Cortical thickness, surface area and volume measures in Parkinson's disease, multiple system atrophy and progressive supranuclear palsy

OBJECTIVE Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) are neurodegenerative diseases that can be difficult to distinguish clinically. The objective of the current study was to use surface-based analysis techniques to assess cortical thickness, surface area and grey matter volume to identify unique morphological patterns of cortical atrophy in PD, MSA and PSP and to relate these patterns of change to disease duration and clinical features. METHODS High resolution 3D T1-weighted MRI volumes were acquired from 14 PD patients, 18 MSA, 14 PSP and 19 healthy control participants. Cortical thickness, surface area and volume analyses were carried out using the automated surface-based analysis package FreeSurfer (version 5.1.0). Measures of disease severity and duration were assessed for correlation with cortical morphometric changes in each clinical group. RESULTS Results show that in PSP, widespread cortical thinning and volume loss occurs within the frontal lobe, particularly the superior frontal gyrus. In addition, PSP patients also displayed increased surface area in the pericalcarine. In comparison, PD and MSA did not display significant changes in cortical morphology. CONCLUSION These results demonstrate that patients with clinically established PSP exhibit distinct patterns of cortical atrophy, particularly affecting the frontal lobe. These results could be used in the future to develop a useful clinical application of MRI to distinguish PSP patients from PD and MSA patients

The economic pressures for biosimilar drug use in cancer medicine

The main rationale for using biosimilar drugs is for cost saving. The market development for biosimilar drugs will therefore depend on the degree to which cost saving measures are required by nations, medical insurers and individuals and the absolute savings that could be gained by switching from original drugs. This paper is designed to discover the degree to which financial constraints will drive future health spending and to discover if legal or safety issues could impact on any trend. A structured literature search was performed for papers and documents to 27 August 2011. Where multiple sources of data were available on a topic, data from papers and reports by multinational or national bodies were used in preference to data from regions or individual hospitals. Almost all health systems face current significant cost pressures. The twin driver of increasing cancer prevalence as populations age and cancer medicine costs rising faster than inflation places oncology as the most significant single cost problem. For some countries, this is predicted to make medicine unaffordable within a decade. Most developed countries have planned to embrace biosimilar use as a cost-control measure. Biosimilar introduction into the EU has already forced prices down, both the price of biosimilar drugs and competitive price reductions in originator drugs. Compound annual growth rates of use have been predicted at 65.8% per year. Most developed countries have planned to embrace biosimilar use as a major cost-control measure. Only legal blocks and safety concerns are likely to act against this trend. For centralised healthcare systems, and those with a strong tradition of generic medicine use, biosimilar use will clearly rise with predictions of more than 80% of prescriptions of some biologic drugs within 1 year of market entry in the USA. Delaying the implementation of such programmes however risks a real crisis in healthcare delivery for many countries and hospitals that few can now afford

A questionnaire-based (UM-PDHQ) study of hallucinations in Parkinson's disease

Background: Hallucinations occur in 20-40% of PD patients and have been associated with unfavorable clinical outcomes (i.e., nursing home placement, increased mortality). Hallucinations, like other non-motor features of PD, are not well recognized in routine primary/secondary clinical practice. So far, there has been no instrument for uniform characterization of hallucinations in PD. To this end, we developed the University of Miami Parkinson's disease Hallucinations Questionnaire (UM-PDHQ) that allows comprehensive assessment of hallucinations in clinical or research settings.Methods: The UM-PDHQ is composed of 6 quantitative and 14 qualitative items. For our study PD patients of all ages and in all stages of the disease were recruited over an 18-month period. The UPDRS, MMSE, and Beck Depression and Anxiety Inventories were used for comparisons.Results and Discussion: Seventy consecutive PD patients were included in the analyses. Thirty-one (44.3%) were classified as hallucinators and 39 as non-hallucinators. No significant group differences were observed in terms of demographics, disease characteristics, stage, education, depressive/anxiety scores or cognitive functioning (MMSE) between hallucinators and non-hallucinators. Single mode hallucinations were reported in 20/31 (visual/14, auditory/4, olfactory/2) whereas multiple modalities were reported in 11/31 patients. The most common hallucinatory experience was a whole person followed by small animals, insects and reptiles.Conclusion: Using the UM-PDHQ, we were able to define the key characteristics of hallucinations in PD in our cohort. Future directions include the validation of the quantitative part of the questionnaire than will serve as a rating scale for severity of hallucinations

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Mixed model approaches for the identification of QTLs within a maize hybrid breeding program

Two outlines for mixed model based approaches to quantitative trait locus (QTL) mapping in existing maize hybrid selection programs are presented: a restricted maximum likelihood (REML) and a Bayesian Markov Chain Monte Carlo (MCMC) approach. The methods use the in-silico-mapping procedure developed by Parisseaux and Bernardo (2004) as a starting point. The original single-point approach is extended to a multi-point approach that facilitates interval mapping procedures. For computational and conceptual reasons, we partition the full set of relationships from founders to parents of hybrids into two types of relations by defining so-called intermediate founders. QTL effects are defined in terms of those intermediate founders. Marker based identity by descent relationships between intermediate founders define structuring matrices for the QTL effects that change along the genome. The dimension of the vector of QTL effects is reduced by the fact that there are fewer intermediate founders than parents. Furthermore, additional reduction in the number of QTL effects follows from the identification of founder groups by various algorithms. As a result, we obtain a powerful mixed model based statistical framework to identify QTLs in genetic backgrounds relevant to the elite germplasm of a commercial breeding program. The identification of such QTLs will provide the foundation for effective marker assisted and genome wide selection strategies. Analyses of an example data set show that QTLs are primarily identified in different heterotic groups and point to complementation of additive QTL effects as an important factor in hybrid performance

Skeletal Plasmacytoma: Progression of disease and impact of local treatment; an analysis of SEER database

<p>Abstract</p> <p>Background</p> <p>Previous reports suggest an as yet unidentifiable subset of patients with plasmacytoma will progress to myeloma. The current study sought to establish the risk of developing myeloma and determine the prognostic factors affecting the progression of disease.</p> <p>Methods</p> <p>Patients with plasmacytoma diagnosed between 1973 and 2005 were identified in the SEER database(1164 patients). Patient demographics and clinical characteristics, treatment(s), cause of death, and survival were extracted. Kaplan-Meier, log-rank, and Cox regression were used to analyze prognostic factors.</p> <p>Results</p> <p>The five year survival among patients initially diagnosed with plasmacytoma that later progressed to multiple myeloma and those initially diagnosed with multiple myeloma were almost identical (25% and 23%; respectively). Five year survival for patients with plasmacytoma that did not progress to multiple myeloma was significantly better (72%). Age > 60 years was the only factor that correlated with progression of disease (p = 0.027).</p> <p>Discussion</p> <p>Plasmacytoma consists of two cohorts of patients with different overall survival; those patients that do not progress to systemic disease and those that develop myeloma. Age > 60 years is associated with disease progression. Identifying patients with systemic disease early in the treatment will permit aggressive and novel treatment strategies to be implemented.</p

Dopamine Agonists and their risk to induce psychotic episodes in Parkinson's disease: a case-control study

<p>Abstract</p> <p>Background</p> <p>Psychosis is rare in untreated patients with Parkinson's disease (PD) but the prevalence rises to 40% during dopaminergic treatment. So far, no systematic comparison of the psychogenic potential of different dopaminergic drugs had been performed.</p> <p>Methods</p> <p>Eighty PD patients with psychotic episodes were compared to an age-matched control group of PD patients without psychotic episodes (n = 120) in a cross-sectional retrospective study.</p> <p>Results</p> <p>We found a positive correlation between psychotic episodes and dementia, number of concomitant medication, and pergolide intake. Odds ratio calculation confirmed the association with dementia. With respect to dopaminergic treatment, pergolide showed the highest odds ratio, levodopa the lowest. An adjusted logistic regression model confirmed the strong association with psychotic episodes and pergolide and no association with levodopa (adjusted odds ratio 2.01 and 0.11, respectively).</p> <p>Conclusion</p> <p>The analysis indicates that dementia and concomitant medication are factors in PD associated with psychotic symptoms. Furthermore, different dopaminergic drugs showed markedly different associations with psychotic symptoms</p

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Background PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Methods Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. Results 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. Conclusions Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. Trial registration NCT Clinicaltrials.gov identifier: NCT0215863