Symptoms and quality of life in late stage Parkinson syndromes: a longitudinal community study of predictive factors

BACKGROUND Palliative care is increasingly offered earlier in the cancer trajectory but rarely in Idiopathic Parkinson's Disease(IPD), Progressive Supranuclear Palsy(PSP) or Multiple System Atrophy(MSA). There is little longitudinal data of people with late stage disease to understand levels of need. We aimed to determine how symptoms and quality of life of these patients change over time; and what demographic and clinical factors predicted changes. METHODS We recruited 82 patients into a longitudinal study, consenting patients with a diagnosis of IPD, MSA or PSP, stages 3-5 Hoehn and Yahr(H&Y). At baseline and then on up to 3 occasions over one year, we collected self-reported demographic, clinical, symptom, palliative and quality of life data, using Parkinson's specific and generic validated scales, including the Palliative care Outcome Scale (POS). We tested for predictors using multivariable analysis, adjusting for confounders. FINDINGS Over two thirds of patients had severe disability, over one third being wheelchair-bound/bedridden. Symptoms were highly prevalent in all conditions - mean (SD) of 10.6(4.0) symptoms. More than 50% of the MSA and PSP patients died over the year. Over the year, half of the patients showed either an upward (worsening, 24/60) or fluctuant (8/60) trajectory for POS and symptoms. The strongest predictors of higher levels of symptoms at the end of follow-up were initial scores on POS (AOR 1.30; 95%CI:1.05-1.60) and being male (AOR 5.18; 95% CI 1.17 to 22.92), both were more predictive than initial H&Y scores. INTERPRETATION The findings point to profound and complex mix of non-motor and motor symptoms in patients with late stage IPD, MSA and PSP. Symptoms are not resolved and half of the patients deteriorate. Palliative problems are predictive of future symptoms, suggesting that an early palliative assessment might help screen for those in need of earlier intervention

Accretion Disks Around Black Holes: Twenty Five Years Later

We study the progress of the theory of accretion disks around black holes in last twenty five years and explain why advective disks are the best bet in explaining varied stationary and non-stationary observations from black hole candidates. We show also that the recently proposed advection dominated flows are incorrect.Comment: 30 Latex pages including figures. Kluwer Style files included. Appearing in `Observational Evidence for Black Holes in the Universe', ed. Sandip K. Chakrabarti, Kluwer Academic Publishers (DORDRECHT: Holland

F-Theory and the Mordell-Weil Group of Elliptically-Fibered Calabi-Yau Threefolds

The Mordell-Weil group of an elliptically fibered Calabi-Yau threefold X contains information about the abelian sector of the six-dimensional theory obtained by compactifying F-theory on X. After examining features of the abelian anomaly coefficient matrix and U(1) charge quantization conditions of general F-theory vacua, we study Calabi-Yau threefolds with Mordell-Weil rank-one as a first step towards understanding the features of the Mordell-Weil group of threefolds in more detail. In particular, we generate an interesting class of F-theory models with U(1) gauge symmetry that have matter with both charges 1 and 2. The anomaly equations --- which relate the Neron-Tate height of a section to intersection numbers between the section and fibral rational curves of the manifold --- serve as an important tool in our analysis.Comment: 29 pages + appendices, 5 figures; v2: minor correction

INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized controlled trial of percutaneous vertebroplasty

Background: The treatment of painful osteoporotic vertebral compression fractures has historically been limited to several weeks of bed rest, anti-inflammatory and analgesic medications, calcitonin injections, or external bracing. Percutaneous vertebroplasty (the injection of bone cement into the fractured vertebral body) is a relatively new procedure used to treat these fractures. There is increasing interest to examine the efficacy and safety of percutaneous vertebroplasty and to study the possibility of a placebo effect or whether the pain relief is from local anesthetics placed directly on the bone during the vertebroplasty procedure. Methods/Designs: Our goal is to test the hypothesis that patients with painful osteoporotic vertebral compression fractures who undergo vertebroplasty have less disability and pain at 1 month than patients who undergo a control intervention. The control intervention is placement of local anesthesia near the fracture, without placement of cement. One hundred sixty-six patients with painful osteoporotic vertebral compression fractures will be recruited over 5 years from US and foreign sites performing the vertebroplasty procedure. We will exclude patients with malignant tumor deposit (multiple myeloma), tumor mass or tumor extension into the epidural space at the level of the fracture. We will randomly assign participants to receive either vertebroplasty or the control intervention. Subjects will complete a battery of validated, standardized measures of pain, functional disability, and health related quality of life at baseline and at post-randomization time points (days 1, 2, 3, and 14, and months 1, 3, 6, and 12). Both subjects and research interviewers performing the follow-up assessments will be blinded to the randomization assignment. Subjects will have a clinic visit at months 1 and 12. Spine X-rays will be obtained at the end of the study (month 12) to determine subsequent fracture rates. Our co-primary outcomes are the modified Roland score and pain numerical rating scale at 1 month. Discussion: Although extensively utilized throughout North America for palliation of pain, vertebroplasty still has not undergone rigorous study. The study outlined above represents the first randomized, controlled study that can account for a placebo effect in the setting of vertebroplasty. Trial Registration: Current Controlled Trials ISRCTN81871888.The source of funding for the study and all authors for this publication was National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

The influence of semantic and phonological factors on syntactic decisions: An event-related brain potential study

During language production and comprehension, information about a word's syntactic properties is sometimes needed. While the decision about the grammatical gender of a word requires access to syntactic knowledge, it has also been hypothesized that semantic (i.e., biological gender) or phonological information (i.e., sound regularities) may influence this decision. Event-related potentials (ERPs) were measured while native speakers of German processed written words that were or were not semantically and/or phonologically marked for gender. Behavioral and ERP results showed that participants were faster in making a gender decision when words were semantically and/or phonologically gender marked than when this was not the case, although the phonological effects were less clear. In conclusion, our data provide evidence that even though participants performed a grammatical gender decision, this task can be influenced by semantic and phonological factors

Anomaly Equations and Intersection Theory

Six-dimensional supergravity theories with N=(1,0) supersymmetry must satisfy anomaly equations. These equations come from demanding the cancellation of gravitational, gauge and mixed anomalies. The anomaly equations have implications for the geometrical data of Calabi-Yau threefolds, since F-theory compactified on an elliptically fibered Calabi-Yau threefold with a section generates a consistent six-dimensional N=(1,0) supergravity theory. In this paper, we show that the anomaly equations can be summarized by three intersection theory identities. In the process we also identify the geometric counterpart of the anomaly coefficients---in particular, those of the abelian gauge groups---that govern the low-energy dynamics of the theory. We discuss the results in the context of investigating string universality in six dimensions.Comment: 29 pages + appendices, 8 figures; v2: minor corrections, references added; v3: minor corrections, reference adde

The effect of Tai Chi Chuan in reducing falls among elderly people: design of a randomized clinical trial in the Netherlands [ISRCTN98840266]

BACKGROUND: Falls are a significant public health problem. Thirty to fifty percent of the elderly of 65 years and older fall each year. Falls are the most common type of accident in this age group and can result in fractures and subsequent disabilities, increased fear of falling, social isolation, decreased mobility, and even an increased mortality. Several forms of exercise have been associated with a reduced risk of falling and with a wide range of physiological as well as psychosocial health benefits. Tai Chi Chuan seems to be the most promising form of exercise in the elderly, but the evidence is still controversial. In this article the design of a randomized clinical trial is presented. The trial evaluates the effect of Tai Chi Chuan on fall prevention and physical and psychological function in older adults. METHODS/DESIGN: 270 people of seventy years and older living at home will be identified in the files of the participating general practitioners. People will be asked to participate when meeting the following inclusion criteria: have experienced a fall in the preceding year or suffer from two of the following risk factors: disturbed balance, mobility problems, dizziness, or the use of benzodiazepines or diuretics. People will be randomly allocated to either the Tai Chi Chuan group (13 weeks, twice a week) or the no treatment control group. The primary outcome measure is the number of new falls, measured with a diary. The secondary outcome measures are balance, fear of falling, blood pressure, heart rate, lung function parameters, physical activity, functional status, quality of life, mental health, use of walking devices, medication, use of health care services, adjustments to the house, severity of fall incidents and subsequent injuries. Process parameters will be measured to evaluate the Tai Chi Chuan intervention. A cost-effectiveness analysis will be carried out alongside the evaluation of the clinical results. Follow-up measurements will be collected at 3, 6 and 12 months after randomization. DISCUSSION: As far as we know this is the first trial in Europe considering Tai Chi Chuan and fall prevention. This project will answer a pragmatic research question regarding the efficacy of Tai Chi Chuan regarding fall reduction

A new method for determining physician decision thresholds using empiric, uncertain recommendations

<p>Abstract</p> <p>Background</p> <p>The concept of risk thresholds has been studied in medical decision making for over 30 years. During that time, physicians have been shown to be poor at estimating the probabilities required to use this method. To better assess physician risk thresholds and to more closely model medical decision making, we set out to design and test a method that derives thresholds from actual physician treatment recommendations. Such an approach would avoid the need to ask physicians for estimates of patient risk when trying to determine individual thresholds for treatment. Assessments of physician decision making are increasingly relevant as new data are generated from clinical research. For example, recommendations made in the setting of ocular hypertension are of interest as a large clinical trial has identified new risk factors that should be considered by physicians. Precisely how physicians use this new information when making treatment recommendations has not yet been determined.</p> <p>Results</p> <p>We derived a new method for estimating treatment thresholds using ordinal logistic regression and tested it by asking ophthalmologists to review cases of ocular hypertension before expressing how likely they would be to recommend treatment. Fifty-eight physicians were recruited from the American Glaucoma Society. Demographic information was collected from the participating physicians and the treatment threshold for each physician was estimated. The method was validated by showing that while treatment thresholds varied over a wide range, the most common values were consistent with the 10-15% 5-year risk of glaucoma suggested by expert opinion and decision analysis.</p> <p>Conclusions</p> <p>This method has advantages over prior means of assessing treatment thresholds. It does not require physicians to explicitly estimate patient risk and it allows for uncertainty in the recommendations. These advantages will make it possible to use this method when assessing interventions intended to alter clinical decision making.</p

Long-term results after Boston brace treatment in late-onset juvenile and adolescent idiopathic scoliosis

<p>Abstract</p> <p>Background</p> <p>It is recommended that research in patients with idiopathic scoliosis should focus on short- and long-term patient-centred outcome. The aim of the present study was to evaluate outcome in patients with late-onset juvenile or adolescent idiopathic scoliosis 16 years or more after Boston brace treatment.</p> <p>Methods</p> <p>272 (78%) of 360 patients, 251 (92%) women, responded to follow-up examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment. Fifty-eight (21%) patients had late-onset juvenile and 214 had adolescent idiopathic scoliosis. All patients had clinical and radiological examination and answered a standardised questionnaire including work status, demographics, General Function Score (GFS) (100 - worst possible) and Oswestry Disability Index (ODI) (100 - worst possible), EuroQol (EQ-5D) (1 - best possible), EQ-VAS (100 - best possible), and Scoliosis Research Society - 22 (SRS - 22) (5 - best possible).</p> <p>Results</p> <p>The mean age at follow-up was 40.4 (31-48) years. The prebrace major curve was in average 33.2 (20 - 57)°. At weaning and at the last follow-up the corresponding values were 28.3 (1 - 58)° and 32.5 (7 - 80)°, respectively. Curve development was similar in patients with late-onset juvenile and adolescent start. The prebrace curve increased > 5° in 31% and decreased > 5° in 26%. Twenty-five patients had surgery. Those who did not attend follow-up (n = 88) had a lower mean curve at weaning: 25.4 (6-53)°. Work status was 76% full-time and 10% part-time. Eighty-seven percent had delivered a baby, 50% had pain in pregnancy. The mean (SD) GFS was 7.4 (10.8), ODI 9.3 (11.0), EQ-5D 0.82 (0.2), EQ-VAS 77.6 (17.8), SRS-22: pain 4.1 (0.8), mental health 4.1 (0.6), self-image 3.7 (0.7), function 4.0 (0.6), satisfaction with treatment 3.7 (1.0). Surgical patients had significantly reduced scores for SRS-physical function and self-image, and patients with curves ≥ 45° had reduced self-image.</p> <p>Conclusion</p> <p>Long-term results were satisfactory in most braced patients and similar in late-onset juvenile and idiopathic adolescent scoliosis.</p