Web-based trial to evaluate the efficacy and safety of tolterodine ER 4 mg in participants with overactive bladder: REMOTE trial.

INTRODUCTION: Participatory patient-centered, web-based methods could streamline and improve the convenience of clinical trial participation. We used an entirely web-based approach to conduct a randomized, placebo-controlled, Phase 4 (REMOTE) trial under an Investigational New Drug (IND) application to evaluate tolterodine extended release (ER) 4 mg for overactive bladder. METHODS: The trial was designed to replicate previous clinic-based trials of tolterodine ER but was conducted via the web from one clinical site overseen by physicians. Participants were recruited via the web, screened for eligibility using web-based questionnaires, had laboratory testing in their community, and entered a run-in phase requiring bladder e-diaries. Informed consent was obtained using an interactive web-based method with physician countersignature. Study medication was shipped directly to participants. RESULTS: With a goal of 283 randomized participants, 5157 registered on the trial website. Of 456 who passed initial screening, identification verification, and signed consent, 237 passed additional medical screening and were countersigned by the investigator. After laboratory testing, 118 entered the placebo run-in; only 18 passed e-diary assessments and were randomized to treatment. At week 12, the mean change from the baseline in micturitions/24 hours (primary endpoint) was -2.4 for tolterodine ER versus -0.8 for placebo [treatment difference (95% CI): -1.6 (-3.9, 0.6)]. CONCLUSION: The REMOTE trial is the first entirely web-based trial conducted under an IND application. The efficacy observed was consistent with results from conventional trials. With simplification of multi-step screening and testing, web-based trials or their component parts should provide a participant-friendly approach to many clinical trials.

Symptom management with massage and acupuncture in postoperative cancer patients: a randomized controlled trial.

The level of evidence for the use of acupuncture and massage for the management of perioperative symptoms in cancer patients is encouraging but inconclusive. We conducted a randomized, controlled trial assessing the effect of massage and acupuncture added to usual care vs. usual care alone in postoperative cancer patients. Cancer patients undergoing surgery were randomly assigned to receive either massage and acupuncture on postoperative Days 1 and 2 in addition to usual care, or usual care alone, and were followed over three days. Patients' pain, nausea, vomiting, and mood were assessed at four time points. Data on health care utilization were collected. Analyses were done by mixed-effects regression analyses for repeated measures. One hundred fifty of 180 consecutively approached cancer patients were eligible and consented before surgery. Twelve patients rescheduled or declined after surgery, and 138 patients were randomly assigned in a 2:1 scheme to receive massage and acupuncture (n=93) or to receive usual care only (n=45). Participants in the intervention group experienced a decrease of 1.4 points on a 0-10 pain scale, compared to 0.6 in the control group (P=0.038), and a decrease in depressive mood of 0.4 (on a scale of 1-5) compared to +/-0 in the control group (P=0.003). Providing massage and acupuncture in addition to usual care resulted in decreased pain and depressive mood among postoperative cancer patients when compared with usual care alone. These findings merit independent confirmation using larger sample sizes and attention control.

Milk thistle for alcoholic and/or hepatitis B or C liver diseases--a systematic cochrane hepato-biliary group review with meta-analyses of randomized clinical trials.

OBJECTIVES: Our objectives were to assess the beneficial and harmful effects of milk thistle (MT) or MT constituents versus placebo or no intervention in patients with alcoholic liver disease and/or hepatitis B and/or C liver diseases. METHODS: Randomized clinical trials studying patients with alcoholic and/or hepatitis B or C liver diseases were included (December 2003). The randomized clinical trials were evaluated by components of methodological quality. RESULTS: Thirteen randomized clinical trials assessed MT in 915 patients with alcoholic and/or hepatitis B or C liver diseases. The methodological quality was low: only 23% of the trials reported adequate allocation concealment and only 46% were considered double blind. MT versus placebo or no intervention for a median duration of 6 months had no significant effects on all-cause mortality (relative risk (RR) 0.78, 95% confidence interval (CI) 0.53-1.15), complications of liver disease, or liver histology. Liver-related mortality was significantly reduced by MT in all trials (RR 0.50, 95% CI 0.29-0.88), but not in high-quality trials (RR 0.57, 95% CI 0.28-1.19). MT was not associated with a significantly increased risk of adverse events. CONCLUSIONS: Based on high-quality trials, MT does not seem to significantly influence the course of patients with alcoholic and/or hepatitis B or C liver diseases. MT could potentially affect liver injury. Adequately conducted randomized clinical trials on MT versus placebo may be needed.

An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia.

The herbal extracts kava and valerian are the leading dietary supplements used in the self-management of anxiety and insomnia, respectively. There is limited evidence to support their effectiveness for these common symptoms. The Internet has been used to a limited extent for research, but it is not known whether randomized controlled trials can be conducted entirely using Internet technology. We performed a randomized, double-blind, placebo-controlled trial using a novel Internet-based design to determine if kava is effective for reducing anxiety and if valerian is effective for improving sleep quality. E-mail recruitment letters and banner advertisements on websites were used to recruit a large pool of interested participants (1551) from 45 states over an 8-week period. Participants were first asked to read study information, complete an online informed consent process, and undergo electronic identity verification. In order to be eligible for the study, participants were required to have 1) anxiety as documented by scores of at least 0.5 standard deviations above the mean on the State-Trait Anxiety Inventory State subtest (STAI-State) on 2 separate occasions, and 2) insomnia, defined as a "problem getting to sleep or staying asleep over the past 2 weeks." We randomly assigned 391 eligible participants to 1 of the following 3 groups, and mailed 28 days' supply: kava with valerian placebo (n = 121), valerian with kava placebo (n = 135), or double placebo (n = 135). The primary outcome measures were changes from baseline in anxiety (STAI-State questionnaire) and insomnia (Insomnia Severity Index [ISI]) compared with placebo. Participants receiving placebo had a 14.4 point decrease in anxiety symptoms on the STAI-State score and an 8.3 point decrease in insomnia symptoms on the ISI. Those receiving kava had similar reductions in STAI-State score (2.7 point greater reduction in placebo compared with kava; 95% confidence interval [CI], -0.8 to +6.2). Those receiving valerian and placebo had similar improvements in sleep (0.4 point greater reduction in the placebo than the valerian group; 95% CI, -1.3 to +2.1). Results were similar when limited to the 83% of participants who adhered to study compounds for all 4 weeks. Neither kava nor valerian relieved anxiety or insomnia more than placebo. This trial demonstrates the feasibility of conducting randomized, blinded trials entirely via the Internet.

The psychosocial work environment and musculoskeletal disorders: design of a comprehensive interviewer-administered questionnaire.

BACKGROUND: Psychosocial working conditions are likely to contribute to work-related musculoskeletal disorders (WRMSDs), but a lack of standardized measurement tools reflects both the theoretical and methodological limitations of current research. METHODS: An interdisciplinary team including biomedical, behavioral, and social science researchers used an iterative process to adapt existing instruments for an interviewer-administered questionnaire assessing psychosocial workplace exposure related to musculoskeletal disorders. RESULTS: The resulting questionnaire included measures of psychosocial workplace factors based on two theoretical models (the demand-control-support and the effort-reward imbalance models), supplemented by the additional constructs of "emotional demands," and "experiences of discrimination." Other psychosocial and physical measures selected for questionnaire inclusion address physical workload, sociodemographic and anthropometric characteristics, social relations and life events, health behaviors, and physical and psychological health. CONCLUSION: Using an interdisciplinary approach facilitated the development of a comprehensive questionnaire inclusive of key measures of psychosocial factors that may play a role in the complex mechanisms leading to WRMSDs.

Milk thistle for the treatment of liver disease: a systematic review and meta-analysis.

PURPOSE: Milk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease. METHODS: We searched English and non-English reports through July 1999 using thirteen databases and reference lists, and contacting manufacturers and technical experts. Reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated milk thistle for the treatment of liver disease. Outcomes of primary interest included mortality, histological findings on liver biopsy specimens, serum aminotransferase and albumin levels, and prothrombin times. RESULTS: Fourteen trials met inclusion criteria. Four trials reported outcomes for mortality among 433 participants. The overall summary odds ratio for mortality in the milk thistle group compared with placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.5; P = 0.6). Three trials assessed histology on liver biopsy; study quality was inversely associated with the likelihood of histological benefit for milk thistle compared with placebo. There were no differences in serum alanine aminotransferase, aspartate aminotransferase, or albumin levels, or prothrombin times, among participants assigned to milk thistle compared with those assigned to placebo. The only statistically significant difference was a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (-9 IU/L, 95% CI: -18 to -1 IU/L; P = 0.05), but this reduction was of negligible clinical importance and no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo. CONCLUSION: Treatment with milk thistle appears to be safe and well tolerated. We found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to support recommending this herbal compound for the treatment of liver disease.

Mind-body medicine. An introduction and review of the literature.

MBM is a well-established phenomenon in modern medicine. If one accepts a model of mind/body that is truly nondualistic, it could be said that the MBM phenomenon is inherent to medicine. Because of its popularity and efficacy for common chronic conditions, MBM may have its greatest presence in primary care medicine. The flourishing of MBM techniques resulting from the public's enthusiastic embrace of these therapies has created a great need for rigorous scientific examination. The MBM literature may be said to be in its adolescence, having grown out of its early years of enthusiastic case reports and small studies, but not yet fully grown into a broad catalogue of large controlled experimental trials. Nevertheless, clinical trials suggest that certain MBM therapies are effective in improving quality of life, anxiety, and pain intensity for a variety of conditions. There is moderate evidence to suggest these techniques improve chronic pain, headache, insomnia, and other common conditions. There is preliminary evidence to suggest these techniques may affect coronary artery disease and cancer. MBM techniques ultimately may prove to be most effective in combinations or in conjunction with traditional treatment.