Levodopa response in early Parkinson's disease

To further characterize the short‐term levodopa response in early PD, we performed a retrospective analysis of the ELLDOPA study which randomized 361 early PD subjects to placebo, levodopa 150, 300, or 600 mg/day. We evaluated change in UPDRS motor scores (UPDRSm) from baseline to weeks 9 and 24, and identified changes in UPDRSm that best discriminated treatment with levodopa from placebo. Linear regressions were used to determine associations between baseline characteristics and changes in UPDRSm. Mean percent improvement in UPDRSm in levodopa‐treated subjects was greater than that for placebo‐treated subjects (27.4% vs. 5.8% at 9 weeks, P < 0.001 and 26.2% vs. 4.0% at 24 weeks, P < 0.001). UPDRSm change at 9 weeks ranged from –92.9% (improvement) to 85.7% (worsening) for levodopa and –86.7% to 160% for placebo, and at 24 weeks ranged from –100.0% to 242.9% for levodopa and –87.5% to 112.5% for placebo. UPDRSm improvements of 22.0% at 9 weeks and 23.8% at 24 weeks best discriminated treatment with levodopa 300 mg/day (a common initial maintenance dosage in clinical practice) from placebo. Significant associations were not observed between baseline subject characteristics and magnitude of response from baseline to week 24. We conclude that although levodopa treatment significantly improved PD signs when compared with placebo, there was a wide range and considerable overlap in clinical responses to levodopa and placebo. A substantial proportion of subjects with early PD did not experience a robust response to levodopa. An improvement in UPDRSm of ～22% best discriminated levodopa treatment from placebo. © 2009 Movement Disorder Society     

A meta-analysis of six prospective studies of falling in Parkinson's disease.

Recurrent falls are a disabling feature of Parkinson's disease (PD). We have estimated the incidence of falling over a prospective 3 month follow-up from a large sample size, identified predictors for falling for PD patients repeated this analysis for patients without prior falls, and examined the risk of falling with increasing disease severity. We pooled six prospective studies of falling in PD (n = 473), and examined the predictive power of variables that were common to most studies. The 3-month fall rate was 46% (95% confidence interval: 38-54%). Interestingly, even among subjects without prior falls, this fall rate was 21% (12-35%). The best predictor of falling was two or more falls in the previous year (sensitivity 68%; specificity 81%). The risk of falling rose as UPDRS increased, to about a 60% chance of falling for UPDRS values 25 to 35, but remained at this level thereafter with a tendency to taper off towards later disease stages. These results confirm the high frequency of falling in PD, as almost 50% of patients fell during a short period of only 3 months. The strongest predictor of falling was prior falls in the preceding year, but even subjects without any prior falls had a considerable risk of sustaining future falls. Disease severity was not a good predictor of falls, possibly due to the complex U-shaped relation with falls. Early identification of the very first fall therefore remains difficult, and new prediction methods must be developed.     

Ethical issues in clinical neuroscience research: A patient’s perspective

A patient-centered paradigm for clinical research and medical care is presented as a solution to the problem of declining innovation and increasing costs and development time in the pipeline for new therapies. Fundamental differences in values and motivations among scientists, clinicians, industry sponsor, and patients in neurotherapeutics provide a framework for analysis of ethical conflicts and the loss of public confidence in medical research. Parkinson advocates’ views on clinical trial participation, perceived risks and benefits, placebo controls, and sham surgery are presented. These views reflect the sense of urgency and the unique perspective that comes from living with this progressive, debilitating condition full time. A patient-centered paradigm that includes authentic voices of patients as collaborators at every stage of development will help to resolve conflicts, build trust, recruit trial participants, and accelerate new therapies. Key elements are adaptive clinical trial methods and the development of information technology for the assessment of outcomes and surveillance of safety over the life cycle of a medical product. Supported by the Parkinson’s Disease Foundation, the Parkinson Pipeline Project is a grassroots group of Parkinson’s patients whose goal is to represent an authentic voice for patients in the treatment development process. This group promotes education and communication between members of the Parkinson’s community and active stakeholders in medical research, industry, and regulatory agencies. Its members are an example of a new breed of knowledgeable consumers, armed with first-hand access to research findings and reinforced by on-line connections to like-minded peers throughout the world.     

Potassium channel blockers and openers as CNS neurologic therapeutic agents

Potassium (K+) channels are the most heterogeneous and widely distributed class of ion channels. K(+) channels are dynamic pore-forming transmembrane proteins known to play important roles in all cell types underlying both normal and pathophysiological functions. Essential for such diverse physiological processes as nerve impulse propagation, muscle contraction, cellular activation and the secretion of biologically active molecules, various K(+) channels are recognized as potential therapeutic targets in the treatment of multiple sclerosis, Alzheimer's disease, Parkinson's disease, epilepsy, stroke, brain tumors, brain/spinal cord ischemia, pain and schizophrenia, migraine, as well as cardiac arrhythmias, pulmonary hypertension, diabetes, cervical cancer, urological diseases and sepsis. In addition to their importance as therapeutic targets, certain K(+) channels are gaining attention for their beneficial roles in anesthesia, neuroprotection and cardioprotection. The K(+) channel gene families (subdividing into multiple subfamilies) include voltage-gated (K(v): K(v)1-K(v)12 or KCNA-KCND, KCNF-KCNH, KCNQ, KCNS), calcium-activated (K(Ca): K(Ca)1-K(Ca)5 or KCNM-KCNN), inwardly rectifying (K(ir): K(ir)1-K(ir)7 or KCNJ) and background/leak or tandem 2-pore (K(2P): K(2P)1-K(2P)7, K(2P)9-K(2P)10, K(2P)12-K(2P)13, K(2P)15-K(2P)18 or KCNK) K(+) channels. Worldwide, the pharmaceutical industry is actively developing better strategies for targeting ion channels, in general, and K(+) channels, in particular, already generating over $6 billion in sales per annum from drugs designed to block or modulate ion channel function. This review provides an overview of recent patents on emerging K(+) channel blockers and activators (openers) with potential for development as new and improved nervous system therapeutic agents.     

Readiness-to-Change Cluster Profiles Among Adults with Mental Illness Who were Homeless Participating in a Life Skills Intervention

This longitudinal study examined differences in intervention outcomes based on readiness-to-change cluster profiles among 73 adults with a mental illness at risk for homelessness participating in a manualized life skills intervention. Intervention topics included money management, food management, safe community participation, and room- and self-care. Life skill knowledge and readiness-to-change, measured using the University of Rhode Island Change Assessment, was examined at baseline, post-intervention, and 3-6?months later. Two scoring patterns emerged for readiness-to-change at each time point: Pre-Engaged and Engaged. Participants who were Engaged at the time of assessment scored significantly better than Pre-Engaged on post-intervention life skill testing, however group identification changed over time. Baseline readiness-to-change did not predict future performance or attrition, and therefore may not provide accurate indication of client investment for future learning or participation. Further investigation is needed to determine what factors contribute to Engaged membership.     

Autism Spectrum Disorders in Gender Dysphoric Children and Adolescents

Only case reports have described the co-occurrence of gender identity disorder (GID) and autism spectrum disorders (ASD). This study examined this co-occurrence using a systematic approach. Children and adolescents (115 boys and 89 girls, mean age 10.8, SD = 3.58) referred to a gender identity clinic received a standardized assessment during which a GID diagnosis was made and ASD suspected cases were identified. The Dutch version of the Diagnostic Interview for Social and Communication Disorders (10th rev., DISCO-10) was administered to ascertain ASD classifications. The incidence of ASD in this sample of children and adolescents was 7.8% (n = 16). Clinicians should be aware of co-occurring ASD and GID and the challenges it generates in clinical management.     

Implementation of patient education software in an anticoagulation clinic to decrease visit times for new patient appointments

Objective

Patient education on high-risk medications such as warfarin is important, and they require quick follow-up after initiation to maximize efficacy and safety. In our Anticoagulation Clinic, two 60-minute new patient appointments are available each day, contributing to prolonged lead-time. We instituted standardized warfarin video education to shorten in-clinic-room visit time, to potentially increase new patient appointments.

Autonomic Activity during Desflurane Anesthesia in Patients with Brain Tumors

Objective Although intracranial tumors may affect autonomic function, there are few reports of autonomic changes during anesthesia. The purpose of this study was to evaluate autonomic effects of anesthesia in patients with brain tumors compared to neurosurgical controls. Methods Two groups were evaluated: group 1 = 10 neurosurgical patients undergoing spinal cord surgery, group 2 = 10 patients with intracranial tumors. After placement of electrocardiogram and Response Entropy electroencephalogram (EEG) electrodes, 10 min baseline measures were made. Heart periods were transformed into a percentage index and heart rate entropy determined as a measure of variance of autonomic activity. Tone was evaluated as the balance between accelerator and inhibitory activity. Tone-entropy was measured during propofol anesthetic induction and the first 60 min of desflurane anesthesia before the start of surgery. Results Blood pressure and heart rate were similar between the groups. Starting at awake levels, vagal heart tone was observed. Anesthesia decreased vagal dominance to near zero in both groups. Heart rate entropy and EEG activity decreased during anesthesia with no significant difference between the groups. Desflurane concentrations required to maintain anesthesia were significantly lower in patients in brain tumors. Conclusion Tone-entropy analysis of heart rate indicates anesthetic related depression of autonomic activity with no difference between groups. Normal titration of desflurane concentrations to maintain adequate blood pressure produced desflurane requirements that were lower in patients with brain tumors, while autonomic and EEG activity were similar. Paisansathan C, Hoffman WE, Lee M, Ananda RC, Wheeler P. Autonomic activity during Desflurane anesthesia in patients with brain tumors. This research was presented at the Society of Neurosurgical Anesthesia and Critical Care meeting October, 2006 in Chicago.     

Self-reported weight, weight goals, and weight control strategies of a midwestern population

OBJECTIVE: To elicit from individuals in a population their current weight and height, weight goals, and weight control strategies to aid in design of effective interventions to prevent and treat obesity. SUBJECTS AND METHODS: By random digit dial telephone survey, 1224 adult residents of Olmsted County, Minnesota, were contacted between February 28 and May 5, 2000. They self-reported weights and weight goals and described physical characteristics associated with their desire to lose weight. RESULTS: Among the 1224 respondents, 65.6% of men and 47.9% of women reported that they were overweight (body mass index [BMI], 25.0-29.9 kg/m2) or obese (BMI, > or =30.0 kg/m2). Only 0.4% of men and 3.7% of women reported that they were underweight (BMI, <18.5 kg/m2). Of the respondents 72.6% of men and 85.1% of women reported that they were either trying to lose or not gain weight. The average weight loss goal for individuals trying to lose weight was 23.4 pounds for men and 28.0 pounds for women. Only one third of individuals trying to lose weight and one fifth of individuals trying not to gain weight reported using the recommended approach of combining energy restriction with at least 150 minutes of exercise per week. CONCLUSIONS: The prevalence of overweight and obesity in the population and the underutilization of combining both restricting energy intake and exercising at least 150 minutes per week for weight control is high. Like the majority of people in the United States, the majority of people in Olmsted County desire to control their weight. The community has responded with plans to help residents meet their goals, although efficacy and outcomes remain to be determined.