Suja S. Rajan

Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial.

IMPORTANCE There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies. OBJECTIVE To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease. DESIGN, SETTING, AND PATIENTS The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013. INTERVENTIONS Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years). MAIN OUTCOMES AND MEASURES The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes. RESULTS The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system. CONCLUSIONS AND RELEVANCE Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00449865.

Cost effectiveness of gene expression profiling for early stage breast cancer: a decision-analytic model.

Gene expression profiling (GEP) is being used increasingly for risk stratification to identify women with lymph node‐negative, estrogen receptor‐positive, early stage breast cancer who are most likely to benefit from adjuvant chemotherapy. The authors of this report evaluated the cost effectiveness of recurrence score‐guided treatment using 2 commercially available GEP tests, Oncotype DX (Genomic Health, Redwood City, Calif) and MammaPrint (Agendia Inc., Irvine, Calif), from a third‐party payers perspective.

Benefits of Stroke Treatment Using a Mobile Stroke Unit Compared With Standard Management The BEST-MSU Study Run-In Phase

Background and Purpose— Faster treatment with intravenous tissue-type plasminogen activator (tPA) is likely to improve outcomes. Optimizing prehospital triage by mobile stroke units (MSUs) may speed treatment times. The Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit (BEST-MSU) study was launched in May 2014 using the first MSU in the United States to compare stroke management using an MSU versus standard management (SM). Herein, we describe the results of the prespecified, nonrandomized run-in phase designed to obtain preliminary data on study logistics. Methods— The run-in phase consisted of 8 MSU weeks when all-patient care occurred on the MSU and 2 SM weeks when the MSU nurse met personnel on scene or at the emergency department to ensure comparability with MSU patients. Telemedicine was independently performed in 9 MSU cases. Results— Of 130 alerts, 24 MSU and 2 SM patients were enrolled. Twelve of 24 MSU patients received tPA on board; 4 were treated within 60 minutes of last seen normal, and 4 went on to endovascular treatment. There were no hemorrhagic complications. Four had primary intracerebral hemorrhage. Agreement on tPA eligibility between the onsite and telemedicine physician was 90%. Conclusions— The run-in phase provided a tPA treatment rate of 1.5 patients per week, assured us that treatment within 60 minutes of onset is possible, and enabled enrollment of patients on SM weeks. We also recognized the opportunity to assess the effect of the MSU on endovascular treatment and intracerebral hemorrhage. Challenges include the need to control biased patient selection on MSU versus SM weeks and establish inter-rater agreement for tPA treatment using telemedicine.

Implementing a Mobile Stroke Unit Program in the United States: Why, How, and How Much?

IMPORTANCE There are many ways a mobile stroke unit (MSU) might prove valuable for patients with ischemic and hemorrhagic stroke, such as earlier recognition, more accurate triage, improved management of blood pressure and other critical physiological variables, and eventually earlier implementation of effective therapies. The MSU may be particularly valuable for treatment of patients with acute ischemic stroke with tissue plasminogen activator (tPA) within 4.5 hours of symptom onset, the most evidence-based effective emergency treatment for the most prevalent stroke diagnosis. OBJECTIVES To review existing data on prehospital stroke treatment, especially relevant to MSU technology, to identify gaps in our understanding of MSU feasibility, especially relevant to applying the MSU strategy in the United States, and to describe the Houston MSU program and clinical trial. EVIDENCE REVIEW Published data from English-language journals in PubMed from 1995 to present reviewing early treatment with tPA and prehospital stroke evaluation and treatment. FINDINGS The MSU may result in an overall shift toward earlier evaluation and treatment with tPA, particularly into the first hour after symptom onset, leading to substantially better outcomes. As a result of improved clinical outcomes owing to earlier treatment, the costs of an MSU program may be offset by a reduction in the costs of long-term stroke care and an increase in quality-adjusted life-years, thereby supporting more widespread use of this technology. To make MSU deployment more practical, the vascular neurologist aboard the MSU must be replaced by a remote vascular neurologist connected to the MSU by telemedicine, reducing manpower requirements and costs. CONCLUSIONS AND RELEVANCE The MSU strategy could dramatically transform the way acute stroke is managed in the United States. A prospective study evaluating the logistics, outcomes, and cost-effectiveness of this approach is needed and under way.

Sociodemographic and Personality Characteristics of Canadian Donors Contributing to International Charity

This study aims to establish a sociodemographic and personality profile of Canadians who donate internationally, fills the gap in the literature with regard to individual-level determinants of international giving, and compares these determinants with those of domestic donors. Women, volunteers, and individuals of non-Canadian origin, with higher income, higher education, higher level of religiosity, higher political awareness and participation, and higher frequency of extended family participation were more likely to contribute internationally. Higher education and a higher level of religiosity seem to influence international giving more than they did domestic giving. In terms of the variations in amount of international donations the important determinants are income, education, level of religiosity, and feeling of financial security. These results suggest that international charities should probably target their efforts at more-educated, higher-income and more-religious individuals. The other target donors are volunteers, women, individuals of non-Canadian origin, and politically aware and socially involved individuals.

Effectiveness of FDA’s new over-the-counter acetaminophen warning label in improving consumer risk perception of liver damage

What is known and Objectives:  The Food and Drug Administration (FDA) issued new organ‐specific warning label requirements for over‐the‐counter (OTC) analgesic products in order to make consumers aware of the risk of liver damage when using acetaminophen. However, awareness of a health risk alone cannot ensure consumers’ engagement in safe and preventive behaviour. In this study, we attempted to: (i) measure consumer risk perception of liver damage due to the OTC acetaminophen products and (ii) analyse the effectiveness of the new organ‐specific warning label in improving consumer risk perception of liver damage and intention to perform protective behaviours while using OTC acetaminophen products.

Effect of primary prophylactic G-CSF use on systemic therapy administration for elderly breast cancer patients

Effective systemic therapy is vital for successful breast cancer treatment, but early onset toxicities like neutropenia hinder systemic therapy administration, especially in the elderly. Primary prophylactic use of granulocyte-colony stimulating factors (G-CSF) helps prevent neutropenia, and according to some clinical trials, facilitates chemotherapy completion. Nevertheless, evidence supporting the effectiveness of primary prophylactic G-CSF in the elderly is limited. Thus, the ASCO recommendations for primary prophylactic G-CSF use in the elderly are not explicit. This retrospective observational study examined the association between primary prophylactic G-CSF administration at the start of first course chemotherapy with adequate first course chemotherapy and radiation therapy administration in elderly breast cancer patients. The study analyzes newly diagnosed breast cancer patients receiving chemotherapy present in the SEER-Medicare data from 1994 to 2003. To account for the non-random nature of the observational data, a non-parametric matching technique was used to pre-process the data before estimating the effect of primary prophylactic G-CSF on adequate chemotherapy and radiation therapy administration. Adequate chemotherapy was defined as administration of six or more cycles during the first course. Primary prophylactic G-CSF administered at the start of the first course chemotherapy was associated with a statistically significant increase in the probability of administration of six or more first course chemotherapy cycles by 29% [95% CI 7.7–50.6%] and any radiation therapy administration by 42% [95% CI 25.2–58.4%]. Primary prophylactic G-CSF use with the first course of chemotherapy is associated with improved chemotherapy completion rates and radiation therapy. These findings emphasize the clinical value of primary prophylactic G-CSF use for systemic therapy completion, and have implications for ASCO guidelines and medicare coverage policies.

Waterpipe smoking among students in one US university: predictors of an intention to quit.

Abstract Objective: To examine the intention to quit waterpipe smoking among college students. Participants: A total of 276 University of Houston students identified through an online survey administered in February 2011. Participants indicated they had smoked a waterpipe in the month prior to the survey. Methods: Cross-sectional study. Questions included demographics, tobacco use, perceived risk of waterpipe smoking, and social acceptability. Multivariate logistic regression was used to determine predictors of an intention to quit. Results: Most of the sample participants (n = 227; 83%) reported that they had no intention to quit. Students believing that waterpipe smoking was harmful were more likely to have an intention to quit (odd ratio [OR] = 2.38, 95% confidence interval [CI; 1.05, 5.36]). Those who smoked for more than 60 minutes were less likely to have a desire to quit (OR = 0.29, 95% CI [0.12, 0.73]). Conclusions: The low level of a desire to quit demonstrated underscores the urgent need to develop interventions that educate users about expected harms of continued use.

Effect of primary prophylactic granulocyte-colony stimulating factor use on incidence of neutropenia hospitalizations for elderly early-stage breast cancer patients receiving chemotherapy.

ObjectiveChemotherapy is vital for breast cancer management, but early-onset toxicities like neutropenia hinder its administration, especially in the elderly. Primary prophylactic (PP) use of granulocyte-colony stimulating factors (G-CSF) helps prevent neutropenia and its complications while receiving chemotherapy. Nevertheless, evidence supporting the effectiveness of PPG-CSF in the elderly is limited. Thus, the American Society of Clinical Oncology (ASCO) guidelines for PPG-CSF use in the elderly are not explicit. This study analyzed the effects of administration of PPG-CSF and duration of administration on the occurrence of chemotherapy-induced neutropenia hospitalizations in elderly breast cancer patients. MethodsThis retrospective observational study of newly diagnosed breast cancer patients receiving chemotherapy used Surveillance, Epidemiology, and End Results-Medicare data from 1994 to 2003. To account for the nonrandom nature of the observational data, a nonparametric matching technique was used to preprocess the data before parametrically estimating the treatment effects. ResultsAdministration of PPG-CSF during the first course chemotherapy reduced neutropenia hospitalizations by 16% within the first 3 months and 17% within the first 6 months of chemotherapy initiation (P < 0.05). Hospitalization rates within the first 3 months of chemotherapy initiation were 3 times higher in women receiving less than 5 consecutive days of PPG-CSF compared with women receiving PPG-CSF for 5 or more days (P < 0.05). Hospitalization rates within the first 1 and 6 months were also lower with longer PPG-CSF duration (≥5 d) (P < 0.10). ConclusionsPPG-CSF use is associated with reductions in in-patient healthcare utilization. These findings have implications for ASCO guidelines and Medicare coverage policies for PPG-CSF administration in elderly breast cancer patients.

Chemotherapy characteristics are important predictors of primary prophylactic CSF administration in older patients with breast cancer

Chemotherapy is vital for breast cancer management, but early onset toxicities like neutropenia hinder its administration. Primary prophylactic (PP) use of colony- stimulating factors (CSF) helps prevent neutropenia and ensures successful chemotherapy completion. Nevertheless, lack of specific guidelines for CSF administration in older patients has lead to unexplained geographic and racial, and counter-intuitive clinical variations in CSF administration. This study examined the reasons for these variations and for the first time looked at variations in PP-CSF administration and duration of administration in breast cancer patients receiving chemotherapy. This retrospective observational study of newly diagnosed breast cancer patients receiving chemotherapy used SEER-Medicare data from 1994–2003. Regression analyses were used to explore the factors associated with PP-CSF administration and duration of administration. Clinical and therapeutic characteristics previously unexplored by other studies were included. Univariate analyses demonstrated geographic, racial and clinical disparities similar to previous studies. However, clinical correlations resolved to statistical insignificance after inclusion of chemotherapy characteristics. The analysis showed that significant geographic and racial disparities existed. History of recent antibiotic use was associated with shorter PP-CSF administration. Physicians’ decision to administer PP-CSF is predominantly driven by neutropenia risk associated with pre-planned chemotherapy regimen. Older, sicker women at a higher risk of neutropenia receive less intense/toxic chemotherapy and thus do not require PP-CSF. Geographic variations are driven by proportion of physicians administering PP-CSF with no evidence for overuse among specific physicians. Association of recent antibiotic use with shorter PP-CSF administration suggests intended substitution of the expensive PP-CSF with prophylactic antibiotics.