp in a recirculating aquaculture system

NASA Astrophysics Data System (ADS)

Goran, Siraj Muhammed Abdulla; Omar, Samad Sofy; Anwer, Ayub Youns

2017-09-01

Feeding experiment was accomplished at the Aquaculture unit (Close system), Grdarasha station, Agriculture College, University of Salahaddin, Erbil, Kurdistan Region, to investigate different levels of Aquagrow E (AGEY) brewer's yeast cell Saccharomyces cerevisiae on the haematological and water quality of common carp fingerlings Cyprinus carpio. The basal diet was formulated to contain 34% protein and 10% lipid and the dietary treatments were supplemented with 0.5%, 1% and 1.5% of AGEY diet. A total of 180 Common carp (10.30 ± 0.27 g) fed on experimental diets for 10 weeks. Water quality assessment for well water and pond water for rearing Cyprinus carpio in cage system conducted weekly, while some parameters including pH, EC, water temperature and DO were monitored daily during the entire periods of study. Values of total hardness, alkalinity, ammonia and nitrate for studied water samples were within normal ranges for rearing Cyprinus carpio. Mean concentration of GPT, GOT and Glucose were 104 to 170 U/L, 1371 to 3308 U/L and 34 to 63mg/dl respectively, moreover, highest levels were observed in treatments with higher concentrations of yeast in its food except for blood sugar. Slight variation in lipase enzyme were found between control and treatment groups, while levels of amylase enzyme were increased toward cages with higher levels of yeast until T1 and then decreased toward T3. Total protein levels were increased to toward higher levels of yeast in food of Cyprinus carpio fish. Haematological results showed highest levels of WBC and platelets in treatments cages than control group. Levels of RBCs and hemoglobin were highest in treatment group 1 with 0.5%of yeast than treatments higher yeast concentrations. Significant correlation was found in haematological parameters between control and treatments.

Clinical strategies to aim an adequate safety profile for patients and effective training for surgical residents: The laparoscopic cholecystectomy model.

PubMed

Bresadola, Vittorio; Pravisani, Riccardo; Pighin, Marina; Seriau, Luca; Cherchi, Vittorio; Giuseppe, Sergio; Risaliti, Andrea

2016-11-01

Training programs for resident surgeons represent a challenge for the mentoring activity. The aim of the present study is to investigate the impact of our training program for laparoscopic cholecystectomy on patient's safety and on the modulation of the residents' exposure to clinical scenario with different grades of complexity. This is a retrospective study based on a clinical series of laparoscopic cholecystectomy performed in a teaching hospital. Study population was grouped according to the expertise of the attending primary operator among resident surgeons. Four groups were identified: consultant (C), senior resident (SR); intermediate level resident (IR); junior resident (JR). The intraoperative and postoperative outcomes were confronted to evaluate the patient's safety profile. 447 patients were submitted to LC: 96 cases were operated by a C, 200 by SR, 112 by IR and 39 by JR. The mean operative time was the longest for the JR group. A statistically higher rate of conversion to open approach was registered in C and IR groups in comparison to JR and SR groups. However, in C and IR groups, patients had worse ASA score, higher BMI and more frequent past history of previous abdominal surgery, cholecystitis or pancreatitis. Overall, it was not registered any statistically significant difference among the groups in terms of length of hospital stay and prevalence of major postoperative complications. Applying an educational model based on both graduated levels of responsibility and modulated grade of clinical complexity can guarantee an high safety profile.

Correlation between normal glucose-6-phosphate dehydrogenase level and haematological parameters.

PubMed

Ajlaan, S K; al-Naama, L M; al-Naama, M M

2000-01-01

The study involved 143 individuals and aimed to correlate normal glucose-6-phosphate dehydrogenase (G6PD) level with haematological parameters. A statistically significant negative correlation was found between G6PD level and haemoglobin, packed cell volume, red blood cell count, mean corpuscular haemoglobin and mean corpuscular volume. A statistically significant positive correlation was found between G6PD level and white blood cell count and reticulocyte count, but no significant correlation was found between G6PD level and mean corpuscular haemoglobin concentration. The negative correlation between G6PD level and haemoglobin suggests that anaemic people have higher G6PD levels than normal individuals. The positive correlation between G6PD level and white blood cell count indicates that white blood cells may play an important role in contributing to G6PD level.

Blood gases, biochemistry and haematology of Galápagos marine iguanas (Amblyrhynchus cristatus)

PubMed Central

Lewbart, Gregory A.; Hirschfeld, Maximilian; Brothers, J. Roger; Muñoz-Pérez, Juan Pablo; Denkinger, Judith; Vinueza, Luis; García, Juan; Lohmann, Kenneth J.

2015-01-01

The marine iguana, Amblyrhynchus cristatus, is an iconic lizard endemic to the Galápagos Islands of Ecuador, but surprisingly little information exists on baseline health parameters for this species. We analysed blood samples drawn from 35 marine iguanas captured at three locations on San Cristóbal Island. A portable blood analyser (iSTAT) was used to obtain near-immediate field results for pH, lactate, partial pressure of O2, partial pressure of CO2, bicarbonate (HCO3−), percentage O2 saturation, haematocrit, haemoglobin, sodium, potassium, ionized calcium and glucose. Parameter values affected by temperature were auto-corrected by the iSTAT. Standard laboratory haematology techniques were employed for differential white blood cell counts and haematocrit determination; resulting values were also compared with the haematocrit values generated by the iSTAT. Body temperature, heart rate, respiratory rate and body measurements were also recorded. Body length was positively correlated with several blood chemistry values (HCO3− and glucose) and two haematology parameters (haemoglobin and manually determined haematocrit). A notable finding was the unusually high blood sodium level; the mean value of 178 mg/dl is among the highest known for any reptile. This value is likely to be a conservative estimate because some samples exceeded the maximal value the iSTAT can detect. For haematocrit determination, the iSTAT blood analyser yielded results significantly lower than those obtained with high-speed centrifugation. The values reported in this study provide baseline data that may be useful in comparisons among populations and in detecting changes in health status among marine iguanas affected by natural disturbances or anthropogenic threats. The findings might also be helpful in future efforts to demonstrate associations between specific biochemical parameters and disease. PMID:27293719

[The safety profile of escitalopram in pregnancy and breastfeeding].

PubMed

Bellantuono, Cesario; Orsolini, Laura; Bozzi, Francesca

2013-01-01

Escitalopram (ESC) is considered one of the most effective selective serotonin reuptake inhibitors (SSRI) for the treatment of major depression disorder. However, little is known on its potential risk of inducing major malformations (MM) and/or perinatal complications (PC). Aim of the present study is to provide a review of the available literature on the safety profile of ESC during pregnancy and breastfeeding and to compare data with the maternal and neonatal outcomes of 8 cases of the DEGRA Center. MEDLINE and PubMed databases were searched for English language articles by using the following keywords: "escitalopram", "selective serotonin reuptake inhibitors", "major malformations", "perinatal complications", "pregnancy", "breastfeeding". We also reported 8 cases of women treated with ESC during their pregnancy and breastfeeding at the Clinic of Affective Disorders in Pregnancy and Postpartum of the United Hospital of Ancona (DEGRA Center). Although some cases of MM have been reported in the literature after maternal exposure to ESC during early pregnancy, the rate of MM is substantially in the range of those reported in unexposed women. ESC exposure seems to be significantly associated with some PC such as lower rates of live births and higher rates of newborns with low birth weight. On the contrary, no short-term adverse effects in newborns were reported in the 5 studies evaluating the safety of ESC during breastfeeding. Data coming from DEGRA Center are consistent with the literature: all pregnancy were full term, all newborns were healthy and obtained normal APGAR score; no MM or miscarriage were reported. Only one case of mild withdrawal syndrome was reported in a newborn who was also exposed to benzodiazepines and paroxetine late in pregnancy. Two infants exposed to ESC also during the lactation did not reported any adverse effects at short-term. Data coming from published studies and from our cases seem to support the notion that ESC might be considered

Driver behaviour profiles for road safety analysis.

PubMed

Ellison, Adrian B; Greaves, Stephen P; Bliemer, Michiel C J

2015-03-01

Driver behaviour is a contributing factor in over 90 percent of road crashes. As a consequence, there is significant benefit in identifying drivers who engage in unsafe driving practices. Driver behaviour profiles (DBPs) are introduced here as an approach for evaluating driver behaviour as a function of the risk of a casualty crash. They employ data collected using global positioning system (GPS) devices, supplemented with spatiotemporal information. These profiles are comprised of common risk scores that can be used to compare drivers between each other and across time and space. The paper details the development of these DBPs and demonstrates their use as an input into modelling the factors that influence driver behaviour. The results show that even having controlled for the influence of the road environment, these factors remain the strongest predictors of driver behaviour suggesting different spatiotemporal environments elicit a variety of psychological responses in drivers. The approach and outcomes will be of interest to insurance companies in enhancing the risk-profiling of drivers with on-road driving and government through assessing the impacts of behaviour-change interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of invasive fungal infections in high-risk haematological patients: what have we learnt in the past 10 years?

PubMed

Vallejo, Carlos; Vázquez, Lourdes; Cabrera Martín, José Rafael; Carreras, Enric; García Rodríguez, Julio; Ruiz Camps, Isabel; Fortún, Jesús; Mensa, Josep; Barberán, José

2013-12-01

Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haematological diseases. Last advances in the diagnostic and therapeutic fields, today we know that their contributions are limited. Something similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversification of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sensitivity of AGA testing in some circumstances, and the potential delay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strategy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last decade and to present a set of recommendations.

The effect of fasting during Ramadan on parameters of the haematological and steroidal modules of the athletes biological passport - a pilot study.

PubMed

Alsaadi, K; Voss, S C; Kraiem, S; Alwahaibi, A; Alyazedi, S; Dbes, N; Goebel, R; Mohamed-Ali, V; Alsowaidi, S; Seyam, A M; Bashraheel, A S; Alsayrafi, M; Georgakopoulos, C

2015-01-01

This study investigated the effect of Ramadan on the haematological and steroid module of the Athletes Biological Passport (ABP) of the World Anti-Doping Agency (WADA). Nine healthy physically active subjects were tested in the morning and afternoon for two days before and three days during Ramadan. Sample collection and all analyses were performed according to WADA technical documents. Although there were significant changes in the haemoglobin concentration during Ramadan, especially during the first fasting week, none of the subjects in this study exceeded the individually calculated thresholds of the ABP. No significant effects on testosterone/epitestosterone (T/E) ratio were observed but only the afternoon specific gravity (SG) of the urine was elevated. Thus, when urinary steroid concentrations are required, SG corrections need to be performed. The haematological and the steroid module of the ABP can be reliably applied during Ramadan as the observed changes are only marginal. Copyright © 2015 John Wiley & Sons, Ltd.

Haematological features in children less than 12 years on cotrimoxazole prophylaxis seen in opportunistic infection clinics at Harare and Parirenyatwa Teaching Hospitals.

PubMed

Mateveke-Kuona, P; Bwakura, M F; Dzangare, J; Pazvakavambwa, I

2010-01-01

To determine the prevalence of peripheral haematological abnormalities in children receiving cotrimoxazole prophylaxis. An outpatient hospital based cross sectional study. The study was conducted at two tertiary peadiatric HIV clinics that offer comprehensive care to children living with HIV. 202 HIV infected, antiretroviral therapy naive children aged between 3 months and 12 years who were receiving cotrimoxazole prophylaxis for at least 1 month with more than95% adherence to prophylaxis were included. Haematological abnormalities on full blood count and peripheral film. The prevalence of anaemia was 62% with normocytic normochromic anaemia being the most frequent type (45%). The commonest red blood cell abnormality was rouleaux formation on the peripheral film. Monocytosis occurred in 62%, leucopaenia in 39%, eosinophilia in 34%, neutropaenia in 18% and lymphopaenia in 10% of the children. This study showed a high prevalence ofhaematological abnormalities in HIV infected children on cotrimoxazole prophylaxis. It emphasizes the need for evaluation for anaemia and its management in children on cotrimoxazole prophylaxis.

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.

PubMed

Okamoto, Isamu; Schuette, Wolfgang H W; Stinchcombe, Thomas E; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J; Zinner, Ralph G

2017-05-01

This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. All patients received pemetrexed 500 mg/m 2 every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated

Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses.

PubMed

Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

2011-08-01

The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Impact of supplementing diets with propolis on productive performance, egg quality traits and some haematological variables of laying hens.

PubMed

Abdel-Kareem, A A A; El-Sheikh, T M

2017-06-01

One hundred and twenty eight, 28-weeks-old Lohmann LSL hybrid layers were used in this experiment, which lasted 12 weeks to investigate the effect of propolis supplementation on the productive performance, egg quality traits and haematological variables of laying hens. All hens were randomly classified into four equal experimental groups, eight replicates (4 birds/each). Hens in group 1 were fed on a commercial diet and considered as control group, while those in groups 2, 3 and 4 were fed on the same commercial diet and supplemented with 250, 500 and 1000 mg propolis/kg diet. The obtained results revealed that daily feed consumption/hen increased insignificantly with increasing propolis level than that of the control group. Regarding the means of egg mass and egg production rate, it was observed that the laying hens fed diets containing 250 and 1000 mg propolis/kg significantly (p < 0.05) produced more and heaver egg in comparison with control group. External egg quality traits have not affected with increasing the level of propolis, while eggshell weight was significantly (p < 0.05) increased. The internal egg quality traits except albumen and yolk percentages increased significantly (p < 0.05) with increasing propolis level for treated hens as compared to those in the control. Concerning the haematological parameters, the results showed that the levels of total protein and globulin increased significantly with increasing propolis level, while cholesterol and liver enzymes were significantly decreased (p < 0.05). Heterophils count of hens in the treated groups significantly decreased, whereas the lymphocyte count significantly increased, resulting in a decreased H/L ratio than that of the control group. Thus, it could be concluded that the supplementation of 250 mg propolis/kg diet is highly recommended to improving egg production, blood constituent and haematological parameters of the commercial laying hens. Journal of Animal Physiology and Animal

A pilot study evaluating changes to haematological and biochemical tests after Flexible Ureterorenoscopy for the treatment of kidney stones.

PubMed

Moyes, Alyson Jayne; Lamb, Rebecca May; Ella-Tongwiis, Peter; Pushkaran, Anish; Ahmed, Issam; Shergill, Iqbal; Hughes, Stephen Fôn

2017-01-01

Currently there is limited research documenting the changes in blood parameters, following Flexible Ureterorenoscopy. This study aims to determine whether there are any changes in haematology and biochemistry parameters, following Flexible Ureterorenoscopy for the treatment of kidney stones. 40 consecutive patients aged between 27-87 years (median 49 years) undergoing Flexible Ureterorenoscopy for the treatment of kidney stones were recruited (26 male, 14 female). Blood samples were collected from each patient at four time points: baseline (pre-operatively) followed by 30 minutes, 120 minutes and 240 minutes post-operatively. On these samples, routine haematological and biochemistry tests were carried out. In addition to the assessment of clinical parameters prospectively from the medical notes. There was a significant decrease observed following Flexible Ureterorenoscopy in the following parameters: lymphocytes (p = 0.007), eosinophils (p = 0.001), basophils (p = 0.001), haemoglobin (p = 0.002), red blood cells (p = 0.001), platelet count (p = 0.001), fibrinogen concentration (p = 0.001), von Willebrand factor (p = 0.046), C reactive protein (p = 0.01), total protein (p = 0.001), albumin (p = 0.001), globulin (p = 0.001) and alkaline phosphatase (p = 0.001). In addition, there was a significant increase observed in the following parameters: white blood cells (p = 0.001), neutrophils (p = 0.001), activated partial thromboplastin time (p = 0.001), total bilirubin (p = 0.012), creatinine (p = 0.008), sodium (p = 0.002) and potassium (p = 0.001). Limiting factors for this study were the sample size, and restriction on the recruitment time points. Significant changes were noted to occur in haematology and biochemistry parameters following Flexible Ureterorenoscopy. Some of the data presented in this study may represent the 'normal' post-operative response following FURS, as no major complications occurred, in the majority of our patients. This data on the 'normal

Protective effects of vitamin C against haematological and biochemical toxicity induced by deltamethrin in male Wistar rats.

PubMed

Mongi, Saoudi; Mahfoud, Messarah; Amel, Boumendjel; Kamel, Jamoussi; Abdelfattah, El Feki

2011-09-01

Deltamethrin is a synthetic pyrethroid insecticide. It is known for its wide toxic manifestations. The present experiment pertains to the protective role of vitamin C against haematological and biochemical toxicity induced by deltamethrin during 4 weeks. Male Wistar rats were divided into four groups of eight each: Group I served as control rats; Group II received deltamethrin (1.28 mg/kg BW) in drinking water. Group III received both deltamethrin and vitamin C (200mg/kg BW; by i.p. injection); Group IV received vitamin C (200mg/kg BW). Exposure of rats to deltamethrin caused significant changes of some haematological parameters (red blood cells (RBC), haemoglobin (Hb), haematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet (Plt) and white blood cells (WBC)) in treated rats compared to controls. Significant increases in the levels of hepatic markers enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), γ-Glutamyl transpeptidase (γ-GT)). Furthermore, renal markers such as urea and creatinine were increased in deltamethrin treated rats. Additionally, serum cholesterol and lipid peroxidation were significantly enhanced. Co-administration of vitamin C to the group III restored all the parameters cited above to near-normal values. Therefore, our investigation revealed that vitamin C appeared to be a promising agent for protection against deltamethrin-induced toxicity. Published by Elsevier Inc.

Multidimensional Characterization of Sexual Minority Adolescents’ Sexual Safety Strategies

PubMed Central

Masters, N. Tatiana; Beadnell, Blair; Morrison, Diane M.; Hoppe, Marilyn J.; Wells, Elizabeth A.

2013-01-01

Young adults have high rates of sexually transmitted infections (STIs). Sexual minority youths’ risk for STIs, including HIV, is as high as or higher than sexual majority peers’. Sexual safety, while often treated as a single behavior such as condom use, can be best conceptualized as the result of multiple factors. We used latent class analysis to identify profiles based on ever-used sexual safety strategies and lifetime number of partners among 425 self-identified LGBTQ youth aged 14-19. Data collection took place anonymously online. We identified four specific subgroup profiles for males and three for females, with each subgroup representing a different level and type of sexual safety. Profiles differed from each other in terms of age and outness for males, and in outness, personal homonegativity, and amount of education received about sexual/romantic relationships for females. Youths’ sexual safety profiles have practice implications for sexuality educators, health care professionals, and parents. PMID:24011111

Safety profile of hymenoptera venom immunotherapy (VIT) in monosensitized patients: lack of new sensitization to nontreated insect venom.

PubMed

Spoerl, D; Bircher, A J; Scherer, K

2011-01-01

Venom immunotherapy (VIT) has proven to be efficacious in reducing the severity of anaphylactic reactions following field stings in patients with Hymenoptera venom allergy. Due to sequence homologies in the allergens used in Hymenoptera vaccines, there is concern that immunotherapy could lead to sensitization to allergens to which patients were not previously sensitized. The relevance of such an undesired phenomenon is unclear. To investigate the incidence of sensitization to Hymenoptera venoms other than those to which the patients were already sensitized and to assess the overall safety profile of VIT in order to compare the risk-benefit ratio in a subpopulation of monosensitized individuals. We performed a retrospective analysis of specific immunoglobulin E (sIgE) levels in patients with no prior detectable sIgE to Hymenoptera venom other than the one for which they received VIT. We assessed the safety profile of VIT using serological and clinical parameters. Of the 56 monosensitized patients who had VIT, 3 (5%) developed sIgE to the other insect with no history of field sting to explain it. This rate was similar to the rate of new sensitization due to field stings during VIT. VIT was well-tolerated and levels of serological markers improved. No patient had a systemic anaphylactic reaction after having been stung by an insect other than the one he/she was desensitized for during follow-up. VIT seems to be safe with respect to clinically significant new sensitizations.

Physics-model-based nonlinear actuator trajectory optimization and safety factor profile feedback control for advanced scenario development in DIII-D

DOE PAGES

Barton, Justin E.; Boyer, Mark D.; Shi, Wenyu; ...

2015-07-30

DIII-D experimental results are reported to demonstrate the potential of physics-model-based safety factor profile control for robust and reproducible sustainment of advanced scenarios. In the absence of feedback control, variability in wall conditions and plasma impurities, as well as drifts due to external disturbances, can limit the reproducibility of discharges with simple pre-programmed scenario trajectories. The control architecture utilized is a feedforward + feedback scheme where the feedforward commands are computed off-line and the feedback commands are computed on-line. In this work, firstly a first-principles-driven (FPD), physics-based model of the q profile and normalized beta (β N) dynamics is embeddedmore » into a numerical optimization algorithm to design feedforward actuator trajectories that sheer the plasma through the tokamak operating space to reach a desired stationary target state that is characterized by the achieved q profile and β N. Good agreement between experimental results and simulations demonstrates the accuracy of the models employed for physics-model-based control design. Secondly, a feedback algorithm for q profile control is designed following a FPD approach, and the ability of the controller to achieve and maintain a target q profile evolution is tested in DIII-D high confinement (H-mode) experiments. The controller is shown to be able to effectively control the q profile when β N is relatively close to the target, indicating the need for integrated q profile and β N control to further enhance the ability to achieve robust scenario execution. Furthermore, the ability of an integrated q profile + β N feedback controller to track a desired target is demonstrated through simulation.« less

Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

PubMed

Scavone, Cristina; Bonagura, Angela Colomba; Fiorentino, Sonia; Cimmaruta, Daniela; Cenami, Rosina; Torella, Marco; Fossati, Tiziano; Rossi, Francesco

2016-06-01

According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations. The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the

Comparative evaluation of haematological parameters and erythrocyte membrane stability in pregnant and lactating goats in different seasons of tropical Savannah.

PubMed

Habibu, B; Makun, H J; Yaqub, L S; Buhari, H U; Aluwong, T; Kawu, M U

2017-09-01

Haematological parameters and erythrocyte osmotic fragility (EOF) are commonly used as indicators of health status and erythrocyte membrane integrity. Variations in haematological parameters and EOF in late gestation and early lactation during the cold-dry (CDS), hot-dry (HDS) and rainy (RAS) seasons were studied in sixty (n = 60) Red Sokoto goats (20 goats for each season). The ambient temperatures and temperature-humidity index recorded were higher in the afternoon hours of the HDS and RAS, but lower in the morning hours of the CDS as compared with the thermoneutral zone of goats. Results revealed that the pregnant goats had significantly (P < 0.05) lower PCV and RBC, but higher haemoglobin parameters (Hb, MCH and MCHC) in RAS. Unlike in the pregnant goats, higher (P < 0.05) values of PCV and RBC were observed during the HDS as compared with the CDS and RAS in lactating goats. The EOF was significantly higher during lactation than pregnancy in the CDS and HDS. Similarly, the magnitude of the left shift in fragiligram during the CDS was more marked in pregnant compared with lactating goats. During gestation, the CDS had lower (P < 0.05) EOF than HDS and RAS, with a marked left shift in the fragiligram of both pregnant and lactating goats during the CDS. In conclusion, seasonal variations exist in physiology of erythrocytes of goats during the peri-partum period, with an increase in PCV and RBC, but a decrease in haemoglobin parameters in pregnant compared with lactating goats during the RAS. Erythrocyte stability and membrane integrity were higher in pregnant than lactating goats, and also higher during the CDS than the HDS and RAS, irrespective of reproductive status. This information may be useful in the design of animal breeding and is of value in animal welfare, research, diagnosis and management of haematological conditions during the peri-partum period. Copyright © 2017 Elsevier Inc. All rights reserved.

Preclinical toxicity profile of oral bilastine.

PubMed

Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

2012-06-01

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Perspectives of patients with haematological cancer on how clinicians meet their information needs: "Managing" information versus "giving" it.

PubMed

Atherton, Kirsten; Young, Bridget; Kalakonda, Nagesh; Salmon, Peter

2018-03-23

Practitioners treating patients with haematological cancers have extensive clinical information available to give to patients, and patients need to be informed. However, many patients want to be protected from having information that is too detailed or threatening. To illuminate how practitioners can address this dilemma and help patients feel appropriately informed, we explored patients' experience of feeling informed or uninformed. Semi-structured interviews were conducted with 20 patients who had been diagnosed with haematological cancer and had recently received results from clinical investigations or from evaluations of treatment response. Inductive and interpretive analysis of the transcribed audio-recorded interviews drew on constant comparison. Patients described the need for practitioners carefully to manage the information that they provided, and many felt alarmed by information that they did not experience as having been managed for them. A few patients who had difficulty trusting practitioners were not content with the information provided. These findings can be understood using attachment theory, whereby practitioners' careful management of information demonstrates their care for patients, and patients' trust in the practitioner enables them to feel informed. It follows that, when patients do not feel informed, the solution will not necessarily be more information but might be to help patients feel more secure in a caring clinical relationship. Copyright © 2018 John Wiley & Sons, Ltd.

Modeling pedestrian crossing speed profiles considering speed change behavior for the safety assessment of signalized intersections.

PubMed

Iryo-Asano, Miho; Alhajyaseen, Wael K M

2017-11-01

Pedestrian safety is one of the most challenging issues in road networks. Understanding how pedestrians maneuver across an intersection is the key to applying countermeasures against traffic crashes. It is known that the behaviors of pedestrians at signalized crosswalks are significantly different from those in ordinary walking spaces, and they are highly influenced by signal indication, potential conflicts with vehicles, and intersection geometries. One of the most important characteristics of pedestrian behavior at crosswalks is the possible sudden speed change while crossing. Such sudden behavioral change may not be expected by conflicting vehicles, which may lead to hazardous situations. This study aims to quantitatively model the sudden speed changes of pedestrians as they cross signalized crosswalks under uncongested conditions. Pedestrian speed profiles are collected from empirical data and speed change events are extracted assuming that the speed profiles are stepwise functions. The occurrence of speed change events is described by a discrete choice model as a function of the necessary walking speed to complete crossing before the red interval ends, current speed, and the presence of turning vehicles in the conflict area. The amount of speed change before and after the event is modeled using regression analysis. A Monte Carlo simulation is applied for the entire speed profile of the pedestrians. The results show that the model can represent the pedestrian travel time distribution more accurately than the constant speed model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes

PubMed Central

Hanefeld, Markolf

2007-01-01

Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD) risk-reduction benefits. The efficacy, safety and tolerability of the α-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT). Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum. PMID:17697384

A retrospective analysis of biochemical and haematological parameters in patients with eating disorders.

PubMed

Barron, Leanne J; Barron, Robert F; Johnson, Jeremy C S; Wagner, Ingrid; Ward, Cameron J B; Ward, Shannon R B; Barron, Faye M; Ward, Warren K

2017-01-01

The objective of the study was to determine whether levels of biochemical and haematological parameters in patients with eating disorders (EDs) varied from the general population. Whilst dietary restrictions can lead to nutritional deficiencies, specific abnormalities may be relevant to the diagnosis, pathogenesis and treatment of EDs. With ethics approval and informed consent, a retrospective chart audit was conducted of 113 patients with EDs at a general practice in Brisbane, Australia. This was analysed first as a total group (TG) and then in 4 ED subgroups: Anorexia nervosa (AN), Bulimia nervosa (BN), ED Not Otherwise Specified (EDNOS), and AN/BN. Eighteen parameters were assessed at or near first presentation: cholesterol, folate, vitamin B12, magnesium, manganese, zinc, calcium, potassium, urate, sodium, albumin, phosphate, ferritin, vitamin D, white cell count, neutrophils, red cell count and platelets. Results were analysed using IBM SPSS 21 and Microsoft Excel 2013 by two-tailed, one-sample t-tests (TG and 4 subgroups) and chi-square tests (TG only) and compared to the population mean standards. Results for the TG and each subgroup individually were then compared with the known reference interval (RI). For the total sample, t-tests showed significant differences for all parameters ( p  < 0.05) except cholesterol. Most parameters gave results below population levels, but folate, phosphate, albumin, calcium and vitamin B12 were above. More patients than expected were below the RI for most parameters in the TG and subgroups. At diagnosis, in patients with EDs, there are often significant differences in multiple haematological and biochemical parameters. Early identification of these abnormalities may provide additional avenues of ED treatment through supplementation and dietary guidance, and may be used to reinforce negative impacts on health caused by the ED to the patient, their family and their treatment team (general practitioner, dietitian and mental

The Patient Remote Intervention and Symptom Management System (PRISMS) - a Telehealth- mediated intervention enabling real-time monitoring of chemotherapy side-effects in patients with haematological malignancies: study protocol for a randomised controlled trial.

PubMed

Breen, Sibilah; Ritchie, David; Schofield, Penelope; Hsueh, Ya-Seng; Gough, Karla; Santamaria, Nick; Kamateros, Rose; Maguire, Roma; Kearney, Nora; Aranda, Sanchia

2015-10-19

-and-paper self-report alongside review of the patient medical record. The primary outcome is burden due to nausea, mucositis, constipation and fatigue. Secondary outcomes include: burden due to vomiting and diarrhoea; psychological distress; ability to self-manage health; level of cancer information/support needs and; utilisation of health services. Analyses will be intention-to-treat. A cost-effectiveness analysis is planned. This trial is the first in the world to test a remote monitoring/management intervention for adult haematological cancer patients receiving chemotherapy. Future use of such interventions have the potential to improve patient outcomes/safety and decrease health care costs by enabling early detection/clinical intervention. ACTRN12614000516684 . Date registered: 12 March 2014 (registered retrospectively).

Selected haematological and plasma chemistry parameters in juvenile and adult degus (Octodon degus).

PubMed

Jekl, V; Hauptman, K; Jeklova, E; Knotek, Z

2011-07-16

Thirty-five juvenile (mean age 6.3 weeks) and 35 adult (mean age 2.0 years) healthy degus (Octodon degus) were studied to investigate selected haematological and plasma biochemistry parameters. Animals were anaesthetised with isoflurane, and blood was withdrawn from the cranial vena cava. Erythrocyte, haematocrit and neutrophil counts (including the percentage of neutrophils) were significantly higher in the adult degus than in the juveniles. In contrast, the reticulocyte count, mean corpuscular volume, mean corpuscular haemoglobin, number of platelets and percentage of lymphocytes were significantly lower in the adult animals. Total protein and globulin levels were significantly higher in the adult degus. The albumin:globulin ratio and plasma levels of urea nitrogen, cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, potassium, total calcium and inorganic phosphorus were significantly lower in adults than in juveniles.

Safety and Side Effect Profile of Liposome Bupivacaine (Exparel) in Peripheral Nerve Blocks.

PubMed

Ilfeld, Brian M; Viscusi, Eugene R; Hadzic, Admir; Minkowitz, Harold S; Morren, Michael D; Lookabaugh, Janice; Joshi, Girish P

2015-01-01

Liposome bupivacaine (Exparel) is a multivesicular liposomal formulation of bupivacaine currently approved in the United States for single-dose administration into the surgical site to provide postsurgical analgesia. This retrospective analysis examined safety data from clinical trials involving the off-label use of this formulation in peripheral nerve blocks. Data from 6 controlled (phases I-III) studies were compiled involving single-injection ankle, femoral nerve, and intercostal nerve blocks (2 each). Adverse events (AEs) were monitored for 1 to 30 days after study drug administration. Of 575 subjects, 335 received liposome bupivacaine (2-310 mg), 33 received bupivacaine HCl (75-125 mg), and 207 received normal saline (placebo). Overall, 76% of subjects receiving liposome bupivacaine experienced 1 or more AEs compared with 61% receiving bupivacaine HCl and 76% receiving placebo. The most frequently reported AEs among subjects receiving liposome bupivacaine were nausea, pyrexia, pruritus, constipation, and vomiting. The most common treatment-related AE was hypesthesia among subjects treated with liposome bupivacaine or bupivacaine HCl. Incidence of nervous system AEs for liposome bupivacaine, bupivacaine HCl, and placebo was 21%, 27%, and 21%, respectively. Similarly, incidence of cardiac AEs was 9%, 0%, and 12%, respectively. At least 1 serious AE occurred in 8% of subjects receiving liposome bupivacaine compared with 10% of those receiving placebo (none assessed by investigators as related to study medication). Liposome bupivacaine has a similar safety and side effect profile to bupivacaine HCl and normal saline, suggesting that most of the more common AEs are related to either opioid rescue or the surgical procedure itself.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

PubMed

Shamsi, T S; Irfan, M; Ansari, S H; Farzana, T; Khalid, M Z; Panjwani, V K; Baig, M I; Shakoor, N

2004-09-01

To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. A single centre descriptive study. Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five

Haematological indices as predictors of atrial fibrillation following isolated coronary artery bypass grafting, valvular surgery, or combined procedures: a systematic review with meta-analysis.

PubMed

Weymann, Alexander; Ali-Hasan-Al-Saegh, Sadeq; Popov, Aron-Frederik; Sabashnikov, Anton; Mirhosseini, Seyed Jalil; Liu, Tong; Tse, Gary; Lotfaliani, Mohammadreza; Ghanei, Azam; Testa, Luca; D'Ascenzo, Fabrizio; Benedetto, Umberto; Dehghan, Hamidreza; Roever, Leonardo; Sá, Michel Pompeu Barros de Oliveira; Baker, William L; Yavuz, Senol; Zeriouh, Mohamed; Mashhour, Ahmed; Nombela-Franco, Luis; Jang, Jae-Sik; Meng, Lei; Gong, Mengqi; Deshmukh, Abhishek J; Palmerini, Tullio; Linde, Cecilia; Filipiak, Krzysztof J; Biondi-Zoccai, Giuseppe; Calkins, Hugh; Stone, Gregg W

2018-01-01

New postoperative atrial fibrillation (POAF) is one of the most critical and common complications after cardio¬vascular surgery precipitating early and late morbidities. Complete blood count (CBC) is an imperative blood test in clinical practice, routinely used in the examination of cardiovascular diseases. This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of haematological indices in CBC tests with atrial fibrillation following isolated coronary artery bypass graft (CABG), isolated valvular surgery, or a combination of these treatments. We conducted a meta-analysis of studies evaluating pre- and postoperative haematological indices in patients with POAF. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. A literature search of all major databases retrieved 732 studies. After screening, 22 studies were analysed including a total of 6098 patients. Pooled analysis showed preoperative platelet count (PC) (weighted mean difference [WMD] = -7.07 × 109/L and p < 0.001), preoperative mean platelet volume (MPV) (WMD = 0.53 FL and p < 0.001), preoperative white blood cell count (WBC) (WMD = 0.130 × 109/L and p < 0.001), preoperative neutrophil-to-lymphocyte ratio (NLR) (WMD = 0.33 and p < 0.001), preoperative red blood cell distribution width (RDW) (WMD = 0.36% and p < 0.001), postoperative WBC (WMD = 1.36 × 109/L and p < 0.001), and postoperative NLR (WMD = 0.74 and p < 0.001) as associated factors with POAF. Haematological indices may predict the risk of POAF before surgery. These easily-performed tests should defi¬nitely be taken into account in patients undergoing isolated CABG, valvular surgery, or combined procedures.

Biochemical and haematological assessment of toxic effects of the leaf ethanol extract of Petroselinum crispum (Mill) Nyman ex A.W. Hill (Parsley) in rats.

PubMed

Awe, Emmanuel Olorunju; Banjoko, S Olatunbosun

2013-04-04

Petroselinum crispum, a bright green biennial shrub is widely used traditionally as a food additive and herbal remedies for many ailments. This study therefore aimed to assess the toxic effects of its leaf extract using some biochemical, haematological parameters. The toxic effects were assessed by quantifying liver enzymes such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total serum protein and liver weight. Effects on haematological parameters were assessed by analysis of parked cell volume (PCV), red blood cell count (RBC), white blood cells (WBC) and haemoglobin (Hb) concentrations. Histopathological studies were done on the liver and kidneys. The extract caused significant increase in serum activity of alanine amino transferase and blood urea nitrogen (BUN) levels at the dose of 1000 mg/kg. Other biochemical and haematological parameters were not affected at lower doses. Conversely, the liver weight was not affected after eight weeks of treatment at the dose levels studied. The organs obtained for pathological study, were structurally unchanged under histopathological evaluation at lower doses but inflammatory and necrotic features were observed at doses ≥ 1000 mg/kg. The results indicate that the leaf ethanol extract of Petroselinum crispum was hepatotoxic and nephrotoxic at continued oral doses equal to or more than 1000 mg/kg, but no obvious toxicity when used at lower doses. Therefore, there should be caution in its administration to avoid overdosing and known interaction with some medications. In addition, the plant should be kept away from pets and domestic animals and should not be cultivated on soil irrigated with waste water due to their ability to bio-accumulate toxic metals.

Body experience and mental representation of body image in patients with haematological malignancies and cancer as assessed with the Body Grid.

PubMed

Weber, C; Bronner, E; Thier, P; Schoeneich, F; Walter, O; Klapp, B F; Kingreen, D

2001-12-01

The domain of body image plays a central role in the quality of life of patients with haematological malignancies and metastasized cancer, since the disease itself as well as the enrolled therapies interfere with psychological and bodily well-being. We approached this highly subjective field by using the repertory grid technique and hypothesized that patients would display a restricted body image, focusing on functional aspects of the body. In all, 55 in-patients (27 men, 28 women, M age = 45.7 yrs, N = 46 with haematological malignancies, N = 9 with metastasized cancer), at the time of initial diagnosis, were included in the study and assessed with the Body Grid, an instrument specifically designed by us for the exploration of body image. The data were analysed by principal component analysis (PCA) and construct categorization. Further, 42 chronic tinnitus sufferers (20 male, 22 female, M age = 46.5 yrs) served as a comparison group. Based on the constructs elicited, six construct categories were formulated in the sense of a first attempt of a hierarchical model (emotion, control, activity, strength, function, appearance). The central constructs (373 construct pairs) were assigned to these categories by three inter-raters. The categories appeared in the following order of frequency: function (27.1%), emotion (20.4%), strength (20.1%), activity (15%), control (10.2%) and appearance (7.2%). PCA indicated that the patients mainly demonstrated a restricted view of their body. In the tinnitus group, the most frequent category proved to be activity (21.3%), closely followed by function (21.1%) and control (20.9%). The body image was also restricted (PCA). The restriction of body image, together with the specific construct choice, seen in the haematology and cancer patients reflects the existential threat of the disease and may serve as a coping strategy. The high percentage of emotional constructs may mirror the patients' need for further support. The distinct

Food safety knowledge and practices of abattoir and butchery shops and the microbial profile of meat in Mekelle City, Ethiopia

PubMed Central

Haileselassie, Mekonnen; Taddele, Habtamu; Adhana, Kelali; Kalayou, Shewit

2013-01-01

Objective To assess the food safety knowledge and practices in meat handling, and to determine microbial load and pathogenic organisms in meat at Mekelle city. Methods A descriptive survey design was used to answer questions concerning the current status of food hygiene and sanitation practiced in the abattoir and butcher shops. Workers from the abattoir and butcher shops were interviewed through a structured questionnaire to assess their food safety knowledge. Bacterial load was assessed by serial dilution method and the major bacterial pathogens were isolated by using standard procedures. Results 15.4% of the abattoir workers had no health certificate and there was no hot water, sterilizer and cooling facility in the abattoir. 11.3% of the butchers didn't use protective clothes. There was a food safety knowledge gap within the abattoir and butcher shop workers. The mean values of bacterial load of abattoir meat, butcher shops and street meat sale was found to be 1.1×105, 5.6×105 and 4.3×106 cfu/g, respectively. The major bacterial pathogens isolated were Escherichia coli, Staphylococcus aureus and Bacillus cereus. Conclusions The study revealed that there is a reasonable gap on food safety knowledge by abattoir and butcher shop workers. The microbial profile was also higher compared to standards set by World Health Organization. Due attention should be given by the government to improve the food safety knowledge and the quality standard of meat sold in the city. PMID:23646306

A systematic review on the relationship between the nursing shortage and nurses' job satisfaction, stress and burnout levels in oncology/haematology settings.

PubMed

Gi, Toh Shir; Devi, Kamala M; Neo Kim, Emily Ang

2011-01-01

Nursing shortage is a global issue that which affects oncology nursing. Oncology nurses are more prone to experience job dissatisfaction, stress and burnout when they work in units with poor staffing. There is thus a need for greater understanding of the relationship between the nursing shortage and nursing outcomes in oncology/haematology settings. This review aimed to establish the best available evidence concerning the relationship between the nursing shortage and nurses' job satisfaction, stress and burnout levels in oncology/haematology settings; and to make recommendations for practice and future research. Types of participants: This review considered studies that included oncology registered nurses (RNs) who were more than 18 years of age and worked in either inpatient or outpatient oncology/haematology wards or units for the adult or paediatric patients.Types of intervention: This review considered studies that evaluated the relationship between the nursing shortage and nurses' job satisfaction, stress and burnout levels in oncology/haematology settings.Types of outcomes: This review included studies that measured job satisfaction, stress and burnout levels using different outcomes measures. Job satisfaction was determined by the Measure of Job Satisfaction scale, the Misener Nurse Practitioner Job Satisfaction Scale and the Likert scale, stress by the Pediatric Oncology Nurse Stressor Questionnaire and burnout by the Maslash Burnout Inventory scale.Types of studies: This review included descriptive/descriptive-correlational studies which were published in English. The search strategy sought to identify published and unpublished studies conducted between 1990 and 2010. Using a three-step search strategy, the following databases were accessed: CINAHL, Medline, Scopus, ScienceDirect, PsycInfo, PsycArticles, Web of Science, The Cochrane Library, Proquest and Mednar. Two independent reviewers assessed each paper for methodological validity prior to inclusion in

Induction of ovarian function by using short-term human menopausal gonadotrophin in patients with ovarian failure following cytotoxic chemotherapy for haematological malignancy.

PubMed

Chatterjee, R; Mills, W; Katz, M; McGarrigle, H H; Goldstone, A H

1993-07-01

Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG).

Inherited disorders in the Afrikaner population of southern Africa. Part II. Skeletal, dermal and haematological conditions; the Afrikaners of Gamkaskloof; demographic considerations.

PubMed

Botha, M C; Beighton, P

1983-10-15

In addition to the genetic conditions reviewed in Part I of this article, sclerosteosis, spondyloepimetaphyseal dysplasia, lipoid proteinosis, keratolytic winter erythema and various haematological disorders also occur in high frequency in the Afrikaner community. The recognition of the presence of these serious inherited disorders is important in differential diagnosis and is fundamental to the establishment of public health programmes for amelioration and prevention.

Comprehensive haematological indices reference intervals for a healthy Omani population: First comprehensive study in Gulf Cooperation Council (GCC) and Middle Eastern countries based on age, gender and ABO blood group comparison.

PubMed

Al-Mawali, Adhra; Pinto, Avinash Daniel; Al-Busaidi, Raiya; Al-Lawati, Rabab H; Morsi, Magdi

2018-01-01

Reference intervals for venous blood parameters differs with age, gender, geographic region, and ethnic groups. Hence local laboratory reference intervals are important to improve the diagnostic accuracy of health assessments and diseases. However, there have been no comprehensive published reference intervals established in Oman, the Gulf Cooperation Council or Middle Eastern countries. Hence, the aim of this study was to establish reference intervals for full blood count in healthy Omani adults. Venous blood specimens were collected from 2202 healthy individuals aged 18 to 69 years from January 2012 to April 2017, and analysed by Sysmex XS-1000i and Cell-Dyn Sapphire automated haematology analysers. Results were statistically analysed and compared by gender, age, and ABO blood group. The lower and upper reference limits of the haematology reference intervals were established at the 2.5th and 97.5th percentiles respectively. Reference intervals were calculated for 17 haematology parameters which included red blood cell, white blood cell, and platelet parameters. Red blood cell (RBC), haemoglobin (HGB), haematocrit (HCT), platelet and platelet haematocrit counts of the healthy donors were significantly different between males and females at all ages (p < 0.05), with males having higher mean values of RBC, HGB and HCT than females. Other complete blood count parameters showed no significant differences between genders, age groups, instruments, or blood groups. Our study showed a lower haemoglobin limit for the normal reference interval in males and females than the currently used in Oman. Data from this study established specific reference intervals which could be considered for general use in Oman. The differences in haematology reference intervals highlights the necessity to establish reference intervals for venous blood parameters among the healthy population in each country or at least in each region.

Clinical trial designs to obtain marketing authorization of drugs for haematological malignancy in Japan, the EU and the US.

PubMed

Nagai, Sumimasa; Ozawa, Keiya

2016-07-01

Differences in regulatory actions between Japan, the European Union (EU) and the United States (US) regarding the approval date and primary endpoints of pivotal trials have never been analysed comprehensively. This study aimed to examine such differences in haematological malignancy indications not only in applications for new molecular entity agents but also in supplemental applications for additional indications. A total of 101 haematological malignancy indications were examined for 58 drugs. Only 30 indications were approved by the regulatory agencies of all three regions with 25, 9 and 67 indications being first approved in Japan, the EU and the US, respectively. Regarding the 18 indications approved only in the US, 13 were approved based on results of single-arm trials. The approval of all nine indications approved first in the EU was based on results of comparative trials. The primary endpoints were different between the EU and the US in 4 of 49 indications approved by both regulatory agencies, all of which were approved earlier in the US than in the EU. This analysis shows that the US Food and Drug Administration has taken the most active attitude to acceptance of surrogate endpoints in single-arm trials. Therefore, not only shorter review time but also this attitude may lead to earlier approval in US. © 2016 John Wiley & Sons Ltd.

Perceived need for information among patients with a haematological malignancy: associations with information satisfaction and treatment decision-making preferences.

PubMed

Rood, Janneke A J; van Zuuren, Florence J; Stam, Frank; van der Ploeg, Tjeerd; Eeltink, Corien; Verdonck-de Leeuw, Irma M; Huijgens, Peter C

2015-06-01

For patients with haematological malignancies, information on disease, prognosis, treatment and impact on quality of life is of the utmost importance. To gain insight into the perceived need for information in relation to sociodemographic and clinical parameters, comorbidity, quality of life (QoL) and information satisfaction, we compiled a questionnaire based on existing validated questionnaires. A total of 458 patients diagnosed with a haematological malignancy participated. The perceived need for information was moderate to high (40-70%). Multivariate regression analyses showed that a higher need for information was related to younger age, worse QoL, being member of a patient society and moderate comorbidity. The need for disease and treatment-related information was higher than the need for psychosocial information. A higher need for disease and treatment-related information was associated to being diagnosed with multiple myeloma. A higher need for psychosocial information was related to a lower educational level. The information provision could be improved according to 41% of the patients. Higher satisfaction with provided information was associated with better QoL. Most patients (62%) reported that they wanted to be fully informed about their illness and actively involved in treatment decision-making. The results contribute to improving patient-tailored information provision and shared decision-making in clinical practice. Copyright © 2014 John Wiley & Sons, Ltd.

Haematological, biochemical and histopathological aspects of Hericium erinaceus ingestion in a rodent model: A sub-chronic toxicological assessment.

PubMed

Lakshmanan, Hariprasath; Raman, Jegadeesh; David, Pamela; Wong, Kah-Hui; Naidu, Murali; Sabaratnam, Vikineswary

2016-12-24

Hericium erinaceus is a culinary-medicinal mushroom and has a long history of usage in traditional Chinese medicine as a tonic for stomach disorders, ulcers and gastrointestinal ailments. The present investigation was aimed to evaluate the potential toxic effects of the aqueous extract from the fruiting bodies of H. erinaceus in rats by a sub-chronic oral toxicity study. In this sub-chronic toxicity study, rats were orally administered with the aqueous extract of H. erinaceus (HEAE) at doses of 250, 500 and 1000mg/kg body weight (b.w.) for 90 days. Body weights were recorded on a weekly basis and general behavioural changes were observed. The blood samples were subjected to haematological, biochemical, serum electrolyte, and antioxidant enzyme estimations. The rats were sacrificed and organs were processed and examined for histopathological changes. No mortality or morbidity was observed in all the treated and control rats. The results showed that the oral administration of HEAE daily at three different doses for 90 days had no adverse effect on the general behaviour, body weight, haematology, clinical biochemistry, and relative organ weights. Histopathological examination at the end of the study showed normal architecture except for few non-treatment related histopathological changes observed in liver, heart and spleen. The results of this sub-chronic toxicity study provides evidence that oral administration of HEAE is safe up to 1000mg/kg and H. erinaceus consumption is relatively non-toxic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Massive Online Needs Assessment (MONA) to inform the development of an emergency haematology educational blog series.

PubMed

Chan, Teresa M; Jo, David; Shih, Andrew W; Bhagirath, Vinai C; Castellucci, Lana A; Yeh, Calvin; Thoma, Brent; Tseng, Eric K; de Wit, Kerstin

2018-06-01

Online educational resources are criticized as being teacher-centred, failing to address learner's needs. Needs assessments are an important precursor to inform curriculum development, but these are often overlooked or skipped by developers of online educational resources due to cumbersome measurement tools. Novel methods are required to identify perceived and unperceived learning needs to allow targeted development of learner-centred curricula. To evaluate the feasibility of performing a novel technique dubbed the Massive Online Needs Assessment (MONA) for the purpose of emergency haematology online educational curricular planning, within an online learning community (affiliated with the Free Open Access Medical education movement). An online survey was launched on CanadiEM.org using an embedded Google Forms survey. Participants were recruited using the study website and a social media campaign (utilizing Twitter, Facebook, Blogs, and a poster) targeting a specific online community. Web analytics were used to monitor participation rates in addition to survey responses. The survey was open from 20 September to 10 December 2016 and received 198 complete responses representing 6 medical specialties from 21 countries. Most survey respondents identified themselves as staff physicians (n = 109) and medical trainees (n = 75). We identified 17 high-priority perceived needs, 17 prompted needs, and 10 topics with unperceived needs through our MONA process. A MONA is a feasible, novel method for collecting data on perceived, prompted, and unperceived learning needs to inform an online emergency haematology educational blog. This methodology could be useful to the developers of other online education resources.

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

PubMed

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

PubMed

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

2017-01-01

Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.

Biochemical and haematological assessment of toxic effects of the leaf ethanol extract of Petroselinum crispum (Mill) Nyman ex A.W. Hill (Parsley) in rats

PubMed Central

2013-01-01

Background Petroselinum crispum, a bright green biennial shrub is widely used traditionally as a food additive and herbal remedies for many ailments. This study therefore aimed to assess the toxic effects of its leaf extract using some biochemical, haematological parameters. Methods The toxic effects were assessed by quantifying liver enzymes such as serum aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total serum protein and liver weight. Effects on haematological parameters were assessed by analysis of parked cell volume (PCV), red blood cell count (RBC), white blood cells (WBC) and haemoglobin (Hb) concentrations. Histopathological studies were done on the liver and kidneys. Results The extract caused significant increase in serum activity of alanine amino transferase and blood urea nitrogen (BUN) levels at the dose of 1000 mg/kg. Other biochemical and haematological parameters were not affected at lower doses. Conversely, the liver weight was not affected after eight weeks of treatment at the dose levels studied. The organs obtained for pathological study, were structurally unchanged under histopathological evaluation at lower doses but inflammatory and necrotic features were observed at doses ≥ 1000 mg/kg. Conclusion The results indicate that the leaf ethanol extract of Petroselinum crispum was hepatotoxic and nephrotoxic at continued oral doses equal to or more than 1000 mg/kg, but no obvious toxicity when used at lower doses. Therefore, there should be caution in its administration to avoid overdosing and known interaction with some medications. In addition, the plant should be kept away from pets and domestic animals and should not be cultivated on soil irrigated with waste water due to their ability to bio-accumulate toxic metals. PMID:23557241

Tales from the Jazz ASH: highlights from the 2013 American Society of Haematology meeting.

PubMed

Mazzarella, Luca

2014-01-01

The 55th annual ASH meeting was held in pleasant New Orleans and was the largest in its history, with 22,495 participants coming from 113 nations. A 'bench-to-bedside and back' attitude characterises haematology probably more than any other discipline in medicine and, as usual, this was reflected in the extremely wide breadth of the topics covered, including the last results from clinical trials and cutting-edge advancements in basic science. This year, the balance was arguably skewed: few truly clinical practice-changing results were presented. On the other hand, a great number of basic and translational studies significantly increased our understanding of the biology of numerous malignancies and heralded the coming of age of disruptive technologies. Namely, above all, next generation sequencing and T cell engineering-based cell therapy.

An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the Microarray Innovations in LEukemia study prephase

PubMed Central

Kohlmann, Alexander; Kipps, Thomas J; Rassenti, Laura Z; Downing, James R; Shurtleff, Sheila A; Mills, Ken I; Gilkes, Amanda F; Hofmann, Wolf-Karsten; Basso, Giuseppe; Dell’Orto, Marta Campo; Foà, Robin; Chiaretti, Sabina; De Vos, John; Rauhut, Sonja; Papenhausen, Peter R; Hernández, Jesus M; Lumbreras, Eva; Yeoh, Allen E; Koay, Evelyn S; Li, Rachel; Liu, Wei-min; Williams, Paul M; Wieczorek, Lothar; Haferlach, Torsten

2008-01-01

Gene expression profiling has the potential to enhance current methods for the diagnosis of haematological malignancies. Here, we present data on 204 analyses from an international standardization programme that was conducted in 11 laboratories as a prephase to the Microarray Innovations in LEukemia (MILE) study. Each laboratory prepared two cell line samples, together with three replicate leukaemia patient lysates in two distinct stages: (i) a 5-d course of protocol training, and (ii) independent proficiency testing. Unsupervised, supervised, and r2 correlation analyses demonstrated that microarray analysis can be performed with remarkably high intra-laboratory reproducibility and with comparable quality and reliability. PMID:18573112

The use of body condition and haematology to detect widespread threatening processes in sleepy lizards (Tiliqua rugosa) in two agricultural environments.

PubMed

Smyth, Anita K; Smee, Elizabeth; Godfrey, Stephanie S; Crowther, Mathew; Phalen, David

2014-12-01

Agricultural practices, including habitat alteration and application of agricultural chemicals, can impact wildlife resulting in their decline. Determining which of these practices are contributing to declines is essential if the declines are to be reversed. In this study, the health of two geographically separated sleepy lizard (Tiliqua rugosa) populations was compared between a rangeland environment and cropping environment using linear body size index (LBSI) and haematology. Animals in the cropping site were smaller, suggesting genetic differences as the result of geographical isolation. The animals in the cropping site had a lower LBSI and many were experiencing a regenerative anaemia. The anaemia was postulated to be the cause of the low LBSI. The anaemia appeared to be the result of haemolysis and was likely to be caused by exposure to agricultural chemicals applied in the cropping site but not the rangeland site. Elevated white blood cell counts in lizards in the rangeland site suggested that they were experiencing an inflammatory disease of possible ecological significance. Together, these results demonstrate the value of combining physical and haematological parameters when studying the impact of agricultural practices on wildlife. They also show that reptiles may be useful as sentinel species for livestock and humans.

Safety profile of topical VEGF neutralization at the cornea.

PubMed

Bock, Felix; Onderka, Jasmine; Rummelt, Carmen; Dietrich, Tina; Bachmann, Björn; Kruse, Friedrich E; Schlötzer-Schrehardt, Ursula; Cursiefen, Claus

2009-05-01

Bevacizumab eyedrops inhibit corneal neovascularization. The purpose of this study was to analyze the safety profile of VEGF-A neutralization at the ocular surface. Bevacizumab eyedrops (5 mg/mL) and an antimurine VEGF-A antibody (250 microg/mL) were applied to normal murine corneas five times a day for 7 and 14 days. Subsequently, corneas were analyzed for morphologic changes by light and electron microscopy. In a mouse model of corneal epithelial abrasion, the effects of topically applied anti-VEGF antibodies on epithelial wound healing were analyzed: the treatment group received bevacizumab (5 mg/mL) or the antimurine VEGF-A antibody (250 microg/mL) as eyedrops, and the control group received an equal volume of saline solution. After 12, 18, and 24 hours, corneas were photographed in vivo with and without fluorescein staining for morphometry. Afterwards the mice were killed, and eyes were removed for histology, immunohistochemistry with Ki67/DAPI, and electron microscopy. The effect of midterm anti-VEGF therapy on corneal nerve density was assessed by staining corneas treated with an FITC-conjugated anti-neurofilament antibody and morphometric analysis. Murine corneas treated with two different types of anti-VEGF antibody eyedrops did not show obvious corneal morphologic changes at the light and electron microscopic levels. Furthermore, anti-VEGF antibody eyedrops had no significant impact on the wound healing process after corneal epithelial injury or on normal murine corneal nerve fiber density. Topical neutralization of VEGF-A at the corneal surface does not have significant side effects on normal corneal epithelial wound healing, normal corneal integrity, or normal nerve fiber density. Therefore, anti-VEGF eyedrops seem to be a relatively safe option to treat corneal neovascularization.

A safety study of oral tangeretin and xanthohumol administration to laboratory mice.

PubMed

Vanhoecke, Barbara W; Delporte, Femke; Van Braeckel, Eva; Heyerick, Arne; Depypere, Herman T; Nuytinck, Margareta; De Keukeleire, Denis; Bracke, Marc E

2005-01-01

The detection of molecular targets for flavonoids in cell signalling has opened new perspectives for their application in medicine. Both tangeretin, a citrus methoxyflavone, and xanthohumol, the main prenylated chalcone present in hops (Humulus lupulus L.), act on the mitogen-activated protein kinase pathway and await further investigation for administration in vivo. A safety study was designed in laboratory mice orally administered concentrates of purified tangeretin (1 x 10(-4) M) or xanthohumol (5 x 10(-4) M) at libitum for 4 weeks. Blood samples were collected for the analysis of a variety of haematological and biochemical parameters. A reduction of the circulating lymphocyte number was noticed for tangeretin, while all other parameters were unaffected by treatment with either tangeretin or xanthohumol. The parameters encompassed an integrity check of the following tissues and organs: bone marrow, liver, exocrine pancreas, kidneys, muscles, thyroid, ovaries and surrenal cortex. Furthermore, no differences were noted in the metabolism of proteins, lipids, carbohydrates and uric acid, as well as in ion concentrations. All data indicate that oral administration of tangeretin or xanthohumol to laboratory mice does not affect major organ functions and opens the gate for further safety studies in humans.

Safety and Pharmacokinetic Profiles of Repeated-Dose Micafungin in Children and Adolescents Treated for Invasive Candidiasis

PubMed Central

Benjamin, Daniel K.; Deville, Jaime G.; Azie, Nkechi; Kovanda, Laura; Roy, Mike; Wu, Chunzhang; Arrieta, Antonio

2013-01-01

Background Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida species. Objective To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable, or suspected invasive candidiasis. Methods Micafungin safety and pharmacokinetics were assessed in two Phase I, open-label, repeat-dose trials. In Study 2101, children aged 2–16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10–14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. Results Safety was analyzed in seventy-eight and nine children in Studies 2101 and 2102, respectively. Although adverse events were experienced by most children (2101: n = 62; 2102: n = 9), micafungin-related adverse events were less common (2101: n = 28; 2102: n = 1), and the number of patients discontinuing due to adverse events was low (2101: n = 4; 2102: n = 1). The most common micafungin-related adverse events were infusion-associated symptoms, pyrexia, and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. Conclusions In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support U.S. dosing recommendations in children. PMID:23958810

Avascular necrosis after chemotherapy for haematological malignancy in childhood.

PubMed

Salem, K H; Brockert, A-K; Mertens, R; Drescher, W

2013-12-01

Avascular necrosis (AVN) is a serious complication of high-dose chemotherapy for haematological malignancy in childhood. In order to describe its incidence and main risk factors and to evaluate the current treatment options, we reviewed 105 children with a mean age of 8.25 years (1 to 17.8) who had acute lymphoblastic or acute myeloid leukaemia, or a non-Hodgkin's lymphoma. Overall, eight children (7.6%) developed AVN after a mean of 16.8 months (8 to 49). There were four boys and four girls with a mean age of 14.4 years (9.8 to 16.8) and a total of 18 involved sites, 12 of which were in the femoral head. All these children were aged > nine years (p < 0.001). All had received steroid treatment with a mean cumulative dose of prednisone of 5967 mg (4425 to 9599) compared with a mean of 3943 mg (0 to 18 585) for patients without AVN (p = 0.005). No difference existed between genders and no thrombophilic disorders were identified. Their initial treatment included 11 core decompressions and two bipolar hip replacements. Later, two salvage osteotomies were done and three patients (four hips) eventually needed a total joint replacement. We conclude that AVN mostly affects the weight-bearing epiphyses. Its risk increases with age and higher steroid doses. These high-risk patients may benefit from early screening for AVN.

Quality specification in haematology: the automated blood cell count.

PubMed

Buttarello, Mauro

2004-08-02

Quality specifications for automated blood cell counts include topics that go beyond the traditional analytic stage (imprecision, inaccuracy, quality control) and extend to pre- and post-analytic phases. In this review pre-analytic aspects concerning the choice of anticoagulants, maximum conservation times and differences between storage at room temperature or at 4 degrees C are considered. For the analytic phase, goals for imprecision and bias obtained with various approaches (ratio to biologic variation, state of the art, specific clinical situations) are evaluated. For the post-analytic phase, medical review criteria (algorithm, decision limit and delta check) and the structure of the report (general part and comments), which constitutes the formal act through which a laboratory communicates with clinicians, are considered. K2EDTA is considered the anticoagulant of choice for automated cell counts. Regarding storage, specimens should be analyzed as soon as possible. Storage at 4 degrees C may stabilize specimens from 24 to 72 h when complete blood count (CBC) and differential leucocyte count (DLC) is performed. For precision, analytical goals based on the state of the art are acceptable while for bias this is satisfactory only for some parameters. In haematology quality specifications for pre- and analytical phases are important, but the review criteria and the quality of the report play a central role in assuring a definite clinical value.

Current trends in the management of anaemia in solid tumours and haematological malignancies.

PubMed

van Eeden, Ronwyn; Rapoport, Bernardo L

2016-06-01

Anaemia is a common problem in patients with solid tumors and haematological malignancies. Certain cancer therapies also contribute to anaemia. This article reviews the pathophysiology of cancer-related anaemia, investigation of a cancer patient with anaemia as well as how anaemia impacts patients in terms of quality of life, disease-related outcomes and treatment choices. Different treatments for anaemia include transfusions, erythropoiesis-stimulating agents (ESA) and iron therapy. Within this context, we review the advantages and disadvantages concerning anaemia management in cancer patients as well as the risk-benefit ratio of different treatment choices, particularly the increased risk of thromboembolic events of ESAs and concern around mortality and effect on tumor growth. This review is aimed at guiding treating physicians to make the best evidence-based treatment choices according to the product label and according to current guidelines for patients with cancer-related anaemia.

Bilaterally cleft lip, limb defects, and haematological manifestations: Roberts syndrome versus TAR syndrome.

PubMed

Urban, M; Opitz, C; Bommer, C; Enders, H; Tinschert, S; Witkowski, R

1998-09-23

We report on a 13-year-old patient followed since birth. He is the only offspring of young, non-consanguineous German parents. His mother has an isolated left cleft of lip and a cleft palate. At birth, our patient presented with bilaterally cleft lip/cleft palate, phocomelia of upper limbs with normal hands, and mild symmetrical deficiencies of the long bones of the lower limbs. Haematological evaluation demonstrated a leukaemoid reaction during a urinary tract infection as well as intermittent thrombocytopenia and episodes of marked eosinophilia during the first two years of life. Intellectual development has been normal. Comparison with two similar cases from the literature suggests a non-random phenotypic overlap of Roberts syndrome (MIM 268300) and TAR syndrome (MIM 274000). Such clinical constellations may be key observations to understand the genetic relationship of Roberts syndrome and TAR syndrome in future phenotype-genotype correlations.

Haematological alterations in Rattus norvegicus (Wistar) experimentally infected with Echinostoma paraensei (Trematoda: Echinostomatidae).

PubMed

Garcia, J S; Pinheiro, J; Hooper, C S; Simões, R O; Ferraz, J S; Maldonado, A

2012-07-01

Laboratory rats (Rattus norvegicus) were infected with Echinostoma paraensei (Trematoda: Echinostomatidae). The rodents received 150 metacercariae each and blood samples were collected weekly until the fifth week of infection. The blood samples were analyzed for determination of haematocrit, total red blood cells with their dimensions, haemoglobin and haematimetric index (mean corpuscular volume, MCV; mean corpuscular haemoglobin, MCH; and mean corpuscular haemoglobin concentration, MCHC) and platelets. Red blood cells, haematocrit and haemoglobin in the first week had significantly lower levels than those of uninfected (control) rats, suggesting the development of normocytic and normocromic anaemia with anisocytic alteration. The number of eosinophils did not increase significantly among the groups. We concluded that E. paraensei produces haematological alterations in R. norvegicus, causing regenerative anaemia. This system can therefore be a useful model to study the direct and indirect effects of gastrointestinal infections. Copyright © 2012 Elsevier Inc. All rights reserved.

Effect of petroleum products inhalation on some haematological indices of fuel attendants in Calabar metropolis, Nigeria.

PubMed

Okoro, A M; Ani, E J; Ibu, J O; Akpogomeh, B A

2006-01-01

The Haematotoxic implications of exposure to petroleum fumes through inhalation in human subjects were investigated. A total of 400 subjects (200 males and 200 females) aged between 18-30 years participated. Each gender was further categorized into two groups of 100 each for control and test, respectively. The test group was again subdivided into test 1 (T1) and test 2 (T2) in both sexes. T1 subjects were exposed to petroleum fumes for two years and below while T2 subjects were exposed for more than two years. Samples of blood were collected daily and subjected to haematological analysis. The results obtained showed that in males and females, red blood cell counts (10(6) /mm3) was significantly [P < 0.001] decreased in T1 (4.4 +/- 0.13) and T2 (3.85 +/- 0.07) compared to control (4.76 +/- 0.01). White blood cell counts, haematocrit, haemoglobin concentration and mean corpusclular haemoglobin concentration (MCHC) were significantly [P < 0.01] decreased in both sexes of test groups when compared with control. There was also a significant [P < 0.001] decrease in mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) in test 2 males compared with control. Most subjects exposed for longer than two years (T2) had significantly [P < 0.001] lower values of red blood cell count, haemoglobin concentration and haematocrit than those exposed for less than two years. The odds/odds ratio that a subject would become anaemic progressively rose from less than 1 in the control to greater than 1 or infinity on exposure to petroleum fumes. These results indicate that the petroleum fumes cause a reduction in haematological indices which worsens with prolonged exposure.

Developing patient safety in dentistry.

PubMed

Pemberton, M N

2014-10-01

Patient safety has always been important and is a source of public concern. Recent high profile scandals and subsequent reports, such as the Francis report into the failings at Mid Staffordshire, have raised those concerns even higher. Mortality and significant morbidity associated with the practice of medicine has led to many strategies to help improve patient safety, however, with its lack of associated mortality and lower associated morbidity, dentistry has been slower at systematically considering how patient safety can be improved. Recently, several organisations, researchers and clinicians have discussed the need for a patient safety culture in dentistry. Strategies are available to help improve patient safety in healthcare and deserve further consideration in dentistry.

Analysis of some biochemical and haematological parameters for Mucuna pruriens (DC) seed powder in male rats.

PubMed

Chukwudi, Ndukwe Henry; Simeon, Omale; Chinyere, Aguiyi John

2011-10-01

The biochemical and haematological effects of the seed powder of Mucuna pruriens in male rats were evaluated to establish some biological properties of this potential biopesticide currently undergoing investigation. The result showed that Mucuna pruriens seed extract produced a significant (p<0.05) increase in white blood cell (WBC) count, as well as in bilirubin concentrations, alkaline phosphatase (ALP), protein and creatinine levels measured. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly reduced (P<0.05) in comparison with the experimental control. PCV, Hb, albumin level and WBC differential counts gave no significant difference between treated and control groups. The results revealed metabolic imbalance in the rats which suggests a mild cholestasis effect of the extract.

21 CFR 601.35 - Evaluation of safety.

Code of Federal Regulations, 2010 CFR

2010-04-01

... established, low-risk profile). Upon reviewing the relevant product characteristics and safety information..., carrier, or ligand; (3) The risks of an incorrect diagnostic determination; (4) The adverse reaction profile of the drug; (5) Results of human experience with the radiopharmaceutical for other uses; and (6...

Applications of aerospace technology in industry, a technology transfer profile: Fire safety

NASA Technical Reports Server (NTRS)

Kottenstette, J. P.; Freeman, J. E.; Heins, C. R.; Hildred, W. M.; Johnson, F. D.; Staskin, E. R.

1971-01-01

The fire safety field is considered as being composed of three parts: an industry, a technology base, and a user base. An overview of the field is presented, including a perspective on the magnitude of the national fire safety problem. Selected NASA contributions to the technology of fire safety are considered. Communication mechanisms, particularly conferences and publications, used by NASA to alert the community to new developments in the fire safety field, are reviewed. Several examples of nonaerospace applications of NASA-generated fire safety technology are also presented. Issues associated with attempts to transfer this technology from the space program to other sectors of the American economy are outlined.

Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support

PubMed Central

Estcourt, Lise J; Malouf, Reem; Trivella, Marialena; Fergusson, Dean A; Hopewell, Sally; Murphy, Michael F

2017-01-01

Background Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies. Objectives To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). Search methods We searched for randomised controlled trials (RCTs) and non-randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status. Selection criteria We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT. Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results

Profiles of Bullying Victimization, Discrimination, Social Support, and School Safety: Links with Latino/a Youth Acculturation, Gender, Depressive Symptoms, and Cigarette Use

PubMed Central

Lorenzo-Blanco, Elma I.; Unger, Jennifer B.; Oshri, Assaf; Baezconde-Garbanati, Lourdes; Soto, Daniel

2016-01-01

Latino/a youth are at risk for symptoms of depression and cigarette smoking but this risk varies by acculturation and gender. To understand why some youth are at greater risk than others, we identified profiles of diverse community experiences (perceived discrimination, bullying victimization, social support, perceived school safety) and examined associations between profiles of community experience and depressive symptoms, cigarette smoking, acculturation, and gender. Data came from Project Red (Reteniendo y Entendiendo Diversidad para Salud), a school-based longitudinal study of acculturation among 1919 Latino/a adolescents (52% female; 84% 14 years old; 87% U.S. born). Latent profile analysis (LPA) revealed four distinct profiles of community experience which varied by gender and acculturation. Boys were overrepresented in profile groups with high perceived discrimination, some bullying, and lack of positive experiences, while girls were overrepresented in groups with high bullying victimization in the absence and presence of other community experiences. Youth low on both U.S. and Latino/a cultural orientation described high perceived discrimination and lacked positive experiences, and were predominantly male. Profiles characterized by high perceived discrimination and/or high bullying victimization in the absence of positive experiences had higher levels of depressive symptoms and higher risk of smoking, relative to the other groups. Findings suggest that acculturation comes with diverse community experiences that vary by gender and relate to smoking and depression risk. Results from this research can inform the development of tailored intervention and prevention strategies to reduce depression and/or smoking for Latino/a youth at risk for depression and/or smoking. PMID:26752445

Profiles of bullying victimization, discrimination, social support, and school safety: Links with Latino/a youth acculturation, gender, depressive symptoms, and cigarette use.

PubMed

Lorenzo-Blanco, Elma I; Unger, Jennifer B; Oshri, Assaf; Baezconde-Garbanati, Lourdes; Soto, Daniel

2016-01-01

Latino/a youth are at risk for symptoms of depression and cigarette smoking but this risk varies by acculturation and gender. To understand why some youth are at greater risk than others, we identified profiles of diverse community experiences (perceived discrimination, bullying victimization, social support, perceived school safety) and examined associations between profiles of community experience and depressive symptoms, cigarette smoking, acculturation, and gender. Data came from Project Red (Reteniendo y Entendiendo Diversidad para Salud), a school-based longitudinal study of acculturation among 1,919 Latino/a adolescents (52% female; 84% 14 years old; 87% U.S. born). Latent profile analysis (LPA) revealed 4 distinct profiles of community experience that varied by gender and acculturation. Boys were overrepresented in profile groups with high perceived discrimination, some bullying, and lack of positive experiences, while girls were overrepresented in groups with high bullying victimization in the absence and presence of other community experiences. Youth low on both U.S. and Latino/a cultural orientation described high perceived discrimination and lacked positive experiences, and were predominantly male. Profiles characterized by high perceived discrimination and /or high bullying victimization in the absence of positive experiences had higher levels of depressive symptoms and higher risk of smoking, relative to the other groups. Findings suggest that acculturation comes with diverse community experiences that vary by gender and relate to smoking and depression risk. Results from this research can inform the development of tailored intervention and prevention strategies to reduce depression and/or smoking for Latino/a youth. (c) 2016 APA, all rights reserved).

Curriculum Design of a Flipped Classroom to Enhance Haematology Learning

NASA Astrophysics Data System (ADS)

Porcaro, Pauline A.; Jackson, Denise E.; McLaughlin, Patricia M.; O'Malley, Cindy J.

2016-06-01

A common trend in higher education is the "flipped" classroom, which facilitates active learning during class. The flipped approach to teaching was instituted in a haematology `major' class and the students' attitudes and preferences for the teaching materials were surveyed. The curriculum design was explicit and involved four major components (1) the preparation of the students; (2) the weekly pre-class work; (3) the in-class active learning strategies and (4) closing the learning loop using formative quizzes. Each of these components is discussed in detail and was informed by sound pedagogical strategies. Several different sources of information and several freely available software tools to engage the students are discussed. Two iterations are reported here, with improved pass rate for the final examination from 47 to 48 % in the traditional class to 56-65 % in the flipped classroom approach. The majority of students (93 and 89 %) came to the class prepared, after viewing the screencasts and engaged fully with the activities within the face-to-face time. The students perceived that solving case studies (93 %) was the most beneficial activity for their learning and this was closely followed by the production of essay plans (71 %). The majority of students recommended that this approach be repeated the following year (69 and 75 %).

First UK trial of Xenex PX-UV, an automated ultraviolet room decontamination device in a clinical haematology and bone marrow transplantation unit.

PubMed

Beal, A; Mahida, N; Staniforth, K; Vaughan, N; Clarke, M; Boswell, T

2016-06-01

There is growing interest in the use of no-touch automated room decontamination devices within healthcare settings. Xenex PX-UV is an automated room disinfection device using pulsed ultraviolet (UV) C radiation with a short cycle time. To investigate the microbiological efficacy of this device when deployed for terminal decontamination of isolation rooms within a clinical haematology unit. The device was deployed in isolation rooms in a clinical haematology unit. Contact plates were applied to common touch points to determine aerobic total colony counts (TCCs) and samples collected using Polywipe™ sponges for detection of vancomycin-resistant enterococci (VRE). The device was easy to transport, easy to use, and it disinfected rooms rapidly. There was a 76% reduction in the TCCs following manual cleaning, with an additional 14% reduction following UV disinfection, resulting in an overall reduction of 90% in TCCs. There was a 38% reduction in the number of sites where VRE was detected, from 26 of 80 sites following manual cleaning to 16 of 80 sites with additional UV disinfection. The Xenex PX-UV device can offer a simple and rapid additional decontamination step for terminal disinfection of patient rooms. However, the microbiological efficacy against VRE was somewhat limited. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Neural network evaluation of tokamak current profiles for real time control

NASA Astrophysics Data System (ADS)

Wróblewski, Dariusz

1997-02-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q0, minimum value of q, qmin, and the location of qmin. Very good performance of the trained neural network both for simulated test data and for experimental datais demonstrated.

Safety assessment of adjuvanted vaccines: Methodological considerations

PubMed Central

Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

2015-01-01

Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

Safety profile comparison between extemporaneous and a licensed preparation of caffeine citrate in preterm infants with apnea of prematurity.

PubMed

Vatlach, Scarlet; Arand, Joerg; Engel, Corinna; Poets, Christian F

2014-01-01

Given the lack of a licensed product (LP), extemporaneous caffeine citrate (ECC) has been used by many hospital pharmacies. Since July 2011, an LP has been available in Germany. We prospectively compared the safety profile of ECC and LP in preterm infants with apnea of prematurity. Between April 2010 and April 2013, selected side effects occurring with ECC or LP were documented in 6 German NICUs for infants ≤34 weeks' gestation using a longitudinal study design. The software developed for daily prescriptions in NICU residents requires entries if any of the following symptoms occurred during the last 24 h: tachycardia (resting heart rate >200/min), clinical or encephalographic seizures, gastric residuals, vomiting, or necrotizing enterocolitis (NEC). ECC and LP were administered at identical doses (20 mg/kg/day loading, 5-10 mg/kg/day maintenance) and in similar formulations either orally or intravenously. 562 infants with 14,590 treatment days on ECC and 538 infants with 12,813 treatment days on LP were evaluated. The mean gestational age was similar (29.20 weeks for ECC vs. 29.14 weeks for LP). No relevant differences were seen concerning tachycardia, gastric residuals, or vomiting, but ECC was associated with a higher risk of NEC (risk ratio: 2.68, 95% CI: 1.01-7.23, p = 0.047) and, albeit not significantly so, seizures (risk ratio: 1.91, 95% CI: 0.53-6.96, p = 0.35). This survey demonstrates a similar safety profile for both forms of caffeine citrate. The lower NEC and seizure rate seen with the LP is intriguing, but requires confirmation in a controlled study design. © 2013 S. Karger AG, Basel.

Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia.

PubMed

Botzenhardt, Sebastian; Sing, Chor W; Wong, Ian C K; Chan, Godfrey Chi-Fung; Wong, Lisa Y L; Felisi, Mariagrazia; Rascher, Wolfgang; Ceci, Adriana; Neubert, Antje

2016-01-01

There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal. • Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.

Managing risk in healthcare: understanding your safety culture using the Manchester Patient Safety Framework (MaPSaF).

PubMed

Parker, Dianne

2009-03-01

To provide sufficient information about the Manchester Patient Safety Framework (MaPSaF) to allow healthcare professionals to assess its potential usefulness. The assessment of safety culture is an important aspect of risk management, and one in which there is increasing interest among healthcare organizations. Manchester Patient Safety Framework offers a theory-based framework for assessing safety culture, designed specifically for use in the NHS. The framework covers multiple dimensions of safety culture, and five levels of safety culture development. This allows the generation of a profile of an organization's safety culture in terms of areas of relative strength and challenge, which can be used to identify focus issues for change and improvement. Manchester Patient Safety Framework provides a useful method for engaging healthcare professionals in assessing and improving the safety culture in their organization, as part of a programme of risk management.

Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies.

PubMed

Giovannoni, Gavin; Kappos, Ludwig; Gold, Ralf; Khatri, Bhupendra O; Selmaj, Krzysztof; Umans, Kimberly; Greenberg, Steven J; Sweetser, Marianne; Elkins, Jacob; McCroskery, Peter

2016-09-01

Daclizumab has been evaluated in multicentre, randomised, double-blind studies for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS). Safety and tolerability are key considerations in MS treatment selection, as they influence adherence to medication. Evaluate the safety of daclizumab in patients with RRMS from an integrated analysis of six clinical studies. Patients treated with at least one dose of subcutaneous daclizumab 150mg or 300mg monthly in three completed and three ongoing clinical studies were included in this integrated analysis. Cumulative incidence of treatment-emergent adverse events (AEs) was the primary endpoint. This analysis included 2236 patients with 5214 patient-years of exposure to daclizumab. The cumulative incidence of any AE was 84% and of any serious AE excluding MS relapse was 16%. The incidences of AEs when evaluated by 6-month intervals remained stable over the 6.5 years of maximum follow-up. Most AEs were mild or moderate in severity. An important safety concern associated with daclizumab therapy involved hepatic AEs (16%) and serum transaminase elevations at least three times the upper limit of normal (10%), most of which were asymptomatic, self-limiting, and non-recurring. Cumulative incidences of cutaneous, infectious, and gastrointestinal AEs were 33%, 59%, and 25%, respectively; most events either resolved spontaneously or were treated successfully with standard medical interventions and did not result in discontinuation of treatment. This integrated analysis demonstrates that treatment of RRMS with daclizumab for periods of up to 6.5 years is associated with an acceptable safety profile with no evidence of cumulative toxicity over time. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Pentraxin 3 predicts complicated course of febrile neutropenia in haematological patients, but the decision level depends on the underlying malignancy.

PubMed

Juutilainen, Auni; Vänskä, Matti; Pulkki, Kari; Hämäläinen, Sari; Nousiainen, Tapio; Jantunen, Esa; Koivula, Irma

2011-11-01

This study aimed at assessing the cut-off levels for pentraxin 3 (PTX3) in predicting complications of neutropenic fever (bacteraemia, septic shock) in haematological patients. A prospective study during 2006-2009 was performed at haematology ward in Kuopio University Hospital. A patient was eligible for the study if having neutropenic fever after intensive therapy for acute myeloid leukaemia (AML) (n = 32) or non-Hodgkin lymphoma (NHL) (n = 35). Blood cultures were taken, and maximal PTX3 and C-reactive protein (CRP) were evaluated during d0 to d3 from the beginning of fever onset. The level of PTX3 was associated with both the underlying malignancy and the presence of complications, with highest level in NHL patients with complicated course of febrile neutropenia and lowest in AML patients with non-complicated course. The cut-off level of PTX3 to predict complications was ten-fold in patients with NHL (115 μg/L) in comparison with patients with AML (11.5 μg/L). In combined analysis based on separate cut-offs, PTX3 predicted complications of febrile neutropenia with sensitivity of 0.86, specificity of 0.83, positive predictive value of 0.57 and negative predictive value of 0.96.   PTX3 was superior to CRP in predicting complicated course of febrile neutropenia, but only when the effect of the underlying malignancy had been taken into account. © 2011 John Wiley & Sons A/S.

Selective estrogen receptor modulators in clinical practice: a safety overview.

PubMed

Ellis, Amanda J; Hendrick, Vicky M; Williams, Robert; Komm, Barry S

2015-06-01

Selective estrogen receptor (ER) modulators (SERMs) are a class of nonsteroidal compounds that interact with ERs, each with a distinct tissue-specific profile. Depending upon the degree of ER agonism/antagonism at the target tissue, SERMs show efficacy for various indications including osteoporosis, dyspareunia, and breast cancer, and are associated with safety risks. This review describes the safety profile of SERMs (tamoxifen, raloxifene, toremifene, bazedoxifene, lasofoxifene, and ospemifene) and fulvestrant (a pure ER antagonist) from Phase III trials, long-term extension studies, and active comparator studies. Tamoxifen, a first-generation SERM, is indicated for breast cancer prevention and treatment but is associated with serious safety concerns including endometrial cancer, venous thromboembolic events (VTE), and stroke. Toremifene, raloxifene, bazedoxifene, lasofoxifene, and ospemifene present generally improved, though distinctly different, safety profiles compared with tamoxifen, especially with endometrial cancer and stroke. However, the risk of VTE remains a concern for most SERMs. Each SERM presents a unique risk/benefit profile based on varying indications and tissue-specific ER agonist and antagonist effects, making careful patient selection and ongoing patient monitoring crucial aspects of treatment. Future research may focus on identifying new SERMs for endocrine-resistant and endocrine-responsive cancers and post-menopausal symptoms.

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

PubMed

Chaudhuri, Jasodhara; Biswas, Tamoghna; Datta, Jyotishka; Sabui, Tapas Kumar; Chatterjee, Sukanta; Ray, Somosri; Raychaudhuri, Dibyendu; Mandal, Kalyanbrata; Chatterjee, Kaushani; Chakraborty, Swapna

2016-07-01

Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged <5 years, weight for height, height for age and weight for age were used as criteria for defining malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2)  = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged <5 years (OR 14, 95% CI 1.135-172.642, one-tailed P = 0.036). Logistic regression analyses at episode level revealed that phase of treatment and respiratory system involvement were significant predictors of death, while malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Multivitamin supplementation improves haematologic status in children born to HIV-positive women in Tanzania

PubMed Central

Liu, Enju; Duggan, Christopher; Manji, Karim P; Kupka, Roland; Aboud, Said; Bosch, Ronald J; Kisenge, Rodrick R; Okuma, James; Fawzi, Wafaie W

2013-01-01

Introduction Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality. Objective To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding. Methods A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations<11 g/dL and severe anaemia<8.5 g/dL. Results Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79–0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56–0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79–1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV. Conclusions Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in

Multivitamin supplementation improves haematologic status in children born to HIV-positive women in Tanzania.

PubMed

Liu, Enju; Duggan, Christopher; Manji, Karim P; Kupka, Roland; Aboud, Said; Bosch, Ronald J; Kisenge, Rodrick R; Okuma, James; Fawzi, Wafaie W

2013-08-13

Anaemia is prevalent among children born to HIV-positive women, and it is associated with adverse effects on cognitive and motor development, growth, and increased risks of morbidity and mortality. To examine the effect of daily multivitamin supplementation on haematologic status and mother-to-child transmission (MTCT) of HIV through breastfeeding. A total of 2387 infants born to HIV-positive women from Dar es Salaam, Tanzania were enrolled in a randomized, double-blind, placebo-controlled trial, and provided a daily oral supplement of multivitamins (vitamin B complex, C and E) or placebo at age 6 weeks for 24 months. Among them, 2008 infants provided blood samples and had haemoglobin concentrations measured at baseline and during a follow-up period. Anaemia was defined as haemoglobin concentrations <11 g/dL and severe anaemia <8.5 g/dL. Haemoglobin concentrations among children in the treatment group were significantly higher than those in the placebo group at 12 (9.77 vs. 9.64 g/dL, p=0.03), 18 (9.76 vs. 9.57 g/dL, p=0.004), and 24 months (9.93 vs. 9.75 g/dL, p=0.02) of follow-up. Compared to those in the placebo group, children in the treatment group had a 12% lower risk of anaemia (hazard ratio (HR): 0.88; 95% CI: 0.79-0.99; p=0.03). The treatment was associated with a 28% reduced risk of severe anaemia among children born to women without anaemia (HR: 0.72; 95% CI: 0.56-0.92; p=0.008), but not among those born to women with anaemia (HR: 1.10; 95% CI: 0.79-1.54; p=0.57; p for interaction=0.007). One thousand seven hundred fifty three infants who tested HIV-negative at baseline and had HIV testing during follow-up were included in the analysis for MTCT of HIV. No association was found between multivitamin supplements and MTCT of HIV. Multivitamin supplements improve haematologic status among children born to HIV-positive women. Further trials focusing on anaemia among HIV-exposed children are warranted in the context of antiretroviral therapy.

Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient's compliance.

PubMed

Adewoyin, Ademola Samson; Oghuvwu, Omokiniovo Sunday; Awodu, Omolade Augustina

2017-03-01

The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects. A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review. The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-compliance included poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects. Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

Motor carrier industry profile study : financial and operating performance profiles by industry segment, 2001-2002.

DOT National Transportation Integrated Search

2004-09-01

This report profiles the motor carrier industry and its significant operating segments. It is one of a series of reports analyzing various aspects of the motor carrier industry. Other reports in the series focus on the safety performance of the indus...

Neural network evaluation of tokamak current profiles for real time control (abstract)

NASA Astrophysics Data System (ADS)

Wróblewski, Dariusz

1997-01-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q0, minimum value of q, qmin, and the location of qmin. Very good performance of the trained neural network both for simulated test data and for experimental data is demonstrated.

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

16 CFR Figure 8 to Subpart A of... - Standard Radiant Heat Energy Flux Profile

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Standard Radiant Heat Energy Flux Profile 8... PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 8 Figure 8 to Subpart A of Part 1209—Standard Radiant Heat Energy Flux Profile EC03OC91...

Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd.

PubMed

Hughes, Timothy P; Munhoz, Eduardo; Aurelio Salvino, Marco; Ong, Tee Chuan; Elhaddad, Alaa; Shortt, Jake; Quach, Hang; Pavlovsky, Carolina; Louw, Vernon J; Shih, Lee-Yung; Turkina, Anna G; Meillon, Luis; Jin, Yu; Acharya, Sandip; Dalal, Darshan; Lipton, Jeffrey H

2017-10-01

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188). © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Variable haematological and clinical presentation of β-thalassaemia carriers and homozygotes with the Poly A (T→C) mutation in the Indian population.

PubMed

Italia, Khushnooma; Sawant, Pratibha; Surve, Reema; Wadia, Marukh; Nadkarni, Anita; Ghosh, Kanjaksha; Colah, Roshan

2012-08-01

To study the varied clinical and haematological profile of β-thalassaemia homozygotes, compound heterozygotes and heterozygotes with the Poly A (T→C) mutation and its implication in prenatal diagnosis. Forty individuals were included in the study. Peripheral smear examination, complete blood count and haemoglobin analysis were carried out. β-thalassaemia mutation analysis was carried out by reverse-dot-blot hybridization, amplification refractory mutation system and DNA sequencing of the β-globin gene. Five of the six β-thalassaemia homozygotes with the Poly A (T→C) mutation and five individuals who were compound heterozygous for the Poly A (T→C) mutation along with another common Indian β-thalassaemia mutation showed a severe β-thalassaemia major phenotype, while one individual presented as a thalassaemia intermedia. Majority of the 28 heterozygous individuals with this mutation showed borderline HbA₂ (mean HbA₂ = 3.7 ± 0.4%) levels as compared to individuals with common β-thalassaemia mutations (mean HbA₂ = 5.2 ± 1.4%). The Mean Corpuscular Volume (MCV) levels in individuals heterozygous for the Poly A (T→C) mutation (mean MCV 70.0 ± 5.2 fl) were significantly higher than in individuals with other common β-thalassaemia mutations (mean MCV 60.7 ± 7.7 fl) (P < 0.001). It is important to identify these often silent carriers of β-thalassaemia for prenatal diagnosis as homozygotes have a severe disease. © 2012 John Wiley & Sons A/S.

In-vivo study for anti-hyperglycemic potential of aqueous extract of Basil seeds (Ocimum basilicum Linn) and its influence on biochemical parameters, serum electrolytes and haematological indices.

PubMed

Chaudhary, Sachin; Semwal, Amit; Kumar, Hitesh; Verma, Harish Chandra; Kumar, Amit

2016-12-01

The study introduced anti-hyperglycemic influence of aqueous extract of Ocimum basilicum seeds (AEOBS) in Streptozotocin (STZ) induced diabetic rats and estimating its potential to ameliorate altered level of biochemical parameters, serum electrolytes level and haematological indices along with its effect on body weight of treated rats. The albino rats were selected to observe oral glucose tolerance test by oral intake of aq. glucose solution (4g/kg, body weight) in normal rats and estimation of blood glucose level after administration of AEOBS at 250mg/kg, 500mg/kg and standard drug glibenclamide at 0.6mg/kg, body weight. Antidiabetic activity was evaluated in chronic study models by STZ induced diabetes in rats followed by blood glucose estimation. Chronic study model was selected to carry out further studies to evaluate the effect of AEOBS at 250mg/kg, 500mg/kg and standard drug on body weight, alterations in biochemical parameters including AST, ALT, ALP, total bilirubin and total protein, alterations in serum electrolytes like Na + , K + , Cl - , HCO 3 - along with estimation of haematological indices like red blood cells (RBC), white blood cells (WBC), hemoglobin (Hb), lymphocytes, neutrophils, eosinophils, monocytes and basophils. AEOBS significantly reduced the blood glucose level of diabetic rats at both doses. Body weight was also improved significantly. Similarly, the levels of biochemical parameters, serum electrolytes, and haematological indices were significantly ameliorated at both doses of AEOBS. The histopathological results revealed reconstitution of pancreatic islets towards normal cellular architecture in rats treated with AEOBS. The results illustrated that AEOBS have eminent antidiabetic potential in STZ effectuated diabetes in rats and can be extensively used for the treatment of diabetes mellitus-II and its associated complications including anaemia, diabetic nephropathy, liver dysfunction, and immunosuppression. Copyright © 2016 Elsevier

Safety and Efficacy of Microinvasive Glaucoma Surgery

PubMed Central

Chen, David Z.

2017-01-01

Microinvasive glaucoma surgery (MIGS) is emerging as a new therapeutic option for glaucoma patients who wish to reduce their medication burden and avoid the postoperative complications of conventional glaucoma filtration surgery. These devices differ in terms of their efficacy and safety profile. Schlemm's canal devices have the most favorable safety profile at the compromise of modest efficacy, while subconjunctival and suprachoroidal devices are potentially more effective at lowering the intraocular pressure at the expense of a higher rate of complications. This review consolidates the latest evidence on the efficacy and safety of the MIGS devices in clinical use and provides an overview on upcoming devices which would likely also become viable treatment options in the near future. These clinical data would assist a glaucoma surgeon in selecting the most appropriate MIGS device for each patient based on the glaucoma severity and patient expectations. PMID:28512578

Growth performance, haematological traits, meat variables, and effects of treadmill and transport stress in veal calves supplied different amounts of iron.

PubMed

Lindt, F; Blum, J W

1994-06-01

Effects of serum iron (Fe), haematological variables and on blood lactate levels before and after treadmill exercise or transport to the slaughterhouse, on meat traits, and on growth performance of feeding milk replacer (MR), planned to contain 10, 20, 30, 40, 50 or 80 mg Fe/kg, were studied in veal calves. If supplied less than 50 mg Fe/kg MR, calves developed hypoferraemia and anaemia, the degree of which was dependent on Fe intake. Serum Fe concentration, saturation of transferrin with Fe and the degree of anaemia in calves fed 20 or 10 mg Fe/kg MR were nearly identical. Serum Fe concentration and haematological traits barely changed in calves fed 50 mg Fe/kg MR during the growth trail, but serum Fe concentration increased when MR contained 80 mg Fe/kg in calves fed 50 or more Fe/kg MR. Growth performance was smaller in calves fed 10 mg Fe/kg MR than in those fed greater amounts of Fe/kg MR. Carcass taxation was inversely related to Fe intake. In conclusion, MR containing only 10 mg Fe/kg caused marked anaemia and reduced growth performance. Feeding MR with only 20 mg Fe/kg is not necessarily sufficient to prevent development of severe anaemia. Feeding MR with 50 mg Fe/kg would seem to be physiologically the most appropriate amount of Fe for veal calves, but was too high for acceptable carcass taxation.

Immature granulocyte detection by the SE-9000 haematology analyser during pregnancy.

PubMed

Fernández-Suárez, A; Pascual, V T; Gimenez, M T F; Hernández, J F S

2003-12-01

The objective of this study was to determine the nature of the alarm for immature granulocytes appearing in haemograms from pregnant women, as detected by the immature cell information channel (IMI) of the SE-9000 automated haematology analyser. Of all tests run on pregnant women in a 4-month period (n = 698), the first 100 haemograms with immature granulocyte alarms (14.33%) were collected. Each of these samples was then stained with Wright-Giemsa stain. The following variables were also analysed: age of the mother, trimester and days of gestation, type of delivery, weight and sex of the baby, and Apgar score. Most pregnant women were in the third trimester of gestation (82%) when an alarm was noted on the IMI channel. Of the patients, 62% had normal deliveries. The most frequent complication was obstructed delivery (23%). Mean percentages by microscopic counts of band cells, metamyelocytes, and myelocytes were 2.99, 0.45, and 0.19%, respectively. There was a statistically significant correlation for all cell types between the SE-9000 and the manual count method. No association was observed between the presence of immature granulocytes and the clinical variables analysed. The SE-9000 analyser shows high sensitivity in the IMI channel for detection of immature forms.

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition.

PubMed

Rankine-Mullings, Angela E; Morrison-Levy, Nadine; Soares, Deanne; Aldred, Karen; King, Lesley; Ali, Susanna; Knight-Madden, Jennifer M; Wisdom-Phipps, Margaret; Adams, Robert J; Ware, Russell E; Reid, Marvin

2018-04-01

This study investigated the association of nutritional and haematological variables with maximum time-averaged mean velocity (TAMV) measured by transcranial Doppler (TCD) velocity and the agreement of classification between two protocols. TCD categories included: normal (<170 cm/s), conditional (170-199 cm/s) and abnormal (≥200 cm/s) based on TAMV in distal internal carotid artery (dICA), middle cerebral artery (MCA), internal carotid bifurcation, anterior and posterior cerebral arteries. Of 358 children with sickle cell anaemia (SCA) examined, the mean age (±standard deviation) was 7·4 ± 2·7 years; 13·1% and 6·7% had conditional and abnormal velocities, respectively. Children with abnormal TCD velocities had higher prevalence of prior stroke (P = 0·006). Increased TAMV was associated with younger age (P = 0·001), lower weight (P = 0·001), height (P = 0·007) and oxygen saturation (P = 0·005). There was no association of TAMV with height-age or body mass index (BMI) z-scores. Adjusting for gender, BMI z-score, age, previous stroke and oxygen saturation, mean corpuscular volume (P = 0·005) and reticulocyte count (P = 0·013) were positively associated with TAMV, while haemoglobin concentration (P = 0·009) was negatively associated. There was good agreement [99%; weighted Kappa 0·98 (95% confidence interval 0·89-1), P = 0·0001] in TCD classification using data from five vessels versus two vessels (dICA and MCA). Haematological variables, rather than nutritional status, may be useful markers that identify high-risk children with SCA. © 2018 John Wiley & Sons Ltd.

Specialist integrated haematological malignancy diagnostic services: an Activity Based Cost (ABC) analysis of a networked laboratory service model.

PubMed

Dalley, C; Basarir, H; Wright, J G; Fernando, M; Pearson, D; Ward, S E; Thokula, P; Krishnankutty, A; Wilson, G; Dalton, A; Talley, P; Barnett, D; Hughes, D; Porter, N R; Reilly, J T; Snowden, J A

2015-04-01

Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS) were introduced as a standard of care within the UK National Health Service to reduce diagnostic error and improve clinical outcomes. Two broad models of service delivery have become established: 'co-located' services operating from a single-site and 'networked' services, with geographically separated laboratories linked by common management and information systems. Detailed systematic cost analysis has never been published on any established SIHMDS model. We used Activity Based Costing (ABC) to construct a cost model for our regional 'networked' SIHMDS covering a two-million population based on activity in 2011. Overall estimated annual running costs were £1 056 260 per annum (£733 400 excluding consultant costs), with individual running costs for diagnosis, staging, disease monitoring and end of treatment assessment components of £723 138, £55 302, £184 152 and £94 134 per annum, respectively. The cost distribution by department was 28.5% for haematology, 29.5% for histopathology and 42% for genetics laboratories. Costs of the diagnostic pathways varied considerably; pathways for myelodysplastic syndromes and lymphoma were the most expensive and the pathways for essential thrombocythaemia and polycythaemia vera being the least. ABC analysis enables estimation of running costs of a SIHMDS model comprised of 'networked' laboratories. Similar cost analyses for other SIHMDS models covering varying populations are warranted to optimise quality and cost-effectiveness in delivery of modern haemato-oncology diagnostic services in the UK as well as internationally. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Analysis of haematological changes in tofacitinib-treated patients with rheumatoid arthritis across phase 3 and long-term extension studies.

PubMed

Schulze-Koops, Hendrik; Strand, Vibeke; Nduaka, Chudy; DeMasi, Ryan; Wallenstein, Gene; Kwok, Kenneth; Wang, Lisy

2017-01-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. The aim of this analysis was to characterize changes in haematological parameters following tofacitinib treatment, and to compare changes in haemoglobin with markers of disease activity, fatigue and vitality. Changes in neutrophil counts, lymphocyte counts and haemoglobin levels were analysed in patients with RA from six phase 3 randomized controlled trials (n = 4271) of tofacitinib 5 or 10 mg bd, placebo or active comparators of up to 24 months' duration, and two long-term extension (LTE) studies (n = 4858) of tofacitinib of up to 84 months' duration. Disease activity markers included CRP and ESR. Fatigue and vitality were assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Short Form Health Survey-36 vitality domain scores. In phase 3 studies, mean neutrophil and lymphocyte counts decreased and mean haemoglobin levels increased in all tofacitinib treatment groups. Haemoglobin levels and neutrophil counts stabilized in the LTE studies, while lymphocyte count decreases stabilized at approximately month 48. Increased haemoglobin was associated with decreased ESR and CRP levels. Clinically meaningful reductions in haemoglobin levels (⩾3 g/dl from baseline or haemoglobin ⩽7 g/dl) occurred in <1.0% of patients in all treatment groups. FACIT-F and Short Form Health Survey-36 vitality scores were weakly correlated with haemoglobin levels. Small changes in haematological parameters were seen with tofacitinib treatment, which stabilized over time in the LTE studies. Changes in haemoglobin levels, although associated with changes in ESR and CRP, were not associated with fatigue or vitality. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology.

The G8 screening tool detects relevant geriatric impairments and predicts survival in elderly patients with a haematological malignancy.

PubMed

Hamaker, Marije E; Mitrovic, M; Stauder, R

2014-06-01

The G8 screening tool was developed to separate fit older cancer patients who were able to receive standard treatment from those that should undergo a geriatric assessment to guide tailoring of therapy. We set out to determine the discriminative power and prognostic value of the G8 in older patients with a haematological malignancy. Between September 2009 and May 2013, a multi-dimensional geriatric assessment was performed in consecutive patients aged ≥67 years diagnosed with blood cancer at the Innsbruck University Hospital. The assessment included (instrumental) activities of daily living, cognition, mood, nutritional status, mobility, polypharmacy and social support. In parallel, the G8 was also administered (cut-off ≤ 14). Using a cut-off of ≥2 impaired domains, 70 % of the 108 included patients were considered as having an impaired geriatric assessment while 61 % had an impaired G8. The G8 lacked discriminative power for impairments on full geriatric assessment: sensitivity 69, specificity 79, positive predictive value 89 and negative predictive value 50 %. However, G8 was an independent predictor of mortality within the first year after inclusion (hazard ratio 3.93; 95 % confidence interval 1.67-9.22, p < 0.001). Remarkably, patients with impaired G8 fared poorly, irrespective of treatment choices (p < 0.001). This is the first report on the clinical and prognostic relevance of G8 in elderly patients with haematological malignancies. Although the G8 lacked discriminative power for outcome of multi-dimensional geriatric assessment, this score appears to be a powerful prognosticator and could potentially represent a useful tool in treatment decisions. This novel finding certainly deserves further exploration.

Comparative biodistribution and safety profiling of olmesartan medoxomil oil-in-water oral nanoemulsion.

PubMed

Gorain, Bapi; Choudhury, Hira; Tekade, Rakesh Kumar; Karan, Saumen; Jaisankar, P; Pal, Tapan Kumar

2016-12-01

Poor aqueous solubility and unfavourable de-esterification of olmesartan medoxomil (a selective angiotensin II receptor blocker), results in low oral bioavailability of less than 26%. Improvement of oral bioavailability with prolonged pharmacodynamics activity of olmesartan in Wistar rats had been approached by nanoemulsification strategy in our previous article [Colloid Surface B, 115, 2014: 286]. In continuation to that work, we herewith report the biodistribution behaviour and 28-day repeated dose sub-chronic toxicity of olmesartan medoxomil nanoemulsion in Wistar rats following oral administration. The levels of olmesartan in collected biological samples were estimated using our validated LC-MS/MS technique. Our biodistribution study showed significantly higher brain concentrations of olmesartan (0.290 ± 0.089 μg/mL, 0.333 ± 0.071 μg/mL and 0.217 ± 0.062 μg/mL at 0.5, 2.0 and 8.0 h post dosing, respectively) when administered orally as nanoemulsion formulation as compared to the aqueous suspension. In addition, the olmesartan nanoemulsion was found to be safe and non-toxic, as it neither produced any lethality nor remarkable haematological, biochemical and structural adverse effects as observed during the 28-days sub-chronic toxicity studies in experimental Wistar rats. It is herewith envisaged that the developed nanoemulsion formulation approach for the delivery of olmesartan medoxomil via oral route can further be explored in memory dysfunction and brain ischemia, for better brain penetration and improved clinical application in stroke patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Curcuma longa L. as a therapeutic agent in intestinal motility disorders. 2: Safety profile in mouse.

PubMed

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K(+) induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.

Curcuma longa L. as a Therapeutic Agent in Intestinal Motility Disorders. 2: Safety Profile in Mouse

PubMed Central

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Background Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Methods Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. Results In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K+ induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Conclusions Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered. PMID:24260512

Effects of age and season on haematological parameters of donkeys during the rainy and cold-dry seasons.

PubMed

Zakari, Friday Ocheja; Ayo, Joseph Olusegun; Rekwot, Peter Ibrahim; Kawu, Mohammed Umar

2015-12-01

The aim of the study was to investigate the effects of age and season on haematological parameters of donkeys at rest during the rainy and cold-dry seasons. Thirty healthy donkeys divided into three groups based on their age served as the subjects. During each season, blood sample was collected from each donkey thrice, 2 weeks apart, for haematological analysis, and the dry-bulb temperature (DBT), relative humidity (RH) and temperature-humidity index (THI) were obtained thrice each day during the experimental period using standard procedures. During the rainy season, the mean DBT (33.05 ± 0.49 °C), RH (73.63 ± 1.09 %) and THI (84.39 ± 0.71) were higher (P < 0.0001) than the corresponding values of 24.00 ± 0.44 °C, 36.80 ± 0.92 % and 64.80 ± 0.62, during the cold-dry season. Packed cell volume (PCV), erythrocyte count [red blood cell (RBC)], haemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), platelet count (PLT), leucocyte count [white blood cell (WBC)], lymphocyte count (LYM) and neutrophil/lymphocyte ratio (N/L) were higher (P < 0.05) in adults than foals during the rainy season. The MCV, MCH, WBC, NEU, LYM and PLT of adult and yearling donkeys were higher (P < 0.05) during the rainy than the cold-dry season. The PCV, RBC, Hb, MCV, MCH, and NEU of foals were higher in the rainy than the cold-dry season. The N/L of adult and foal donkeys were higher (P < 0.05) in the rainy than in the cold-dry season. In conclusion, PCV, RBC, Hb and LYM were considerably higher in foals than yearlings or adults during the rainy season, while erythrocytic indices and platelet counts were higher in adults or yearlings than in foals in both seasons. Erythrocytic indices, PLT and N/L were higher in the rainy than the cold-dry season in adults, yearlings and foals.

Effects of age and season on haematological parameters of donkeys during the rainy and cold-dry seasons

NASA Astrophysics Data System (ADS)

Zakari, Friday Ocheja; Ayo, Joseph Olusegun; Rekwot, Peter Ibrahim; Kawu, Mohammed Umar

2015-12-01

The aim of the study was to investigate the effects of age and season on haematological parameters of donkeys at rest during the rainy and cold-dry seasons. Thirty healthy donkeys divided into three groups based on their age served as the subjects. During each season, blood sample was collected from each donkey thrice, 2 weeks apart, for haematological analysis, and the dry-bulb temperature (DBT), relative humidity (RH) and temperature-humidity index (THI) were obtained thrice each day during the experimental period using standard procedures. During the rainy season, the mean DBT (33.05 ± 0.49 °C), RH (73.63 ± 1.09 %) and THI (84.39 ± 0.71) were higher ( P < 0.0001) than the corresponding values of 24.00 ± 0.44 °C, 36.80 ± 0.92 % and 64.80 ± 0.62, during the cold-dry season. Packed cell volume (PCV), erythrocyte count [red blood cell (RBC)], haemoglobin concentration (Hb), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), platelet count (PLT), leucocyte count [white blood cell (WBC)], lymphocyte count (LYM) and neutrophil/lymphocyte ratio (N/L) were higher ( P < 0.05) in adults than foals during the rainy season. The MCV, MCH, WBC, NEU, LYM and PLT of adult and yearling donkeys were higher ( P < 0.05) during the rainy than the cold-dry season. The PCV, RBC, Hb, MCV, MCH, and NEU of foals were higher in the rainy than the cold-dry season. The N/L of adult and foal donkeys were higher ( P < 0.05) in the rainy than in the cold-dry season. In conclusion, PCV, RBC, Hb and LYM were considerably higher in foals than yearlings or adults during the rainy season, while erythrocytic indices and platelet counts were higher in adults or yearlings than in foals in both seasons. Erythrocytic indices, PLT and N/L were higher in the rainy than the cold-dry season in adults, yearlings and foals.

Phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a comparison of safety profiles.

PubMed

Locatelli, Francesco; Del Vecchio, Lucia; Violo, Leano; Pontoriero, Giuseppe

2014-05-01

Hyperphosphatemia is common in the late stages of chronic kidney disease (CKD) and is associated with elevated parathormone levels, abnormal bone mineralization, extraosseous calcification and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control phosphorus levels. Although effective at lowering serum phosphorus, they all have safety issues that need to be considered when selecting which one to use. This paper reviews the use of phosphate binders in patients with CKD on dialysis, with a focus on safety and tolerability. In addition to the more established agents, a new resin-based phosphate binder, colestilan, is discussed. Optimal phosphate control is still an unmet need in CKD. Nonetheless, we now have an extending range of phosphate binders available. Aluminium has potentially serious toxic risks. Calcium-based binders are still very useful but can lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, but there is insufficient evidence about possible long-term effects of tissue deposition. The resin-based binders, colestilan and sevelamer, appear to have profiles that would lead to less vascular calcification, and the main adverse events seen with these agents are gastrointestinal effects.

First-Principles-Driven Model-Based Optimal Control of the Current Profile in NSTX-U

NASA Astrophysics Data System (ADS)

Ilhan, Zeki; Barton, Justin; Wehner, William; Schuster, Eugenio; Gates, David; Gerhardt, Stefan; Kolemen, Egemen; Menard, Jonathan

2014-10-01

Regulation in time of the toroidal current profile is one of the main challenges toward the realization of the next-step operational goals for NSTX-U. A nonlinear, control-oriented, physics-based model describing the temporal evolution of the current profile is obtained by combining the magnetic diffusion equation with empirical correlations obtained at NSTX-U for the electron density, electron temperature, and non-inductive current drives. In this work, the proposed model is embedded into the control design process to synthesize a time-variant, linear-quadratic-integral, optimal controller capable of regulating the safety factor profile around a desired target profile while rejecting disturbances. Neutral beam injectors and the total plasma current are used as actuators to shape the current profile. The effectiveness of the proposed controller in regulating the safety factor profile in NSTX-U is demonstrated via closed-loop predictive simulations carried out in PTRANSP. Supported by PPPL.

Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides

PubMed Central

Mesnage, Robin; Antoniou, Michael N.

2018-01-01

Commercial formulations of pesticides are invariably not single ingredients. Instead they are cocktails of chemicals, composed of a designated pesticidal “active principle” and “other ingredients,” with the latter collectively also known as “adjuvants.” These include surfactants, antifoaming agents, dyes, etc. Some adjuvants are added to influence the absorption and stability of the active principle and thus promote its pesticidal action. Currently, the health risk assessment of pesticides in the European Union and in the United States focuses almost exclusively on the stated active principle. Nonetheless, adjuvants can also be toxic in their own right with numerous negative health effects having been reported in humans and on the environment. Despite the known toxicity of adjuvants, they are regulated differently from active principles, with their toxic effects being generally ignored. Adjuvants are not subject to an acceptable daily intake, and they are not included in the health risk assessment of dietary exposures to pesticide residues. Here, we illustrate this gap in risk assessment by reference to glyphosate, the most used pesticide active ingredient. We also investigate the case of neonicotinoid insecticides, which are strongly suspected to be involved in bee and bumblebee colony collapse disorder. Authors of studies sometimes use the name of the active principle (for example glyphosate) when they are testing a commercial formulation containing multiple (active principle plus adjuvant) ingredients. This results in confusion in the scientific literature and within regulatory circles and leads to a misrepresentation of the safety profile of commercial pesticides. Urgent action is needed to lift the veil on the presence of adjuvants in food and human bodily fluids, as well as in the environment (such as in air, water, and soil) and to characterize their toxicological properties. This must be accompanied by regulatory precautionary measures to

Haematological and biochemical measurements in healthy, adult, free-ranging golden jackals (Canis aureus syriacus) held in captivity.

PubMed

Aroch, I; Shpigel, N Y; Avidar, Y; Yakobson, B; King, R; Shamir, M

2005-09-10

Blood from 31 healthy, free-ranging golden jackals held in captivity for seven days was collected while they were anaesthetised. Haematological and serum biochemical measurements were analysed and the 95 per cent confidence interval for each variable was compared with the reference value for domestic dogs. The measurements of their red blood cells were within the reference interval for dogs, but the jackals had higher white blood cell counts and eosinophil counts than dogs. The male jackals had a higher haematocrit, red blood cell count, mean corpuscular volume and mean corpuscular haemoglobin concentration, and a lower red blood cell distribution width than the female jackals. High activities of muscle enzymes were detected in many of the jackals, in several of which the activity of creatine kinase exceeded 5000 U/l; these were considered abnormal.

Safety and efficacy of first-line bevacizumab-based therapy in advanced non-squamous non-small-cell lung cancer (SAiL, MO19390): a phase 4 study.

PubMed

Crinò, Lucio; Dansin, Eric; Garrido, Pilar; Griesinger, Frank; Laskin, Janessa; Pavlakis, Nick; Stroiakovski, Daniel; Thatcher, Nick; Tsai, Chun-Ming; Wu, Yi-long; Zhou, Caicun

2010-08-01

Results of two phase 3 trials have shown first-line bevacizumab in combination with chemotherapy improves clinical outcomes in patients with advanced or recurrent non-squamous non-small-cell lung cancer (NSCLC). The SAiL (MO19390) study was undertaken to assess the safety and efficacy of first-line bevacizumab combined with standard chemotherapy regimens in clinical practice. Between August, 2006, and June, 2008, patients with untreated locally advanced, metastatic, or recurrent non-squamous NSCLC were recruited to this open-label, single group, phase 4 study from centres in 40 countries. Eligible patients had histologically or cytologically documented inoperable, locally advanced, metastatic, or recurrent disease (stage IIIB-IV); an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, hepatic, and renal function. Patients received bevacizumab (7.5 or 15 mg/kg every 3 weeks) plus standard chemotherapy for up to six cycles, followed by single-agent bevacizumab until disease progression. The primary endpoint was safety; analysis was by intention to treat (ITT). This study is registered with ClinicalTrials.gov, number NCT00451906. At the final data cutoff (July 24, 2009), an ITT population of 2212 patients was assessed. The incidence of clinically significant (grade > or = 3) adverse events of special interest was generally low; thromboembolism occurred in 172 (8%) patients, hypertension in 125 (6%), bleeding in 80 (4%), proteinuria in 67 (3%), and pulmonary haemorrhage in 15 (1%). 57 (3%) patients died because of these adverse events, with thromboembolism (26 patients, 1%) and bleeding (17, 1%) as the most common causes. The most common grade 3 or higher serious adverse events deemed by investigators to be associated with bevacizumab were pulmonary embolism (28 patients; 1%) and epistaxis, neutropenia, febrile neutropenia, and deep vein thrombosis (all of which occurred in 13 patients [1%]). Bevacizumab was temporarily

Cross-modal work helps OMC improve the safety of commercial transportation

DOT National Transportation Integrated Search

1997-01-01

This article describes the Commercial Vehicle Information System (CVIS), designed to deploy a national safety program for the U.S. commercial trucking fleet. CVIS is built around a safety analysis algorithm called SafeStat which constructs a profile ...

Monitoring product safety in the postmarketing environment.

PubMed

Sharrar, Robert G; Dieck, Gretchen S

2013-10-01

The safety profile of a medicinal product may change in the postmarketing environment. Safety issues not identified in clinical development may be seen and need to be evaluated. Methods of evaluating spontaneous adverse experience reports and identifying new safety risks include a review of individual reports, a review of a frequency distribution of a list of the adverse experiences, the development and analysis of a case series, and various ways of examining the database for signals of disproportionality, which may suggest a possible association. Regulatory agencies monitor product safety through a variety of mechanisms including signal detection of the adverse experience safety reports in databases and by requiring and monitoring risk management plans, periodic safety update reports and postauthorization safety studies. The United States Food and Drug Administration is working with public, academic and private entities to develop methods for using large electronic databases to actively monitor product safety. Important identified risks will have to be evaluated through observational studies and registries.

Creatine metabolism and safety profiles after six-week oral guanidinoacetic acid administration in healthy humans.

PubMed

Ostojic, Sergej M; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities.

Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

PubMed Central

Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

2013-01-01

Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

Suspected botulism in dairy cows and its implications for the safety of human food.

PubMed

Cobb, S P; Hogg, R A; Challoner, D J; Brett, M M; Livesey, C T; Sharpe, R T; Jones, T O

2002-01-05

A large outbreak of suspected botulism occurred on a dairy farm. The affected animals were listless and showed signs ranging from hindlimb unsteadiness to lateral recumbency, although the most common presentation was sternal recumbency with an apparent hindlimb weakness when stimulated to rise. Postmortem examinations revealed no conclusive gross pathology or histopathology. The affected cattle were found to have neutrophilia and hyperglycaemia with no other consistent haematological or biochemical abnormalities. The combination of clinical signs, disease epidemiology and the ruling out of other differential diagnoses strongly supported a diagnosis of unconfirmed botulism; however, the source of toxin was not demonstrated. Botulism is a severe disease in human beings and there are uncertainties about the pharmacokinetics and pharmacodynamics of Clostridium botulinum toxins. In such circumstances, a precautionary approach to food safety is essential. Restrictions were placed on the movement of livestock and sale of milk from the farm premises until 14 days after the onset of the last clinical case.

Safety assessment of transgenic Bacillus thuringiensis with VIP insecticidal protein gene by feeding studies.

PubMed

Peng, Donghai; Chen, Shouwen; Ruan, Lifang; Li, Lin; Yu, Ziniu; Sun, Ming

2007-07-01

The aim of this study was to evaluate the toxicology safety of a genetically modified (GM) Bacillus thuringiensis with vegetative insecticidal protein (VIP) gene. Acute and subacute toxicity studies by using its powder preparation were conducted in Wistar rats. The result of the acute study showed the no-observable-adverse-effect level (NOAEL) of this GM B. thuringiensis powder preparation was greater than 5000 mg/kg body weight (BW). In the subacute study, the data analysis of body weight gain, food and water consumptions, clinical observations, haematology, serum biochemistry, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. These results proved the NOAEL of this GM B. thuringiensis powder preparation in subacute test was greater than 5000 mg/kg BW. Since both the acute and subacute oral toxicity were not detected at the highest dose recommended by OECD guidelines, this GM B. thuringiensis could be generally regarded as safe for use in bio-pesticide industry.

An update of safety of clinically used atypical antipsychotics.

PubMed

Orsolini, L; Tomasetti, C; Valchera, A; Vecchiotti, R; Matarazzo, I; Vellante, F; Iasevoli, F; Buonaguro, E F; Fornaro, M; Fiengo, A L C; Martinotti, G; Mazza, M; Perna, G; Carano, A; De Bartolomeis, A; Di Giannantonio, M; De Berardis, D

2016-10-01

The atypical antipsychotic (APs) drugs have become the most widely used agents to treat a variety of psychoses because of their superiority with regard to safety and tolerability profile compared to conventional/'typical' APs. We aimed at providing a synthesis of most current evidence about the safety and tolerability profile of the most clinically used atypical APs so far marketed. Qualitative synthesis followed an electronic search made inquiring of the following databases: MEDLINE, Embase, PsycINFO and the Cochrane Library from inception until January 2016, combining free terms and MESH headings for the topics of psychiatric disorders and all atypical APs as following: ((safety OR adverse events OR side effects) AND (aripiprazole OR asenapine OR quetiapine OR olanzapine OR risperidone OR paliperidone OR ziprasidone OR lurasidone OR clozapine OR amisulpride OR iloperidone)). A critical issue in the treatment with atypical APs is represented by their metabolic side effect profile (e.g. weight gain, lipid and glycaemic imbalance, risk of diabetes mellitus and diabetic ketoacidosis) which may limit their use in particular clinical samples. Electrolyte imbalance, ECG abnormalities and cardiovascular adverse effects may recommend a careful baseline and periodic assessments.

Sage Gene Expression Profiles Characterizing Cure

DTIC Science & Technology

2005-10-01

achieved in haematological malignancies. In addition, tumour cell lines showed a log-linear dose re- sponse when exposed to alkylating agents [26,27...direct carcinogen, N-methyl nitrosourea (NMU) and an indirect carcinogen, 7,12- dimethylbenzanthracene each depend upon the estrous cycle phase at the...a single dose of N-methyl-N- nitrosourea . Cancer Res 45: 3042–3047, 1995 8. Nagasawa H, Yanai R, Taniguchi H: Importance of mammary gland DNA synthesis

Toxicopathological Evaluation of Hydroethanol Extract of Dianthus basuticus in Wistar Rats

PubMed Central

Ashafa, Anofi Omotayo Tom

2015-01-01

Background. Dianthus basuticus is a commonly used medicinal plant in Basotho traditional medicine for the treatment of diabetes, but there is no report on its safety or toxicity. Therefore, we evaluated the toxicity profile of the hydroethanol whole plant extract of Dianthus basuticus in Wistar rats. Methods. Acute toxicity test was performed with single oral administration of 100–3200 mg/kg body weight of D. basuticus extract to rats and the animals were observed for 14 days for signs of toxicity. The subacute toxicity experiment was conducted by oral administration of graded doses (200, 400, and 800 mg/kg) of D. basuticus extract daily for 28 days. Behavioural changes as well as haematological, biochemical, and histological parameters were then evaluated. Results. There was no observable sign of toxicity in the acute toxicity test. There were significant decreases (P < 0.05) in the feed and water intake as well as total cholesterol and triglycerides of the D. basuticus extract-treated rats in subacute toxicity study. There were no treatment related differences in the haematological, biochemical, and histopathological evaluations. Conclusions. Administration of hydroethanol extract of D. basuticus may be safe at the dosages tested in this study but its continuous usage can cause anorexia. PMID:26504473

Audit of compliance with the British Committee for Standards in Haematology (BCSH) revised guidelines for the diagnosis and assessment of treatment response of hairy cell leukemia in University Hospital Galway.

PubMed

Velazquez-Kennedy, K; Crowe, C; Craven, B; Walsh, J; Prendergast, C; Krawczyk, J

2017-05-01

Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferative disorder. The object of the present audit was to assess whether the investigation and management of HCL in University College Hospital Galway (UCHG) complies with the British Committee for Standards in Haematology (BCSH) guidelines. Following a review of the records in our Haematology Department, 18 cases of HCL were identified between January 2006 and October 2014. Blood film examination had been performed in all cases. Flow cytometry of liquid material had been undertaken in 89 % (n = 16) of cases, of which only 31 % (n = 5) included all four hairy cell panel markers (CD11c, CD25, CD103, CD123). Although all initial trephine biopsies included CD20, none analyzed DBA44. Only 65 % (n = 11) of treated patients had a post-treatment bone marrow biopsy preformed. This audit highlights areas of improvement in the diagnosis and management of HCL in UCHG, which do not currently adhere to the BCSH recommendations.

[Occurrence of AmpC-positive Klebsiella pneumoniae strains in patients with haematological malignancies].

PubMed

Chromá, Magdaléna; Kolár, Milan; Sauer, Pavel; Faber, Edgar; Stosová, Tatána; Koukalová, Dagmar; Indrák, Karel

2008-10-01

Currently, important bacterial beta-lactamases of increasing clinical significance include AmpC enzymes. The aim was to assess their occurrence in Klebsiella pneumoniae strains isolated from patients with haematological malignancies in a prospective study. Over a 2-month period, strains of the species were isolated from clinical material obtained from patients hospitalized at the Department of Haemato-Oncology of the University Hospital Olomouc. The strains were identified using standard microbiological techniques and the Vitek 2 automated system. Production of AmpC beta-lactamases was roughly determined by phenotypic tests and subsequently confirmed by PCR detection of genes encoding these enzymes. During the above-mentioned period, a total of 35 K. pneumoniae isolates were collected. In 7 of them, production of AmpC beta-lactamases was preliminarily detected by phenotypic test. The multiplex PCR method confirmed phenotyping and determined DHA types in all the isolates. All AmpC-positive isolates were false-susceptible to at least one of the tested third-generation cephalosporins. In one patient, clinically apparent infection caused by this strain was documented. The reported results suggest the possibility of occurrence of AmpC-beta-lactamases in K. pneumoniae strains with clinical significance.

A pilot study to evaluate the safety and feasibility of the administration of AZT/3TC fixed dose combination to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil

PubMed Central

Lambert, J; Nogueira, S; Abreu, T; Machado, E; Costa, T; Bondarovsky, M; Andrade, M; Halpern, M; Barbosa, R; Perez, M

2003-01-01

Objectives: To evaluate the safety and feasibility of zidovudine and lamivudine (AZT/3TC) given to HIV infected pregnant women and their infants in Rio de Janeiro, Brazil. Methods: This open label phase II study enrolled 40 HIV infected antiretroviral naive women ⩾20 weeks gestation, CD4 <500 cells x106/l, from two public hospitals. Treatment: fixed dose AZT 300 mg/3TC 150 mg by mouth every 12 hours until labour; AZT 300 mg by mouth every 3 hours until delivery; infants: AZT 4 mg/kg every 12 hours plus 3TC 2 mg/kg every 12 hours for 6 weeks. Blood haematology and chemistry were monitored; adherence evaluated by pills count; efficacy measured by changes in lymphocyte (CD4) and viral load, and by HIV RNA-PCR tests performed at birth, 6 and 12 weeks, to diagnose infant infection. No women breast fed. Results: Patient characteristics: mean age 24.48 (SD 3.5) years; gestational age 24.5 (4.5) weeks; AZT/3TC duration 14.4 (4.4) weeks; vaginal delivery: 11/39; caesarean section: 28/39. Entry and pre-labour CD4: 310/486 cells x106/l (p<0.001); entry and pre-labour viral load: 53 818/2616 copies/ml (p<0.001). Thirty nine women tolerated treatment with >80% adherence; one was lost to follow up. Five newborns were excluded from 3TC receipt. All 39 babies were uninfected. Haematological toxicity in newborns was common: anaemia in 27; neutropenia in five (two severe); platelets counts <100 000 in two. All values recovered on study completion. Conclusions: Fixed dose AZT/3TC is well accepted, gives improvements in CD4 and viral load; no infants were HIV infected. Haematological toxicity in infants needs careful monitoring. PMID:14663118

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

PubMed Central

Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

2016-01-01

Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

Effects of aflatoxin on some haematological parameters and protective effectiveness of esterified glucomannan in Merino rams.

PubMed

Dönmez, Nurcan; Dönmez, H H; Keskin, E; Kısadere, İ

2012-01-01

The objective of the present study was to evaluate the toxic effects of aflatoxin on some hematological parameters and to determine the preventive effectiveness of added glucomannan. In the study, 32 Merino rams were used, and the rams were separated equally to four groups as control (C), glucomannan (G), glucomannan + aflatoxin (AG), and aflatoxin (A). Erythrocyte, leukocyte count, hemoglobin, and hematocrit levels were decreased in A group compared with the other groups, and there was a reduction in similar parameters in AG group compared to control values. On the other hand, these parameters were tended to increase in AG group compared to A group values. Aflatoxicosis caused the lymphocytopenia and monocytopenia but increased percentage of neutrophil counts. In conclusion, the results determined in the study might be important to demonstrate the effects of aflatoxicosis and glucomannan on some haematological parameters before the clinical symptoms appear.

Bioequivalence of HX575 (recombinant human epoetin alfa) and a comparator epoetin alfa after multiple intravenous administrations: an open-label randomised controlled trial.

PubMed

Sörgel, Fritz; Thyroff-Friesinger, Ursula; Vetter, Andrea; Vens-Cappell, Bernhard; Kinzig, Martina

2009-05-22

HX575 is a human recombinant epoetin alfa that was approved for use in Europe in 2007 under the European Medicines Agency biosimilar approval pathway. Therefore, in order to demonstrate the bioequivalence of HX575 to an existing epoetin alfa, the pharmacokinetic and pharmacodynamic response to steady state circulating concentrations of HX575 and a comparator epoetin alfa were compared following multiple intravenous administrations. An open, randomised, parallel group study was conducted in 80 healthy adult males. Subjects were randomised to multiple intravenous doses of 100 IU/kg body weight of HX575 or of the comparator epoetin alfa three-times-weekly for four weeks. Serum epoetin concentrations were measured using an enzyme-linked immunosorbent assay and pharmacokinetic parameters for the two treatments were compared. The time course and area under the effect curve ratio of haematological characteristics were used as surrogate parameters for efficacy evaluation. The haematological profiles of both treatments were similar, as determined from their population mean curves and the AUECHb ratio and 90% confidence interval (99.9% [98.5-101.2%]), the primary pharmacodynamic endpoint of this study. The pharmacokinetic parameters after the treatments showed minor differences after single dosing, but not at steady state doses. After multiple doses, HX575 was bioequivalent to the comparator with respect to the rate and extent of exposure of exogenous epoetin (AUCtau ratio and 90% confidence interval: 89.2% [82.5-96.2%]). Study medication was well tolerated with no clinically relevant differences between safety profiles of the treatments. Anti-epoetin antibodies were not detected. HX575 and the comparator epoetin alfa were bioequivalent at steady state circulating drug concentrations with respect to their pharmacokinetic profile and pharmacodynamic action. This supports the conclusion that HX575 and the comparator epoetin alfa, when administered intraveneously, will be

Evaluation of bioavailability, efficacy, and safety profile of doxorubicin-loaded solid lipid nanoparticles

NASA Astrophysics Data System (ADS)

Patro, Nagaraju M.; Devi, Kshama; Pai, Roopa S.; Suresh, Sarasija

2013-12-01

We investigated the bioavailability, efficacy, and toxicity of doxorubicin-loaded solid lipid nanoparticles (DOX-SLNs) prepared by a simple modified double-emulsification method. A 3-factor, 3-level Box-Behnken statistical design was adopted in the optimization of DOX-SLN formulation considering dependent factors particle size and entrapment efficiency. Optimized SLN formulation composed of lipid (2 %) consisting of soya lecithin and Precirol ATO 5 (1:3) with Pluronic F68 (0.3 %) resulted in 217.36 ± 3.31 nm particle size and 59.45 ± 1.75 % entrapment efficiency. DOX-SLN exhibited significant enhancement ( p < 0.05) in bioavailability as compared with free DOX in Sprague-Dawley (SD) rats. DOX-SLN exhibited higher peak plasma concentration (6.761 ± 0.08 vs. 2.412 ± 0.04 μg/ml), increased AUC (61.368 ± 3.54 vs. 5.812 ± 0.49 μg/ml h), decreased clearance (36 ± 0.01 vs. 619 ± 0.005 mL/h kg), and volume of distribution (733 ± 0.092 vs. 2,064 ± 0.061 mL/kg) when compared to free DOX. The collective results of cardiac and kidney enzyme assay, antioxidant enzyme levels, hematological parameters, effect on body weight and tumor volume, tumor necrosis factor-α level, histopathological examination, and survival analysis confirmed the improved efficacy and safety profile of DOX-SLN in 7,12-dimethyl benzanthracene-induced breast cancer in SD rats.

Pharmacokinetics, safety and tolerability of a novel tocopheryl phosphate mixture/oxycodone transdermal patch system: a Phase I study.

PubMed

Gavin, Paul D; Simon, Lee S; Schlagheck, Thomas; Smith, Alisha J; Shakib, Sepehr

2017-07-01

To characterize the pharmacokinetic profile and evaluate the safety and tolerability of a transdermal oxycodone patch containing tocopheryl phosphate mixture (TPM). Eleven healthy subjects received a single application of three TPM/oxycodone patches applied to the torso for 72 h. Oxycodone was detected 8.0 ± 2.7-h postpatch administration, reaching a mean maximum plasma concentration of 3.41 ± 1.34 ng/ml at 49.3 ± 21.2 h. The safety profile was consistent with the application method and known side-effect profile of oxycodone and naltrexone. No treatment-limiting skin irritation was observed. A 3-day application of the TPM/oxycodone patch demonstrated an acceptable safety profile and was well tolerated by healthy subjects, with limited dermal irritation following application.

Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.

PubMed

Mateos, María-Victoria; Granell, Miguel; Oriol, Albert; Martinez-Lopez, Joaquin; Blade, Joan; Hernandez, Miguel T; Martín, Jesus; Gironella, Mercedes; Lynch, Mark; Bleickardt, Eric; Paliwal, Prashni; Singhal, Anil; San-Miguel, Jesus

2016-11-01

Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM. © 2016 John Wiley & Sons Ltd.

Clinical biochemistry, haematology and body weight in piglets.

PubMed

Egeli, A K; Framstad, T; Morberg, H

1998-01-01

Reference ranges for clinical biochemical parameters commonly investigated in pigs were determined in one- (day 1), 21- and 35-day old piglets. The mean and standard deviation were also estimated for body weight, and haematological and clinical biochemical parameters at these ages. The piglets were divided into 2 investigation groups according to whether they had a haemoglobin concentration < or = 80 g/l ("anaemic group") or > 80 g/l ("normal group") on days 14, 21 and 28. The "anaemic group" was compared to the "normal group" on days 21 and 35. Many of the clinical biochemical parameters varied according to age. Some of the enzymes had high average values and wide reference ranges in piglets, especially on day 1, compared to the reference ranges for sows given in the literature. The reference ranges for some of the metabolic parameters were broader on day 1 than later in the preweaning period. The reference ranges for albumin, total iron-binding capacity and serum iron were, however, lower and more narrow on day 1. On days 21 and 35, relatively high values for phosphorus must be considered "normal" compared to the figures given in the literature for adult pigs. The other minerals seemed to be quite unaffected of age, but some were affected by anaemia. The anaemic piglets had lower average serum iron but higher total iron-binding capacity than the "normal" piglets on days 21 and 35. However, variation between piglets gave wide reference ranges, indicating that these parameters will only have limited usefulness in detecting iron deficiency anaemia in piglets. The electrolytes seemed also to be affected by the existence of anaemia. The body weight and leukocyte counts were significantly lower in the "anaemic group" than the "normal group" on day 35, while the greatest differences in clinical biochemical parameters between the groups were found on day 21, when the piglets in the "anaemic group" were most severely anaemic. Although these piglets suffered from severe

The concentrations of methaemoglogin, carboxyhaemoglobin and some haematological parameters in tobacco snuff addicts in Igbo of Nigeria.

PubMed

Ureme, S O; Ibeagha, I D; Maduka, I G; Ibeagbulam, O G

2007-01-01

Methaemoglobin, carboxyhaemoglobin concentrations and some haematological parameters were studied in fifty tobacco snuff addicts (40 males and 10 females) in some villages of Anambra State, Nigeria. The aim was to investigate possible adverse effects of tobacco snuff in addicts in Igbos of Anambra State. Fifty apparently healthy persons (25 males and 25 females) who do not inhale snuff were used as controls. The age range of tests and control subjects was 25-65 years. The results showed no statistically significant difference when the tests group was compared with the control group. A comparison of the results on the basis of sex, age and period of exposure, showed no significant differences. Blood picture in test and control groups was normocytic and normochromic. The results suggest that tobacco snuff may not have any adverse effect on haemoglobin metabolism and erythropoiesis.

The Evaluation Of Therapeutic Efficacy and Safety Profile of Simvastatin Prodrug Micelles in a Closed Fracture Mouse Model

PubMed Central

Zhang, Yijia; Jia, Zhenshan; Yuan, Hongjiang; Dusad, Anand; Ren, Ke; Wei, Xin; Fehringer, Edward V.; Purdue, P. Edward; Daluiski, Aaron; Goldring, Steven R.; Wang, Dong

2016-01-01

Purpose To evaluate the therapeutic efficiency of a micellar prodrug formulation of simvastatin (SIM/SIM-mPEG) and explore its safety in a closed femoral fracture mouse model. Methods The amphiphilic macromolecular prodrug of simvastatin (SIM-mPEG) was synthesized and formulated together with free simvastatin into micelles. It was also labeled with a near infrared dye for in vivo imaging purpose. A closed femoral fracture mouse model was established using a three-point bending device. The mice with established closed femoral fracture were treated with SIM/SIM-mPEG micelle, using free simvastatin and saline as controls. The therapeutic efficacy of the micelles was evaluated using a high-resolution micro-CT. Serum biochemistry and histology analyses were performed to explore the potential toxicity of the micelle formulation. Results Near Infrared Fluorescence (NIRF) imaging confirmed the passive targeting of SIM/SIM-mPEG micelles to the bone lesion of the mice with closed femoral fracture. The micelle was found to promote fracture healing with an excellent safety profile. In addition, the accelerated healing of the femoral fracture also helped to prevent disuse-associated same-side tibia bone loss accompanying the femur fracture. Conclusion SIM/SIM-mPEG micelle was found to be an effective and safe treatment for closed femoral fracture repair in mice. The evidence obtained in this study suggests that it may have the potential to be translated into a novel therapy for clinical management of skeletal fractures and non-union. PMID:27164897

Safety of vedolizumab in the treatment of Crohn's disease and ulcerative colitis.

PubMed

Hagan, Matilda; Cross, Raymond K

2015-01-01

Vedolizumab is the latest FDA-approved anti-integrin therapy for treatment of moderate-to-severe inflammatory bowel disease (IBD). The safety and efficacy of vedolizumab have been studied in short-term clinical trials. This paper reviews the safety profile of vedolizumab compared with other biologics. It also highlights the mechanism of action of the medication. We discuss the current position of vedolizumab in our current algorithm for IBD management and comment on future prospects of the drug. Vedolizumab appears to be a safe and effective option in the treatment of moderate-to-severe IBD in the short term. Long-term observational studies and post-marketing safety data are needed to ascertain the long-term efficacy and side effect profile.

Bone marrow solid core biopsy needle: a critical assessment of the utility, benefits and limitations of the instruments employed in current day haematology and oncology.

PubMed

Islam, Anwarul

2018-06-01

The optimal clinical evaluation of the bone marrow requires an examination of air-dried and well-stained films of the aspirated tissue along with a histopathological evaluation of adequately processed and properly stained core biopsy specimens. A bone marrow evaluation can be essential in establishing a diagnosis, determining the efficacy of treatment in haematological disorders and to monitor haematological status of patients following bone marrow/stem cell transplantation. It is also an essential component of the staging process for newly diagnosed malignancies. Currently available bone marrow aspiration needles are quite satisfactory and if properly used provide good-quality specimens for morphological evaluation. However, if a bone marrow core biopsy is concerned, several needles are currently in use but not all of them provide good-quality biopsy specimens for histological evaluation or are user friendly. We have compared the recently introduced Moeller Medical single use bone marrow core biopsy needle with the Jamshidi needle with marrow acquisition cradle (CareFusion), J-needle (Cardinal Health) and OnControl device (Vidacare). It is concluded that the Moeller Medical needle system has definite advantages over others and is recommended for routine use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The biomedical piglet: establishing reference intervals for haematology and clinical chemistry parameters of two age groups with and without iron supplementation.

PubMed

Ventrella, Domenico; Dondi, Francesco; Barone, Francesca; Serafini, Federica; Elmi, Alberto; Giunti, Massimo; Romagnoli, Noemi; Forni, Monica; Bacci, Maria L

2017-01-17

The similarities between swine and humans in physiological and genomic patterns, and the great correlation in size and anatomy, make pigs extremely useful in preclinical studies. New-born piglets can represent a model for congenital and genetic diseases in new-born children. It is known that piglets may have significant differences in clinicopathological results compared to adult pigs. Therefore, adult laboratory reference intervals cannot be applied to piglets. The aim of this study was to compare haematological and chemical variables in piglets of two ages and determinate age-related reference intervals for commercial hybrid young pigs. Blood samples were collected under general anaesthesia from 130 animals divided into five- (P5) and 30- (P30) day-old piglets. Only P30 animals were treated with parenteral iron after birth. Samples were analysed using automated haematology (ADVIA 2120) and chemistry analysers, and age-related reference intervals were calculated. Significant higher values of RBC, Hb and HCT were observed in P30 animals when compared to P5, with an opposite trend for MCV. These results were associated with a reduction of the RBC regeneration process and the thrombopoietic response. The TSAT and TIBC were significantly higher in P30 compared to P5; however, piglets remained iron deficient compared to adult reference intervals reported previously. In conclusion, this paper emphasises the high variability occurring in clinicopathological variables between new-born and 30-day-old pigs, and between piglets and adult pigs. This study provides valuable reference data for piglets at precise ages and could be used in the future as historical control improving the Reduction in animal experiments, as suggested by the 3Rs principle.

Epidemiological, clinical, haematological and biochemical characteristics of canine hypothyroidism.

PubMed

Dixon, R M; Reid, S W; Mooney, C T

1999-10-23

Hypothyroidism was diagnosed in 50 dogs and excluded in 86 dogs suspected of hypothyroidism, on the basis of the results of bovine thyrotropin response tests. Breed, pedigree, sex or neutering status did not significantly influence the likelihood of the dogs being hypothyroid. The hypothyroid dogs were significantly older than the non-hypothyroid dogs referred to the University of Glasgow during the same period. However, when dogs under two years of age were excluded from the statistical analyses there was no significant difference in age between the two groups. The most common clinical characteristics associated with hypothyroidism were metabolic signs (84 per cent of cases), particularly lethargy (76 per cent), obesity or weight gain (44 per cent), and exercise intolerance (24 per cent); and dermatological abnormalities (80 per cent), including alopecia (56 per cent), poor coat quality (30 per cent) and hyperpigmentation (20 per cent). When compared with the laboratory reference limits the most common biochemical and haematological abnormalities were increased concentrations of triglycerides (88 per cent), cholesterol (78 per cent), glucose (49 per cent), and fructosamine (43 per cent), and increased activities of creatine kinase (35 per cent), and decreased concentrations of inorganic phosphate (63 per cent), and a low red blood cell count (40 per cent). When compared with reference limits derived from the euthyroid dogs the most common abnormalities were increased concentrations of gamma-glutamyltransferase (21 per cent), cholesterol (18 per cent), and aspartate aminotransferase (15 per cent) and a decreased red blood cell count (29 per cent), and decreased neutrophils (18 per cent) and decreased activity of creatine kinase (15 per cent). Assessment of cholesterol, creatine kinase, aspartate aminotransferase, gamma-glutamyltransferase, and red blood cell and neutrophil counts may be particularly useful in distinguishing hypothyroid dogs from euthyroid animals

SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT.

PubMed

Chhablani, Jay; Narayanan, Raja; Mathai, Annie; Yogi, Rohit; Stewart, Michael

2016-06-01

To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration. Eligible eyes with choroidal neovascularization secondary to age-related macular degeneration each received a single intravitreal injection of ziv-aflibercept. Comprehensive ophthalmic examinations and detailed systemic evaluations were performed at baseline and Days 1, 7, and 30 after injection, and International Society for Clinical Electrophysiology of Vision standard electroretinography was performed at baseline and Day 30. Primary outcome measures were safety parameters that included signs of clinical and electroretinographic toxicity. Secondary outcome measures included changes in best-corrected visual acuity and central subfield thickness. Twelve eyes of 12 patients were treated. None of the patients complained of blurred vision, ocular pain, or bulbar injection at any of the follow-up visits, nor was intraocular inflammation noted. There were no significant differences in implicit times, "a" and "b" wave amplitudes, or b/a ratios at 1 month when compared with baseline (P = 0.4). None of the patients experienced serious ocular or systemic adverse events. Mean best-corrected visual acuity improved only slightly at 30 days (LogMAR 0.45 ± 0.31 [Snellen equivalent: 20/60]) compared with baseline (LogMAR 0.37 ± 0.24 [Snellen equivalent: 20/50]; P = 0.51). Single intravitreal injections of ziv-aflibercept into eyes with neovascular age-related macular degeneration appear to be safe through 1 month. Ziv-aflibercept could become a safe, low-cost therapy for macular diseases in developing countries and in those where intravitreal aflibercept (Eylea) is not available.

Active SMS-based influenza vaccine safety surveillance in Australian children.

PubMed

Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

2017-12-18

Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6-71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has

Applying principles from safety science to improve child protection.

PubMed

Cull, Michael J; Rzepnicki, Tina L; O'Day, Kathryn; Epstein, Richard A

2013-01-01

Child Protective Services Agencies (CPSAs) share many characteristics with other organizations operating in high-risk, high-profile industries. Over the past 50 years, industries as diverse as aviation, nuclear power, and healthcare have applied principles from safety science to improve practice. The current paper describes the rationale, characteristics, and challenges of applying concepts from the safety culture literature to CPSAs. Preliminary efforts to apply key principles aimed at improving child safety and well-being in two states are also presented.

A novel comprehensive set of fungal Real time PCR assays (fuPCR) for the detection of fungi in immunocompromised haematological patients-A pilot study.

PubMed

Rahn, Sebastian; Schuck, Anna; Kondakci, Mustafa; Haas, Rainer; Neuhausen, Nicole; Pfeffer, Klaus; Henrich, Birgit

2016-12-01

Fungal infections are recognized in an increasing number of patients with immunological deficits and are associated with high rates of mortality (Brown et al., 2012a). In this pilot-study, a rapid Real time PCR (fuPCR) was designed for the detection and differentiation of fungal pathogens in clinical specimens of haematological patients. The fuPCR, targeting the internal transcribed spacer region 2 (ITS2) of rDNA region, is comprised of seven multiplex reactions, which were shown to be specific and sensitive for a comprehensive spectrum of clinically relevant fungal species. This was validated by testing respective fungal DNAs in each fuPCR reaction and 28 respiratory samples of fungal pneumonia-proven patients. Clinical sample sets of throat swab, EDTA-blood and blood sera from 50 patients with severe haematological malignancies, including haematopoietic stem cell transfer (HSCT), and samples from 30 healthy individuals were then analysed. In a first step, 198 samples of immunosuppressed patients were solely examined by fuPCR; and 50.8% (33/65) respiratory swabs, 4.8% (3/63) EDTA blood samples and 1.4% (1/70) blood serum samples were tested positive. In a second step, 56 respiratory samples of immunosuppressed patients and 30 of healthy individuals were simultaneously analysed by fuPCR and standard cultivation techniques. By both methods 30.4% (17/56) swabs of the immunocompromised patients were tested positive, 37.5% (21/56) were tested negative and 32.1% (18/56) were tested fuPCR positive and culture negative. In analysing the blood samples of the immunocompromised patients 5.4% (3/56) EDTA blood samples and 16.1% (9/56) sera samples were tested fuPCR-positive, whereas all samples of 30 healthy individuals with no signs of immunological deficits were tested negative by fuPCR. 38.9% (14/36) of the fungi detected in respiratory samples of the immunosuppressed patients, belonged to Candida spp., 47.2% (17/36) to Saccharomyces spp., 5.6% (2/36) to Cladosporium spp

Assessment of the short-term safety and tolerability of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii (PR 259 CT1) in healthy volunteers: a clinical phase I study.

PubMed

Mesia, Kahunu; Cimanga, Kanyanga; Tona, Lutete; Mampunza, Ma Miezi; Ntamabyaliro, Nsengi; Muanda, Tsobo; Muyembe, Tamfum; Totté, Jozef; Mets, Tony; Pieters, Luc; Vlietinck, Arnold

2011-01-01

The aim of this study was to evaluate the short-term safety and tolerability of an antimalarial herbal medicinal product (PR 259 CT1) consisting of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii when given orally to healthy adult male volunteers. The amount of the major alkaloid strictosamide in the extract was determined by a validated HPLC method and was shown to be 5.6 %. The herbal preparation was formulated in a gelatine capsule form containing 500 mg of PCR 259 CT1. A sample of 15 healthy male volunteers, selected using the Lot Quality Assurance of Sampling (LQAS) method, was eligible for inclusion after fulfillment of the inclusion criteria and clinical examination by a physician. The volunteers were treated in an outpatient clinic with a drug regimen of two 500 mg capsules three times daily (each eight hours) for seven days, during meals. Safety and tolerability were monitored clinically, haematologically, biochemically and by electrocardiographic (ECG) examination at days 0, 1, 3, 7 and 14. Adverse effects were recorded by self-reporting of the participants or by detection of abnormalities in clinical examinations by a physician. The oral administration of PR 259 CT1 at high doses of 2 × 500 mg/capsule/day for 7 days was found to induce no significant changes in the concentration levels of all investigated haematological, biochemical, electrocardiogram and vital sign parameters and physical characteristics after 14 days of treatment compared to those seen in the baseline data. The concentration levels of all evaluated parameters were within the normal limits as reported in the literature. All adverse events noted were mild and self-resolving including increase of appetite (33 %), headache (20 %) and nausea (20 %). Other minor side effects were insomnia, somnolence and asthenia (7 %). Thus, PR 259 CT1 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II

Evaluation of the platelet counting by Abbott CELL-DYN SAPPHIRE haematology analyser compared with flow cytometry.

PubMed

Grimaldi, E; Del Vecchio, L; Scopacasa, F; Lo Pardo, C; Capone, F; Pariante, S; Scalia, G; De Caterina, M

2009-04-01

The Abbot Cell-Dyn Sapphire is a new generation haematology analyser. The system uses optical/fluorescence flow cytometry in combination with electronic impedance to produce a full blood count. Optical and impedance are the default methods for platelet counting while automated CD61-immunoplatelet analysis can be run as selectable test. The aim of this study was to determine the platelet count performance of the three counting methods available on the instrument and to compare the results with those provided by Becton Dickinson FACSCalibur flow cytometer used as reference method. A lipid interference experiment was also performed. Linearity, carryover and precision were good, and satisfactory agreement with reference method was found for the impedance, optical and CD61-immunoplatelet analysis, although this latter provided the closest results in comparison with flow cytometry. In the lipid interference experiment, a moderate inaccuracy of optical and immunoplatelet counts was observed starting from a very high lipid value.

Granulocytic sarcoma in a patient with chronic myeloid leukaemia in complete haematological, cytogenetic and molecular remission.

PubMed

Kittai, Adam; Yu, Eun-Mi; Tabbara, Imad

2014-12-23

Granulocytic sarcoma, also known as myeloid sarcoma, is an extramedullary tumour composed of immature myeloid cells. Granulocytic sarcoma is typically found in patients with acute myeloid leukaemia, accelerated phase or blast crisis of chronic myeloid leukaemia, myelodysplastic syndrome, or as an isolated event without bone marrow involvement. We present a case of granulocytic sarcoma in a patient with chronic myeloid leukaemia in the setting of complete haematological, molecular and cytogenetic remission. Our patient was first treated with imatinib for chronic-phase chronic myeloid leukaemia. After maintaining remission for 42 months, he developed a granulocytic sarcoma in his spine. In this case report, we describe our case, along with the three other cases reported in the literature. In addition to being a rare diagnosis, this case demonstrates the importance of being vigilant in diagnosing the cause of back pain and atypical symptoms in patients with a history of leukaemia. 2014 BMJ Publishing Group Ltd.

Effects of two diets on the haematology, plasma chemistry and intestinal flora of budgerigars (Melopsittacus undulatus).

PubMed

Fischer, I; Christen, C; Lutz, H; Gerlach, H; Hässig, M; Hatt, J-M

2006-10-07

Two groups of 22 budgerigars (Melopsittacus undulatus) were housed for 12 months under identical conditions. One group was fed a commercial seed mixture plus carrots and a mineral supplement, and the other group was fed a commercially formulated diet plus carrots. Samples of blood and faeces were collected initially and after three, six, nine and 12 months. There were no significant differences between the haematological values of the two groups. The group fed the seed mixture had significantly higher concentrations of glucose, albumin, triglycerides and uric acid, and higher activity of aspartate aminotransferase, but the values were within the published reference ranges for normal birds. There were no significant differences between the faecal samples from the two groups, except that the fungus Macrorhabdus ornithogaster was identified in 48.3 per cent of the samples from the group fed the commercially formulated diet but from only 3.4 per cent of the samples from the group fed the seed mixture.

The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients

PubMed Central

Jung, Donald; AbdelHameed, Magdy H; Hunter, John; Teitelbaum, Philip; Dorr, Albert; Griffy, Kay

1999-01-01

Aims We investigated the pharmacokinetics and safety profile of oral ganciclovir coadministered with trimethoprim in HIV-and CMV-seropositive patients. Methods In an open-label, randomized, 3-way crossover study, 12 adult males received oral ganciclovir 1000 mg every 8h, oral trimethoprim 200 mg once daily, or both drugs concomitantly in a sequence of three 7-day treatment periods. Pharmacokinetic parameters were determined and adverse events recorded for each treatment. Results The presence of trimethoprim significantly decreased CLr (12.9%, P = 0.0068) and increased t1/2 (18.1%, P = 0.0378) of ganciclovir. However, these changes are unlikely to be clinically meaningful. There were no statistically significant changes in trimethoprim pharmacokinetic parameters in the presence of ganciclovir, with the exception of a 12.7% increase in Cmin. Ganciclovir was well tolerated when administered alone or in combination with trimethoprim. Conclusions There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethoprim when coadministered. PMID:10215748

Efficacy and safety of biologic therapies for systemic lupus erythematosus treatment: systematic review and meta-analysis.

PubMed

Borba, Helena Hiemisch Lobo; Wiens, Astrid; de Souza, Thais Teles; Correr, Cassyano Januário; Pontarolo, Roberto

2014-04-01

The objectives of this study were to evaluate the efficacy, safety, and tolerability of biologic drugs compared with placebo for systemic lupus erythematosus (SLE) treatment. A systematic review evaluating the efficacy and safety of biologic therapies compared with placebo in adult SLE patients treatment was performed. Data from studies performed before September 2013 were collected from several databases (MEDLINE, Cochrane Library, SCIELO, Scopus, and International Pharmaceutical Abstracts). Study eligibility criteria included randomized, double-blind, placebo-controlled trials; regarding treatment with biologic agents in SLE adult patients; and published in English, German, Portuguese, and Spanish. Extracted data were statistically analyzed in a meta-analysis using the Review Manager (RevMan) 5.1 software. Efficacy outcomes included the SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus National Assessment version of the SLE Disease Activity Index) score, the SRI (Systemic Lupus Erythematosus Responder Index), normalization of low C3 (<90 mg/dL), anti-double-stranded DNA positive to negative, and no new BILAG (British Isles Lupus Assessment Group index) 1A or 2B flares. Data on safety profile included adverse events, serious and severe adverse events, death, malignancy, infections, and infusion reactions. We also evaluated withdrawals from treatment due to lack of efficacy or adverse events. Thirteen randomized placebo-controlled trials met the criteria for data extraction for systematic review. A meta-analysis regarding the efficacy and safety of belimumab compared with placebo involving four of these trials was undertaken and the remainder contributed to a meta-analysis of the safety of biologic agents. In addition, two trials allowed the performance of a meta-analysis regarding the efficacy and safety of rituximab compared with placebo. Belimumab was more effective than placebo in most evaluated outcomes. No significant differences in the safety and

Summary of School Safety Statistics. National Institute of Justice Report

ERIC Educational Resources Information Center

Carlton, Mary Poulin

2017-01-01

Several high-profile incidents of violence at U.S. schools have, understandably, raised concerns about the safety of students while at school. Just one incident of violence causes significant harm. In light of this, it is important to examine commonly held beliefs about school safety and violence because they sometimes reflect a misperception or…

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour-bearing dogs: A phase I dose finding study.

PubMed

Wouda, R M; Hocker, S E; Higginbotham, M L

2018-03-01

Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low-dose metronomic and/or anti-angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose-finding clinical trial assumed an open-label 3 + 3 cohort design. Client-owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled. No preference for tumour histology, grade or stage was expressed. Toceranib was administered at a dose of 2.75 mg kg -1 by mouth (PO) every other day (EOD), and carboplatin administered intravenously (IV) every 21 days at a starting dose of 200 mg m -2 . A total of 25% dose escalation was proposed for carboplatin, to a maximum of 300 mg m -2 . AEs were graded according to the Veterinary Cooperative Oncology Group's common terminology criteria for AEs (VCOG-CTCAE). Grade 3 haematologic or gastrointestinal AEs were nominated dose-limiting. Response to therapy was evaluated according to the VCOG's revised RECIST criteria. Eleven dogs were enrolled. Tumour histologies included sinonasal carcinoma, osteosarcoma, thyroid carcinoma, melanoma and apocrine gland anal sac adenocarcinoma. MTDs of carboplatin and toceranib were identified as 200 mg m -2 IV every 21 days and approximately 2.75 mg kg -1 PO EOD, respectively. The dose-limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well-tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials. © 2017 John Wiley & Sons Ltd.

The Psychosocial Experience of Adolescents with Haematological Malignancies in Jordan: An Interpretive Phenomenological Analysis Study

PubMed Central

2014-01-01

The qualitative research method of interpretive phenomenological analysis was used to explore the lived experience of 14 Jordanian adolescents with haematological malignancies. They were admitted to two hospitals in Jordan and were interviewed for this study twice during the first six months after receiving their diagnosis. The results of this study revealed three themes: (1) Being in hospital, (2) The changing self, and (3) Fearing the unknown. When the participants were hospitalised due to their illness they were removed from their families and friends and prevented from engaging in their normal daily routine. Participants also reported receiving limited emotional and psychological support from health team members during hospitalisation. From the onset of cancer treatments, the bio-psychosocial side effects of the chemotherapy became one of the most distressing factors for participants affecting all aspects of their life and generated uncertainty about their future. The findings add to existing understanding of the lived experiences of cancer patients and in particular Jordanian adolescents. They provide a valuable insight for clinicians into improvements in service delivery to this group of patients. PMID:24550700

Safety and pharmacokinetic profile of rufinamide in pediatric patients aged less than 4 years with Lennox-Gastaut syndrome: An interim analysis from a multicenter, randomized, active-controlled, open-label study.

PubMed

Arzimanoglou, Alexis; Ferreira, Jose A; Satlin, Andrew; Mendes, Shannon; Williams, Betsy; Critchley, David; Schuck, Edgar; Hussein, Ziad; Kumar, Dinesh; Dhadda, Shobha; Bibbiani, Francesco

2016-05-01

A good knowledge of safety and age group-specific pharmacokinetics (PK) of antiepileptic drugs (AEDs) in young pediatric patients is of great importance in clinical practice. This paper presents 6-month interim safety and PK from an ongoing 2-year open-label study (Study 303) of adjunctive rufinamide treatment in pediatric subjects ≥ 1 to < 4 years with inadequately controlled epilepsies of the Lennox-Gastaut syndrome (LGS) spectrum. Subjects (N = 37) were randomized to either rufinamide or any other approved AED chosen by the investigator as adjunctive therapy to the subject's existing regimen of 1-3 AEDs. Interim safety results showed that treatment-emergent adverse events (TEAEs) were similar between the rufinamide (22 [88.0%]) and any-other-AED group (9 [81.8%]), with most events considered mild or moderate. A population PK analysis was conducted including plasma rufinamide concentrations from Study 303 and two other study populations of LGS subjects ≥ 4 years. The rufinamide PK profile was dose independent. The apparent clearance (CL/F) estimated from the PK model was 2.19 L/h; it was found to increase significantly as a function of body weight. Coadministration of valproic acid significantly decreased rufinamide CL/F. CL/F was not significantly affected by other concomitant AEDs, age, gender, race, hepatic function, or renal function. No adjustments to body weight-based rufinamide dosing in subjects ≥ 1 to < 4 years are necessary. Rufinamide was safe and well tolerated in these pediatric subjects. Results from the interim analysis demonstrate that rufinamide's safety and PK profile is comparable in subjects ≥ 1 to < 4 and ≥ 4 years with LGS. Study 303 (clinicaltrials.gov: NCT01405053). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The effect of dietary cricket meal (Gryllus bimaculatus) on growth performance, antioxidant enzyme activities, and haematological response of African catfish (Clarias gariepinus).

PubMed

Taufek, Norhidayah Mohd; Aspani, Firdaus; Muin, Hasniyati; Raji, Ameenat Abiodun; Razak, Shaharudin Abdul; Alias, Zazali

2016-08-01

This study was conducted to investigate the growth performance, biomarkers of oxidative stress, catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) as well as the haematological response of African catfish after being fed with fish feed containing different levels of cricket meal. The juvenile fish were assigned to three different treatments with isonitrogenous (35 %) and isoenergetic (19 kJ g(-1)) diets containing 100 % cricket meal (100 % CM), 75 % cricket meal (75 % CM), and 100 % fishmeal (100 % FM) as control groups for 7 weeks. The results indicated that a diet containing 100 % CM and 75 % CM improved growth performance in terms of body weight gain and specific growth rate, when compared to 100 % FM. The feed conversion ratio (FCR) and protein efficiency ratio (PER) did not differ significantly between all diets, but reduced FCR and increased PER were observed with a higher inclusion of cricket meal. A haematological examination of fish demonstrated no significant difference of red blood cells in all diets and white blood cells showed a significantly higher value in fishmeal-fed fish. On the other hand, haemoglobin and haematocrit significantly increased with increasing amounts of cricket meal in the diet. Antioxidant activity of CAT was higher in the 100 % CM group compared to fish fed other diets, whereas GST and SOD showed increasing trends with a higher incorporation of cricket, although insignificant differences were observed between all diets. These results suggest that cricket meal could be an alternative to fishmeal as a protein source in the African catfish diet.

Fishmeal replacement with Spirulina Platensis and Chlorella vulgaris in African catfish (Clarias gariepinus) diet: Effect on antioxidant enzyme activities and haematological parameters.

PubMed

Raji, Ameenat Abiodun; Alaba, Peter Adeniyi; Yusuf, Hindatu; Abu Bakar, Noor Hidayati; Mohd Taufek, Norhidayah; Muin, Hasniyati; Alias, Zazali; Milow, Pozi; Abdul Razak, Shaharudin

2018-05-25

This study explored fishmeal replacement with two freshwater microalgae: Spirulina Platensis and Chlorella vulgaris in African catfish (Clarias gariepinus) diet. The effect of inclusion of the two microalgae on biomarkers of oxidative stress, haematological parameters, enzyme activities and growth performance were investigated. The juvenile fish were given 3 distinct treatments with isonitrogenous (35.01-36.57%) and isoenergetic (417.24-422.27 Kcal 100 g - 1) diets containing 50% S. platensis (50SP), 75% S. platensis (75SP), 50% C. vulgaris (50CL), 75% C. vulgaris (75CL) and 100% fishmeal (100% FM) was used as the control diet. The result shows that all the diets substituted with both S. platensis, and C. vulgaris boosted the growth performance based on specific growth rate (SGR) and body weight gain (BDWG) when compared with the control diet. The feed conversion ratio (FCR) and protein efficiency ratio (PER) was significantly influenced by all the supplementations. The haematological analysis of the fish shows a significant increase in the value of red and white blood cells upon supplementation with 50SP and 50CL but decrease slightly when increased to 75SP and 75CL. Furthermore, the value of haematocrit and haemoglobin also increased upon supplementation with 50SP and 50CL but decrease slightly when increased to 75SP and 75CL. The white blood cell (WBC), red blood cell (RBC) increased, while total cholesterol (TCL), and Plasma glucose levels decreased significantly upon supplementation of algae. This is a clear indication that S. platensis and C. vulgaris are a promising replacement for fishmeal, which is a source protein in the C. gariepinus diet. Copyright © 2018 Elsevier Ltd. All rights reserved.

An Airborne Millimeter-Wave FM-CW Radar for Thickness Profiling of Freshwater Ice

DTIC Science & Technology

1992-11-01

commercial and recreational application, including safety and trafficability surveys. A proto- type broadband millimeter wave (26.5 to 40 GHz) Frequency...and utility for ice safety and traffica- appropriate antenna for transmission. Morey (1974) bility studies. Other important applications include...resolution and a 2.7- which can provide reliable safety survey profiling for GHz center frequency, that is capable of airborne pro- the entire practical

Optimising a curriculum for clinical haematology and biochemistry in sports medicine: a Delphi approach

PubMed Central

Fallon, K E; Trevitt, A C

2006-01-01

Objectives To investigate issues of curriculum in the context of a postgraduate sports medicine training programme, specifically in the field of clinical biochemistry and haematology. Methods Following the Delphi methodology, a series of sequential questionnaires was administered to curriculum developers, clinical teachers, examiners, and registrars. Results Agreement on a core syllabus for this subject with an indication of the core aims and objectives of teaching and learning in this field and the associated required skills and competencies. An indication of current and ideal teaching and learning methods and reasons for these preferences. A consensus of key features of a teaching module for this field and of appropriate methods of examination. Conclusions The data derived from this study, as well as the experience of engaging in it, will better inform curriculum developers, teachers, and students of one another's perceptions as to what is important in and appropriate to teaching and learning in this field of sports medicine. Engagement in the exercise and broader consideration of the outcomes by those who develop the curriculum, teach, and formulate the examination process will facilitate attainment of the ideal of well aligned teaching, learning, and examination in this specific field. PMID:16432001

Budesonide Foam Has a Favorable Safety Profile for Inducing Remission in Mild-to-Moderate Ulcerative Proctitis or Proctosigmoiditis.

PubMed

Rubin, David T; Sandborn, William J; Bosworth, Brian; Zakko, Salam; Gordon, Glenn L; Sale, Mark E; Rolleri, Robert L; Golden, Pamela L; Barrett, Andrew C; Bortey, Enoch; Forbes, William P

2015-11-01

Budesonide foam, a rectally administered, second-generation corticosteroid with extensive hepatic first-pass metabolism, is efficacious for the treatment of mild-to-moderate ulcerative proctitis and ulcerative proctosigmoiditis. The aim of this study was to comprehensively assess the safety and pharmacokinetic profile of budesonide foam. Data from five phase III studies were pooled to further evaluate safety, including an open-label study (once-daily treatment for 8 weeks), an active-comparator study (once-daily treatment for 4 weeks), and two placebo-controlled studies and an open-label extension study (twice-daily treatment for 2 weeks, then once daily for 4 weeks). Data from the placebo-controlled studies and two phase I studies (i.e., patients with mild-to-moderate ulcerative colitis and healthy volunteers) were pooled to evaluate the pharmacokinetics of budesonide foam. A similar percentage of patients reported adverse events in the budesonide foam and placebo groups, with the majority of adverse events being mild or moderate in intensity (93.3 vs 96.0%, respectively). Adverse events occurred in 41.4 and 36.3% of patients receiving budesonide foam and placebo, respectively. Mean morning cortisol concentrations remained within the normal range for up to 8 weeks of treatment; there were no clinically relevant effects of budesonide foam on the hypothalamic-pituitary-adrenal axis. Population pharmacokinetic analysis demonstrated low systemic exposure after budesonide foam administration. This integrated analysis demonstrated that budesonide foam for the induction of remission of distal ulcerative colitis is safe overall, with no clinically relevant effects on the hypothalamic-pituitary-adrenal axis.

Preliminary studies on haematological and plasmatic parameters in gilthead sea bream (Sparus aurata) held under day/night temperature variations.

PubMed

Matias, Ana C; Ribeiro, Laura; Araujo, Ravi L; Pousão-Ferreira, Pedro

2018-02-01

This study aimed to evaluate to what extent diel water temperature oscillations over a short period of time (41 h) affected haematologic and plasmatic parameters of gilthead sea bream. Sea bream juveniles (160 fish; 177.2 ± 20.9 g) were divided in two homogenous groups, experimental and control. The experimental group was exposed to water at 22.3 ± 0.6 °C between 5 a.m. and 5 p.m. and to colder water from 5 p.m. to 5 a.m. (temperature variation of 8.6 ± 0.3 °C) during 41h period, whereas for the control group, water temperature was maintained constant (22.4 ± 0.7 °C) for the same period. Fish were fed three times per day (10:30 a.m., 2 p.m., 4 p.m.). Blood was collected from fish caudal veins (n = 6) at different time points (10 a.m., 1 p.m., 5 p.m., 6:30 p.m., 8 p.m. and 10 a.m. of the following day) from each group, for haematologic (haematocrit and haemoglobin) and plasmatic (glucose, cortisol, triglycerides and total protein) determinations. All parameters studied tended to vary throughout the study period, both for experimental and control groups. Significant differences were observed between the two groups for all the studied parameters at different sampling points. These differences were observed near the influence of the cold-water period or during the cooling-water period. Results suggested that colder water temperature cycles depressed fish metabolic activity and affected the levels of the analysed blood-circulating metabolites. Overall, results suggested that stress response was similar for experimental and control groups and that gilthead sea bream were able to cope with diel water temperature variations.

Safety and tolerability of new-generation anti-obesity medications: a narrative review.

PubMed

Patel, Dhiren K; Stanford, Fatima Cody

2018-03-01

The prevalence of obesity and associated comorbidities is rising. Despite their weight-loss efficacy, new generation anti-obesity medications are only prescribed to a minority of adults with obesity, possibly, which in part may be due to safety concerns. This review presents detailed safety profiles for orlistat, phentermine/topiramate, lorcaserin, naltrexone/bupropion and liraglutide 3.0 mg, and discusses the associated risk-benefit profiles. Two anti-obesity medications presented safety issues that warranted further discussion; phentermine/topiramate (fetal toxicity) and liraglutide 3.0 mg (risk of gallstone disease and mild, acute pancreatitis), whereas the adverse events associated with orlistat, lorcaserin, and naltrexone/bupropion were mostly transient tolerability issues. The difficulties surrounding the objective determination of risk-benefit for anti-obesity medications is discussed. The need for more long-term data, thorough patient assessment, individualization of pharmacological interventions and adherence to stopping rules to maximize risk-benefit are highlighted. Overall, the majority of new generation anti-obesity medications present encouraging tolerability profiles; however, in some cases a lack of long-term clinical trials confounds the accurate determination of risk-benefit.

Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology.

PubMed

Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne; Albertsen, Birgitte K; Frisk, Tony; Tedgård, Ulf; Jónsson, Ólafur G; Pruunsild, Kaie; Gretenkort Andersson, Nadine; Winther Gunnes, Maria; Saulyte Trakymiene, Sonata; Frandsen, Thomas; Heyman, Mats; Ruud, Ellen; Helgestad, Jon

2015-02-01

We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL 2008 protocol. The cumulative incidence of CSVT was 2%. Sixteen of the thromboses were related to asparaginase and 16 to steroids. Most CSVTs occurred in the consolidation phase. Nearly all were treated with low molecular weight heparin without bleeding complications. Mortality related to CSVT directly or indirectly was 10%, emphasizing the importance of this complication. © 2014 John Wiley & Sons Ltd.

Nonbibliographic Databases in a Corporate Health, Safety, and Environment Organization.

ERIC Educational Resources Information Center

Cubillas, Mary M.

1981-01-01

Summarizes the characteristics of TOXIN, CHEMFILE, and the Product Profile Information System (PPIS), nonbibliographic databases used by Shell Oil Company's Health, Safety, and Environment Organization. (FM)

Burnout and occupational stress in the medical residents of Oncology, Haematology and Radiotherapy: a prevalence and predictors study in Portugal.

PubMed

Joaquim, Ana; Custódio, Sandra; Savva-Bordalo, Joana; Chacim, Sérgio; Carvalhais, Inês; Lombo, Liliana; Lopes, Heitor; Araújo, António; Gomes, Rui

2018-03-01

Burnout is a professional syndrome associated with stress caused by overwork. Our aim was to calculate the prevalence of burnout and stress on medical residents of Oncology, Haematology and Radiotherapy in Portugal, as well as to determine predictors of burnout and stress. An anonymous questionnaire was applied (n = 118). Statistical analysis consisted of a descriptive and inferential analysis. The prevalence of burnout and stress was calculated to be 45.2 and 50%, respectively. The dimensions that generated higher levels of stress were 'dealing with patients' and 'overwork'. Burnout was directly related with stress dimension 'overwork'. The prevalence of burnout in Portuguese oncological residents is high as in other European countries and in the U.S. Therefore, interventional strategies can be designed.

Orlando Magic: report from the 57th meeting of the American Society of Haematology, 5-7 December 2015, Orlando, USA.

PubMed

Mazzarella, Luca

2016-01-01

The 57th American Society of Haematology (ASH) meeting held in Orlando, FL was certainly the year when myeloma management changed for good, with a plethora of newly Food and Drug Administration (FDA)-approved drugs showing impressive outcome improvements and the introduction of new techniques for disease monitoring. Also, chimeric antigen receptor (CAR) T cells continued their triumphal march, consolidating their success in lymphoma and chronic lymhocytic leukaemia (CLL) and venturing into new fields such as again multiple myeloma. Some experimental drugs showed long-awaited results (midostaurin in FLT3-mutated acute myeloid leukaemia (AML)) and some brand new drugs showed promising results in the clinic after extensive preclinical studies, such as those targeting new epigenetic factors (histone methyltransferases) and apoptosis.

Drug safety evaluation of defibrotide.

PubMed

Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

2013-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

PubMed

2010-09-29

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

Nanodrugs: pharmacokinetics and safety

PubMed Central

Onoue, Satomi; Yamada, Shizuo; Chan, Hak-Kim

2014-01-01

To date, various nanodrug systems have been developed for different routes of administration, which include dendrimers, nanocrystals, emulsions, liposomes, solid lipid nanoparticles, micelles, and polymeric nanoparticles. Nanodrug systems have been employed to improve the efficacy, safety, physicochemical properties, and pharmacokinetic/pharmacodynamic profile of pharmaceutical substances. In particular, functionalized nanodrug systems can offer enhanced bioavailability of orally taken drugs, prolonged half-life of injected drugs (by reducing immunogenicity), and targeted delivery to specific tissues. Thus, nanodrug systems might lower the frequency of administration while providing maximized pharmacological effects and minimized systemic side effects, possibly leading to better therapeutic compliance and clinical outcomes. In spite of these attractive pharmacokinetic advantages, recent attention has been drawn to the toxic potential of nanodrugs since they often exhibit in vitro and in vivo cytotoxicity, oxidative stress, inflammation, and genotoxicity. A better understanding of the pharmacokinetic and safety characteristics of nanodrugs and the limitations of each delivery option is necessary for the further development of efficacious nanodrugs with high therapeutic potential and a wide safety margin. This review highlights the recent progress in nanodrug system development, with a focus on the pharmacokinetic advantages and safety challenges. PMID:24591825

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data.

PubMed

Endrikat, J; Schwenke, C; Prince, M R

2015-07-01

To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18-64 years. Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. Copyright © 2015 The Royal College of Radiologists. All rights reserved.

Cardiovascular risk-benefit profile of sibutramine.

PubMed

Scheen, A J

2010-01-01

Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of these complex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular outcomes might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT

2011 Annual Meeting of the Safety Pharmacology Society: an overview.

PubMed

Cavero, Icilio

2012-03-01

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

Formalising multidisciplinary peer review: developing a haematological malignancy-specific electronic proforma and standard operating procedure to facilitate procedural efficiency and evidence-based clinical practice.

PubMed

Trotman, Judith; Trinh, Jimmy; Kwan, Yiu Lam; Estell, Jane A; Fletcher, Julie; Archer, Kate; Lee, Kenneth; Foo, Kerwin; Curnow, Jennifer; Bianchi, Alessandra; Wignall, Lynda; Verner, Emma; Gasiorowski, Robin; Siedlecka, Elizabeth; Cunningham, Ilona

2017-05-01

Multidisciplinary team (MDT) meetings aimed at facilitating peer review have become standard practice in oncology. However, there is scant literature on the optimal structure and conduct of such meetings. To develop a process for formal peer review of patients with haematological malignancies and to audit any resulting changes made to the management recommendations of the treating physician. A standard operating procedure (SOP) for MDT meetings was developed essentially to integrate clinical peer review with weekly pathology and radiology meetings. The centrepiece is the electronic submission of a patient-specific proforma (Microsoft InfoPath) prior to the meeting. It serves as the template for presentation, discussion and recording of recommendations and conclusions. The final verified document is stored in the electronic patient record, and a copy is sent to the general practitioner. The proposed management plans were compared to the consensus recommendations of the meeting for the first 4 years since inception. Both SOP and proforma underwent continual improvements. These provided the framework for the conduct of a robust weekly MDT meeting for peer review of the management of patients with haematological malignancies. On 20% of occasions, patient management plans were altered to optimise patient care as a direct consequence on peer review at the MDT. Our streamlined process, in its ultimate format, has provided a mature and efficient forum for formal peer review in a genuine multidisciplinary environment. Both initial data and informal feedback support its ongoing activity as an integral component of delivering quality patient care. © 2016 Royal Australasian College of Physicians.

Speed Profiles for Deceleration Guidance During Rollout and Turnoff (ROTO)

NASA Technical Reports Server (NTRS)

Barker, L. Keith; Hankins, Walter W., III; Hueschen, Richard M.

1999-01-01

Two NASA goals are to enhance airport safety and to improve capacity in all weather conditions. This paper contributes to these goals by examining speed guidance profiles to aid a pilot in decelerating along the runway to an exit. A speed profile essentially tells the pilot what the airplane's speed should be as a function of where the airplane is on the runway. While it is important to get off the runway as soon as possible (when striving to minimize runway occupancy time), the deceleration along a speed profile should be constrained by passenger comfort. Several speed profiles are examined with respect to their maximum decelerations and times to reach exit speed. One profile varies speed linearly with distance; another has constant deceleration; and two related nonlinear profiles delay maximum deceleration (braking) to reduce time spent on the runway.

Transarterial Chemoembolization for Hepatocellular Carcinoma with a New Generation of Beads: Clinical–Radiological Outcomes and Safety Profile

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spreafico, Carlo, E-mail: carlo.spreafico@istitutotumori.mi.it; Cascella, Tommaso, E-mail: tommaso.cascella@istitutotumori.mi.it; Facciorusso, Antonio, E-mail: antonio.facciorusso@istitutotumori.mi.it

PurposeTo evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT).MethodsForty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response.ResultsAll patients had well-compensated cirrhosismore » (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures).ConclusionDEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.« less

Changes in haematology measurements with the Sysmex XT-2000iV during storage of feline blood sampled in EDTA or EDTA plus CTAD.

PubMed

Granat, Fanny; Geffré, Anne; Bourgès-Abella, Nathalie; Braun, Jean-Pierre; Trumel, Catherine

2013-06-01

In veterinary medicine a complete blood cell count (CBC) cannot always be performed within 24 h as usually recommended, particularly for specimens shipped to a reference laboratory. This raises the question of the stability of the variables, especially in ethylenediamine tetra-acetic acid (EDTA) feline blood specimens, known to be prone to in vitro platelet aggregation. Citrate, theophylline, adenosine and dipyridamole (CTAD) has been reported to limit platelet aggregation in feline blood specimens. The aim of this study was to measure the stability of the haematological variables and the platelet aggregation score in EDTA and EDTA plus CTAD (EDCT) feline blood specimens during 48 h of storage at room temperature. Forty-six feline EDTA and EDCT blood specimens were analysed with a Sysmex XT-2000iV analyser, and the platelet count and score of platelet aggregation were estimated immediately and after 24 and 48 h of storage. A significant increase in mean corpuscular volume, haematocrit, reticulocyte and eosinophil counts, and a significant decrease in mean corpuscular haemoglobin concentration and monocyte count were observed. Haemoglobin, mean corpuscular haemoglobin, and red blood cell, white blood cell, neutrophil and lymphocyte counts remained stable. Changes in reticulocyte indexes with time (low fluorescence ratio, medium fluorescence ratio, high fluorescence ratio and immature reticulocyte fraction) were not significant. Changes were generally more pronounced in EDTA than in EDCT. Platelet aggregation decreased markedly in initially highly aggregated EDTA specimens, and increased slightly in initially non- or mildly-aggregated EDTA or EDCT specimens. Platelet counts increased and decreased, or remained stable, respectively. CTAD can reduce storage-induced changes of the haematological variables in feline samples, thus improving the reliability of a CBC and limiting clinical misinterpretations.

Evaluation of biochemical and haematological parameters and prevalence of selected pathogens in feral cats from urban and rural habitats in South Korea.

PubMed

Hwang, Jusun; Gottdenker, Nicole; Min, Mi-Sook; Lee, Hang; Chun, Myung-Sun

2016-06-01

In this study, we evaluated the potential association between the habitat types of feral cats and the prevalence of selected infectious pathogens and health status based on a set of blood parameters. We live-trapped 72 feral cats from two different habitat types: an urban area (n = 48) and a rural agricultural area (n = 24). We compared blood values and the prevalence of feline immunodeficiency virus (FIV), feline leukaemia virus (FeLV) and haemotropic Mycoplasma infection in feral cats from the two contrasting habitats. Significant differences were observed in several blood values (haematocrit, red blood cells, blood urea nitrogen, creatinine) depending on the habitat type and/or sex of the cat. Two individuals from the urban area were seropositive for FIV (3.0%), and eight (12.1%) were positive for FeLV infection (five from an urban habitat and three from a rural habitat). Haemoplasma infection was more common. Based on molecular analysis, 38 cats (54.3%) were positive for haemoplasma, with a significantly higher infection rate in cats from rural habitats (70.8%) compared with urban cats (47.8%). Our study recorded haematological and serum biochemical values, and prevalence of selected pathogens in feral cat populations from two different habitat types. A subset of important laboratory parameters from rural cats showed values under or above the corresponding reference intervals for healthy domestic cats, suggesting potential differences in the health status of feral cats depending on the habitat type. Our findings provide information about the association between 1) blood values (haematological and serum biochemistry parameters) and 2) prevalence of selected pathogen infections and different habitat types; this may be important for veterinarians who work with feral and/or stray cats and for overall cat welfare management. © ISFM and AAFP 2015.

Advanced Range Safety System for High Energy Vehicles

NASA Technical Reports Server (NTRS)

Claxton, Jeffrey S.; Linton, Donald F.

2002-01-01

The advanced range safety system project is a collaboration between the National Aeronautics and Space Administration and the United States Air Force to develop systems that would reduce costs and schedule for safety approval for new classes of unmanned high-energy vehicles. The mission-planning feature for this system would yield flight profiles that satisfy the mission requirements for the user while providing an increased quality of risk assessment, enhancing public safety. By improving the speed and accuracy of predicting risks to the public, mission planners would be able to expand flight envelopes significantly. Once in place, this system is expected to offer the flexibility of handling real-time risk management for the high-energy capabilities of hypersonic vehicles including autonomous return-from-orbit vehicles and extended flight profiles over land. Users of this system would include mission planners of Space Launch Initiative vehicles, space planes, and other high-energy vehicles. The real-time features of the system could make extended flight of a malfunctioning vehicle possible, in lieu of an immediate terminate decision. With this improved capability, the user would have more time for anomaly resolution and potential recovery of a malfunctioning vehicle.

Alteration of plasma biochemical, haematological and ocular oxidative indices of alloxan induced diabetic rats by aqueous extract of Tridax procumbens Linn (Asteraceae).

PubMed

Ikewuchi, Jude Chigozie

2012-01-01

In this study, the effects of an aqueous extract of the leaves of Tridax procumbens on the haematology, plasma biochemistry and ocular indices of oxidative stress was investigated in alloxan induced diabetic rats. Diabetes mellitus was induced by injection of alloxan (80 mg/kg body weight), via the tail vein. The extract was administered orally at 100, 200 and 300 mg/kg (both to normal and diabetic rats), and metformin at 50 mg/kg. On gas chromatographic analysis of the alkaloid fraction of the aqueous extract, thirty nine known alkaloids were detected, consisting mainly of 73.91 % akuamidine, 22.33 % voacangine, 1.27 % echitamine, 0.55 % echitamidine, 0.36 % lupanine, 0.27 % crinamidine, 0.23 % augustamine and 0.10 % 6-hydroxypowelline. Tannic acid and β-sitosterol were detected in high quantities. Compared to Test control, the treatment dose-dependently, significantly lowered (P<0.05) plasma glucose, triglyceride, very low density lipoprotein cholesterol, total bilirubin, urea, blood urea nitrogen; plasma alkaline phosphatase, alanine and aspartate transaminases, and ocular superoxide dismutase activities, and lymphocyte count. It also significantly increased (P<0.05) plasma calcium and ocular ascorbic acid contents, haemoglobin concentration and neutrophil count. This study showed that the extract was hypoglycemic, positively affected the haemopoietic system and integrity and function (dose dependently) of the liver and kidney of the diabetic rats; improved the lipid profile and had no deleterious effect on red cell morphology and protected against oxidative stress in ocular tissues. This study also revealed the presence of pharmacologically active compounds in the leaf extract. All of these, highlight the cardioprotective potential of the leaves of Tridax procumbens, and support its use in traditional health care practices for the management of diabetes mellitus.

Alteration of plasma biochemical, haematological and ocular oxidative indices of alloxan induced diabetic rats by aqueous extract of Tridax procumbens Linn (Asteraceae)

PubMed Central

Ikewuchi, Jude Chigozie

2012-01-01

In this study, the effects of an aqueous extract of the leaves of Tridax procumbens on the haematology, plasma biochemistry and ocular indices of oxidative stress was investigated in alloxan induced diabetic rats. Diabetes mellitus was induced by injection of alloxan (80 mg/kg body weight), via the tail vein. The extract was administered orally at 100, 200 and 300 mg/kg (both to normal and diabetic rats), and metformin at 50 mg/kg. On gas chromatographic analysis of the alkaloid fraction of the aqueous extract, thirty nine known alkaloids were detected, consisting mainly of 73.91 % akuamidine, 22.33 % voacangine, 1.27 % echitamine, 0.55 % echitamidine, 0.36 % lupanine, 0.27 % crinamidine, 0.23 % augustamine and 0.10 % 6-hydroxypowelline. Tannic acid and β-sitosterol were detected in high quantities. Compared to Test control, the treatment dose-dependently, significantly lowered (P<0.05) plasma glucose, triglyceride, very low density lipoprotein cholesterol, total bilirubin, urea, blood urea nitrogen; plasma alkaline phosphatase, alanine and aspartate transaminases, and ocular superoxide dismutase activities, and lymphocyte count. It also significantly increased (P<0.05) plasma calcium and ocular ascorbic acid contents, haemoglobin concentration and neutrophil count. This study showed that the extract was hypoglycemic, positively affected the haemopoietic system and integrity and function (dose dependently) of the liver and kidney of the diabetic rats; improved the lipid profile and had no deleterious effect on red cell morphology and protected against oxidative stress in ocular tissues. This study also revealed the presence of pharmacologically active compounds in the leaf extract. All of these, highlight the cardioprotective potential of the leaves of Tridax procumbens, and support its use in traditional health care practices for the management of diabetes mellitus. PMID:27418906

Guidelines for May-Grünwald-Giemsa staining in haematology and non-gynaecological cytopathology: recommendations of the French Society of Clinical Cytology (SFCC) and of the French Association for Quality Assurance in Anatomic and Cytologic Pathology (AFAQAP).

PubMed

Piaton, E; Fabre, M; Goubin-Versini, I; Bretz-Grenier, M-F; Courtade-Saïdi, M; Vincent, S; Belleannée, G; Thivolet, F; Boutonnat, J; Debaque, H; Fleury-Feith, J; Vielh, P; Egelé, C; Bellocq, J-P; Michiels, J-F; Cochand-Priollet, B

2016-10-01

Since the guidelines of the International Committee for Standardisation in Haematology (ICSH) in 1984 and those of the European Committee for External Quality Assessment Programmes in Laboratory Medicine (EQALM) in 2004, no leading organisation has published technical recommendations for the preparation of air-dried cytological specimens using May-Grünwald-Giemsa (MGG) staining. Literature data were retrieved using reference books, baseline-published studies, articles extracted from PubMed/Medline and Google Scholar, and online-available industry datasheets. The present review addresses all pre-analytical issues concerning the use of Romanowsky's stains (including MGG) in haematology and non-gynaecological cytopathology. It aims at serving as actualised, best practice recommendations for the proper handling of air-dried cytological specimens. It, therefore, appears complementary to the staining criteria of the non-gynaecological diagnostic cytology handbook edited by the United Kingdom National External Quality Assessment Service (UK-NEQAS) in February 2015. © 2016 John Wiley & Sons Ltd.

Vitamin D3 supplementation does not modify cardiovascular risk profile of adults with inadequate vitamin D status.

PubMed

Seibert, Eric; Lehmann, Ulrike; Riedel, Annett; Ulrich, Christof; Hirche, Frank; Brandsch, Corinna; Dierkes, Jutta; Girndt, Matthias; Stangl, Gabriele I

2017-03-01

The Nutrition Societies in Germany, Austria, and Switzerland recommend a daily intake of 20 µg vitamin D 3 for adults when endogenous synthesis is absent. The current study aimed to elucidate whether this vitamin D 3 dose impacts cardiovascular risk markers of adults during the winter months. The study was conducted in Halle (Saale), Germany (51 o northern latitude) as a placebo-controlled, double-blinded, randomised trial (from January to April). A total of 105 apparently healthy subjects (male and female, 20-71 years old) were included. Subjects were randomly allocated to two groups. One group received a daily 20-µg vitamin D 3 dose (n = 54), and the other group received a placebo (n = 51) for 12 weeks. Outcome measures included blood pressure, heart rate, concentrations of renin, aldosterone, serum lipids and vascular calcification markers, and haematologic variables such as pro-inflammatory monocytes. Blood pressure and systemic cardiovascular risk markers remained unchanged by vitamin D 3 supplementation, although serum 25-hydroxyvitamin D 3 increased from 38 ± 14 to 73 ± 16 nmol/L at week 12. The placebo and vitamin D groups did not differ in their final cardiovascular risk profile. Daily supplementation of 20 µg vitamin D 3 during winter is unlikely to change cardiovascular risk profile.

Haematology and serum chemistry of Pyrenean chamois (Rupicapra pyrenaica) naturally infected with a border disease virus.

PubMed

Fernández-Sirera, L; Mentaberre, G; López-Olvera, J R; Cuenca, R; Lavín, S; Marco, I

2011-06-01

In 2005 and 2006 an outbreak of disease associated with border disease virus (BDV) infection caused high mortality in the Pyrenean chamois (Rupicapra pyrenaica) in the Catalan Pyrenees (NE Spain). The aim of this study was to determine values for different haematological and serum biochemical analytes in 32 free-ranging Pyrenean chamois affected by the disease and to compare them with those obtained from healthy chamois. In the affected chamois red blood cell counts, haemoglobin concentrations, packed cell volumes, mean corpuscular volumes and lymphocyte counts were all lower, while the neutrophil and platelet counts were higher. Glucose, lactate, triglycerides, creatinine, total protein concentrations and alkaline phosphatase activity were also lower, in contrast to the concentrations of total bilirubin, urea and aspartate aminotransferase activity, which were higher. Most of the observed changes could be associated with cachexia and inflammation in the affected chamois. Lymphopenia could be directly related to the BDV, which would lead to immunosuppression and explain the high rate of secondary infection observed in these animals. Copyright © 2010 Elsevier Ltd. All rights reserved.

Profiler Support for Operations at Space Launch Ranges

NASA Technical Reports Server (NTRS)

Merceret, Francis; Wilfong, Timothy; Lambert, Winifred; Short, David; Decker, Ryan; Ward, Jennifer

2006-01-01

Accurate vertical wind profiles are essential to successful launch or landing. Wind changes can make it impossible to fly a desired trajectory or avoid dangerous vehicle loads, possibly resulting in loss of mission. Balloons take an hour to generate a profile up to 20 km, but major wind changes can occur in 20 minutes. Wind profilers have the temporal response to detect such last minute hazards. They also measure the winds directly overhead while balloons blow downwind. At the Eastern Range (ER), altitudes from 2 to 20 km are sampled by a 50-MHz profiler every 4 minutes. The surface to 3 km is sampled by five 915-MHz profilers every 15 minutes. The Range Safety office assesses the risk of potential toxic chemical dispersion. They use observational data and model output to estimate the spatial extent and concentration of substances dispersed within the boundary layer. The ER uses 915-MHz profilers as both a real time observation system and as input to dispersion models. The WR has similar plans. Wind profilers support engineering analyses for the Space Shuttle. The 50-IVl11z profiler was used recently to analyze changes in the low frequency wind and low vertical wavenumber content of wind profiles in the 3 to 15 km region of the atmosphere. The 915-MHz profiler network was used to study temporal wind change within the boundary layer.

CD56‐positive haematological neoplasms of the skin: a multicentre study of the Cutaneous Lymphoma Project Group of the European Organisation for Research and Treatment of Cancer

PubMed Central

Assaf, Chalid; Gellrich, Sylke; Whittaker, Sean; Robson, Alistair; Cerroni, Lorenzo; Massone, Cesare; Kerl, Helmut; Rose, Christian; Chott, Andreas; Chimenti, Sergio; Hallermann, Christian; Petrella, Tony; Wechsler, Janine; Bagot, Martine; Hummel, Michael; Bullani‐Kerl, Katrin; Bekkenk, Marcel W; Kempf, Werner; Meijer, Chris J L M; Willemze, Rein; Sterry, Wolfram

2007-01-01

Background Cutaneous lymphomas expressing CD56, a neural cell adhesion molecule, are characterised in most cases by a highly aggressive clinical course and a poor prognosis. However, prognostic subsets within the CD56+ group have been difficult to identify due to the lack of uniform clinicopathological and immunophenotypical criteria. Methods A multicentre study was conducted by the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer to define prognostic parameters and establish diagnostic and therapeutic guidelines for CD56+ haematological neoplasms presenting primarily in the skin. Results Four different subtypes of lymphoproliferations with CD56 expression were identified: (1) haematodermic neoplasm; (2) skin infiltration as the first manifestation of CD56+ acute myeloid leukaemia; (3) nasal‐type extranodal natural killer/T‐cell lymphoma; and (4) “classical” cases of cutaneous T‐cell lymphoma (CTCL) with co‐expression of the CD56 molecule. Patients in the first three groups had a poor outcome (93% died) with a median survival rate of 11 months (95% CI 2–72 months), whereas all patients with CD56+ CTCL were alive at the last follow‐up. Conclusion Results show that CD56+ cutaneous lymphoproliferative disorders, with the exception of CD56+ CTCL have a very poor prognosis. It is therefore clinically important to separate CD56+ CTCL from the remaining CD56+ haematological disorders. PMID:17018683

How is dietary diversity related to haematological status of preschool children in Ghana?

PubMed

Saaka, Mahama; Galaa, Sylvester Zakaria

2017-01-01

Background: The role of dietary diversity on blood biomarkers may be significant, but the evidence is limited. Objective: This study assessed the association between dietary diversity and haematological status of children aged 6-59 months controlling for various known confounders. Design: The analysis in this study is based on the 2014 Ghana Demographic and Health survey data.The study involved 2,388 pre-school children aged 6-59 months who constituted the sub-sample for anaemia assessment. Results: The mean haemoglobin concentration (Hb) was 10.2 g/dl ± 1.50 (95 % CI: 10.1 to 10.3), and anaemia prevalence (Hb < 11 g/dl) among children aged 6-59 months was 66.8 % (CI: 63.7 to 69.8). In multivariable logistic regression analysis,continued breastfeeding [Adjusted odds ratio (AOR) = 1.9 (95% CI: 1.19-2.91], 12-23 months of age (AOR = 2.4 (95% CI: 1.40-3.98), having fever in last two weeks (AOR = 1.7 (95% CI: 1.20-2.45, birth interval ≤ 24 months (AOR = 1.9 (1.20-2.84), and poorest wealth quintile (AOR = 2.6 (95% CI: 1.48-4.48) were positively associated with anaemia. Conclusion: The current study showed that factors other than poor dietary diversity predicted anaemia among children aged 6-59 months in Ghana.

Evaluation of the safety profile of an electronic vapour product used for two years by smokers in a real-life setting.

PubMed

Walele, Tanvir; Bush, Jim; Koch, Annelize; Savioz, Rebecca; Martin, Claire; O'Connell, Grant

2018-02-01

The safety profile of Puritane™, a closed system electronic vapour product (EVP), was evaluated when used by smokers of conventional cigarettes (CCs) for 24 months in a real-life setting. The study was a two-centre ambulatory clinical study with 209 healthy volunteers. Outcome measures included adverse events (AEs), vital signs, electrocardiogram, lung function tests, exposure to nicotine and selected smoke constituents, nicotine withdrawal effects and smoking desire. No serious AEs related to EVP use were observed. The most frequently reported AEs were headache, nasopharyngitis, sore throat and cough, reported by 28.7%, 28.7%, 19.6% and 16.7% of subjects, respectively, which dissipated over time. Small decreases in lung function were not considered clinically relevant. No clinically relevant findings were observed in the other safety parameters. From Month 2, nicotine withdrawal symptoms decreased. Smoking desire and CC consumption steadily decreased over time in all subjects. EVP use was associated with reduced exposure to cigarette smoke constituents, whereas urinary nicotine levels remained close to baseline. Body weight did not increase in CC subjects switching to the EVP. In conclusion, the aerosol of the EVP at study was well tolerated and not associated with any clinically relevant health concerns after usage for up to 24 months. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

International Council for Standardization in Haematology (ICSH) Recommendations for Laboratory Measurement of Direct Oral Anticoagulants.

PubMed

Gosselin, Robert C; Adcock, Dorothy M; Bates, Shannon M; Douxfils, Jonathan; Favaloro, Emmanuel J; Gouin-Thibault, Isabelle; Guillermo, Cecilia; Kawai, Yohko; Lindhoff-Last, Edelgard; Kitchen, Steve

2018-03-01

This guidance document was prepared on behalf of the International Council for Standardization in Haematology (ICSH) for providing haemostasis-related guidance documents for clinical laboratories. This inaugural coagulation ICSH document was developed by an ad hoc committee, comprised of international clinical and laboratory direct acting oral anticoagulant (DOAC) experts. The committee developed consensus recommendations for laboratory measurement of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban), which would be germane for laboratories assessing DOAC anticoagulation. This guidance document addresses all phases of laboratory DOAC measurements, including pre-analytical (e.g. preferred time sample collection, preferred sample type, sample stability), analytical (gold standard method, screening and quantifying methods) and post analytical (e.g. reporting units, quality assurance). The committee addressed the use and limitations of screening tests such as prothrombin time, activated partial thromboplastin time as well as viscoelastic measurements of clotting blood and point of care methods. Additionally, the committee provided recommendations for the proper validation or verification of performance of laboratory assays prior to implementation for clinical use, and external quality assurance to provide continuous assessment of testing and reporting method. Schattauer GmbH Stuttgart.

Patients with haematological malignancies show a restricted body image focusing on function and emotion.

PubMed

Weber, C S; Fliege, H; Arck, P C; Kreuzer, K-A; Rose, M; Klapp, B F

2005-05-01

The diagnosis of cancer threatens the psychological and bodily integrity. Based on this assumption, we aimed to explore how newly diagnosed patients cope with special regard to the body image (BI). In total, 40 patients (32 haematological malignancies) were assessed by questionnaires on mood, complaints, self-regulation and quality of life (QOL). The BI was assessed by the 'Body Grid' which reveals the constructs patients choose to characterize the body. The constructs were categorized using a model of six predefined categories comprising: emotion, control, activity, strength, function and appearance. Tinnitus sufferers and medical students served as comparison groups. Cancer patients showed significantly more anxious depression and a significantly lower QOL than controls. Their BI was restricted, focusing the functional status of body organs (e.g. opposing healthy vs. ill organs) as well as emotional aspects (e.g. trust vs. fear). The data convey fundamental psychological distress in newly diagnosed cancer patients. Restriction of BI and use of functional constructs may help to buffer the threat to body integrity. The emotional constructs reflect the existential impact. The data give a clear indication for the need for early psychosocial support which should aim at stabilizing the psychological and bodily integrity of the patient.

Use of a risk characterisation approach to contextualise the safety profile of new rheumatoid arthritis treatments: a case study using tofacitinib.

PubMed

Curtis, Jeffrey R; Zhang, Richard; Krishnaswami, Sriram; Anisfeld, Andrew; Chen, Yan; Strengholt, Sander; Chen, Connie; Geier, Jamie

2017-03-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To characterise the relative safety profile of tofacitinib to biologic disease-modifying antirheumatic drugs (bDMARDs), the accrued patient-years (pt-yrs) of exposure needed in an RA clinical trial programme to detect a potential increase in risk of specific adverse events (AEs) was determined. This case study/framework was constructed on the pt-yrs' accrual within pooled phase (P)1, P2 and P3, as well as long-term extension, studies of tofacitinib in RA (March 2015 data-cut) and published AE incidence rates for bDMARDs. Sample size calculations were based on a Poisson distribution to estimate pt-yrs' exposure required for 90 % probability that the lower bound of the 95 % confidence interval for tofacitinib/bDMARD would be >1, assuming that tofacitinib rates were 1.2×/1.5×/2.0× greater than comparator rates. AE rates for bDMARDs were derived from sources intended to optimise similarity with the tofacitinib database in terms of baseline characteristics, study duration and follow-up. Based on the tofacitinib exposure accrued (19,406 pt-yrs), data were sufficient (90 % probability) to detect potential differences over external bDMARD comparator rates in serious infections (≥1.2×), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, major adverse cardiovascular events (MACE) and lymphoma (each ≥1.5×), as well as opportunistic infections and gastrointestinal perforations (≥2×), should they exist. This risk characterisation approach can support the comparative safety of new RA medications. To date, tofacitinib safety appears similar to approved published data from bDMARDs with respect to serious infections, malignancies (excluding NMSC), NMSC, MACE, lymphoma, opportunistic infections and gastrointestinal perforations.

The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese patients with osteoporosis: interim report.

PubMed

Saito, Hitoshi; Kakihata, Hiroyuki; Nishida, Yosuke; Yatomi, Sawako; Nihojima, Shigeru; Kobayashi, Yumiko; Tabata, Hidehiro; Nomura, Makoto

2017-07-01

This large-scale post-marketing surveillance study was conducted to assess the safety and effectiveness of eldecalcitol treatment in patients with osteoporosis in a Japanese clinical setting. A total of 3567 patients with osteoporosis were enrolled and received eldecalcitol 0.75 μg/day for 12 months. For this interim report, 3285 patients were eligible for analysis. Mean age was 74.9 ± 8.7 years; 86.8 % (2854/3285) were women. There were 142 reported adverse drug reactions (ADRs) in 129 patients (3.92 % of the total 3285 patients): the most common were hypercalcemia and increased blood calcium (0.88 %), renal impairment (0.27 %), abdominal discomfort (0.24 %), constipation (0.24 %), and pruritus (0.24 %). The incidence of ADRs was 5.10 % in men and 3.74 % in women. Although 10 serious ADRs were reported in 9 patients (0.27 %), no clinically significant safety issues were identified. Incidence of hypercalcemia or increased blood calcium was 8.47 % in patients with renal impairment and only 0.74 % in patients without renal impairment. At last observation, the incidence of new vertebral and nonvertebral fractures was 2.44 % and 1.70 %, respectively. There was a significant increase in bone mineral density at the lumbar spine and distal radius. The bone turnover markers BAP, serum NTX, urinary NTX, and TRACP-5b were suppressed by eldecalcitol treatment in both sexes. In conclusion, consistent with the findings of the phase III pivotal clinical trial, eldecalcitol was shown to have a favorable safety profile and effectiveness in Japanese patients with osteoporosis. However, periodic measurements of serum calcium were required to prevent occurrence of hypercalcemia during eldecalcitol treatment, especially in patients with renal impairment.

Pharmacokinetics of piperaquine and safety profile of dihydroartemisinin-piperaquine co-administered with antiretroviral therapy in malaria-uninfected HIV-positive Malawian adults.

PubMed

Banda, Clifford G; Dzinjalamala, Fraction; Mukaka, Mavuto; Mallewa, Jane; Maiden, Victor; Terlouw, Dianne J; Lalloo, David G; Khoo, Saye H; Mwapasa, Victor

2018-05-21

There are limited data on the pharmacokinetic and safety profiles of dihydroartemisinin-piperaquine (DHA-PQ) among human immunodeficiency virus infected (HIV+) individuals taking antiretroviral therapy (ART). In a two step (parallel-group) pharmacokinetic trial with intensive blood sampling, we compared area under the concentration-time curve (AUC 0-28 days ) and safety outcomes of piperaquine among malaria-uninfected HIV+ adults. In step 1, half the adult dose of DHA-PQ was administered for three days as an intitial safety check in four groups (n=6/group) of HIV+ adults (age≥18 years): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART, and (iv) on ritonavir-boosted lopinavir-based ART. In step 2, a full adult treatment course of DHA-PQ was administered to a different cohort of participants in three groups: (i) antiretroviral naïve, (ii) on efavirenz-based ART and (iii) on nevirapine-based ART (n=10-15/group). Ritonavir-boosted lopinavir-based ART group was dropped in step 2 due to limited number of participants who were on this second line ART and were eligible for recruitment. Piperaquine's AUC 0-28 days in both steps was 43% lower among participants on efavirenz-based ART compared to ART naïve participants. There were no significant differences in AUC 0-28 days between the other ART groups and the ART naïve group in each of the two steps. Furthermore, no differences in treatment-emergent clinical and laboratory adverse events were observed across the groups in steps 1 and 2. Although well tolerated at half and full standard adult treatment courses, efavirenz based antiretroviral regimen was associated with reduced piperaquine exposure which may compromise dihydroartemisinin-piperaquine's effectiveness in programmatic settings. Copyright © 2018 Banda et al.

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryan, Patricia C., E-mail: ryanp@medimmune.com; Sleeman, Matthew A.; Rebelatto, Marlon

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters othermore » than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus

A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.

PubMed

Hadjigeorgiou, G M; Doxani, C; Miligkos, M; Ziakas, P; Bakalos, G; Papadimitriou, D; Mprotsis, T; Grigoriadis, N; Zintzaras, E

2013-12-01

The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments. © 2013 John Wiley & Sons Ltd.

Psychosocial influences on safety climate: evidence from community pharmacies.

PubMed

Phipps, Denham L; Ashcroft, Darren M

2011-12-01

To examine the relationship between psychosocial job characteristics and safety climate. Cross-sectional survey. Community pharmacies in Great Britain. Participants A random sample of community pharmacists registered in Great Britain (n = 860). Survey instruments Effort-reward imbalance (ERI) indicator and Job Content Questionnaire (JCQ). Main outcome measures Pharmacy Safety Climate Questionnaire (PSCQ). The profile of scores from the ERI indicated a relatively high risk of adverse psychological effects. The profile of scores from the JCQ indicated both high demand on pharmacists and a high level of psychological and social resources to meet these demands. Path analysis confirmed a model in which the ERI and JCQ measures, as well as the type of pharmacy and pharmacist role, predicted responses to the PSCQ (χ(2)(36) = 111.38, p < 0.001; Tucker-Lewis index = 0.96; comparative fit index = 0.98; root mean square error of approximation=0.05). Two general factors (effort vs reward and control vs demand) accounted for the effect of job characteristics on safety climate ratings; each had differential effects on the PSCQ scales. The safety climate in community pharmacies is influenced by perceptions of job characteristics, such as the level of job demands and the resources available to meet these demands. Hence, any efforts to improve safety should take into consideration the effect of the psychosocial work environment on safety climate. In addition, there is a need to address the presence of work-related stressors, which have the potential to cause direct or indirect harm to staff and service users. The findings of the current study provide a basis for future research to improve the safety climate and well-being, both in the pharmacy profession and in other healthcare settings.

Biological safety cabinetry.

PubMed Central

Kruse, R H; Puckett, W H; Richardson, J H

1991-01-01

The biological safety cabinet is the one piece of laboratory and pharmacy equipment that provides protection for personnel, the product, and the environment. Through the history of laboratory-acquired infections from the earliest published case to the emergence of hepatitis B and AIDS, the need for health care worker protection is described. A brief description with design, construction, function, and production capabilities is provided for class I and class III safety cabinets. The development of the high-efficiency particulate air filter provided the impetus for clean room technology, from which evolved the class II laminar flow biological safety cabinet. The clean room concept was advanced when the horizontal airflow clean bench was manufactured; it became popular in pharmacies for preparing intravenous solutions because the product was protected. However, as with infectious microorganisms and laboratory workers, individual sensitization to antibiotics and the advent of hazardous antineoplastic agents changed the thinking of pharmacists and nurses, and they began to use the class II safety cabinet to prevent adverse personnel reactions to the drugs. How the class II safety cabinet became the mainstay in laboratories and pharmacies is described, and insight is provided into the formulation of National Sanitation Foundation standard number 49 and its revisions. The working operations of a class II cabinet are described, as are the variations of the four types with regard to design, function, air velocity profiles, and the use of toxins. The main certification procedures are explained, with examples of improper or incorrect certifications. The required levels of containment for microorganisms are given. Instructions for decontaminating the class II biological safety cabinet of infectious agents are provided; unfortunately, there is no method for decontaminating the cabinet of antineoplastic agents. Images PMID:2070345

Consensus guidelines for the treatment of invasive mould infections in haematological malignancy and haemopoietic stem cell transplantation, 2014.

PubMed

Blyth, C C; Gilroy, N M; Guy, S D; Chambers, S T; Cheong, E Y; Gottlieb, T; McGuinness, S L; Thursky, K A

2014-12-01

Mould species represent the pathogens most commonly associated with invasive fungal disease in patients with haematological malignancies and patients of haemopoietic stem cell transplants. Invasive mould infections in these patient populations, particularly in the setting of neutropenia, are associated with high morbidity and mortality, and significantly increase the complexity of management. While Aspergillus species remain the most prevalent cause of invasive mould infections, Scedosporium and Fusarium species and the Mucormycetes continue to place a significant burden on the immunocompromised host. Evidence also suggests that infections caused by rare and emerging pathogens are increasing within the setting of broad-spectrum antifungal prophylaxis and improved survival times placing immunosuppressed patients at risk for longer. These guidelines present evidence-based recommendations for the antifungal management of common, rare and emerging mould infections in both adult and paediatric populations. Where relevant, the role of surgery, adjunctive therapy and immunotherapy is also discussed. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

An evaluation of two conducted electrical weapons and two probe designs using a swine comparative cardiac safety model.

PubMed

Dawes, Donald Murray; Ho, Jeffrey D; Moore, Johanna C; Miner, James R

2013-09-01

Despite human laboratory and field studies that have demonstrated a reasonable safety profile for TASER brand conducted electrical weapons (CEW), the results of some swine studies and arrest related deaths temporal to the use of the CEWs continue to raise questions regarding cardiac safety. TASER International, Inc., has released a new CEW, the TASER X2, touted to have a better safety profile than its long-standing predecessor, the TASER X26. We have developed a model to assess the relative cardiac safety of CEWs and used it to compare the TASER X2 and the TASER X26. This safety model was also used to assess the relative safety of an experimental probe design as compared to the standard steel probe. Our results suggest that the TASER X2 has an improved safety margin over the TASER X26. The new probe design also has promise for enhanced cardiac safety, although may have some disadvantages when compared to the existing design which would make field use impractical.

The Influence of Acute Handling Stress on Some Blood Parameters in Cultured Sea Bream (Sparus Aurata Linnaeus, 1758)

PubMed Central

Fazio, Francesco; Ferrantelli, Vincenzo; Fortino, Gianluca; Giangrosso, Giuseppe; Faggio, Caterina

2015-01-01

The effect of acute handling stress on haematological profile, blood glucose and lactate (secondary stress markers) in cultured sea bream Sparus aurata was evaluated. Sixty six Sparus aurata were used and equally divided into two groups (A and B). Group A was not subjected to stress, Group B was subjected to acute handling stress. From each fish, biometric data and blood samples were collected to evaluate haematological profile, blood glucose and lactate. Unpaired t-test Student was applied to evaluate possible differences in parameters between the two groups. Red blood cells, haematocrit, haemoglobin, white blood cells (WBC), glucose and lactate showed an increase (P<0.05) in Group B compared with Group A, while mean corpuscular volume decreased (P<0.05) in Group B. The results highlight the role of studied parameters in monitoring the stressful conditions of aquaculture production which affect animal welfare and fish products quality. PMID:27800375

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

PubMed

Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits

Nuclear safety for the space exploration initiative

NASA Technical Reports Server (NTRS)

Dix, Terry E.

1991-01-01

The results of a study to identify potential hazards arising from nuclear reactor power systems for use on the lunar and Martian surfaces, related safety issues, and resolutions of such issues by system design changes, operating procedures, and other means are presented. All safety aspects of nuclear reactor power systems from prelaunch ground handling to eventual disposal were examined consistent with the level of detail for SP-100 reactor design at the 1988 System Design Review and for launch vehicle and space transport vehicle designs and mission descriptions as defined in the 90-day Space Exploration Initiative (SEI) study. Information from previous aerospace nuclear safety studies was used where appropriate. Safety requirements for the SP-100 space nuclear reactor system were compiled. Mission profiles were defined with emphasis on activities after low earth orbit insertion. Accident scenarios were then qualitatively defined for each mission phase. Safety issues were identified for all mission phases with the aid of simplified event trees. Safety issue resolution approaches of the SP-100 program were compiled. Resolution approaches for those safety issues not covered by the SP-100 program were identified. Additionally, the resolution approaches of the SP-100 program were examined in light of the moon and Mars missions.

Safety of intranasal corticosteroids in acute rhinosinusitis.

PubMed

Demoly, Pascal

2008-01-01

Treatment guidelines for acute rhinosinusitis (RS) recommend the use of intranasal corticosteroids (INSs) as monotherapy or adjunctive therapy. However, the adverse event (AE) profiles of oral glucocorticoids, which result largely from the systemic absorption of those agents, have engendered concerns about the safety of INSs. These concerns persist for INSs despite significant or marked clinical differences between them and systemic corticosteroids in systemic absorption and among the INSs in bioavailability, mechanism of action, and lipophilicity, which may contribute to differences in AEs. For example, the systemic bioavailability of the INSs as a percentage of the administered drug is less than 0.1% for mometasone furoate, less than 1% for fluticasone propionate, 46% for triamcinolone acetonide, and 44% for beclomethasone dipropionate. A review of the safety profiles of INSs, as reported in clinical trials in acute and chronic RS and allergic rhinitis, shows primarily local AEs (eg, epistaxis and headache) that are generally classified as mild to moderate, with occurrence rates that are similar to those with placebo. Studies of the safety of mometasone furoate, fluticasone propionate, budesonide, and triamcinolone acetonide did not identify any evidence of systemic AEs, such as growth retardation in children due to suppression of the hypothalamic-pituitary-adrenal axis, bone mineral density loss, or cataracts, which suggests that INSs can be safely administered in patients with acute RS without concern for systemic AEs.

Comparative study of growth traits and haematological parameters of Anak and Nigerian heavy ecotype chickens fed with graded levels of mango seed kernel (Mangifera indica) meal.

PubMed

Mbunwen, Ndofor-Foleng Harriet; Ngongeh, Lucas Atehmengo; Okolie, Peter Nzeribe; Okoli, Emeka Linus

2015-08-01

One hundred fifty Anak and 120 Nigerian heavy local ecotype (NHLE) chickens were used to study the effects of feeding graded levels of mango seed kernel meal (MKM) replacing maize diet on growth traits and haematological parameters. A 2 × 5 factorial arrangement was employed: two breeds and five diets. The birds were randomly allocated to five finisher diets formulated such that MKM replaced maize at 0, 10, 20, 30 and 40% (T1, T2, T3, T4 and T5) inclusion levels, respectively. The effect of breed and dietary treatments on growth performance and blood characteristics were determined. The results showed a significant (P < 0.05) breed effect on body weight and gain, shank length, thigh length, body width and body length. The growth traits of Anak breed were found to be superior to NHLE chickens. Within treatments, chicks on T1, T2 and T3, grew heavier than those on T4 and T5. However, feed intake, feed conversion ratio (FCR) and haematological indices (RBC, Hb, MCV, MCH and MCHC count) were not significant (P > 0.05) when the breeds and treatments were compared. It was concluded that inclusion of dietary MKM below 30% could replace maize in the diets of Anak and NHLE growing chickens without adverse effect on growth performance and blood constituents. This work suggests that genetic differences exist in growth traits of these breeds of chickens. This advantage could be useful in breed improvement programmes and better feeding managements of the NHLE and Anak chickens.

Enteric fever in Mumbai--clinical profile, sensitivity patterns and response to antimicrobials.

PubMed

Jog, S; Soman, R; Singhal, T; Rodrigues, C; Mehta, A; Dastur, F D

2008-04-01

Enteric fever is endemic in Mumbai and its diagnosis poses several problems. Our main aim was to study the clinical profile, haematological features of culture proven typhoid cases, the antimicrobial susceptibility pattern of the isolates and the time to defervescence with the treatment received. This was a retospective chart review of all cases of culture proven enteric fever carried out at a tertiary care private hospital in Mumbai over the period January 2003 to September 2005. Culture positivity in our study was 52.6%. Sixty one percent of the isolates were Salmonella typhi while 39% were Salmonella paratyphi A. An absolute eosinopenia was seen in 76.9% of the patients. Before being admitted to the hospital, 46.2% received antibiotics. The mean time to defervescence in patients who received prior antibiotics was 4.5 days while that in those who did not receive prior antibiotics was 5.1 days. A high culture positivity despite prior or ongoing antibiotic treatment was seen. Absolute eosinophil count of 0% could be an important marker of typhoid. High prevalence of nalidixic acid resistance, a marker of resistance to fluoroquinolones was observed. Combination treatment was not found to be superior to treatment with a single antibiotic.

The Public Safety Impact of Community Notification Laws: Rearrest of Convicted Sex Offenders

ERIC Educational Resources Information Center

Freeman, Naomi J.

2012-01-01

Sex offender management is one of the highest-profile issues in public safety today. Although states have enacted community notification laws as a means to protect communities from sexual offending, limited research has been conducted to examine the impact of these laws on public safety. As such, this study used a quasi-experimental design to…

Immunogenicity, reactogenicity and safety of human rotavirus vaccine (RIX4414) in Indian infants.

PubMed

Narang, Anil; Bose, Anuradha; Pandit, Anand Nilkanth; Dutta, Phalguni; Kang, Gagandeep; Bhattacharya, Sujit Kumar; Datta, Sanjoy Kumar; Suryakiran, P V; Delem, Andrée; Han, Htay Htay; Bock, Hans Ludwig

2009-06-01

This study was undertaken to assess the immunogenicity, reactogenicity and safety of two doses of an oral live-attenuated human rotavirus vaccine, strain RIX4414 (Rotarix()) in an Indian setting. The seroconversion rate observed one month post-dose 2 in the RIX4414 group 58.3% [95% CI: 48.7; 67.4] was significantly higher when compared to the placebo group 6.3%; [95% CI: 2.5; 12.5]. The reactogenicity and safety profile was similar for both groups. Healthy infants (N = 363), approximately eight weeks of age were enrolled to receive two doses of RIX4414 vaccine (n = 182) or placebo (n = 181) separated by one month. To assess the immune response, blood samples were taken before vaccination and one month post-dose 2 of RIX4414/placebo. Solicited symptoms were collected for eight-days post each dose and safety data was collected throughout the study. Two doses of RIX4414 (Rotarix()) were immunogenic, had a good safety profile and were well-tolerated when administered to healthy Indian infants. ClinicalTrials.gov; NCT00289172; eTrack 103792.

Intra-articular administration of lidocaine in anaesthetized dogs: pharmacokinetic profile and safety on cardiovascular and nervous systems.

PubMed

Di Salvo, A; Bufalari, A; De Monte, V; Cagnardi, P; Marenzoni, M L; Catanzaro, A; Vigorito, V; Della Rocca, G

2015-08-01

The intra-articular administration of lidocaine is a frequent practice in human orthopaedic surgical procedures, but an eventual absorption of the drug into the bloodstream can lead to toxicity, mainly concerning the central nervous system and the cardiovascular systems. The purpose of this study was to determine the pharmacokinetic profile and the safety, in terms of cardiovascular and CNS toxicity, of lidocaine after intra-articular administration to anesthetized dogs undergoing arthroscopy. Lidocaine 2% was administered to eight dogs before surgery in differing amounts, depending on the volume of the joints involved, and blood samples were taken at predetermined time points. The maximum serum concentration of lidocaine ranged from 0.50 to 3.01 μg/mL (mean ± SD: 2.18 ± 0.91 μg/mL), and the time to reach it was 28.75 ± 15.74 min. No signs of cardiac toxicity were detected during the entire procedure, and possible signs of CNS toxicity were masked by the anaesthesia. However, concentrations reported in literature as responsible for neurotoxicity in dog were achieved in three of eight investigated subjects. Pending further studies, veterinarians should consider the possibility of side effects occurring following the intra-articular administration of local anaesthetics. © 2014 John Wiley & Sons Ltd.

Antiretroviral Simplification with Darunavir/Ritonavir Monotherapy in Routine Clinical Practice: Safety, Effectiveness, and Impact on Lipid Profile

PubMed Central

Santos, José R.; Moltó, José; Llibre, Josep M.; Negredo, Eugenia; Bravo, Isabel; Ornelas, Arelly; Clotet, Bonaventura; Paredes, Roger

2012-01-01

Background Simplification of antiretroviral treatment (ART) with darunavir/ritonavir (DRV/r) monotherapy has achieved sustained suppression of plasma viral load (pVL) in clinical trials; however, its effectiveness and safety profile has not been evaluated in routine clinical practice. Methodology/Principal Findings We performed a retrospective cohort analysis of HIV-1-infected patients who initiated DRV/r monotherapy once daily with a pVL <50 copies/mL under ART and at least 1 subsequent follow-up visit in our clinic. The primary study endpoints were the percentage of patients with virological failure (VF, defined as 2 consecutive pVL>50 copies/mL) at week 48, and time to VF. Other causes of treatment discontinuation and changes in lipid profile were evaluated up to week 48. Ninety-two patients were followed for a median (IQR) of 73 (57–92) weeks. The median baseline and nadir CD4+ T-cell counts were 604 (433–837) and 238 (150–376) cells/mm3, respectively. Patients had previously received a median of 5 (3–9) ART lines and maintained a pVL<50 copies/mL for a median of 76 (32–176) weeks before initiating DRV/r monotherapy. Nine (9.8%) patients developed VF at week 48; time to VF was 47.1 (IQR: 36.1–47.8) weeks among patients with VF. Other reasons for changing ART were gastrointestinal disturbances (n = 3), rash (n = 1), and impaired CD4 recovery (n = 2). Median low-density lipoprotein cholesterol levels increased from 116.1 mg/dL at baseline to 137.3 mg/dL at 48 weeks (p = 0.001). Conclusions/Significance Treatment simplification with DRV/r monotherapy seems safe and effective in routine clinical practice. Further research is needed to elucidate the effect of DRV/r monotherapy on cholesterol levels. PMID:22666357

Safety of discontinuing cotrimoxazole prophylaxis among HIV infected adults on anti-retroviral therapy in Uganda (COSTOP trial): Design.

PubMed

Anywaine, Zacchaeus; Abaasa, Andrew; Levin, Jonathan; Kasirye, Ronnie; Kamali, Anatoli; Grosskurth, Heiner; Munderi, Paula; Nunn, Andrew

2015-07-01

Cotrimoxazole (CTX) prophylaxis is recommended by the World Health Organisation for HIV infected persons. However, once HIV infected patients have commenced ART in resource limited settings, the benefits of continued CTX prophylaxis are not known. The few studies that investigated the safety of discontinuing CTX prophylaxis in these settings had limitations due to their design. COSTOP is a randomised double blind placebo controlled non-inferiority trial among HIV infected Ugandan adults stabilised on anti-retroviral treatment (ART). Participants with CD4 count of 250 or more cells/mm(3) are randomised to two arms: the intervention arm in which CTX is discontinued and the control arm in which CTX prophylaxis is continued. The study aims to assess whether the intervention regimen is not inferior, with respect to the incidence of pre-defined CTX-preventable events, to the control regimen and superior with respect to the incidence of haematological adverse events. Studies that have previously evaluated the safety of discontinuing CTX prophylaxis among HIV infected adults in resource limited settings have provided moderate to low quality evidence owing in part to methodological limitations. COSTOP is designed and conducted with sufficient rigour to answer this question. The results of the trial will assist in guiding policy recommendations. This paper describes the design and methodological considerations important for the conduct of CTX cessation studies. Copyright © 2015. Published by Elsevier Inc.

Evaluation of plasma chemistry and haematological studies on chickens infected with Eimeria tenella and E acervulina.

PubMed

Fukata, T; Komba, Y; Sasai, K; Baba, E; Arakawa, A

1997-07-12

Plasma chemistry and haematological studies were conducted on chickens with coccidiosis. Male White Leghorn chickens, of two weeks old, were inoculated with 5 x 10(4) Eimeria tenella sporulated oocysts or with 1 x 10(6) E acervulina sporulated oocysts. Blood samples were taken four, seven and 11 days after inoculation. A wet chemistry system was applied to measure the plasma activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, creatine kinase, amylase and lactate dehydrogenase and the concentrations of creatine, total bilirubin, urate, total cholesterol, total protein, albumin, glucose and triglycerides. A dry chemistry system was applied to measure sodium, potassium, chloride and calcium. The number of red blood cells and packed cell volume were determined by a micro cell counter and blood pH was measured with a blood gas analyser. The erythrocyte count, packed cell volume, sodium and chloride levels in the chickens infected with E tenella were significantly (P < 0.05) lower than those of the uninfected controls. The significant decrease in blood pH of the chickens infected with E acervulina suggests malabsorption associated with duodenal lesions induced by the infection.

Safety of human papillomavirus vaccines: a review.

PubMed

Macartney, Kristine K; Chiu, Clayton; Georgousakis, Melina; Brotherton, Julia M L

2013-06-01

Vaccination to prevent human papillomavirus (HPV)-related infection leading to cancer, particularly cervical cancer, is a major public health breakthrough. There are currently two licensed HPV vaccines, both of which contain recombinant virus-like particles of HPV types 16 and 18 (which account for approximately 70 % of cervical cancer). One vaccine also protects against HPV types 6 and 11, which cause genital warts. The safety profile of both vaccines was assessed extensively in randomised controlled clinical trials conducted prior to licensure and has been further elucidated following licensure from surveillance and specific studies in large populations. This review aims to examine current evidence regarding the safety of HPV vaccines. In summary, both vaccines are associated with relatively high rates of injection site reactions, particularly pain, but this is usually of short duration and resolves spontaneously. Systemic reactions have generally been mild and self-limited. Post vaccination syncope has occurred, but can be avoided with appropriate care. Serious vaccine-attributable adverse events, such as anaphylaxis, are rare, and although not recommended for use in pregnancy, abnormal pregnancy outcomes following inadvertent administration do not appear to be associated with vaccination. HPV vaccines are used in a three-dose schedule predominantly in adolescent females: as such case reports linking vaccination with a range of new onset chronic conditions, including autoimmune diseases, have been made. However, well-conducted population-based studies show no association between HPV vaccine and a range of such conditions. Whilst this reassuring safety profile affirms the positive risk benefit of vaccination, as HPV vaccine use expands into more diverse populations, including males, ongoing safety assessment using well-conducted studies is appropriate.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

PubMed

Muñoz, Jose; Ballester, Maria Rosa; Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia; Krolewiecki, Alejandro J

2018-01-01

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers

PubMed Central

Antonijoan, Rosa Maria; Gich, Ignasi; Rodríguez, Montse; Colli, Enrico; Gold, Silvia

2018-01-01

Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax) of the reference product (WA-ref) with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI) and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax) was not associated with BMI

Haematological toxicity: a marker of adjuvant chemotherapy efficacy in stage II and III breast cancer.

PubMed Central

Saarto, T.; Blomqvist, C.; Rissanen, P.; Auvinen, A.; Elomaa, I.

1997-01-01

Two hundred and eleven patients with node-positive stage II and III breast cancer were treated with eight cycles of adjuvant chemotherapy comprising cyclophosphamide, doxorubicin and oral ftorafur (CAFt), with and without tamoxifen. All patients had undergone radical surgery, and 148 patients were treated with post-operative radiotherapy in two randomized studies. The impact of haematological toxicity of CAFt on distant disease-free (DDFS) and overall survival (OS) was recorded. Dose intensity of all given cycles (DI), dose intensity of the two initial cycles (DI2) and total dose (TD) were calculated separately for all chemotherapy drugs and were correlated with DDFS and OS. Patients with a lower leucocyte nadir during the chemotherapy had significantly better DDFS and OS (P = 0.01 and 0.04 respectively). Dose intensity of the two first cycles also correlated significantly with DDFS (P = 0.05) in univariate but not in multivariate analysis, while the leucocyte nadir retained its prognostic value. These results indicate that the leucocyte nadir during the adjuvant chemotherapy is a biological marker of chemotherapy efficacy; this presents the possibility of establishing an optimal dose intensity for each patient. The initial dose intensity of adjuvant chemotherapy also seems to be important in assuring the optimal effect of adjuvant chemotherapy. PMID:9010042

Analysis of the effects of malaria chemoprophylaxis in children on haematological responses, morbidity and mortality.

PubMed Central

Geerligs, Paul D. Prinsen; Brabin, Bernard J.; Eggelte, Teunis A.

2003-01-01

This paper reviews the evidence for beneficial effects of malaria chemoprophylaxis on haematological responses, morbidity, mortality, health service utilization and rebound immunity in children. As anaemia may play an important role in childhood mortality, it is important to assess evidence from controlled trials of the potential of chemoprophylaxis to reduce childhood anaemia. An analysis of trials found good evidence that malaria chemoprophylaxis improves mean haemoglobin levels and reduces severe anaemia, clinical malaria attacks, parasite and spleen rates. Significant reductions in outpatient attendance and hospital admissions have been achieved, and substantial evidence from Gambian studies shows reductions in mortality. Chemoprophylaxis in children does not seem to produce any sustained impairment of immunity to malaria, although rebound effects may be greater in children who receive prophylaxis during infancy. Short periods of targeted prophylaxis are likely to be preferable to continuous drug administration. Evidence of the protective efficacy of malaria chemoprophylaxis in children shows that this strategy could be considered within integrated health programmes for specific time periods. Intermittent routine combination therapy early in childhood may be appropriate for those living under holoendemic conditions. Large-scale studies over a number of years are needed to address this issue and the impact of this approach on health service utilization, mortality, and the emergence of drug-resistant parasites. PMID:12764517

Computing factors of safety against wind-induced tree stem damage.

PubMed

Niklas, K J

2000-04-01

The drag forces, bending moments and stresses acting on stems differing in size and location within the mechanical infrastructure of a large wild cherry (Prunus serotina Ehrh.) tree are estimated and used to calculate the factor of safety against wind-induced mechanical failure based on the mean breaking stress of intact stems and samples of wood drawn from this tree. The drag forces acting on stems are calculated based on stem projected areas and field measurements of wind speed taken within the canopy and along the length of the trunk. The bending moments and stresses resulting from these forces are shown to increase basipetally in a nearly log-log linear fashion toward the base of the tree. The factor of safety, however, varies in a sinusoidal manner such that the most distal stems have the highest factors of safety, whereas stems of intermediate location and portions of the trunk near ground level have equivalent and much lower factors of safety. This pattern of variation is interpreted to indicate that, as a course of normal growth and development, trees similar to the one examined in this study maintain a cadre of stems prone to wind-induced mechanical damage that can reduce the probability of catastrophic tree failure by reducing the drag forces acting on older portions of the tree. Comparisons among real and hypothetical stems with different taper experiencing different vertical wind speed profiles show that geometrically self-similar stems have larger factors of safety than stems tapering according to elastic or stress self-similarity, and that safety factors are less significantly influenced by the 'geometry' of the wind-profile.

Pharmacokinetic properties and safety profile of histamine dihydrochloride injection in Chinese healthy volunteers: a phase I, single-center, open-label, randomized study.

PubMed

Li, Jiapeng; Huang, Xiaojun; Wang, Qian; Jing, Shan; Jiang, Hao; Wei, Zhongna; Zang, Yannan; Liu, Yang; Zhao, Libo; Fang, Yi; Feng, Wanyu

2015-10-01

Histamine dihydrochloride (HDC) injection has been approved in Europe for the treatment of adults with acute myeloid leukemia, used in combination therapy with the T-cell-derived cytokine interleukin-2. Despite years of clinical applications of HDC in Europe, no data are available on its tolerability and pharmacokinetic properties in Chinese patients. The objective of this study was to determine the safety profile and pharmacokinetic properties of HDC in Chinese healthy volunteers (HVs). In this Phase I, single-center, open-label, randomized study, 20 Chinese HVs were randomized to receive a single dose of 0.5 or 1.0 mg HDC via a 10-minute subcutaneous injection. Whole-blood and urine samples were collected at designated time points after dosing. Plasma and urine concentrations of histamine and metabolite N-methyl histamine were measured using a validated HPLC-MS/MS method. Pharmacokinetic parameters were estimated through noncompartmental procedures based on concentration-time data. Adverse events and evaluation of clinical laboratory tests were used to assess the safety profile. The pharmacokinetic profile for a single-dose of 1.0 mg HDC in Chinese HVs was compared with that in Western HVs. No severe adverse events occurred in this study, and the severity of all adverse events was grade I according to the Common Terminology Criteria for Adverse Events, version 4.0. For the pharmacokinetic parameters of histamine at the 0.5-mg and 1.0-mg dose levels, t½ was 0.50 and 1.02 hours; Tmax was 0.15 and 0.14 hours; mean Cmax was 26.59 and 71.01 nmol/L; AUC0-t was 8.35 and 20.43 nmol/h/L; AUC0-∞ was 9.61 and 22.69 nmol/h/L; accumulated amount excreted in urine within 24 hours was 125.93 and 145.52 nmol; and maximum urine excretion rates were 21.85 and 38.94 nmol/h, respectively. For N-methyl histamine at the 0.5-mg and 1.0-mg dose levels, t½ was 0.58 and 0.66 hours; Tmax was 0.28 and 0.26 hours; mean Cmax was 17.01 and 23.54 nmol/L; AUC0-t was 7.72 and 17.08 nmol

Safety assessment of plant varieties using transcriptomics profiling and a one-class classifier.

PubMed

van Dijk, Jeroen P; de Mello, Carla Souza; Voorhuijzen, Marleen M; Hutten, Ronald C B; Arisi, Ana Carolina Maisonnave; Jansen, Jeroen J; Buydens, Lutgarde M C; van der Voet, Hilko; Kok, Esther J

2014-10-01

An important part of the current hazard identification of novel plant varieties is comparative targeted analysis of the novel and reference varieties. Comparative analysis will become much more informative with unbiased analytical approaches, e.g. omics profiling. Data analysis estimating the similarity of new varieties to a reference baseline class of known safe varieties would subsequently greatly facilitate hazard identification. Further biological and eventually toxicological analysis would then only be necessary for varieties that fall outside this reference class. For this purpose, a one-class classifier tool was explored to assess and classify transcriptome profiles of potato (Solanum tuberosum) varieties in a model study. Profiles of six different varieties, two locations of growth, two year of harvest and including biological and technical replication were used to build the model. Two scenarios were applied representing evaluation of a 'different' variety and a 'similar' variety. Within the model higher class distances resulted for the 'different' test set compared with the 'similar' test set. The present study may contribute to a more global hazard identification of novel plant varieties. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com; Nolte, Marc W.; Solomon, Cristina

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii)more » the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well

Novel potent pyridoxine-based inhibitors of AChE and BChE, structural analogs of pyridostigmine, with improved in vivo safety profile.

PubMed

Strelnik, Alexey D; Petukhov, Alexey S; Zueva, Irina V; Zobov, Vladimir V; Petrov, Konstantin A; Nikolsky, Evgeny E; Balakin, Konstantin V; Bachurin, Sergey O; Shtyrlin, Yurii G

2016-08-15

We report a novel class of carbamate-type ChE inhibitors, structural analogs of pyridostigmine. A small library of congeneric pyridoxine-based compounds was designed, synthesized and evaluated for AChE and BChE enzymes inhibition in vitro. The most active compounds have potent enzyme inhibiting activity with IC50 values in the range of 0.46-2.1μM (for AChE) and 0.59-8.1μM (for BChE), with moderate selectivity for AChE comparable with that of pyridostigmine and neostigmine. Acute toxicity studies using mice models demonstrated excellent safety profile of the obtained compounds with LD50 in the range of 22-326mg/kg, while pyridostigmine and neostigmine are much more toxic (LD50 3.3 and 0.51mg/kg, respectively). The obtained results pave the way to design of novel potent and safe cholinesterase inhibitors for symptomatic treatment of neuromuscular disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database

PubMed Central

2009-01-01

Introduction Patients with haematological malignancy admitted to intensive care have a high mortality. Adverse prognostic factors include the number of organ failures, invasive mechanical ventilation and previous bone marrow transplantation. Severity-of-illness scores may underestimate the mortality of critically ill patients with haematological malignancy. This study investigates the relationship between admission characteristics and outcome in patients with haematological malignancies admitted to intensive care units (ICUs) in England, Wales and Northern Ireland, and assesses the performance of three severity-of-illness scores in this population. Methods A secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database was conducted on admissions to 178 adult, general ICUs in England, Wales and Northern Ireland between 1995 and 2007. Multivariate logistic regression analysis was used to identify factors associated with hospital mortality. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II and ICNARC score were evaluated for discrimination (the ability to distinguish survivors from nonsurvivors); and the APACHE II, SAPS II and ICNARC mortality probabilities were evaluated for calibration (the accuracy of the estimated probability of survival). Results There were 7,689 eligible admissions. ICU mortality was 43.1% (3,312 deaths) and acute hospital mortality was 59.2% (4,239 deaths). ICU and hospital mortality increased with the number of organ failures on admission. Admission factors associated with an increased risk of death were bone marrow transplant, Hodgkin's lymphoma, severe sepsis, age, length of hospital stay prior to intensive care admission, tachycardia, low systolic blood pressure, tachypnoea, low Glasgow Coma Score, sedation, PaO2:FiO2, acidaemia, alkalaemia, oliguria, hyponatraemia, hypernatraemia, low haematocrit, and uraemia. The ICNARC

Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database.

PubMed

Hampshire, Peter A; Welch, Catherine A; McCrossan, Lawrence A; Francis, Katharine; Harrison, David A

2009-01-01

Patients with haematological malignancy admitted to intensive care have a high mortality. Adverse prognostic factors include the number of organ failures, invasive mechanical ventilation and previous bone marrow transplantation. Severity-of-illness scores may underestimate the mortality of critically ill patients with haematological malignancy. This study investigates the relationship between admission characteristics and outcome in patients with haematological malignancies admitted to intensive care units (ICUs) in England, Wales and Northern Ireland, and assesses the performance of three severity-of-illness scores in this population. A secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database was conducted on admissions to 178 adult, general ICUs in England, Wales and Northern Ireland between 1995 and 2007. Multivariate logistic regression analysis was used to identify factors associated with hospital mortality. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II and ICNARC score were evaluated for discrimination (the ability to distinguish survivors from nonsurvivors); and the APACHE II, SAPS II and ICNARC mortality probabilities were evaluated for calibration (the accuracy of the estimated probability of survival). There were 7,689 eligible admissions. ICU mortality was 43.1% (3,312 deaths) and acute hospital mortality was 59.2% (4,239 deaths). ICU and hospital mortality increased with the number of organ failures on admission. Admission factors associated with an increased risk of death were bone marrow transplant, Hodgkin's lymphoma, severe sepsis, age, length of hospital stay prior to intensive care admission, tachycardia, low systolic blood pressure, tachypnoea, low Glasgow Coma Score, sedation, PaO2:FiO2, acidaemia, alkalaemia, oliguria, hyponatraemia, hypernatraemia, low haematocrit, and uraemia. The ICNARC model had the best discrimination

Impact of biomarker development on drug safety assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marrer, Estelle, E-mail: estelle.marrer@novartis.co; Dieterle, Frank

2010-03-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative andmore » 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.« less

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach.

PubMed

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg(-1) day(-1) or 250 mg kg(-1) day(-1) for a period of 7 days (n=4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers. Copyright 2009 Elsevier B.V. All rights reserved.

Immunological, clinical, haematological and oxidative responses to long distance transportation in horses.

PubMed

Padalino, Barbara; Raidal, Sharanne Lee; Carter, Nicole; Celi, Pietro; Muscatello, Gary; Jeffcott, Leo; de Silva, Kumudika

2017-12-01

Horses are transported frequently and often over long distances. Transportation may represent a physiological stressor with consequential health and welfare implications. This study reports the effects of a long distance journey on immunological, clinical, haematological, inflammatory and oxidative parameters in an Experimental Group (EG) of ten horses, comparing them with six horses of similar age and breed used as a non-transported Control Group (CG). Clinical examination and blood sampling were performed twice on all horses: immediately after unloading for the EG, and at rest on the same day for the CG (day 1); at rest on the same day one week later for both groups (day 7). On day 1 EG horses showed increased heart and respiratory rates (P<0.01), rectal temperature (P<0.05), capillary refilling time (P<0.01), neutrophil numbers (P<0.01), serum albumin (P<0.01), plasma total antioxidant status (P<0.01), and a lower rate of mitogen induced proliferation of lymphocytes (P<0.05), in comparison with CG. On day 7 only an increase in total serum protein (P<0.05) and serum globulins (P<0.001) was seen in the EG. No difference in serum cortisol concentration was found. Long distance transportation induced an acute phase response impairing the cell-mediated immune response. Clinical examinations, including assessing CRT and body weight loss, and the monitoring of redox balance may be useful in evaluating the impact of extensive transport events on horses. A better understanding of the link between transportation stress, the immune system and the acute phase response is likely to inform strategies for enhancing the welfare of transported horses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does habitat fragmentation cause stress in the agile antechinus? A haematological approach.

PubMed

Johnstone, Christopher P; Lill, Alan; Reina, Richard D

2012-01-01

Although the vertebrate stress response is essential for survival, frequent or prolonged stress responses can result in chronic physiological stress, which is associated with a suite of conditions that can impair survivorship and reproductive output. Anthropogenic habitat fragmentation and degradation are potential stressors of free-living vertebrates, and in theory could result in chronic stress. To address this issue, we compared haematological indicators of stress and condition in agile antechinus (Antechinus agilis) populations in 30 forest fragments and 30 undisturbed, continuous forest sites (pseudofragments) in south-eastern Australia over 2 years. In peripheral blood, the total leucocyte count was lower and the neutrophil/lymphocyte ratio and percentage of eosinophils in the total leucocyte population was higher in fragment than pseudofragment populations, indicating that fragment populations were probably experiencing higher levels of stress hormone-mediated and/or parasite infection-related chronic physiological stress. The total erythrocyte count and haematocrit were higher and mean erythrocyte haemoglobin content was lower in fragment than pseudofragment populations. This suggests that fragment populations showed possible signs of regenerative anaemia, a syndrome associated with elevated hypothalamus-pituitary-adrenal axis mediated stress. However, mean erythrocyte volume was also lower in fragments, and red blood cell distribution width did not differ between the study populations, findings which were not consistent with this diagnosis. Whole blood and mean cell haemoglobin concentrations were similar in fragment and pseudofragment populations. We suggest that where anthropogenic activity results in habitat fragmentation and degradation, chronic stress could contribute to a decline in agile antechinus populations. The broader implication is that chronic stress could be both symptomatic of, and contributing to, decline of some vertebrate populations in

Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study.

PubMed

Merrill, Joan T; Wallace, Daniel J; Petri, Michelle; Kirou, Kyriakos A; Yao, Yihong; White, Wendy I; Robbie, Gabriel; Levin, Robert; Berney, Seth M; Chindalore, Vishala; Olsen, Nancy; Richman, Laura; Le, Chenxiong; Jallal, Bahija; White, Barbara

2011-11-01

Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets. Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE. received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days. Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014). Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE. Trial registration number NCT00299819.

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.

PubMed

Biagi, C; Conti, V; Montanaro, N; Melis, M; Buccellato, E; Donati, M; Covezzoli, A; Amato, R; Pazzi, L; Venegoni, M; Vaccheri, A; Motola, D

2014-12-01

The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.

Laboratory testing in management of patients with suspected Ebolavirus disease: infection control and safety.

PubMed

Gilbert, G L

2015-08-01

If routine laboratory safety precautions are followed, the risk of laboratory-acquired infection from handling specimens from patients with Ebolavirus disease (EVD) is very low, especially in the early 'dry' stage of disease. In Australia, border screening to identify travellers returning from EVD-affected west African countries during the 2014-2015 outbreak has made it unlikely that specimens from patients with unrecognised EVD would be sent to a routine diagnostic laboratory. Australian public health and diagnostic laboratories associated with hospitals designated for the care of patients with EVD have developed stringent safety precautions for EVD diagnostic and other tests likely to be required for supportive care of the sickest (and most infectious) patients with EVD, including as wide a range of point-of-care tests as possible. However, it is important that the stringent requirements for packaging, transport and testing of specimens that might contain Ebolavirus--which is a tier 1 security sensitive biology agent--do not delay the diagnosis and appropriate management of other potentially serious but treatable infectious diseases, which are far more likely causes of a febrile illness in people returning from west Africa. If necessary, urgent haematology, biochemistry and microbiological tests can be performed safely, whilst awaiting the results of EVD tests, in a PC-2 laboratory with appropriate precautions including: use of recommended personal protective equipment (PPE) for laboratory staff; handling any unsealed specimens in a class 1 or II biosafety cabinet; using only centrifuges with sealed rotors; and safe disposal or decontamination of all used equipment and laboratory waste.

Comparison of the Safety of Seven Iodinated Contrast Media

PubMed Central

Seong, Jong-Mi; Choi, Nam-Kyong; Lee, Joongyub; Chang, Yoosoo; Kim, Ye-Jee; Yang, Bo Ram; Jin, Xue-Mei; Kim, Ju-Young

2013-01-01

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety. PMID:24339697

Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial.

PubMed

Chagas, T R; Borges, D S; de Oliveira, P F; Mocellin, M C; Barbosa, A M; Camargo, C Q; Del Moral, J Â G; Poli, A; Calder, P C; Trindade, E B S M; Nunes, E A

2017-12-01

Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy. © 2017 The British Dietetic Association Ltd.

The effects of strawberry tree water leaf extract, arbutin and hydroquinone on haematological parameters and levels of primary DNA damage in white blood cells of rats.

PubMed

Jurica, Karlo; Brčić Karačonji, Irena; Kopjar, Nevenka; Shek-Vugrovečki, Ana; Cikač, Tihana; Benković, Vesna

2018-04-06

Strawberry tree (Arbutus unedo L., Ericaceae) leaves represent a potent source of biologically active compounds and have been used for a long to relieve symptoms of various health impairments and diseases. Two major compounds related to their beneficial activities in animals and humans are arbutin and hydroquinone. To establish potential benefit/risk ratio associated with daily oral administration of strawberry tree water leaf extract, arbutin and hydroquinone in doses expected to be non-toxic. We performed a 14-day and a 28-day study on male and female Lewis rats and evaluated main haematological parameters and the effects of treatments on the levels of primary DNA damage in white blood cells (WBC) using the alkaline comet assay. Our findings suggest no significant changes in the haematological parameters following prolonged exposure to strawberry tree water leaf extract, arbutin, and hydroquinone. However, hydroquinone causes increased, and extract as well as arbutin decreased WBC count in male rats compared to control after 14 days of treatment. DNA damage measured in WBC of rats treated with all compounds was below 10% of the DNA in the comet tail, which indicates low genotoxicity. The genotoxic potential of strawberry water leaf extract was within acceptable limits and reflected effects of a complex chemical composition upon DNA. We also observed slight gender- and exposure time- related differences in primary DNA damage in the leucocytes of control and treated rats. Future studies should investigate which doses of strawberry tree water leaf extract would be most promising for the potential use as a substitute for bearberry leaves for treatment of urinary infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Safety profile and complications of autologous limbal conjunctival transplantation for primary pterygium

PubMed Central

Prabhakar, Srinivasapuram Krishnachary

2014-01-01

Purpose Primary pterygium is a fibrovascular proliferation over the nasal cornea, probably resulting from the limbal stem cell deficiency. Intraoperative mitomycin-C application seems to associate with reduced recurrences, however produced ocular surface problems and vision threatening complications. The present clinical study investigated the safety profile of autologous limbal conjunctival transplantation in terms of recurrence rate, as the main outcome measure and complications as the secondary outcome. Methods The present study was randomised, interventional and prospective clinical study conducted from a tertiary Hospital. Pterygium excision was performed with limbal conjunctival autograft availed from the affected eye. Secondary pterygia resulting from inflammation, trauma and other diseases were excluded. Patients were followed up for 18 months for recurrence and other complications. Microsoft Office Excel 2007 was used for statistical analysis. Results A total of 71 eyes of sixty-eight patients with primary pterygia included between November 2007 and October 2010. The study recruited 35 (51%) males and 33 (49%) females with mean age of 36.9 with ±12.82 years standard deviation (mean, SD) ranging from 19 to 75 years. Age grouped by range intervals categorised into six groups. Pterygium was diagnosed in 32 (45%) right eyes and 39 (55%) left eyes. There were 65 (91.55%) nasal and 4 (5.63%) temporal pterygium and no case of double head pterygia found. Average horizontal extension of the pterygium measured was 1.67 mm (±4.23) from the apex to the corneal limbus. Graft oedema in 1 (0.71%) patient, graft bleed in 2 (1.42%) cases and 1 (0.72%) case of granuloma observed. No recurrences encountered during 18 months follow up. Conclusions Pterygium occurred predominantly in the younger population group 36.9 mm (±12.82) probably due to the increased outdoor activity with high exposure to sunlight and dusty atmosphere. Absence of recurrences was probably

Safety profile of protein kinase inhibitors in rheumatoid arthritis: systematic review and meta-analysis.

PubMed

Salgado, Eva; Maneiro, Jose R; Carmona, Loreto; Gomez-Reino, Juan J

2014-05-01

To summarise the adverse events (AE) reported in patients with rheumatoid arthritis (RA) treated with protein kinase inhibitors (PKi), and identify family and molecule-related AEs. Systematic review of the PKi used in clinical trials (CTs) in RA. Medline, Embase, Cochrane Library, Web of Knowledge, and international abstracts of congress were reviewed, (up to 31 October 2012). Search was limited to interventional studies of PKi used in CTs in RA, written in English, and reporting frequencies of AE. Diseases with similar comorbidity burden also were included. Frequency of AE, serious AE (SAE), death and discontinuation due to  AEs (DCAE) were recorded. Risk of bias was assessed. Meta-analysis was carried using pooled relative risk (RR) with 95% CI as effect measure. The search produced 4410 hits. Forty-one articles reporting data on 21 PKi of the Janus kinase (JAK), SYK, p38 and cKit families were selected for detailed analysis. In patients treated with p38 inhibitors, RR for dizziness was 2.36 (1.20 to 4.63), and in patients treated with c-Kit inhibitors, RR for oedema was 3.43 (1.58 to 7.42). In patients treated with the JAK inhibitor tofacitinib, RR for hypercholesterolaemia was 1.70 (1.10 to 2.63) that was dose related. In patients treated with the Syk inhibitor fostamatinib, pooled RR for hypertransaminasaemia, hypertension, diarrhoea and neutropenia were 2.93 (1.02 to 8.43), 2.80 (1.58 to 5.99), 5.20 (3.19 to 8.49) and 9.24 (2.22 to 38.42), respectively. Serious infections and malignancies were not significantly more frequent in PKi-treated patients than in comparator groups. Event rates of serious infections and malignancies with PKi are not different from biologics. In addition, PKi have a unique safety profile related to target and off-target inhibition of kinases, at times dose related.

Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer

PubMed Central

Blackhall, Fiona; Ross Camidge, D; Shaw, Alice T; Soria, Jean-Charles; Solomon, Benjamin J; Mok, Tony; Hirsh, Vera; Jänne, Pasi A; Shi, Yuankai; Yang, Pan-Chyr; Pas, Tommaso De; Hida, Toyoaki; Carpeño, Javier De Castro; Lanzalone, Silvana; Polli, Anna; Iyer, Shrividya; Reisman, Arlene; Wilner, Keith D; Kim, Dong-Wan

2017-01-01

Purpose Crizotinib is a potent, orally administered tyrosine kinase inhibitor approved for the treatment of anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We report final results from PROFILE 1005, the largest clinical trial to date for an ALK inhibitor in ALK-positive NSCLC. Patients and methods PROFILE 1005 (NCT00932451) was a multicenter, single-arm phase 2 trial of the efficacy, safety and tolerability of crizotinib (250 mg twice daily; 3 week continuous treatment cycles) in patients with ALK-positive NSCLC after failure of ≥1 lines of systemic treatment for locally advanced/metastatic disease. Patients’ tumour ALK status was initially determined by a central laboratory until a protocol amendment permitted enrolment of patients based on locally determined ALK status. Co-primary endpoints were objective response rate (ORR), evaluated using Response Evaluation Criteria in Solid Tumours V.1.1 and adverse events (AEs). Cancer-specific patient-reported outcomes (PROs) were also assessed using the European Organisation for the Research and Treatment of Cancer QLQ-C30 and its lung cancer module QLQ-LC13. Results 1069 patients were enrolled; 1066 received crizotinib. The as-treated population comprised 908 and 158 patients, in whom tumour positive ALK-status was determined centrally (± locally) or locally only, respectively. At baseline, a majority of patients were <65 years (84%), 66% were never smokers and 46% were Asian. Derived investigator-assessed ORR was 54% (95% CI 51 to 57) and 41% (95% CI 33 to 49) in the central-testing and local-testing subgroups, respectively. The most common treatment-related AEs in the overall population (any grade) were vision disorder (58%), nausea (51%), diarrhoea (47%) and vomiting (47%). PRO scores demonstrated clinically meaningful improvement in lung cancer symptoms and global quality of life. Conclusion The efficacy, safety and PRO profiles of crizotinib in this cohort of 1066

The Effects of Safety Information on Aeronautical Decision Making

NASA Technical Reports Server (NTRS)

Lee, Jang R.; Fanjoy, Richard O.; Dillman, Brian G.

2005-01-01

The importance of aeronautical decision making (ADM) has been considered one of the most critical issues of flight education for future professional pilots. Researchers have suggested that a safety information system based on information from incidents and near misses is an important tool to improve the intelligence and readiness of pilots. This paper describes a study that examines the effect of safety information on aeronautical decision making for students in a collegiate flight program. Data was collected from study participants who were exposed to periodic information about local aircraft malfunctions. Participants were then evaluated using a flight simulator profile and a pen and pencil test of situational judgment. Findings suggest that regular access to the described safety information program significantly improves decision making of student pilots.

Open-label safety assessment of bilastine in elderly patients with allergic rhinoconjunctivitis and/or urticaria.

PubMed

Sologuren, Ander; Vinas, Rosa; Cordon, Esther; Riesgo, Susana E; Del Mar Fores, Maria; Senan, Maria Rosa; Fernandez, Sonia; Labeaga, Luis; Ruiz-Mijan, Manuel

2018-03-20

Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safetyprofile of bilastine 20 mg in patients aged greater than or equal to 65 years with allergic rhinoconjunctivitis and/or urticaria. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. Theincidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88(95% CI, 0.688 -1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95%CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003- 0.048) and0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged greater than or equal to 65 years.The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.

Blood gases, biochemistry and haematology of Galápagos hawksbill turtles (Eretmochelys imbricata).

PubMed

Muñoz-Pérez, Juan Pablo; Lewbart, Gregory A; Hirschfeld, Maximilian; Alarcón-Ruales, Daniela; Denkinger, Judith; Castañeda, Jason Guillermo; García, Juan; Lohmann, Kenneth J

2017-01-01

The hawksbill turtle, Eretmochelys imbricata , is a marine chelonian with a circum-global distribution, but the species is critically endangered and has nearly vanished from the eastern Pacific. Although reference blood parameter intervals have been published for many chelonian species and populations, including nesting Atlantic hawksbills, no such baseline biochemical and blood gas values have been reported for wild Pacific hawksbill turtles. Blood samples were drawn from eight hawksbill turtles captured in near shore foraging locations within the Galápagos archipelago over a period of four sequential years; three of these turtles were recaptured and sampled on multiple occasions. Of the eight sea turtles sampled, five were immature and of unknown sex, and the other three were females. A portable blood analyzer was used to obtain near immediate field results for a suite of blood gas and chemistry parameters. Values affected by temperature were corrected in two ways: (i) with standard formulas and (ii) with auto-corrections made by the portable analyzer. A bench top blood chemistry analyzer was used to measure a series of biochemistry parameters from plasma. Standard laboratory haematology techniques were employed for red and white blood cell counts and to determine haematocrit manually, which was compared to the haematocrit values generated by the portable analyzer. The values reported in this study provide reference data that may be useful in comparisons among populations and in detecting changes in health status among Galápagos sea turtles. The findings might also be helpful in future efforts to demonstrate associations between specific biochemical parameters and disease or environmental disasters.

Social and environmental factors modulate leucocyte profiles in free-living Greylag geese (Anser anser)

PubMed Central

Ludwig, Sonja C.; Hemetsberger, Josef; Kotrschal, Kurt; Wascher, Claudia A.F.

2017-01-01

Background Blood parameters such as haematocrit or leucocyte counts are indicators of immune status and health, which can be affected, in a complex way, by exogenous as well as endogenous factors. Additionally, social context is known to be among the most potent stressors in group living individuals, therefore potentially influencing haematological parameters. However, with few exceptions, this potential causal relationship received only moderate scientific attention. Methods In a free-living and individually marked population of the highly social and long-lived Greylag goose, Anser anser, we relate variation in haematocrit (HCT), heterophils to lymphocytes ratio (H/L) and blood leucocyte counts to the following factors: intrinsic (sex, age, raising condition, i.e. goose- or hand-raised), social (pair-bond status, pair-bond duration and parental experience) and environmental (biologically relevant periods, ambient temperature) factors. Blood samples were collected repeatedly from a total of 105 focal birds during three biologically relevant seasons (winter flock, mating season, summer). Results We found significant relationships between haematological parameters and social as well as environmental factors. During the mating season, unpaired individuals had higher HCT compared to paired and family individuals and this pattern reversed in fall. Similarly, H/L ratio was positively related to pair-bond status in a seasonally dependent way, with highest values during mating and successful pairs had higher H/L ratio than unsuccessful ones. Also, absolute number of leucocytes tended to vary depending on raising condition in a seasonally dependent way. Discussion Haematology bears a great potential in ecological and behavioural studies on wild vertebrates. In sum, we found that HTC, H/L ratio and absolute number of leucocytes are modulated by social factors and conclude that they may be considered valid indicators of individual stress load. PMID:28070455

Safety characteristics of the lithium SO2 system

NASA Technical Reports Server (NTRS)

Watson, T.

1978-01-01

Extensive tests were conducted to quantitatively define the safety characteristics of high-rate SO2 multicell batteries under various discharge and temperature profiles, which closely simulated actual field-use conditions. The resulting behavior patters of the multicell batteries and the corrective action which can be implemented to minimize or prevent hazardous battery performance are briefly summarized.

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Single Enantiomer (+)-Mefloquine Compared with Racemic Mefloquine in Healthy Persons

PubMed Central

Tansley, Robert; Lotharius, Julie; Priestley, Anthony; Bull, Fiona; Duparc, Stephan; Möhrle, Jörg

2010-01-01

Racemic mefloquine is a highly effective antimalarial whose clinical utility has been compromised by its association with neuropsychiatric and gastrointestinal side effects. It is hypothesized that the cause of the side effects may reside in the (−) enantiomer. We sought to compare the safety, tolerability and pharmacokinetic profile of (+)-mefloquine with racemic mefloquine in a randomized, ascending-dose, double-blind, active and placebo-controlled, parallel cohort study in healthy male and female adult volunteers. Although differing in its manifestations, both study drugs displayed a substantially worse tolerability profile compared with placebo. The systemic clearance was slower for (−)-mefloquine than (+)-mefloquine. Thus, (+)-mefloquine has a different safety and tolerability profile compared with racemic mefloquine but its global safety profile is not superior and replacement of the currently used antimalarial drug with (+)-mefloquine is not warranted. PMID:21118921

The grafting of universal T-helper epitopes enhances immunogenicity of HIV-1 Tat concurrently improving its safety profile.

PubMed

Kashi, Venkatesh P; Jacob, Rajesh A; Shamanna, Raghavendra A; Menon, Malini; Balasiddaiah, Anangi; Varghese, Rebu K; Bachu, Mahesh; Ranga, Udaykumar

2014-01-01

Extracellular Tat (eTat) plays an important role in HIV-1 pathogenesis. The presence of anti-Tat antibodies is negatively correlated with disease progression, hence making Tat a potential vaccine candidate. The cytotoxicity and moderate immunogenicity of Tat however remain impediments for developing Tat-based vaccines. Here, we report a novel strategy to concurrently enhance the immunogenicity and safety profile of Tat. The grafting of universal helper T-lymphocyte (HTL) epitopes, Pan DR Epitope (PADRE) and Pol711 into the cysteine rich domain (CRD) and the basic domain (BD) abolished the transactivation potential of the Tat protein. The HTL-Tat proteins elicited a significantly higher titer of antibodies as compared to the wild-type Tat in BALB/c mice. While the N-terminal epitope remained immunodominant in HTL-Tat immunizations, an additional epitope in exon-2 was recognized with comparable magnitude suggesting a broader immune recognition. Additionally, the HTL-Tat proteins induced cross-reactive antibodies of high avidity that efficiently neutralized exogenous Tat, thus blocking the activation of a Tat-defective provirus. With advantages such as presentation of multiple B-cell epitopes, enhanced antibody response and importantly, transactivation-deficient Tat protein, this approach has potential application for the generation of Tat-based HIV/AIDS vaccines.

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

PubMed

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases.

PubMed

Verstockt, Bram; Deleenheer, Barbara; Van Assche, Gert; Vermeire, Séverine; Ferrante, Marc

2017-07-01

Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies. Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD. Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

Natural Resources. Ohio's Competency Analysis Profile. Forest Industry Worker. Resource Conservation.

ERIC Educational Resources Information Center

Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

This competency analysis profile lists 155 competencies that have been identified by employers as core competencies for inclusion in programs to train forest industry and resource conservation workers. The core competencies are organized into 10 units dealing the following: general safety precautions, natural resource industry operations, soil…

Relationship between physician and patient assessment of performance status and survival in a large cohort of patients with haematologic malignancies.

PubMed

Liu, Michael A; Hshieh, Tammy; Condron, Nolan; Wadleigh, Martha; Abel, Gregory A; Driver, Jane A

2016-09-27

Few studies have investigated the relationship between physician and patient-assessed performance status (PS) in blood cancers. Retrospective analysis among 1418 patients with haematologic malignancies seen at Dana-Farber Cancer Institute between 2007 and 2014. We analysed physician-patient agreement of Eastern Cooperative Oncology Group PS using weighted κ-statistics and survival analysis. Mean age was 58.6 years and average follow-up was 38 months. Agreement in PS was fair/moderate (weighted κ=0.41, 95% CI 0.37-0.44). Physicians assigned a better functional status (lower score) than patients (mean 0.60 vs 0.81), particularly when patients were young and the disease was aggressive. Both scores independently predicted survival, but physician scores were more accurate. Disagreements in score were associated with poorer survival when physicians rated PS better than patients, and were modified by age, sex and severity of disease. Physician-patient disagreements in PS score are common and have prognostic significance.

Safety update on the use of recombinant activated factor VII in approved indications.

PubMed

Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

2015-06-01

This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

NASA's Software Safety Standard

NASA Technical Reports Server (NTRS)

Ramsay, Christopher M.

2007-01-01

NASA relies more and more on software to control, monitor, and verify its safety critical systems, facilities and operations. Since the 1960's there has hardly been a spacecraft launched that does not have a computer on board that will provide command and control services. There have been recent incidents where software has played a role in high-profile mission failures and hazardous incidents. For example, the Mars Orbiter, Mars Polar Lander, the DART (Demonstration of Autonomous Rendezvous Technology), and MER (Mars Exploration Rover) Spirit anomalies were all caused or contributed to by software. The Mission Control Centers for the Shuttle, ISS, and unmanned programs are highly dependant on software for data displays, analysis, and mission planning. Despite this growing dependence on software control and monitoring, there has been little to no consistent application of software safety practices and methodology to NASA's projects with safety critical software. Meanwhile, academia and private industry have been stepping forward with procedures and standards for safety critical systems and software, for example Dr. Nancy Leveson's book Safeware: System Safety and Computers. The NASA Software Safety Standard, originally published in 1997, was widely ignored due to its complexity and poor organization. It also focused on concepts rather than definite procedural requirements organized around a software project lifecycle. Led by NASA Headquarters Office of Safety and Mission Assurance, the NASA Software Safety Standard has recently undergone a significant update. This new standard provides the procedures and guidelines for evaluating a project for safety criticality and then lays out the minimum project lifecycle requirements to assure the software is created, operated, and maintained in the safest possible manner. This update of the standard clearly delineates the minimum set of software safety requirements for a project without detailing the implementation for those

Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats.

PubMed

Obici, Simoni; Otobone, Fernanda Jacques; da Silva Sela, Vânia Ramos; Ishida, Kelly; da Silva, José Carlos; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Audi, Elisabeth Aparecida

2008-01-04

Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo" or "Saco de Boi" in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD50 values of 1503.0 and 538.8 mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety.

The effect of stress on haematologic response and physicochemical parameters of muscle meat in rabbits.

PubMed

Reséndiz-Cruz, V; Ramírez-Bribiesca, J E; Mota-Rojas, D; Guerrero-Legarreta, I; Cruz-Monterrosa, R G; Hernandez-Sanchez, D

2018-02-01

Ante-mortem studies of stress in rabbits are few and can potentially impact the haematologic response and physicochemical parameters of muscle meat. The aim of this study was to investigate the induction of stress by transport and simulation at two different times. Two hundred rabbits divided in a similar proportion of male and female were stressed by vehicular transportation and with motion simulation, using a vibration platform. They were divided into five groups: Control (without stress), Stress with Short Transportation (30 min), Stress with Long Transportation (60 min), Stress with Short Vibration Platform (30 min) and Stress with Long Vibration Platform (60 min). Transportation caused a decrease in the haematic potassium in both sexes (<5.2 mmol/L). The glucose and lactate concentrations increased in the transported rabbits (>219 and >61 mg/dl respectively). The differences between sexes showed that the P CO 2 in males decreased <8.5 mmHg in stress groups compared to without stress group. Glucose concentration was 61.5 mg/dl for females and 38.0 mg/dl for males (p < .01). We concluded that in rabbits induced stress by transport increased the energetic metabolites in the blood tissue. This increase did not affect the production parameters and the quality of muscle meat. © 2017 Blackwell Verlag GmbH.

Feeding differently processed soya bean. Part 2. An assessment of haematological responses in the chicken.

PubMed

Aletor, V A; Egberongbe, O

1992-01-01

The use of differently processed soya bean as a major source of dietary protein was evaluated in a haematological study using broiler chickens in which groundnut cake (GNC), raw soya bean (RSB), roasted soya bean (RtSB), cooked soya bean (CSB) and soya bean oil cake (SBC) were fed on equi-protein basis. The results showed that: 1. Red blood cell (RBC) count and haemoglobin content of blood significantly (P less than 0.05) increased in chicks fed RSB relative to the other soya bean diets. Feeding differently processed soya bean significantly (P less than 0.05) influenced mean cell haemoglobin (MCH) and mean corpuscular volume (MCV) while the mean corpuscular haemoglobin concentration (MCHC) was not significantly influenced. 2. Both the total white blood cell (WBC) count and the monocytes were significantly (P less than 0.05) influenced by the dietary treatments. Chicks fed processed soya bean generally had higher number of monocytes. 3. Physical properties determined were specific gravity and erythrocyte sedimentation rate. The latter was significantly (P less than 0.05) lower in all the processed soya bean-fed chicks. 4. Minerals determined in blood were Na, K, Ca, Mg, Fe, Cu and P. Of all these, chicks fed RSB had significantly (P less than 0.01) lower levels of blood Mg and marked decrease in Ca.

Safety Profile of Anticancer and Immune-Modulating Biotech Drugs Used in a Real World Setting in Campania Region (Italy): BIO-Cam Observational Study

PubMed Central

Scavone, Cristina; Sportiello, Liberata; Sullo, Maria G.; Ferrajolo, Carmen; Ruggiero, Rosanna; Sessa, Maurizio; Berrino, Pasquale M.; di Mauro, Gabriella; Berrino, Liberato; Rossi, Francesco; Rafaniello, Concetta; Capuano, Annalisa; Valentini, G.

2017-01-01

expected. Few cases of serious infections occurred, while no case of malignancy did. Overall, the safety profile of biotech drugs used in our population was similar to those observed in pivotal trials. Notwithstanding the positive results of our study, some safety concerns still remain unresolved. In order to collect more effectiveness and safety data on biotech drugs, the collection and analysis of real world data should be endorsed as well as the management of post-authorization studies. PMID:28932193

A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment.

PubMed

Consoli, Agostino; Formoso, Gloria; Baldassarre, Maria Pompea Antonia; Febo, Fabrizio

2018-03-01

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile. Area Covered: adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes. Expert opinion: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a 'similar' safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.

Mode of Action Profiles for Pesticide Compounds with Rodent Liver Tumor Outcomes

EPA Science Inventory

Mode of action (MOA) provides a central framework for assessing human relevance of adverse health outcomes observed in nonclinical safety studies. The goal of this study was to characterize MOA profiles for known rodent liver tumorigens identified from a database of pesticides as...

Safety and efficacy of lactoferrin versus ferrous sulphate in curing iron deficiency and iron deficiency anaemia in hereditary thrombophilia pregnant women: an interventional study.

PubMed

Paesano, Rosalba; Pacifici, Enrica; Benedetti, Samanta; Berlutti, Francesca; Frioni, Alessandra; Polimeni, Antonella; Valenti, Piera

2014-10-01

Objective Evaluate the safety and efficacy of bovine lactoferrin (bLf) versus the ferrous sulphate standard intervention in curing iron deficiency (ID) and ID anaemia (IDA) in pregnant women affected by hereditary thrombophilia (HT). Design Interventional study. Setting Secondary-level hospital for complicated pregnancies in Rome, Italy. Population 295 HT pregnant women (≥18 years) suffering from ID/IDA. Methods Women were enrolled in Arm A or B in accordance with their personal choice. In Arm A, 156 women received oral administration of 100 mg of bLf twice a day; in Arm B, 139 women received 520 mg of ferrous sulphate once a day. Therapies lasted until delivery. Main outcome measures Red blood cells, haemoglobin, total serum iron, serum ferritin (haematological parameters) were assayed before and every 30 days during therapy until delivery. Serum IL-6, key factor in inflammatory and iron homeostasis disorders, was detected at enrolment and after therapy at delivery. Possible maternal, foetal, and neonatal adverse effects were assessed. Results Haematological parameters were significantly higher in Arm A than in Arm B pregnant women (P ≤ 0.0001). Serum IL-6 significantly decreased in bLf-treated women and increased in ferrous sulphate-treated women. BLf did not exert any adverse effect. Adverse effects in 16.5 % of ferrous sulphate-treated women were recorded. Arm A women experienced no miscarriage compared to five miscarriages in Arm B women. Conclusions Differently from ferrous sulphate, bLf is safe and effective in curing ID/IDA associated with a consistent decrease of serum IL-6. The absence of miscarriage among bLf-treated women provided an unexpected benefit. ClinicalTrials.gov Identifier NCT01221844.

Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

PubMed

Persson, Mikael; Hornberg, Jorrit J

2016-12-19

High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

Linagliptin: farmacology, efficacy and safety in type 2 diabetes treatment

PubMed Central

2013-01-01

Type 2 diabetes mellitus (T2DM) has a high prevalence and incidence around the world. The complex pathophysiology mechanism is among the barriers for diabetes treatment. Type 2 diabetes patients have dysfunction in incretin hormones (as glucagon-like peptide-1 or GLP-1, and glucose-dependent insulinotropic polypeptide or GIP). By inhibiting the dipeptidyl peptidase-4 (DPP-4) enzyme, it is possible to slow the inactivation of GLP-1 and GIP, promoting blood glucose level reduction in a glucose-dependent manner. Linagliptin is a highly specific and potent inhibitor of DPP-4 that is currently indicated for the treatment of type 2 diabetes. Clinical studies with linagliptin demonstrated efficacy in reducing glycated hemoglobin (HbA1c) levels in type 2 diabetes patients, while maintaining a placebo-like safety and tolerability profile. Linagliptin has an interesting pharmacokinetic profile in terms of its predominantly non-renal elimination and the main implication of this characteristic is that no dose adjustment is necessary in patients with renal disease. Also, no dose adjustment is required in patients with hepatic insufficiency, as well in elderly or obese patients. This article will review the pharmacokinetic profile, efficacy data and safety aspects of linagliptin in type 2 diabetes patients. PMID:23697612

In vitro evaluation of human hybrid cell lines generated by fusion of B-lymphoblastoid cells and ex vivo tumour cells as candidate vaccines for haematological malignancies.

PubMed

Mohamed, Yehia S; Dunnion, Debbie; Teobald, Iryna; Walewska, Renata; Browning, Michael J

2012-10-12

Fusions of dendritic cells (DCs) and tumour cells have been shown to induce protective immunity to tumour challenge in animal models, and to represent a promising approach to cancer immunotherapy. The broader clinical application of this approach, however, is potentially constrained by the lack of replicative capacity and limited standardisation of fusion cell preparations. We show here that fusion of ex vivo tumour cells isolated from patients with a range of haematological malignancies with the human B-lymphoblastoid cell line (LCL), HMy2, followed by chemical selection of the hybridomas, generated stable, self-replicating human hybrid cell lines that grew continuously in tissue culture, and survived freeze/thawing cycles. The hybrid cell lines expressed HLA class I and class II molecules, and the major T-cell costimulatory molecules, CD80 and CD86. All but two of 14 hybrid cell lines generated expressed tumour-associated antigens that were not expressed by HMy2 cells, and were therefore derived from the parent tumour cells. The hybrid cell lines stimulated allogeneic T-cell proliferative responses and interferon-gamma release in vitro to a considerably greater degree than their respective parent tumour cells. The enhanced T-cell stimulation was inhibited by CTLA4-Ig fusion protein, and by blocking antibodies to MHC class I and class II molecules. Finally, all of five LCL/tumour hybrid cell lines tested induced tumour antigen-specific cytotoxic T-cell responses in vitro in PBL from healthy, HLA-A2+ individuals, as detected by HLA-A2-peptide pentamer staining and cellular cytotoxicity. These data show that stable hybrid cell lines, with enhanced immunostimulatory properties and potential for therapeutic vaccination, can be generated by in vitro fusion and chemical selection of B-LCL and ex vivo haematological tumour cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

A nationwide hospital survey on patient safety culture in Belgian hospitals: setting priorities at the launch of a 5-year patient safety plan.

PubMed

Vlayen, Annemie; Hellings, Johan; Claes, Neree; Peleman, Hilde; Schrooten, Ward

2012-09-01

To measure patient safety culture in Belgian hospitals and to examine the homogeneous grouping of underlying safety culture dimensions. The Hospital Survey on Patient Safety Culture was distributed organisation-wide in 180 Belgian hospitals participating in the federal program on quality and safety between 2007 and 2009. Participating hospitals were invited to submit their data to a comparative database. Homogeneous groups of underlying safety culture dimensions were sought by hierarchical cluster analysis. 90 acute, 42 psychiatric and 11 long-term care hospitals submitted their data for comparison to other hospitals. The benchmark database included 55 225 completed questionnaires (53.7% response rate). Overall dimensional scores were low, although scores were found to be higher for psychiatric and long-term care hospitals than for acute hospitals. The overall perception of patient safety was lower in French-speaking hospitals. Hierarchical clustering of dimensions resulted in two distinct clusters. Cluster I grouped supervisor/manager expectations and actions promoting safety, organisational learning-continuous improvement, teamwork within units and communication openness, while Cluster II included feedback and communication about error, overall perceptions of patient safety, non-punitive response to error, frequency of events reported, teamwork across units, handoffs and transitions, staffing and management support for patient safety. The nationwide safety culture assessment confirms the need for a long-term national initiative to improve patient safety culture and provides each hospital with a baseline patient safety culture profile to direct an intervention plan. The identification of clusters of safety culture dimensions indicates the need for a different approach and context towards the implementation of interventions aimed at improving the safety culture. Certain clusters require unit level improvements, whereas others demand a hospital-wide policy.

Students' Perceptions of Safety at School after Sandy Hook

ERIC Educational Resources Information Center

Fisher, Benjamin W.; Nation, Maury; Nixon, Carol T.; McIlroy, Sarah

2017-01-01

High profile school shootings have served as pivotal events for developing policies to promote student safety. Although previous studies indicate that exposure to violence is associated with feeling unsafe at school and poorer academic and psychosocial outcomes, research on the relationship between widely publicized acts of school violence and…

Comparison of the efficacy and safety profile of morning administration of controlled-release simvastatin versus evening administration of immediate-release simvastatin in chronic kidney disease patients with dyslipidemia.

PubMed

Yi, Yong Jin; Kim, Hyo Jin; Jo, Sang Kyung; Kim, Sung Gyun; Song, Young Rim; Chung, Wookyung; Han, Kum Hyun; Lee, Chang Hwa; Hwang, Young-Hwan; Oh, Kook-Hwan

2014-08-01

Evening administration of the conventional immediate-release (IR) formulation of simvastatin is recommended because of its short half-life (1.9 hours). In a healthy population, morning administration of a controlled-release (CR) formulation of simvastatin was shown to have equivalent lipid-lowering efficacy and a safety profile similar to that of evening doses of IR simvastatin. The present study aimed to verify noninferiority and to compare the safety of morning administration of CR simvastatin with that of evening administration of IR simvastatin in patients with chronic kidney disease (CKD) who have dyslipidemia. The present study was a prospective, multicenter, double-blind, Phase IV trial with an active comparator. We randomly assigned 122 patients with CKD and dyslipidemia to 1 of 2 drug administration groups: morning administration of CR simvastatin 20 mg (test group) and evening administration of IR simvastatin 20 mg (control group). After 8 weeks, the treatment outcomes and adverse effects of the 2 treatments were compared. The mean (SD) percentage of change in serum LDL-C at the end of treatment was -35.1% (15.7%) for the test group and -35.6% (14.6%) for the control group. The difference between the 2 groups was not significant (P = 0.858). The 95% CI of the difference in the percentage of change of LDL-C between the test and control groups was -6.0 to 5.0. There was no difference in the percentage of change of total cholesterol (-24.3% [12.5%] vs -26.5% [12.0%], P = 0.317), triglyceride (-10.6% [35.1%] vs -12.4% [33.2%], P = 0.575) and HDL-C (10.2% [20.7%] vs 4.5% [11.4%], P = 0.064). Treatment-related adverse events were similar in both groups (10 events in the test group vs 8 events in the control group, P = 0.691). The efficacy of morning administration of CR simvastatin was noninferior to evening administration of IR simvastatin in patients with CKD. Furthermore, the safety profile analysis showed no significant difference between the 2 treatments

Monitoring of biological markers indicative of doping: the athlete biological passport.

PubMed

Saugy, Martial; Lundby, Carsten; Robinson, Neil

2014-05-01

The athlete biological passport (ABP) was recently implemented in anti-doping work and is based on the individual and longitudinal monitoring of haematological or urine markers. These may be influenced by illicit procedures performed by some athletes with the intent to improve exercise performance. Hence the ABP is a valuable tool in the fight against doping. Actually, the passport has been defined as an individual and longitudinal observation of markers. These markers need to belong to the biological cascade influenced by the application of forbidden hormones or more generally, affected by biological manipulations which can improve the performance of the athlete. So far, the haematological and steroid profile modules of the ABP have been implemented in major sport organisations, and a further module is under development. The individual and longitudinal monitoring of some blood and urine markers are of interest, because the intraindividual variability is lower than the corresponding interindividual variability. Among the key prerequisites for the implementation of the ABP is its prospect to resist to the legal and scientific challenges. The ABP should be implemented in the most transparent way and with the necessary independence between planning, interpretation and result management of the passport. To ensure this, the Athlete Passport Management Unit (APMU) was developed and the WADA implemented different technical documents associated to the passport. This was carried out to ensure the correct implementation of a profile which can also stand the challenge of any scientific or legal criticism. This goal can be reached only by following strictly important steps in the chain of production of the results and in the management of the interpretation of the passport. Various technical documents have been then associated to the guidelines which correspond to the requirements for passport operation. The ABP has been completed very recently by the steroid profile module

Safety of Sculptra: a review of clinical trial data.

PubMed

Engelhard, Peter; Humble, Gail; Mest, Douglas

2005-12-01

The development of facial lipoatrophy as a result of highly active antiretroviral therapy (HAART) used to treat patients with human immunodeficiency virus (HIV) has adversely affected patient quality of life and compliance with therapy. Thanks to modern pharmacotherapies, HIV can now be viewed as a chronic disease; however, this welcome change has exacerbated the effect of facial lipoatrophy since HIV-infected patients can now expect to live longer and healthier lives but remain subject to public scrutiny of their ongoing disease state. Sculptra (Dermik Laboratories, Berwyn, PA, USA) has recently been introduced in the USA for correction of the appearance of facial lipoatrophy. The device affords long-lasting restoration while still being non-permanent, thus providing an extended but adjustable cosmetic effect. The safety profile of this product has been observed in four investigator-initiated clinical trials of more than 250 HIV patients and in numerous investigator reports, with no serious adverse events or infections deemed associated with the product. Maintenance of the excellent safety profile for this injectable device requires adherence to a novel technique and appreciation of its unique attributes.

Safety of treatment options for spondyloarthritis: a narrative review.

PubMed

D'Angelo, Salvatore; Carriero, Antonio; Gilio, Michele; Ursini, Francesco; Leccese, Pietro; Palazzi, Carlo

2018-05-01

Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations. Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.

Efficacy and safety of novel antipsychotics: a critical review.

PubMed

Balestrieri, Matteo; Vampini, Claudio; Bellantuono, Cesario

2000-10-01

Efficacy and safety of novel antipsychotic (AP) drugs (amisulpride, olanzapine, quetiapine, ziprasidone and zotepine) have been reviewed. Data on their antipsychotic efficacy and side effects profile have been evaluated only on the basis of controlled trials so far published. Overall, all these drugs have shown an antipsychotic efficacy on positive symptoms of schizophrenia similar to that of the conventional AP drugs. On negative symptoms, all novel AP drugs, except quetiapine and ziprasidone, demonstrated a better efficacy than haloperidol. Long-term efficacy of these AP drugs in the maintenance treatment of schizophrenia needs to be explored by further, better-designed, epidemiological studies. The safety profile shows that the novel AP drugs are generally well-tolerated and induce significantly less acute extrapyramidal side effects in comparison with haloperidol. Some methodological flaws in the experimental design of the clinical trials analysed are discussed. Although these novel AP drugs have potential clinical advantages, a number of relevant questions still remain to be addressed, in order to establish the impact of these drugs in the overall treatment of schizophrenia. Copyright 2000 John Wiley & Sons, Ltd.

Driver behavior profiling: An investigation with different smartphone sensors and machine learning

PubMed Central

Ferreira, Jair; Carvalho, Eduardo; Ferreira, Bruno V.; de Souza, Cleidson; Suhara, Yoshihiko; Pentland, Alex

2017-01-01

Driver behavior impacts traffic safety, fuel/energy consumption and gas emissions. Driver behavior profiling tries to understand and positively impact driver behavior. Usually driver behavior profiling tasks involve automated collection of driving data and application of computer models to generate a classification that characterizes the driver aggressiveness profile. Different sensors and classification methods have been employed in this task, however, low-cost solutions and high performance are still research targets. This paper presents an investigation with different Android smartphone sensors, and classification algorithms in order to assess which sensor/method assembly enables classification with higher performance. The results show that specific combinations of sensors and intelligent methods allow classification performance improvement. PMID:28394925

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

PubMed

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer

PubMed Central

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus–exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile. PMID:28096680

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

PubMed Central

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

Exploring Typical and Atypical Safety Climate Perceptions of Practitioners in the Repair, Maintenance, Minor Alteration and Addition (RMAA) Sector in Hong Kong.

PubMed

Hon, Carol K H; Liu, Yulin

2016-09-22

The safety of repair, maintenance, minor alteration and addition (RMAA) work is an under-explored area. This study explored the typical and atypical safety climate perceptions of practitioners in the RMAA sector in Hong Kong, based on a self-administered questionnaire survey of 662 local practitioners in the industry. Profile analysis, via multidimensional scaling of the respondents' scores of three safety climate scales, identified one typical perception: high in management commitment to occupational health and safety (OHS) and employee involvement, low in applicability for safety rules and regulations, and low in responsibility for OHS. The respondents were clustered into typical and atypical perception groups according to their safety climate scores' match to the typical perception. A comparison of demographics between the two groups with logistic regression found that work level and direct employer significantly affect their classification. A multivariate analysis of variance of safety performance measures between the two groups indicated that the typical group had a significantly higher level of safety compliance than the atypical group, with no significant difference in safety participation or injury. The significance of this study lies in revealing the typical safety climate perception profile pattern of RMAA works and offering a new perspective of safety climate research.