Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine from an observational study in Europe

Objective To examine treatment utilization patterns and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine in routine clinical practice. Background Clinical trials support onabotulinumtoxinA for the prophylaxis of headache in patients with chronic migraine, but real-world data are limited. Design/methods A prospective, observational, post-authorization study in adult patients with chronic migraine treated with onabotulinumtoxinA. Data were collected at the first study injection and approximately every three months for 52 weeks for utilization and 64 weeks for safety data, and summarized using descriptive statistics. Results Eighty-five physicians (81% neurologists) at 58 practices in the United Kingdom, Germany, Spain, and Sweden participated and recruited 1160 patients (84.2% female, median age 46.6 years). At baseline, 85.8% of patients had physician diagnoses of chronic migraine/transformed migraine and reported an average of 11.3 (SD=6.9) severe headache days per 28 days;50.6% had previously used onabotulinumtoxinA for chronic migraine. A total of 4017 study treatments were observed. The median number of injection sites (n=31) and total dose (155 U) were consistent across all treatment sessions, with a median 13.7 weeks observed between sessions. At least one treatment-related adverse event was reported by 291 patients (25.1%);the most frequently reported treatment-related adverse event was neck pain (4.4%). Most patients (74.4%) were satisfied/extremely satisfied with onabotulinumtoxinA treatment. Conclusions Patient demographics/characteristics are consistent with published data on the chronic migraine population. Utilization of onabotulinumtoxinA treatment for chronic migraine appears to be consistent with the Summary of Product Characteristics and published PREEMPT injection paradigm. No new safety signals were identified

Evaluation of a Multidisciplinary Team Approach for Generating Survivorship Care Plan Treatment Summaries in Patients With Breast Cancer

INTRODUCTION: The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS: We used the Institute for Healthcare Improvement\u27s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute\u27s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P \u3c .01). CONCLUSION: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted

Evaluation of a Multidisciplinary Team Approach for Generating Survivorship Care Plan Treatment Summaries in Patients With Breast Cancer

INTRODUCTION:: The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS:: We used the Institute for Healthcare Improvement\u27s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute\u27s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS:: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P \u3c .01). CONCLUSION:: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted

Ecological implications of pedogenesis and geochemistry of ultramafic soils in Kinabalu Park (Malaysia)

In Sabah, Malaysia, ultramafic rock outcrops are widespread (totalling 3500 km2, one of the main outcrops in the tropical zone), and predominantly of the peridotite type. However, strongly serpentinised peridotite is also locally common, particularly along fault lines in the Mt. Kinabalu area. This study aimed to determine the extent of chemical variation in ultramafic soils in relation to the degree of serpentinisation and the weathering intensity, and consequent potential ecological implications linked to resulting soil chemical fertility. It was hypothesized that young soils and soils derived from bedrock with a significant degree of serpentinisation strongly differ from typical Geric Ferralsols and result in soil chemistries with more adverse properties to plant life (e.g. low availability of the essential nutrients N, P, K and Ca and high concentrations of potentially phytotoxic Mg and Ni). Ultramafic soil diversity linked to the age of the soil or the degree of serpentinisation would thus be a main factor of plant diversity and distribution. The diverse topography of Kinabalu Park (ultramafic soils present between 400 and 2950 m asl) has given rise to high pedodiversity with the broad overall ultramafic soil types being: (i) deep laterite soils (Geric Ferralsols); (ii) moderately deep montane soils (Dystric Cambisols) with mor humus; (iii) shallow skeletal soils at high altitude (Eutric Cambisols Hypermagnesic); and (iv) bare serpentinite soils (Hypereutric Leptosols Hypermagnesic) at low altitude (200–700 m asl). Leptosols on serpentinite and Eutric Cambisols have the most extreme chemical properties in the whole Kinabalu Park area both with very high Mg:Ca molar quotients, with either high available Ni (Cambisols) or high pH (Leptosols). These soils host specific and adapted vegetation (high level of endemism) that tolerates geochemical peculiarities, including Ni hyperaccumulators. Geric Ferralsols present far less chemical constraints than Hypermagnesian Cambisols soils to the vegetation and host a tall and very diverse rainforest, not so different than that on non-ultramafic soils. It therefore appears that altitude, soil age and degree of bedrock serpentinisation are the main determining factors of soil properties: the qualifier “ultramafic” alone is not sufficient to define soil geochemical and ecological conditions in the Kinabalu Park area, probably more than in any other ultramafic region in the world

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Differentiating first episode substance induced and primary psychotic disorders with concurrent substance use in young people

Objective: Substance use is common in first-episode psychosis, and complicates the accurate diagnosis and treatment of the disorder. The differentiation of substance-induced psychotic disorders (SIPD) from primary psychotic disorders (PPD) is particularly challenging. This cross-sectional study compares the clinical, substance use and functional characteristics of substance using first episode psychosis patients diagnosed with a SIPD and PPD. Method: Participants were 61 young people (15-24 years) admitted to a psychiatric inpatient service with first episode psychosis, reporting substance use in the past month. Diagnosis was determined using the Psychiatric Research Interview for DSM-IV Substance and Mental disorders (PRISM-IV). Measures of clinical (severity of psychotic symptoms, level of insight, history of trauma), substance use (frequency/quantity, severity) and social and occupational functioning were also administered. Results: The PRISM-IV differentially diagnosed 56% of first episode patients with a SIPD and 44% with a PPD. Those with a SIPD had higher rates of substance use and disorders, higher levels of insight, were more likely to have a forensic and trauma history and had more severe hostility and anxious symptoms than those with a PPD. Logistic regression analysis indicated a family history of psychosis, trauma history and current cannabis dependence were the strongest predictors of a SIPD. Almost 80% of diagnostic predictions of a SIPD were accurate using this model. Conclusions: This clinical profile of SIPD could help to facilitate the accurate diagnosis and treatment of SIPD versus PPD in young people with first episode psychosis admitted to an inpatient psychiatric service

A randomised controlled-trial of metacognitive therapy versus exposure therapy for post-traumatic stress disorder

Background: Chronic post-traumatic stress disorder (PTSD) occurs frequently and is characterised by an unremitting course (Kessler et al. 1995). Despite the availability of effective treatments a significant proportion of clients remain symptomatic following intervention (Cahill & Foa, 2004). Existing approaches seem inadequate to tackle this growing problem. Metacognitive therapy (MCT) is a novel approach and has demonstrated efficacy (Wells et al. 2008). This research compared MCT with Exposure therapy and a waitlist control condition (WL). Method: Participants (N=32) with symptom chronicity of~ 3 months were recruited for this . randomised controlled trial (RCT) from four Clinical Psychology Departments across the North West of England. Following an initial assessment those opting into the trial were randomly assigned to one of the three conditions, eight sessions of therapy (MCT v. Exposure) or an eight week wait period (WL) followed by a second randomisation to receive one of the active treatments. It was hypothesised that both active treatments would lead to significant reductions in PTSD, depression and anxiety symptoms compared with the WL and MCT would generate a faster rate of change compared with Exposure. The Impact of Events Scale (IES) was the primary outcome measure. Evaluations were conducted at pre-treatment and post-treatment time points. Results: Both MCT and Exposure resulted in statistically significant reductions in symptoms of PTSD, anxiety and depression compared with the WL control. MCT led to greater reductions than Exposure across symptoms of psychological distress and physiological arousal. Eighty-two percent of those completing MCT and 64% of the Exposure group met clinical significance criteria for recovery at post-treatment. In conclusion, MCT appears to be a highly effective treatment for PTSD when compared with traditional approaches. The clinical implications and suggestions for future research are discussed.EThOS - Electronic Theses Online ServiceGBUnited Kingdo