Introduction
While opioids have become a standard treatment option for those experiencing moderate to severe chronic pain, side effects of constipation and related symptoms have interfered with their ...usage in as many as 40–50% of treated patients. Prior research has elucidated the range of these symptoms, but no study has determined which of these symptoms patients most desire improving or whether improving constipation itself by as little as one more bowel movement per week is deemed an important change.
Methods
We conducted an online patient survey of 513 participants residing in one of six countries who reported having chronic pain, were taking opioids, and experiencing opioid-induced constipation (OIC) to address these questions.
Results
Respondents rank ordered their preferences and the following eight symptoms generated >80% endorsement as important to improve: improvement in having bowel movements without rectal pain, soft stools that are not loose or watery, regular bowel movements, a reduction in rectal straining, relief from feeling bloated, feeling less fear about having OIC when following their opioid medication regime, a desire to worry less overall about having a bowel movement, and with less ‘stomach’ area pain. When asked ‘how important is it you to have 1 more bowel movement per week”, over 90% endorsed it was ‘somewhat’, ‘very’, or ‘extremely important’ with nearly 70% (
n
= 354) endorsing the ‘extremely’ or ‘very important’ response options. In multivariate models, being in more overall pain or reporting fewer than 3 bowel movements per week were found to be independent predictors of the importance.
Conclusions
These results highlight the notable range of OIC symptoms most desired by patients to improve and demonstrate that bowel movements of only one more per week were important to register a meaningful improvement. The latter is particularly helpful for those assessing the minimal clinically important difference in treating this condition.
This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents.
Experts from a variety of ...disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials.
The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them.
The concept for this session was the work of co-chairs Richard Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty, AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD, and Kenneth L. Davis, MD.
The term clinically meaningful effect is an important aspect of designing and interpreting randomized controlled trials but can be particularly difficult in the setting of psychopharmacology where effect size may be modest, particularly over the short term, because of a strong response to placebo. Payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. The use of moderators in success rate differences may help better delineate clinically meaningful effects.
There is no clear consensus on a single definition for clinically meaningful differences in randomized controlled trials, and investigators must be sensitive to specific concerns of stakeholders in psychopharmacology in order to design and execute appropriate clinical trials.
Generative social science Epstein, Joshua M; Epstein, Joshua M
2011., 20120102, 2012, 2007, 2007-01-01, 20060101, Volume:
21
eBook
Agent-based computational modeling is changing the face of social science. In Generative Social Science, Joshua Epstein argues that this powerful, novel technique permits the social sciences to meet ...a fundamentally new standard of explanation, in which one "grows" the phenomenon of interest in an artificial society of interacting agents: heterogeneous, boundedly rational actors, represented as mathematical or software objects. After elaborating this notion of generative explanation in a pair of overarching foundational chapters, Epstein illustrates it with examples chosen from such far-flung fields as archaeology, civil conflict, the evolution of norms, epidemiology, retirement economics, spatial games, and organizational adaptation. In elegant chapter preludes, he explains how these widely diverse modeling studies support his sweeping case for generative explanation.
Patients with basal cell nevus syndrome have a high incidence of multiple basal cell carcinomas, medulloblastomas, and meningiomas. Because somatic PATCHED (PTCH) mutations have been found in ...sporadic basal cell carcinomas, we have screened for PTCH mutations in several types of sporadic extracutaneous tumors. We found that 2 of 14 sporadic medulloblastomas bear somatic nonsense mutations in one copy of the gene and also deletion of the other copy. In addition, we identified missense mutations in PTCH in two of seven breast carcinomas, one of nine meningiomas, and one colon cancer cell line. No PTCH gene mutations were detected in 10 primary colon carcinomas and eighteen bladder carcinomas.
BACKGROUND: National blood donation screening for West Nile virus (WNV) started in June 2003, after the documentation of WNV transfusion‐associated transmission (TAT) in 2002.
STUDY DESIGN AND ...METHODS: Blood donations were screened with investigational nucleic acid amplification assays in minipool formats. Blood collection agencies (BCAs) reported screening results to state and local public health authorities. Donor test results and demographic information were forwarded to CDC via ArboNET, the national electronic arbovirus surveillance system. State health departments and BCAs also reported suspect WNV TATs to CDC, which investigated these reports to confirm WNV infection in blood transfusion recipients in the absence of likely mosquito exposure.
RESULTS: During 2003 to 2005, a total of 1,425 presumptive viremic donors were reported to CDC from 41 states. Of 36 investigations of suspected WNV TAT in 2003, 6 cases were documented. Estimated viremia levels were available for donations implicated in four TAT cases; the median estimated viremia was 0.1 plaque‐forming units (PFUs) per mL (range, 0.06‐0.50 PFU/mL; 1 PFU equals approximately 400 copies/mL).
CONCLUSIONS: National blood screening for WNV identified and removed more than 1,400 potentially infectious blood donations in 2003 through 2005. Despite the success of screening in 2003, some residual WNV TAT risk remained due to donations containing very low levels of virus. Screening algorithms employing selected individual‐donation testing were designed to address this residual risk and were fully implemented in 2004 and 2005. Continued vigilance for TAT will evaluate the effectiveness of these strategies.
The positive association between body weight and bone mineral density (BMD) is well documented; in contrast, the effect of changes in body weight on BMD is not well understood, particularly, in ...normal-weight populations.
We examined the effect of a lifestyle intervention aimed at lowering dietary fat intake and increasing physical activity to produce modest weight loss or prevent weight gain on BMD in a population of 236 healthy, premenopausal women aged 44-50 y.
All women were participating in a clinical trial known as The Women's Healthy Lifestyle Project and were randomly assigned to intervention or control groups. Dual-energy X-ray absorptiometry of BMD at the lumbar spine and proximal femur were made before and after 18 mo of participation in the trial.
The intervention group (n = 115) experienced a mean (+/-SD) weight loss of 3.2 +/- 4.7 kg over the 18 mo compared with a weight gain of 0.42 +/- 3.6 kg in the control group (n = 121) (P < 0.001). The annualized rate of hip BMD loss was 2-fold higher (P < 0.015) in the intervention group (0.81 +/- 1.3%) than in the control group (0.42 +/- 1.1%); a similar, although nonsignificant pattern was observed for the loss in spine BMD: 0.70 +/- 1.4% and 0.37 +/- 1.5% (P = 0.093) in the intervention and control groups, respectively. Large increases in physical activity attenuated spine BMD loss, but had no significant effect on BMD loss at the hip.
The intervention group, who modified their lifestyle to lose weight, had a higher rate of BMD loss at the hip and lumbar spine than did the weight-stable control group. Recommendations for weight loss must be made with consideration that such an endorsement may result in BMD loss.
We reviewed information from a US pharmacy benefits manager database from 2004 through 2005 during periods with little influenza activity. We calculated rates of oseltamivir prescriptions to ...enrollees. Prescription rates increased significantly from 27.3/100,000 in 2004 to 134/100,000 in 2005 (p<0.05), which suggested that personal stockpiling of oseltamivir occurred.
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