Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: A vehicle-controlled, randomized clinical trial.

PURPOSE: Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD. METHODS: A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs). RESULTS: AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug). CONCLUSIONS: Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03652051, ANZCTR Registration Number: AZ201801.

Comparison of 2-year outcomes with CAR T cells (ZUMA-1) vs salvage chemotherapy in refractory large B-cell lymphoma.

The SCHOLAR-1 international retrospective study highlighted poor clinical outcomes and survival among patients with refractory large B-cell lymphoma (LBCL) treated with conventional chemotherapy. Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, demonstrated durable responses in patients with refractory LBCL in the pivotal phase 1/2 ZUMA-1 study (NCT02348216). Here, we compared SCHOLAR-1 with the 2-year outcomes of ZUMA-1. Prior to comparison of clinical outcomes, propensity scoring (based on a broad set of prognostic covariates) was used to create balance between ZUMA-1 and SCHOLAR-1 patients. In the pivotal phase 2 portion of ZUMA-1, 101 patients received axi-cel and were evaluable for response and survival. In SCHOLAR-1, 434 and 424 patients were evaluable for response and survival, respectively. ZUMA-1 patients were more heavily pretreated than were SCHOLAR-1 patients. The median follow-up was 27.1 months in ZUMA-1. The objective response rate (ORR) and complete response rate were 83% and 54% in ZUMA-1 vs 34% and 12% in SCHOLAR-1, respectively. The 2-year survival rate was 54% in ZUMA-1 and 20% in SCHOLAR-1, and a 73% reduction in the risk of death was observed in ZUMA-1 vs SCHOLAR-1. These results were consistent with those of an additional standardization analysis in which strata were limited to 2 prognostic factors (refractory categorization and presence/absence of stem cell transplant after refractoriness to chemotherapy) to conserve sample size. Despite the limitations of a nonrandomized analysis, these results indicate that axi-cel produces durable responses and a substantial survival benefit vs non-CAR T-cell salvage regimens for patients with refractory LBCL.

The Use of an Open Field Model to Assess Sound-Induced Fear and Anxiety Associated Behaviors in Labrador Retrievers.

Previous studies have shown that the playing of thunderstorm recordings during an open-field task elicits fearful or anxious responses in adult beagles. The goal of our study was to apply this open field test to assess sound-induced behaviors in Labrador retrievers drawn from a pool of candidate improvised explosive devices (IED)-detection dogs. Being robust to fear-inducing sounds and recovering quickly is a critical requirement of these military working dogs. This study presented male and female dogs, with 3 minutes of either ambient noise (Days 1, 3 and 5), recorded thunderstorm (Day 2), or gunfire (Day 4) sounds in an open field arena. Behavioral and physiological responses were assessed and compared to control (ambient noise) periods. An observer blinded to sound treatment analyzed video records of the 9-minute daily test sessions. Additional assessments included measurement of distance traveled (activity), heart rate, body temperature, and salivary cortisol concentrations. Overall, there was a decline in distance traveled and heart rate within each day and over the five-day test period, suggesting that dogs habituated to the open field arena. Behavioral postures and expressions were assessed using a standardized rubric to score behaviors linked to canine fear and anxiety. These fear/anxiety scores were used to evaluate changes in behaviors following exposure to a sound stressor. Compared to control periods, there was an overall increase in fear/anxiety scores during thunderstorm and gunfire sound stimuli treatment periods. Fear/anxiety scores were correlated with distance traveled, and heart rate. Fear/anxiety scores in response to thunderstorm and gunfire were correlated. Dogs showed higher fear/anxiety scores during periods after the sound stimuli compared to control periods. In general, candidate IED-detection Labrador retrievers responded to sound stimuli and recovered quickly, although dogs stratified in their response to sound stimuli. Some dogs were robust to fear/anxiety responses. The results suggest that the open field sound test may be a useful method to evaluate the suitability of dogs for IED-detection training.

Variability of performance of wound infusion catheters.

OBJECTIVE: To compare the distribution of flow from two commercial and one handmade multihole wound infusion catheters. STUDY DESIGN: Open label experimental measurement of flow distribution in a bench top apparatus of handmade (n = 10) and two commercial (n = 10 each) wound infusion catheters with 5-6'' (12-15.2 cm) long diffusion surfaces. METHODS: The distribution of 6 mL of distilled water injected at three different injection speeds (0.5, 5, and 120 minutes) through individual triangular pieces of felt cloth fitted over six contiguous regions of the diffusion surface of each catheter was measured in triplicate. RESULTS: The distribution of flow through the six regions was significantly more uniform at the two faster injection speeds. Ninety two per cent of the 120 minute infusion trials resulted in one or more regions producing negligible flow (<5% of total output), and in 16% of the 120 minute trials all the flow came from just one or two regions. CONCLUSIONS: Constant-rate infusions of 3 mL hour(-1) provide erratic distribution of flow from wound infusion catheters in a bench top apparatus. Commercial catheters did not outperform handmade catheters. CLINICAL RELEVANCE: Uneven distribution of flow at low infusion speeds may contribute to inconsistent or unsatisfactory pain relief in patients treated with continuous wound infusions of local anesthetics.

Selective TNF inhibition for chronic stroke and traumatic brain injury: an observational study involving 629 consecutive patients treated with perispinal etanercept.

BACKGROUND: Brain injury from stroke and traumatic brain injury (TBI) may result in a persistent neuroinflammatory response in the injury penumbra. This response may include microglial activation and excess levels of tumour necrosis factor (TNF). Previous experimental data suggest that etanercept, a selective TNF inhibitor, has the ability to ameliorate microglial activation and modulate the adverse synaptic effects of excess TNF. Perispinal administration may enhance etanercept delivery across the blood-CSF barrier. OBJECTIVE: The objective of this study was to systematically examine the clinical response following perispinal administration of etanercept in a cohort of patients with chronic neurological dysfunction after stroke and TBI. METHODS: After approval by an independent external institutional review board (IRB), a chart review of all patients with chronic neurological dysfunction following stroke or TBI who were treated open-label with perispinal etanercept (PSE) from November 1, 2010 to July 14, 2012 at a group medical practice was performed. RESULTS: The treated cohort included 629 consecutive patients. Charts of 617 patients following stroke and 12 patients following TBI were reviewed. The mean age of the stroke patients was 65.8 years ± 13.15 (range 13-97). The mean interval between treatment with PSE and stroke was 42.0 ± 57.84 months (range 0.5-419); for TBI the mean interval was 115.2 ± 160.22 months (range 4-537). Statistically significant improvements in motor impairment, spasticity, sensory impairment, cognition, psychological/behavioural function, aphasia and pain were noted in the stroke group, with a wide variety of additional clinical improvements noted in individuals, such as reductions in pseudobulbar affect and urinary incontinence. Improvements in multiple domains were typical. Significant improvement was noted irrespective of the length of time before treatment was initiated; there was evidence of a strong treatment effect even in the subgroup of patients treated more than 10 years after stroke and TBI. In the TBI cohort, motor impairment and spasticity were statistically significantly reduced. DISCUSSION: Irrespective of the methodological limitations, the present results provide clinical evidence that stroke and TBI may lead to a persistent and ongoing neuroinflammatory response in the brain that is amenable to therapeutic intervention by selective inhibition of TNF, even years after the acute injury. CONCLUSION: Excess TNF contributes to chronic neurological, neuropsychiatric and clinical impairment after stroke and TBI. Perispinal administration of etanercept produces clinical improvement in patients with chronic neurological dysfunction following stroke and TBI. The therapeutic window extends beyond a decade after stroke and TBI. Randomized clinical trials will be necessary to further quantify and characterize the clinical response.

Comparison of body weight distribution, peak vertical force, and vertical impulse as measures of hip joint pain and efficacy of total hip replacement.

OBJECTIVE: To determine whether there is a difference between the ability of peak vertical force (PVF), vertical impulse (VI), and percentage body weight distribution (%BW(dist) ) in differentiating which leg is most affected by hip joint pain before total hip replacement (THR) surgery, and for measuring changes in limb use after THR surgery. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n = 47). METHODS: Ground reaction force (GRF) data were collected using a pressure-sensitive walkway the day before THR surgery and at ∼3, 6, and 12 months postoperatively. PVF and VI expressed as a percentage of body weight (%PVF, %VI), and %BW(dist) were recorded. Regression models performed separately for each outcome were used for statistical analysis. RESULTS: When comparing limb use between the affected limb (AP) and the nonaffected limb (NP) preoperatively, differences between limbs were statistically significant when evaluated using PVF (P = .023), VI (P = .010), and %BW(dist) (P = .012). When evaluating the magnitude of absolute and percentage change difference in AP limb use preoperatively versus postoperatively, differences were statistically significant when evaluated using PVF (P < .001 and P = .001, respectively), VI (P = .001 and P < .001) and %BW(dist) (P < .001 and P < .001). CONCLUSION: There appeared to be no difference in the sensitivity of VI, PVF, and %BW(dist) for evaluating limb use before and after THR.

Evaluation of functional outcome after BFX total hip replacement using a pressure sensitive walkway.

OBJECTIVE: To evaluate stance phase limb use after cementless (BFX) total hip replacement (THR) in dogs and to relate postoperative radiographic variables to static bodyweight distribution after surgery. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n=35) that had THR. METHODS: THR was performed using the BFX THR technique. Postoperative pain management regimens were similar for all dogs. Standing bodyweight distribution (%BW(distrib)) was measured using a pressure sensitive walkway and radiographs made before surgery and at 3, 6, and 12 months after surgery. Repeated measures models (with backwards-stepping to obtain the final model) were used for statistical analysis. RESULTS: Temporally, %BW(distrib) to the operated limb increased (P<.0001; normal by 3 months) and decreased to the unoperated limb (P=.0001) and also increased to the pelvic limbs and decreased to the thoracic limbs. %BW(distrib) to the unoperated limb was significantly less than the operated limb at 3, 6, and 12 months after surgery. Postoperative canal fill and femur flare were significantly negatively correlated with change in %BW(distrib) (estimate=-0.24, P=.0413). CONCLUSION: BFX THR results in normal %BW(distrib) to the operated limb by 3 months after surgery. A greater fill of the proximal femur may be associated with a suboptimal outcome. CLINICAL RELEVANCE: BFX THR normalizes standing bodyweight distribution dogs with hip osteoarthritis. Objective evaluation of THR outcome and radiographic features may reveal factors that could be improved through changes in prosthesis design or surgical technique.

Primary care physicians' evaluation and treatment of depression: Results of an experimental study using video vignettes.

Little is known about how patient and primary care physician characteristics are associated with quality of depression care. The authors conducted structured interviews of 404 randomly selected primary care physicians after their interaction with CD-ROM vignettes of actors portraying depressed patients. Vignettes varied along the dimensions of medical comorbidity, attributions regarding the cause of depression, style, race/ethnicity, and gender. Results show that physicians showed wide variation in treatment decisions; for example, most did not inquire about suicidal ideation, and most did not state that they would inform the patient that there can be a delay before an antidepressant is therapeutic. Several physician characteristics were significantly associated with management decisions. Notably, physician age was inversely correlated with a number of quality-of-care measures. In conclusion, quality of care varies among primary care physicians and appears to be associated with physician characteristics to a greater extent than patient characteristics.

Effects of disclosing financial interests on attitudes toward clinical research.

BACKGROUND: The effects of disclosing financial interests to potential research participants are not well understood. OBJECTIVE: To examine the effects of financial interest disclosures on potential research participants' attitudes toward clinical research. DESIGN AND PARTICIPANTS: Computerized experiment conducted with 3,623 adults in the United States with either diabetes mellitus or asthma, grouped by lesser and greater severity. Respondents read a description of a hypothetical clinical trial relevant to their diagnosis that included a financial disclosure statement. Respondents received 1 of 5 disclosure statements. MEASUREMENTS: Willingness to participate in the hypothetical clinical trial, relative importance of information about the financial interest, change in trust after reading the disclosure statement, surprise regarding the financial interest, and perceived effect of the financial interest on the quality of the clinical trial. RESULTS: Willingness to participate in the hypothetical clinical trial did not differ substantially among the types of financial disclosures. Respondents viewed the disclosed information as less important than other factors in deciding to participate. Disclosures were associated with some respondents trusting the researchers less, although trust among some respondents increased. Most respondents were not surprised to learn of financial interests. Researchers owning equity were viewed as more troubling than researchers who were compensated for the costs of research through per capita payments. CONCLUSIONS: Aside from a researcher holding an equity interest, the disclosure to potential research participants of financial interests in research, as recommended in recent policies, is unlikely to affect willingness to participate in research.

Racial differences in pain during 1 year among women with metastatic breast cancer: a hazards analysis of interval-censored data.

BACKGROUND: Longitudinal tumor-specific studies of cancer pain across the disease trajectory provide insight into the course of pain. Information on pain predictors refines our understanding of patients with greatest distress and need. METHODS: The authors studied 1124 women with metastatic breast cancer and bone metastases, all of whom received standard treatment in an international clinical trial conducted from October 1998 to January 2001. The Brief Pain Inventory (BPI) was administered repeatedly during the course of 1 year. Hazard models were fitted to identify baseline and time-dependent covariates as predictors of pain worsening within cumulative 80-day intervals during the year. RESULTS: Increased severe pain hazards were associated with non-Caucasian race (hazard ratio [HR] = 2.52; 95% CI, 1.69-3.76), restricted performance status (HR = 1.73; 95% CI, 1.13-2.64), and radiation therapy in a previous interval (HR = 2.86; 95% CI, 1.61-5.09). Estimated cumulative rates for not yet reaching a BPI score of 7 or above ranged from 0.79 (0.72-0.85) in the first interval to 0.64 (0.55-0.74) in the last interval for non-Caucasian women, whereas these rates ranged from 0.91 (0.89-0.93) to 0.84 (0.81-0.87) for Caucasian women. CONCLUSIONS: By using a time-to-event hazards analysis for cancer symptom data, the authors demonstrated that non-Caucasian race predicted poorer pain control among women with metastatic breast cancer. Disparity findings from cross-sectional studies were confirmed. Pain management strategies should take race into account as a risk factor for worsening pain outcomes, and further investigation should seek to uncover and resolve the reasons for this obvious disparity.

Perspectives of clinical research coordinators on disclosing financial conflicts of interest to potential research participants.

BACKGROUND: Disclosing financial interests to potential research participants during the informed consent process is one strategy for managing conflicts of interest. Given that clinical research coordinators are typically charged with administering the informed consent process, it is critical to understand their experiences, attitudes and beliefs regarding the disclosure of financial interests in research. PURPOSE: To understand the role of clinical research coordinators in disclosing financial interests in research, and potential barriers to such disclosures. METHODS: We developed a survey designed to measure clinical research coordinators' awareness of financial interests in clinical research, previous experience with disclosing financial interests, comfort with answering questions about financial interests and barriers to disclosing financial interests to potential research participants. Next we conducted cognitive interviews with 10 clinical research coordinators to assess understandability and content validity and to further refine the survey. We then administered the survey to clinical research coordinators attending the 2006 Global Conference of the Association of Clinical Research Professionals. RESULTS: Among 300 clinical research coordinators who completed the survey, there was a general awareness of financial interests in research. Forty-one percent reported disclosing such financial interests to potential research participants, and 28% reported being asked about them. Greater comfort in responding to questions about financial interests was associated with previous experience with disclosure, previous experience answering questions about financial interests, and greater length of time obtaining informed consent. Respondents indicated that there were barriers to disclosure, including lack of information (76%) and that participants would not understand disclosures (26%). LIMITATIONS: Possible sample bias due to using a convenience sample. CONCLUSIONS: Making information about financial interests in research readily available to clinical research coordinators, as well as providing education and training, should facilitate the disclosure of financial interests in research to potential research participants during the informed consent process.

Validity of goniometric joint measurements in cats.

OBJECTIVE: To compare and validate goniometric joint measurements obtained from nonsedated and sedated cats with measurements from radiographic evaluation. ANIMALS: 20 adult cats with no evidence of joint disease. PROCEDURES: Measurements of flexion and extension of the carpus, elbow, shoulder, tarsus, stifle, and hip joints and of carpal and tarsal joints during varus and valgus angulation were made by a single investigator before and after sedation of cats. Measurements were made by use of a goniometer with a masked dial. Joint angle measurements were compared between nonsedated and sedated cats and also with measurements from radiographs made while cats were sedated. Each series of measurements was repeated 4 times. To evaluate repeatability, Cronbach alpha values were calculated for repeated measure results of goniometric joint measurements of nonsedated and sedated cats. An intraclass correlation was calculated to determine reliability among the 3 measurement types (ie, measurements from nonsedated and sedated cats and on radiographic evaluation). RESULTS: Joint measurements did not differ significantly by measurement type, when comparing radiographic measurements with goniometric measurements in sedated and nonsedated cats. Cronbach alpha values were > 0.99 for goniometric joint measurements within individual nonsedated and sedated cats and also for comparison of mean measurements obtained from sedated cats versus nonsedated cats versus radiographs. An intraclass correlation of 0.999 revealed high reliability among measurement types. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that goniometric joint measurements in nonsedated and sedated cats are repeatable and valid.

Hazards for pain severity and pain interference with daily living, with exploration of brief pain inventory cutpoints, among women with metastatic breast cancer.

Few longitudinal studies have assessed risk factors for pain outcomes in tumor-specific populations. Such studies are needed to improve clinical practice guidelines for cancer pain management over the course of treatment. Among patients with metastatic breast cancer, we assessed the impact of baseline clinical and demographic risk factors on patients reaching different pain severity and interference scores. We analyzed data originally collected in a clinical trial of two bisphosphonate therapies. Pain was measured by the Brief Pain Inventory (BPI) severity and interference with daily living 0-10 subscales. We fit univariate (per-cutpoint) and multivariate (cutpoints 3, 4, 5, 6, and 7 on the BPI) proportional hazards models to identify predictors of pain outcomes over 51 weeks among 1,124 women with metastatic breast cancer. Predictors included race, age, education, geographic region, performance status, chemotherapy versus hormonal therapy only, time from first bone metastasis to randomization, and previous skeletal-related event (SRE, e.g., fractures, spinal cord compression). Non-Caucasian women had greater hazards for reaching higher cutpoints (5 and above) on the severity scale than Caucasian women (hazard ratio [HR] for cutpoint 5 interaction term=1.76; 95% confidence interval [CI]=1.37-2.26). For the interference scale, these hazards were greater for those patients with restricted (versus active) baseline Eastern Cooperative Oncology Group (ECOG) performance status (HR for cutpoint 5 interaction term=2.51; 95% CI=2.01-3.13). In the multivariate severity model, other factors associated with higher pain severity were restricted baseline ECOG performance status, previous SRE, and not being employed full-time at baseline (HRs=1.70, 1.23, and 1.33, respectively). Our findings that non-Caucasian race and restricted performance status were associated with greater pain hazards over time confirm previous cross-sectional findings that these characteristics are pain risk factors. Because we found that the most influential demographic and clinical baseline factors had predictive value for worsening outcomes as early as cutpoint 5, we recommend that pain management strategies use cutpoints informed by risk factors for worsening outcomes as cues for earlier intervention, thus delaying or preventing worst pain among women with metastatic disease who are at greatest risk.

Evaluation of client-specific outcome measures and activity monitoring to measure pain relief in cats with osteoarthritis.

BACKGROUND: There are no validated systems for measuring pain from osteoarthritis in cats. HYPOTHESIS: Owner subjective assessments and an activity monitor (AM) can be used to detect pain in cats with osteoarthritis and to assess efficacy of treatments. ANIMALS: Thirteen cats older than 10 years old, with owner-assessed decreases in activity, painful arthritic joints, and clinically normal blood work were included and evaluated for 3 weeks. METHODS: A collar-mounted AM measured activity and a client-specific outcome measure (CSOM) questionnaire characterized the severity of impairment. Overall global quality of life was also evaluated for each treatment. In weeks 2 and 3, meloxicam (0.1 mg/kg, day 1; 0.05 mg/kg, days 2-5) or a placebo was administered in a blinded, randomized, cross-over manner to test the assessment systems. RESULTS: The cats had a median of 4 arthritic appendicular joints. Activity counts for the week when cats (complete data on activity; n=9) were administered meloxicam were significantly higher than at baseline (P = .02) but not after placebo (P = .06). Baseline activity counts were not significantly different from placebo (P = .6). The CSOM data (n=13) showed that owners considered their cats to be more active on meloxicam compared with baseline (P = .001) and placebo (P < .004), and more active on placebo than at baseline (P < .01). Global quality of life improved significantly with meloxicam (P < .042). CONCLUSIONS AND CLINICAL IMPORTANCE: Both an AM and a CSOM system can detect behavior associated with pain relief in cats that are arthritic. Objective activity data might allow subjective assessment systems to be validated for use in clinical studies.

Use and perceptions of clinical practice guidelines by internal medicine physicians.

The authors sought to explore the use and perceptions of clinical practice guidelines among internal medicine physicians. Through a Web-based survey, 201 board-certified internal medicine physicians rated their opinions on several statements using 7-point Likert scales. Most respondents (74.7%) felt that guidelines were suitable for at least half of their patients, although a failure to take comorbid conditions into account was a frequently cited barrier. For patients with cardiovascular disease, there was no difference between individual internists' perceptions of their own compliance with guidelines and their estimates of cardiologists' compliance (P = .14). A large majority of respondents (70.7%) believed that guideline committee member participation in industry-funded research introduces bias into guideline content (median [interquartile range], 5 [4-6]). Although most respondents felt that measuring physicians against guideline-based performance measures encourages evidence-based medicine (76.5%), opinions were split as to whether this practice distracts from patient care or compromises physician autonomy.

Effects of skeletal morbidities on longitudinal patient-reported outcomes and survival in patients with metastatic prostate cancer.

GOALS OF WORK: Patients with prostate cancer metastasized to bone frequently experience skeletal morbidities as a result of their disease. We sought to quantify the longitudinal effects on patient-reported outcomes of skeletal-related events (SREs) and to ascertain the declines in health-related quality of life (HRQOL) and pain experienced by patients who experienced SREs. MATERIALS AND METHODS: Data are from a clinical trial for the treatment of SREs associated with advanced prostate cancer metastatic to bone. Outcome measures included the Functional Assessment of Cancer Therapy-General (FACT-G) and the Brief Pain Inventory. Among patients who survived 6 months after randomization, patients with no SREs in the initial 6 months after randomization were matched via propensity scores with those experiencing one or more SREs. Similarly, patients with one SRE were matched with a subset of patients with two or more SREs. MAIN RESULTS: Patients with SREs in the initial period had significantly worse survival and HRQOL than those with no SREs. Significant differences were found between the pain differences, FACT-G total scores, and FACT-G physical, emotional, and functional subscales. Comparisons of patients with single vs multiple SREs showed similar patterns. CONCLUSIONS: The presence of SREs is significantly associated with worse survival and poorer HRQOL in this patient population. Increasing SRE intensity shows a pattern of increasingly decreased survival and poorer HRQOL.

Measuring trust in medical researchers.

BACKGROUND: Concern is widespread that the public's and participants' trust in medical research is threatened, but few empirical measures of research trust exist. This project aims to enable more rigorous study of researcher trust by developing and testing appropriate survey measures. METHODS: Survey items were developed based on a conceptual model of the primary domains of researcher trust (safety, fidelity, honesty, global trust). Pilot testing was conducted on a regional convenience sample of adults (n = 124). Exploratory factor analyses of the data were performed, and an item selection procedure reduced the number of survey questions. A final set of 12 items was validated, and a 4-item short version of the researcher trust scale was selected and tested in a national web-based survey of asthma and diabetes patients (n = 3623). Further factor analysis and validation were performed on this larger sample. RESULTS: Both the full and short scales have a single-factor structure with acceptable internal reliability (alphas of 0.87 [12 items] and 0.72 [4 items]). Trust in physician researchers and trust in medical researchers generally were found not to be separate constructs. In the national sample, the short scale was positively associated with better health status, prior participation in medical research, and willingness to participate in a hypothetical medical research study, and negatively associated with African-American race and higher education. CONCLUSIONS: Trust in medical researchers is a measurable single-factor construct including trust in safety, researcher fidelity, and honesty. This new scale provides an empirical tool for informing the ethics and public policy of medical research.

Evidence-based therapies and mortality in patients hospitalized in December with acute myocardial infarction.

BACKGROUND: Previous studies suggest that patients hospitalized with acute myocardial infarction (MI) in December have poor outcomes, and some studies have hypothesized that the cause may be the infrequent use of evidence-based therapies during the December holiday season. OBJECTIVE: To compare the care and outcomes of patients with acute MI hospitalized in December and patients hospitalized during other months. DESIGN: Retrospective analysis of data from the Cooperative Cardiovascular Project. SETTING: Nonfederal, acute care hospitals in the United States. PATIENTS: 127 959 Medicare beneficiaries hospitalized between January 1994 and February 1996 with confirmed acute MI. MEASUREMENTS: Use of aspirin, beta-blockers, and reperfusion therapy (thrombolytic therapy or percutaneous coronary intervention), and 30-day mortality. RESULTS: When the authors controlled for patient, hospital, and physician characteristics, the use of evidence-based therapies was not significantly lower but 30-day mortality was higher (21.7% vs. 20.1%; adjusted odds ratio, 1.07 [95% CI, 1.02 to 1.12]) among patients hospitalized in December. LIMITATIONS: This was a nonrandomized, observational study. Unmeasured characteristics may have contributed to outcome differences. CONCLUSIONS: Thirty-day mortality rates were higher for Medicare patients hospitalized with acute MI in December than in other months, although the use of evidence-based therapies was not significantly lower.

Understanding of an aggregate probability statement by patients who are offered participation in Phase I clinical trials.

BACKGROUND: There is concern that patients with poor numeracy may have difficulty understanding the information necessary to make informed treatment decisions. The authors sought to characterize a special form of numeracy among patients with advanced cancer who were offered participation in Phase I oncology clinical trials. METHODS: Surveys were administered to 328 cancer patients who were considering Phase I trials. Their frequency-type numeracy was assessed using a multiple-choice question involving a hypothetical scenario in which a physician stated that an experimental treatment would control cancer in "40% of cases like yours." In univariate and multivariable analyses, patient characteristics that were associated with better numeracy were identified. RESULTS: The correct frequency-type interpretation was selected by 72% of respondents. Fourteen percent of respondents incorrectly selected a belief-type answer, "The doctor is 40% confident that the treatment will control my cancer." In a multivariable model, patients who answered incorrectly tended to have less formal education and less experience with experimental therapies. CONCLUSIONS: Because the misunderstandings some patients demonstrated may influence their treatment decision making adversely, it is critical to identify such patients and to give them special consideration when communicating information about potential risks and benefits of treatment.

An exploration of relative health stock in advanced cancer patients.

OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions.