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1.
Early score fluctuation and placebo response in a study of major depressive disorder.
Targum, SD, Cameron, BR, Ferreira, L, MacDonald, ID
Journal of psychiatric research. 2020;:118-125
Abstract
Early score fluctuation in double-blind, placebo-controlled studies may affect the reliability of the baseline measurement and adversely affect the eventual study outcome. We examined the effect of early score fluctuation during a 2-week double-blind placebo lead-in period in a phase II, double-blind, placebo-controlled trial of adjunctive s-adenosyl methionine (MSI-195) in MDD subjects who had had an inadequate response to ongoing antidepressant treatment. The overall study failed to meet its specified endpoints. We examined the score trajectories of all placebo-assigned subjects during the double-blind placebo lead-in period and subsequent 6-week treatment period. Placebo-assigned subjects with ≥20% HamD17 or MADRS score fluctuations (improvement or worsening) during the double-blind placebo lead-in period (prior to randomization) had significantly higher rates of placebo response and remission at week 8 compared to subjects with <20% response. A post-hoc analysis of evaluable subjects taken from the ITT population that excluded subjects with ≥20% early score response yielded higher effect sizes for both the HamD17 and MADRS sub-groups and statistical significance for MSI-195 over placebo in the MADRS sub-group (p = 0.012) with an effect size of 0.404. A reliable baseline measure is an asset for signal detection. These post-hoc findings suggest that study designs that anticipate and attempt to manage early response prior to randomization may yield more meaningful outcome data for trials of MDD and possibly other disorders as well.
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2.
Generalizability of the FOURIER trial to routine clinical care: Do trial participants represent patients in everyday practice?
Yao, X, Gersh, BJ, Lopez-Jimenez, F, Shah, ND, Noseworthy, PA
American heart journal. 2019;:54-62
Abstract
BACKGROUND In the FOURIER trial, evolocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, reduced cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to examine how closely patients in routine practice resemble the FOURIER trial participants and to assess the observed cardiovascular risks based on trial eligibility and underrepresentativeness. METHODS Using a large US administrative database with linked laboratory data, we identified adult patients with ASCVD between January 1, 2012, and December 31, 2016. We identified the excluded and underrepresented populations and examined the risk of cardiovascular events (a composite endpoint of myocardial infarction [MI], stroke, angina, and coronary revascularization) based on trial eligibility and underrepresentativeness. RESULTS Only 15.2% of 233,977 patients met the FOURIER eligibility. Nearly 60% of the ineligible patients met at least 2 exclusion criteria. Among trial-eligible patients, elderly patients, women, minorities, and those without prior MI were underrepresented in FOURIER. Patients who would have been excluded from FOURIER had a diverse risk profile but, on average, had a lower cardiovascular risk than those who would have qualified (hazard ratio [HR] 0.84 [0.81-0.88], P < .001). Among the underrepresented patients, women and patients without prior MI had a lower cardiovascular risk (HR 0.77 [0.71-0.82], P < .001; HR 0.67 [0.63-0.72], P < .001, respectively). Only 47.2% of patients were on moderate-/high-intensity statins. CONCLUSIONS One in 7 ASCVD patients in practice would have qualified for FOURIER. The excluded and underrepresented populations were at a particularly low or high cardiovascular risk. Statin therapy was underused, and physicians may need to evaluate adherence before adding a proprotein convertase subtilisin-kexin type 9 inhibitor.
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3.
Characteristics and Outcomes of Very Elderly Enrolled in a Prehospital Stroke Research Study.
Sanossian, N, Apibunyopas, KC, Liebeskind, DS, Starkman, S, Burgos, AM, Conwit, R, Eckstein, M, Pratt, F, Stratton, S, Hamilton, S, et al
Stroke. 2016;(11):2737-2741
Abstract
BACKGROUND AND PURPOSE Greater numbers of individuals aged ≥80 years enjoy a high quality of life, yet historically stroke trials have excluded this population. We aimed to describe a population of very elderly successfully enrolled into an acute stroke trial and compare their characteristics and outcomes with the younger cohort. METHODS We analyzed consecutive patients enrolled <2 hours of symptom onset in a prehospital stroke treatment trial, the FAST-MAG clinical trial (Field Administration of Stroke Therapy-Magnesium). We gathered demographic, treatment, and outcome data for nonelderly (<80 years old), very elderly (≥80 years old), and extreme elderly (≥90 years old). We describe key differences in the population of elderly and the impact of their inclusion on the clinical trial. RESULTS Of 1700 participants in FAST-MAG, there were 1210 nonelderly, 490 very elderly, and 60 extreme elderly subjects. Very elderly stroke patients successfully enrolled in a research study were more likely to be women, white, and have an ischemic mechanism rather than an intracerebral hemorrhage. Although the very elderly had generally poorer outcomes, 4 in 10 were functionally independent at 90 days. CONCLUSIONS Inclusion of the very elderly population in acute stroke clinical trials would both significantly increase study participation and generalizability of future acute stroke clinical trials. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059332.
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4.
Testing social-cognitive mediators for objective estimates of physical activity from the Healthy Eating and Active Living for Diabetes in Primary Care Networks (HEALD-PCN) study.
Johnson, ST, Lubans, DR, Mladenovic, AB, Plotnikoff, RC, Karunamuni, N, Johnson, JA
Psychology, health & medicine. 2016;(8):945-53
Abstract
OBJECTIVE More evidence from prospective studies is needed to determine 'if' and 'how' social cognitive constructs mediate behaviour change. In a longitudinal study, we aimed to examine potential social cognitive mediators of objectively measured physical activity (PA) behaviour among people with type 2 diabetes (T2D) who participated in a six-month PA intervention. METHODS All participants from the proven effective Healthy Eating and Active Living for Diabetes in Primary Care Networks trial were included for this secondary analysis. Change in pedometer-derived daily step counts (baseline to six months) was the outcome of interest. Primary constructs of interest were from Social Cognitive Theory, however constructs from and Theory of Planned Behaviour were also tested in a mediating variable framework using a product-of-coefficients test. RESULTS The sample (N = 198) had a mean age of 59.5 (SD 8.3) years, haemoglobin A1c 6.8% (SD 1.1), 50% women, BMI 33.6 kg/m(2) (SD 6.5), systolic pressure 125.6 mmHg (SD 16.2) and average daily steps were 5879 (SD 3130). Daily pedometer-determined steps increased for the intervention group compared to usual care control at six-months (1481 [SD 2631] vs. 336 [SD 2712]; adjusted p = .002). There was a significant action theory test effect for 'planning' (A = .21, SE = .10, p = .037), and significant conceptual theory test results for 'subjective norms' (B = 657, SE = 312, p = .037) and 'cons' (B = -664, SE = 270, p = .015). None of the constructs satisfied the criteria for mediation. CONCLUSIONS We were unable to account for the effect of a pedometer-based PA intervention for people with T2D through our examination of mediators. Our findings are inconsistent with some literature concerning PA interventions in diabetes; this may be due to variability in measures used or in study populations.
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5.
Predictors of Functional Decline in Early Parkinson's Disease: NET-PD LS1 Cohort.
Bega, D, Kim, S, Zhang, Y, Elm, J, Schneider, J, Hauser, R, Fraser, A, Simuni, T
Journal of Parkinson's disease. 2015;(4):773-82
Abstract
BACKGROUND Data on predictors of decline in PD are largely based on de-novo populations and limited to the use of motor outcomes that fail to capture the full scope of disease. OBJECTIVE Determine the clinical predictors of decline in early treated PD using a novel multi-domain measure. METHODS Data from NINDS Exploratory Trials in PD Long-Term Study 1 (NET-PD LS1), a multicenter Phase 3 study of creatine in early treated PD, were analyzed. Functional decline was defined by a global outcome metric (GO) that consisted of: Schwab and England ADL scale, PD 39-item Questionnaire, Unified PD Rating Scale, Ambulatory Capacity Score, Symbol Digit Modalities Test, and Modified Rankin Scale. Univariate and multivariate models were used to test the association of predictors of interest with a standardized rank-sum of the GO. RESULTS 765 of 1741 participants completed five-year assessments and were included. Older age at disease onset (p < 0.0001), higher baseline levodopa equivalent dose (p = 0.01), and worse Scales for Outcomes of Parkinson's Disease Cognition score (p = 0.001) at baseline were the strongest predictors of functional decline in multivariate analysis. PD symptom subtype was not a significant predictor of outcome (p = 0.42). The full model was only a modest predictor of change in GO (R2 = 0.186). CONCLUSIONS This is the largest study to systematically assess predictors of functional decline in early treated PD over several years, and the first to use a multi-domain outcome measure of decline. Older age at disease onset and worse cognition, and not PD subtype, were predictors of decline.
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6.
Effectiveness of standardized Nursing Care Plans in health outcomes in patients with type 2 Diabetes Mellitus: a two-year prospective follow-up study.
Cárdenas-Valladolid, J, Salinero-Fort, MA, Gómez-Campelo, P, de Burgos-Lunar, C, Abánades-Herranz, JC, Arnal-Selfa, R, Andrés, AL
PloS one. 2012;(8):e43870
Abstract
BACKGROUND Implementation of a standardized language in Nursing Care Plans (SNCP) allows for increased efficiency in nursing data management. However, the potential relationship with patientś health outcomes remains uncertain. The aim of this study was to evaluate the effectiveness of SNCP implementation, based on North American Nursing Diagnosis Association (NANDA) and Nursing Interventions Classification (NIC), in the improvement of metabolic, weight, and blood pressure control of Type 2 Diabetes Mellitus (T2DM) patients. METHODS A two-year prospective follow-up study, in routine clinical practice conditions. 31 primary health care centers (Spain) participated with 24,124 T2DM outpatients. Data was collected from Computerized Clinical Records; SNCP were identified using NANDA and NIC taxonomies. Descriptive and ANCOVA analyses were conducted. RESULTS 18,320 patients were identified in the Usual Nursing Care (UNC) group and 5,168 in the SNCP group. At the two-year follow-up, the SNCP group improved all parameters except LDL cholesterol and diastolic blood pressure. We analyzed data adjustming by the baseline value for these variables and variables with statistically significant differences between groups at baseline visit. Results indicated a lowering of all parameters except HbA1c, but a statistically significant reduction was only observed with diastolic blood pressure results. However, the adjusted reduction of diastolic blood pressure is of little clinical relevance. Greater differences of control values for diastolic blood pressure, HbA1c, LDL-cholesterol and Body Mass Index were found in the SNCP group, but only reached statistical significance for HbA1c. A greater proportion of patients with baseline HbA1c ≥7 decreased to <7% at the two-year follow-up in the SNCP group than in the UNC group (16.9% vs. 15%; respectively; p = 0.01). CONCLUSIONS Utilization of SNCP was helpful in achieving glycemic control targets in poorly controlled patients with T2DM (HbA1c ≥7%). Diastolic blood pressure results were slightly improved in the SNCP group compared to the UNC group. TRIAL REGISTRATION ClinicalTrials.gov NCT01482481.
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7.
Single tissue samples from head and neck squamous cell carcinomas are representative regarding the entire tumor's chemosensitivity to cisplatin and docetaxel.
Wichmann, G, Horn, IS, Boehm, A, Mozet, C, Tschop, K, Dollner, R, Dietz, A
Onkologie. 2009;(5):264-72
Abstract
BACKGROUND In multimodal therapy concepts for advanced head and neck squamous cell carcinoma (HNSCC), a valid predictive assay for the quick detection of efficient chemotherapeutic agents is desirable. Questionable so far was whether tissue samples of about 100 mg correctly reflect the chemoresponse of a whole HNSCC. This was proven using an ex-vivo colony-forming assay. MATERIALS AND METHODS Of 14 HNSCC, 3 biopsies each were taken from separate sites, minced, and collagenase digested. HNSCC digests were added to microtiter plates containing serial dilutions of chemotherapeutic agents or medium as control. After 72-h incubation, wells were washed and cultures methanol-fixed before Giemsa-staining. Epithelial colonies were counted. RESULTS 11/14 HNSCC (78.6%) showed sufficient colony formation allowing reliable cut-off detection. Cut-off concentrations (complete chemotherapeutically suppressed colony formation) between 3.3 microM and >50 microM cisplatin, and 0.55 microM and 17.6 microM docetaxel were detected. Inhibition of colony formation to 50% of colonies detected in controls (IC50) was found between 0.2 microM and 17.9 microM cisplatin or 1.5 microM and 13.7 microM docetaxel. Cut-off concentrations and IC50 of the HNSCC fragments showed a strong correlation (docetaxel: r > 0.80, p < 0.005; cisplatin: r > 0.67, p < 0.044), while being only insignificantly different in the t-test for paired samples (docetaxel: p > 0.163; cisplatin: p > 0.167). CONCLUSION In most cases, tissue samples of about 100 mg allow a representative assessment of chemoresponse of HNSCC.
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8.
Intensive nutritional supplements can improve outcomes in stroke rehabilitation.
Rabadi, MH, Coar, PL, Lukin, M, Lesser, M, Blass, JP
Neurology. 2008;(23):1856-61
Abstract
OBJECTIVE Poor nutrition is a common complication of strokes severe enough to require inpatient rehabilitation. We therefore tested whether intensive nutritional supplements given to undernourished patients from the time of their admission to a specialized stroke rehabilitation service would improve patient outcomes. METHODS Randomized, prospective, double-blind, single center study comparing intensive nutritional supplementation to routine nutritional supplementation in 116 undernourished patients admitted to a stroke service. The analysis included the 90% of patients who were not lost to follow-up due to acute or subacute hospitalization (n = 102; 51 in each group). The nutritional supplements are commercially available and Food and Drug Administration approved. The primary outcome variable was change in total score on the Functional Independence Measure (FIM). The secondary outcome measurements included the FIM motor and cognitive subscores, length of stay (taken from day of admission), 2-minute and 6-minute timed walk tests measured at admission and on discharge, and discharge disposition (home/not home). RESULTS Patients receiving intensive nutritional supplementation improved more than those on standard nutritional supplements on measures of motor function (total FIM, FIM motor subscore, 2-minute and 6-minute timed walk tests, all significant at p < 0.002). They did not, however, improve on measures of cognition (FIM cognition score). A higher proportion of patients who received the intensive nutritional supplementation went home compared to those on standard supplementation (p = 0.05). CONCLUSION Intensive nutritional supplementation, using readily available commercial preparations, improves motor recovery in previously undernourished patients receiving intensive in-patient rehabilitation after stroke.
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9.
The effectiveness of multidisciplinary rehabilitation in the treatment of fibromyalgia: a randomized controlled trial.
Lemstra, M, Olszynski, WP
The Clinical journal of pain. 2005;(2):166-74
Abstract
OBJECTIVES To assess the effectiveness of multidisciplinary rehabilitation in the treatment of fibromyalgia in comparison to standard medical care. METHODS Seventy-nine men and women were randomly assigned to one of two groups. The intervention group consisted of a rheumatologist and physical therapist intake and discharge, 18 group supervised exercise therapy sessions, 2 group pain and stress management lectures, 1 group education lecture, 1 group dietary lecture, and 2 massage therapy sessions. The control group consisted of standard medical care with the patients' family physician. Outcome measures included self-perceived health status, pain-related disability, average pain intensity, depressed mood, days in pain, hours in pain, prescription and nonprescription medication usage, and work status. Outcomes were measured at the end of the 6-week intervention and at 15-month follow-up. RESULTS Thirty-five out of 43 patients from the intervention group and 36 out of 36 patients from the control group completed the study. There were no statistically significant differences between the 2 groups prior to intervention. Intention-to-treat analysis revealed that the intervention group, in comparison to the control group, experienced statistically significant changes at intervention completion in self-perceived health status, average pain intensity, pain related disability, depressed mood, days in pain, and hours in pain, but no significant differences in nonprescription drug use, prescription drug use, or work status. At 15 months, all health outcomes retained their significance except health status. Nonprescription and prescription drug use demonstrated significant reductions at 15 months. Binary logistic regression indicated that long-term changes in Pain Disability Index were influenced by long-term exercise adherence and income status. CONCLUSIONS Positive health-related outcomes in this mostly unresponsive condition can be obtained with a low-cost, group multidisciplinary intervention in a community-based, nonclinical setting.
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10.
[Inpatient aftercare in rheumatic diseases--concept, trial, and acceptance].
Ehlebracht-König, I, Bönisch, A
Die Rehabilitation. 2004;(6):358-67
Abstract
BACKGROUND A one-week booster group treatment in rheumatic diseases (rheumatoid arthritis, spondylarthropathies, fibromyalgia) was developed in order to stabilize rehabilitation effects after medical rehabilitation. The program took place in an inpatient setting 3 - 5 months after rehabilitation, aimed at refreshing and deepening already learnt contents as well as teaching new subjects (e. g. about dietetics). Training and educational elements are given priority in this concept. METHOD A total of 140 patients participated in 19 booster weeks. At the end of each booster week the acceptance was assessed by questionnaire and in a round-table discussion. RESULTS Comprehensibility and group atmosphere were judged very positively. The course was also considered very helpful, helpfulness being rated with marks about 2 (1 = very helpful, 6 = not at all helpful). Participants especially appreciated the course's framework as a group setting emphasising the exchange of experience with co-patients. At the same time, however, participants wished more individualized treatment such as physiotherapy or massage. With regard to the quantity of the various therapy elements, participants would have preferred more traditional spa therapy, more medical treatment by a physician, more group physiotherapy and sports. They would also have liked more breaks. In general fewer psychological elements, less discussion and reflection but more physical activity was wished for. Little difference was found between the various diagnoses, but the program was rated slightly more positively by the patients with spondylarthropathies. CONCLUSION Overall, the great number of people participating in the program and their acceptance of the booster week are positive. Patients appreciated the group setting and the possibilities of exchanging experience on a high level. But it was difficult to change patients' traditional expectations concerning medical rehabilitation to a behaviour-orientated course like ours. It is worth thinking about whether this concept should play a greater role in traditional medical inpatient rehabilitation programming.