Prescribing “placebo treatments”: results of national survey of US internists and rheumatologists

Objective To describe the attitudes and behaviours regarding placebo treatments, defined as a treatment whose benefits derive from positive patient expectations and not from the physiological mechanism of the treatment itself

Use of cumulative incidence of novel influenza A/H1N1 in foreign travelers to estimate lower bounds on cumulative incidence in Mexico

Background: An accurate estimate of the total number of cases and severity of illness of an emerging infectious disease is required both to define the burden of the epidemic and to determine the severity of disease. When a novel pathogen first appears, affected individuals with severe symptoms are more likely to be diagnosed. Accordingly, the total number of cases will be underestimated and disease severity overestimated. This problem is manifest in the current epidemic of novel influenza A/H1N1. Methods and Results: We used a simple approach to leverage measures of incident influenza A/H1N1 among a relatively small and well observed group of US, UK, Spanish and Canadian travelers who had visited Mexico to estimate the incidence among a much larger and less well surveyed population of Mexican residents. We estimate that a minimum of 113,000 to 375,000 cases of novel influenza A/H1N1 have occurred in Mexicans during the month of April, 2009. Such an estimate serves as a lower bound because it does not account for underreporting of cases in travelers or for nonrandom mixing between Mexican residents and visitors, which together could increase the estimates by more than an order of magnitude. Conclusions: We find that the number of cases in Mexican residents may exceed the number of confirmed cases by two to three orders of magnitude. While the extent of disease spread is greater than previously appreciated, our estimate suggests that severe disease is uncommon since the total number of cases is likely to be much larger than those of confirmed cases

A Comparison Between Denaturing Gradient Gel Electrophoresis and Denaturing High Performance Liquid Chromatography in Detecting Mutations in Genes Associated with Hereditary Non-Polyposis Colorectal Cancer (HNPCC) and the Identification of 9 New Mutations Previously Unidentified by DGGE

Denaturing high performance liquid chromatography is a relatively new method by which heteroduplex structures formed during the PCR amplification of heterozygote samples can be rapidly identified. The use of this technology for mutation detection in hereditary non-polyposis colorectal cancer (HNPCC) has the potential to appreciably shorten the time it takes to analyze genes associated with this disorder. Prior to acceptance of this method for screening genes associated with HNPCC, assessment of the reliability of this method should be performed. In this report we have compared mutation and polymorphism detection by denaturing gradient gel electrophoresis (DGGE) with denaturing high performance liquid chromatography (DHPLC) in a set of 130 families. All mutations/polymorphisms representing base substitutions, deletions, insertions and a 23 base pair inversion were detected by DHPLC whereas DGGE failed to identify four single base substitutions and a single base pair deletion. In addition, we show that DHPLC has been used for the identification of 5 different mutations in exon 7 of hMSH2 that could not be detected by DGGE

Patients’ attitudes about the use of placebo treatments: telephone survey

Objective To examine the attitudes of US patients about the use of placebo treatments in medical care. Design: One time telephone surveys. Setting: Northern California. Participants 853 members of Kaiser Permanente Northern California, aged 18-75, who had been seen by a primary care provider for a chronic health problem at least once in the prior six months. Results The response rate was 53.4% (853/1598) of all members who were eligible to participate, and 73.2% (853/1165) of all who could be reached by telephone. Most respondents (50-84%) judged it acceptable for doctors to recommend placebo treatments under conditions that varied according to doctors’ level of certainty about the benefits and safety of the treatment, the purpose of the treatment, and the transparency with which the treatment was described to patients. Only 21.9% of respondents judged that it was never acceptable for doctors to recommend placebo treatments. Respondents valued honesty by physicians regarding the use of placebos and believed that non-transparent use could undermine the relationship between patients and physicians. Conclusions: Most patients in this survey seemed favorable to the idea of placebo treatments and valued honesty and transparency in this context, suggesting that physicians should consider engaging with patients to discuss their values and attitudes about the appropriateness of using treatments aimed at promoting placebo responses in the context of clinical decision making

Summer 1981

Editorial (page 3) Results of Field Test to Study Human Exposure to 2,4,5,-T Application (4) Investigation and Treatment of Localized Dry Spots on Sand Golf Greens (6) Aquatic Weed Control- In Review (11) Golf Course Superintendent - A Perspective (14) Four Seasons Ground Maintenance (16

Overview of PNGV Battery Development and Test Programs

Affordable, safe, long-lasting, high-power batteries are requisites for successful commercialization of hybrid electric vehicles. The U.S. Department of Energy’s Office of Advance Automotive Technologies and the Partnership for a New Generation of Vehicles are funding research and development programs to address each of these issues. An overview of these areas is presented along with a summary of battery development and test programs, as well as recent performance data from several of these programs

Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome

Background: Placebo treatment can significantly influence subjective symptoms. However, it is widely believed that response to placebo requires concealment or deception. We tested whether open-label placebo (non-deceptive and non-concealed administration) is superior to a no-treatment control with matched patient-provider interactions in the treatment of irritable bowel syndrome (IBS). Methods: Two-group, randomized, controlled three week trial (August 2009-April 2010) conducted at a single academic center, involving 80 primarily female (70%) patients, mean age 47±18 with IBS diagnosed by Rome III criteria and with a score ≥150 on the IBS Symptom Severity Scale (IBS-SSS). Patients were randomized to either open-label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in IBS symptoms through mind-body self-healing processes” or no-treatment controls with the same quality of interaction with providers. The primary outcome was IBS Global Improvement Scale (IBS-GIS). Secondary measures were IBS Symptom Severity Scale (IBS-SSS), IBS Adequate Relief (IBS-AR) and IBS Quality of Life (IBS-QoL). Findings: Open-label placebo produced significantly higher mean (±SD) global improvement scores (IBS-GIS) at both 11-day midpoint (5.2±1.0 vs. 4.0±1.1, p<.001) and at 21-day endpoint (5.0±1.5 vs. 3.9±1.3, p = .002). Significant results were also observed at both time points for reduced symptom severity (IBS-SSS, p = .008 and p = .03) and adequate relief (IBS-AR, p = .02 and p = .03); and a trend favoring open-label placebo was observed for quality of life (IBS-QoL) at the 21-day endpoint (p = .08). Conclusion: Placebos administered without deception may be an effective treatment for IBS. Further research is warranted in IBS, and perhaps other conditions, to elucidate whether physicians can benefit patients using placebos consistent with informed consent. Trial Registration ClinicalTrials.gov NCT0101019

Critical Issues For Understanding Particle Acceleration in Impulsive Solar Flares

This paper, a review of the present status of existing models for particle acceleration during impulsive solar flares, was inspired by a week-long workshop held in the Fall of 1993 at NASA Goddard Space Flight Center. Recent observations from Yohkoh and the Compton Gamma Ray Observatory, and a reanalysis of older observations from the Solar Maximum Mission, have led to important new results concerning the location, timing, and efficiency of particle acceleration in flares. These are summarized in the first part of the review. Particle acceleration processes are then discussed, with;particular emphasis on new developments in stochastic acceleration by magnetohydrodynamic waves and direct electric field acceleration by both sub- and super-Dreicer electric fields. Finally, issues that arise when these mechanisms are incorporated into the large-scale flare structure are considered. Stochastic and super-Dreicer acceleration may occur either in a single large coronal reconnection site or at multiple \u27\u27fragmented\u27\u27 energy release sites. Sub-Dreicer acceleration requires a highly filamented coronal current pattern. A particular issue that needs to be confronted by all theories is the apparent need for large magnetic field strengths in the flare energy release region

Protein kinetics of superoxide dismutase-1 in familial and sporadic amyotrophic lateral sclerosis

OBJECTIVE: Accumulation of misfolded superoxide dismutase-1 (SOD1) is a pathological hallmark of SOD1-related amyotrophic lateral sclerosis (ALS) and is observed in sporadic ALS where its role in pathogenesis is controversial. Understanding in vivo protein kinetics may clarify how SOD1 influences neurodegeneration and inform optimal dosing for therapies that lower SOD1 transcripts. METHODS: We employed stable isotope labeling paired with mass spectrometry to evaluate in vivo protein kinetics and concentration of soluble SOD1 in cerebrospinal fluid (CSF) of SOD1 mutation carriers, sporadic ALS participants and controls. A deaminated SOD1 peptide, SDGPVKV, that correlates with protein stability was also measured. RESULTS: In participants with heterozygous SOD1 INTERPRETATION: These results highlight the ability of stable isotope labeling approaches and peptide deamidation to discern the influence of disease mutations on protein kinetics and stability and support implementation of this method to optimize clinical trial design of gene and molecular therapies for neurological disorders. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03449212