Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial.

INTRODUCTION Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. METHODS AND ANALYSIS A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. ETHICS AND DISSEMINATION The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. TRIAL REGISTRATION NUMBER NCT01898338.

Treatment rationale and study design for a phase III, double-blind, placebo-controlled study of maintenance pemetrexed plus best supportive care versus best supportive care immediately following induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small cell lung cancer.

BACKGROUND: To improve the efficacy of first-line therapy for advanced non-small cell lung cancer (NSCLC), additional maintenance chemotherapy may be given after initial induction chemotherapy in patients who did not progress during the initial treatment, rather than waiting for disease progression to administer second-line treatment. Maintenance therapy may consist of an agent that either was or was not present in the induction regimen. The antifolate pemetrexed is efficacious in combination with cisplatin for first-line treatment of advanced NSCLC and has shown efficacy as a maintenance agent in studies in which it was not included in the induction regimen. We designed a phase III study to determine if pemetrexed maintenance therapy improves progression-free survival (PFS) and overall survival (OS) after cisplatin/pemetrexed induction therapy in patients with advanced nonsquamous NSCLC. Furthermore, since evidence suggests expression levels of thymidylate synthase, the primary target of pemetrexed, may be associated with responsiveness to pemetrexed, translational research will address whether thymidylate synthase expression correlates with efficacy outcomes of pemetrexed. METHODS/DESIGN: Approximately 900 patients will receive four cycles of induction chemotherapy consisting of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 who have not progressed during induction therapy will randomly receive (in a 2:1 ratio) one of two double-blind maintenance regimens: pemetrexed (500 mg/m2 on day 1 of a 21-day cycle) plus best supportive care (BSC) or placebo plus BSC. The primary objective is to compare PFS between treatment arms. Secondary objectives include a fully powered analysis of OS, objective tumor response rate, patient-reported outcomes, resource utilization, and toxicity. Tumor specimens for translational research will be obtained from consenting patients before induction treatment, with a second biopsy performed in eligible patients following the induction phase. DISCUSSION: Although using a drug as maintenance therapy that was not used in the induction regimen exposes patients to an agent with a different mechanism of action, evidence suggests that continued use of an agent present in the induction regimen as maintenance therapy enables the identification of patients most likely to benefit from maintenance treatment.

Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.

BACKGROUND Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting. METHODS After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided. RESULTS Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment. CONCLUSIONS Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.

Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease.

BACKGROUND AND OBJECTIVES The elective treatment of patients with post-transplant lymphoproliferative disorders is controversial. The purpose of this trial was to evaluate the efficacy of treatment with extended doses of rituximab adapted to the response in patients with post-transplant lymphoproliferative disorders after solid organ transplantation. DESIGN AND METHODS This was a prospective, multicenter, phase II trial. Patients were treated with reduction of immunosuppression and four weekly infusions of rituximab. Those patients who did not achieve complete remission (CR) received a second course of four rituximab infusions. The primary end-point of the study was the CR rate. RESULTS Thirty-eight patients were assesable. One episode of grade 4 neutropenia was the only severe adverse event observed. After the first course of rituximab, 13 (34.2%) patients achieved CR, 8 patients did not respond, and 17 patients achieved partial remission. Among those 17 patients, 12 could be treated with a second course of rituximab, and 10 (83.3%) achieved CR, yielding an intention-to-treat CR rate of 60.5%. Eight patients excluded from the trial because of absence of CR were treated with rituximab combined with chemotherapy, and six (75%) achieved CR. Event-free survival was 42% and overall survival was 47% at 27.5 months. Fourteen patients died, ten of progression of their post-transplant lymphoproliferative disorder. INTERPRETATION AND CONCLUSIONS These results confirm that extended treatment with rituximab can obtain a high rate of CR in patients with post-transplant lymphoproliferative disorders after solid organ transplantation without increasing toxicity, and should be recommended as initial therapy for these patients.

Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

INTRODUCTION Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. METHODS AND ANALYSIS The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. ETHICS AND DISSEMINATION Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. DISCUSSION This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy. TRIAL REGISTRATION NUMBER NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

Effectiveness and costs of phototest in dementia and cognitive impairment screening

BACKGROUND To assess and compare the effectiveness and costs of Phototest, Mini Mental State Examination (MMSE), and Memory Impairment Screen (MIS) to screen for dementia (DEM) and cognitive impairment (CI). METHODS A phase III study was conducted over one year in consecutive patients with suspicion of CI or DEM at four Primary Care (PC) centers. After undergoing all screening tests at the PC center, participants were extensively evaluated by researchers blinded to screening test results in a Cognitive-Behavioral Neurology Unit (CBNU). The gold standard diagnosis was established by consensus of expert neurologists. Effectiveness was assessed by the proportion of correct diagnoses (diagnostic accuracy [DA]) and by the kappa index of concordance between test results and gold standard diagnoses. Costs were based on public prices and hospital accounts. RESULTS The study included 140 subjects (48 with DEM, 37 with CI without DEM, and 55 without CI). The MIS could not be applied to 23 illiterate subjects (16.4%). For DEM, the maximum effectiveness of the MMSE was obtained with different cutoff points as a function of educational level [k = 0.31 (95% Confidence interval [95%CI], 0.19-0.43), DA = 0.60 (95%CI, 0.52-0.68)], and that of the MIS with a cutoff of 3/4 [k = 0.63 (95%CI, 0.48-0.78), DA = 0.83 (95%CI, 0.80-0.92)]. Effectiveness of the Phototest [k = 0.71 (95%CI, 0.59-0.83), DA = 0.87 (95%CI, 0.80-0.92)] was similar to that of the MIS and higher than that of the MMSE. Costs were higher with MMSE (275.9 ± 193.3€ [mean ± sd euros]) than with Phototest (208.2 ± 196.8€) or MIS (201.3 ± 193.4€), whose costs did not significantly differ. For CI, the effectiveness did not significantly differ between MIS [k = 0.59 (95%CI, 0.45-0.74), DA = 0.79 (95%CI, 0.64-0.97)] and Phototest [k = 0.58 (95%CI, 0.45-0.74), DA = 0.78 (95%CI, 0.64-0.95)] and was lowest for the MMSE [k = 0.27 (95%CI, 0.09-0.45), DA = 0.69 (95%CI, 0.56-0.84)]. Costs were higher for MMSE (393.4 ± 121.8€) than for Phototest (287.0 ± 197.4€) or MIS (300.1 ± 165.6€), whose costs did not significantly differ. CONCLUSION MMSE is not an effective instrument in our setting. For both DEM and CI, the Phototest and MIS are more effective and less costly, with no difference between them. However, MIS could not be applied to the appreciable percentage of our population who were illiterate.

Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.

BACKGROUND The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib. METHODS We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival. RESULTS The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy. CONCLUSIONS The addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).

Combined vemurafenib and cobimetinib in BRAF-mutated melanoma.

BACKGROUND The combined inhibition of BRAF and MEK is hypothesized to improve clinical outcomes in patients with melanoma by preventing or delaying the onset of resistance observed with BRAF inhibitors alone. This randomized phase 3 study evaluated the combination of the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib. METHODS We randomly assigned 495 patients with previously untreated unresectable locally advanced or metastatic BRAF V600 mutation-positive melanoma to receive vemurafenib and cobimetinib (combination group) or vemurafenib and placebo (control group). The primary end point was investigator-assessed progression-free survival. RESULTS The median progression-free survival was 9.9 months in the combination group and 6.2 months in the control group (hazard ratio for death or disease progression, 0.51; 95% confidence interval [CI], 0.39 to 0.68; P<0.001). The rate of complete or partial response in the combination group was 68%, as compared with 45% in the control group (P<0.001), including rates of complete response of 10% in the combination group and 4% in the control group. Progression-free survival as assessed by independent review was similar to investigator-assessed progression-free survival. Interim analyses of overall survival showed 9-month survival rates of 81% (95% CI, 75 to 87) in the combination group and 73% (95% CI, 65 to 80) in the control group. Vemurafenib and cobimetinib was associated with a nonsignificantly higher incidence of adverse events of grade 3 or higher, as compared with vemurafenib and placebo (65% vs. 59%), and there was no significant difference in the rate of study-drug discontinuation. The number of secondary cutaneous cancers decreased with the combination therapy. CONCLUSIONS The addition of cobimetinib to vemurafenib was associated with a significant improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma, at the cost of some increase in toxicity. (Funded by F. Hoffmann-La Roche/Genentech; coBRIM ClinicalTrials.gov number, NCT01689519.).

Diagnostic accuracy, effectiveness and cost for cognitive impairment and dementia screening of three short cognitive tests applicable to illiterates

BACKGROUND Illiteracy, a universal problem, limits the utilization of the most widely used short cognitive tests. Our objective was to assess and compare the effectiveness and cost for cognitive impairment (CI) and dementia (DEM) screening of three short cognitive tests applicable to illiterates. METHODS Phase III diagnostic test evaluation study was performed during one year in four Primary Care centers, prospectively including individuals with suspicion of CI or DEM. All underwent the Eurotest, Memory Alteration Test (M@T), and Phototest, applied in a balanced manner. Clinical, functional, and cognitive studies were independently performed in a blinded fashion in a Cognitive Behavioral Neurology Unit, and the gold standard diagnosis was established by consensus of expert neurologists on the basis of these results. Effectiveness of tests was assessed as the proportion of correct diagnoses (diagnostic accuracy [DA]) and the kappa index of concordance (k) with respect to gold standard diagnoses. Costs were based on public prices at the time and hospital accounts. RESULTS The study included 139 individuals: 47 with DEM, 36 with CI, and 56 without CI. No significant differences in effectiveness were found among the tests. For DEM screening: Eurotest (k = 0.71 [0.59-0.83], DA = 0.87 [0.80-0.92]), M@T (k = 0.72 [0.60-0.84], DA = 0.87 [0.80-0.92]), Phototest (k = 0.70 [0.57-0.82], DA = 0.86 [0.79-0.91]). For CI screening: Eurotest (k = 0.67 [0.55-0.79]; DA = 0.83 [0.76-0.89]), M@T (k = 0.52 [0.37-0.67]; DA = 0.80 [0.72-0.86]), Phototest (k = 0.59 [0.46-0.72]; DA = 0.79 [0.71-0.86]). There were no differences in the cost of DEM screening, but the cost of CI screening was significantly higher with M@T (330.7 ± 177.1 €, mean ± sd) than with Eurotest (294.1 ± 195.0 €) or Phototest (296.0 ± 196. 5 €). Application time was shorter with Phototest (2.8 ± 0.8 min) than with Eurotest (7.1 ± 1.8 min) or M@T (6.8 ± 2.2 min). CONCLUSIONS Eurotest, M@T, and Phototest are equally effective. Eurotest and Phototest are both less expensive options but Phototest is the most efficient, requiring the shortest application time.

Utility of the mini-cog for detection of cognitive impairment in primary care: data from two spanish studies.

Objectives. To study the utility of the Mini-Cog test for detection of patients with cognitive impairment (CI) in primary care (PC). Methods. We pooled data from two phase III studies conducted in Spain. Patients with complaints or suspicion of CI were consecutively recruited by PC physicians. The cognitive diagnosis was performed by an expert neurologist, after formal neuropsychological evaluation. The Mini-Cog score was calculated post hoc, and its diagnostic utility was evaluated and compared with the utility of the Mini-Mental State (MMS), the Clock Drawing Test (CDT), and the sum of the MMS and the CDT (MMS + CDT) using the area under the receiver operating characteristic curve (AUC). The best cut points were obtained on the basis of diagnostic accuracy (DA) and kappa index. Results. A total sample of 307 subjects (176 CI) was analyzed. The Mini-Cog displayed an AUC (±SE) of 0.78 ± 0.02, which was significantly inferior to the AUC of the CDT (0.84 ± 0.02), the MMS (0.84 ± 0.02), and the MMS + CDT (0.86 ± 0.02). The best cut point of the Mini-Cog was 1/2 (sensitivity 0.60, specificity 0.90, DA 0.73, and kappa index 0.48 ± 0.05). Conclusions. The utility of the Mini-Cog for detection of CI in PC was very modest, clearly inferior to the MMS or the CDT. These results do not permit recommendation of the Mini-Cog in PC.

HypatiaSalud. Institucional Repository for the Andalusian Public Health System, Spain

HypatiaSalud will be the freely accessible institutional repository for the Public Health System in Andalucía, Spain. Open access and new technologies have changed dramatically the environment in which research is being conducted and disseminated. Traditionally University has been the universal research provider, but at present time there are Government Organizations, as Public Health Systems, which are large-producers of research. Meanwhile most universities are running institutional repositories or have plans of setting up institutional repositories in the short-term, there are not many Government Organizations working on that direction. In this sense, HypatiaSalud represents an innovative initiative. Objectives: - Enhancing institutional efficiency, effectiveness and opportunities for knowledge exchange. -Expanding access and greater use of research findings to a much wider range of users increasing the visibility and reputation of Andalusian Public Health System. - Providing the foundation for effective gathering and long-term preservation of research output. Methodology. Phase I: Researching and learning from other institutional repositories. Phase II: Designing and planning the financial, organizational, legal and technical underlying issues. Phase III: Launching the service. Phase IV: Running the service. Outcomes. Bibliometrics: catalog of the research output of the Institution, in order to determine the conditions to include this scientific output in the Institutional Repository: direct deposit, deposit after a period of embargo, or closed access when publisher will not grant permission. Promote a mandate for the deposit of all peer-reviewed final drafts (postprints) for institutional record-keeping purposes. Access to that immediate postprint deposit in HypatiaSalud may be set immediately as ‘Open Access’ if copyright conditions allows; otherwise access can be set as ‘Closed Access’. International Standards application: HypatiaSalud will support OAI-PMH and DRIVER, to allow that central repositories could harvest its content or metadata. Development of human resources strategies in order to foster self-archiving through merit acknowledge and accreditation. Conclusions. It seems likely that setting up an Institutional Repository for the Public Health System in Andalucía would have substantial net benefits in the longer term for the Institution, despite the lag between the costs and realisation of benefits.

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

Background. In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR). Methods. We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB). Results. 160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant]. We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events. Conclusions. Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.

Telehealth system (e-CUIDATE) to improve quality of life in breast cancer survivors: rationale and study protocol for a randomized clinical trial.

BACKGROUND Breast cancer survivors suffer physical impairment after oncology treatment. This impairment reduces quality of life (QoL) and increase the prevalence of handicaps associated to unhealthy lifestyle (for example, decreased aerobic capacity and strength, weight gain, and fatigue). Recent work has shown that exercise adapted to individual characteristics of patients is related to improved overall and disease-free survival. Nowadays, technological support using telerehabilitation systems is a promising strategy with great advantage of a quick and efficient contact with the health professional. It is not known the role of telerehabilitation through therapeutic exercise as a support tool to implement an active lifestyle which has been shown as an effective resource to improve fitness and reduce musculoskeletal disorders of these women. METHODS / DESIGN This study will use a two-arm, assessor blinded, parallel randomized controlled trial design. People will be eligible if: their diagnosis is of stages I, II, or IIIA breast cancer; they are without chronic disease or orthopedic issues that would interfere with ability to participate in a physical activity program; they had access to the Internet and basic knowledge of computer use or living with a relative who has this knowledge; they had completed adjuvant therapy except for hormone therapy and not have a history of cancer recurrence; and they have an interest in improving lifestyle. Participants will be randomized into e-CUIDATE or usual care groups. E-CUIDATE give participants access to a range of contents: planning exercise arranged in series with breathing exercises, mobility, strength, and stretching. All of these exercises will be assigned to women in the telerehabilitation group according to perceived needs. The control group will be asked to maintain their usual routine. Study endpoints will be assessed after 8 weeks (immediate effects) and after 6 months. The primary outcome will be QoL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0 and breast module called The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire. The secondary outcomes: pain (algometry, Visual Analogue Scale, Brief Pain Inventory short form); body composition; physical measurement (abdominal test, handgrip strength, back muscle strength, and multiple sit-to-stand test); cardiorespiratory fitness (International Fitness Scale, 6-minute walk test, International Physical Activity Questionnaire-Short Form); fatigue (Piper Fatigue Scale and Borg Fatigue Scale); anxiety and depression (Hospital Anxiety and Depression Scale); cognitive function (Trail Making Test and Auditory Consonant Trigram); accelerometry; lymphedema; and anthropometric perimeters. DISCUSSION This study investigates the feasibility and effectiveness of a telerehabilitation system during adjuvant treatment of patients with breast cancer. If this treatment option is effective, telehealth systems could offer a choice of supportive care to cancer patients during the survivorship phase. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01801527.

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial.

BACKGROUND Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, physical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms.Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment.Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children-Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN A phase II randomized, double-blind pilot clinical trial. SCOPE male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. INSTRUMENTATION clinical data, blood analysis, Wechsler Intelligence Scale for Children-Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011).

The effect of post-discharge educational intervention on patients in achieving objectives in modifiable risk factors six months after discharge following an episode of acute coronary syndrome, (CAM-2 Project): a randomized controlled trial

We investigated whether an intervention mainly consisting of a signed agreement between patient and physician on the objectives to be reached, improves reaching these secondary prevention objectives in modifiable cardiovascular risk factors six-months after discharge following an acute coronary syndrome. BACKGROUND: There is room to improve mid-term adherence to clinical guidelines' recommendations in coronary heart disease secondary prevention, specially non-pharmacological ones, often neglected. METHODS: In CAM-2, patients discharged after an acute coronary syndrome were randomly assigned to the intervention or the usual care group. The primary outcome was reaching therapeutic objectives in various secondary prevention variables: smoking, obesity, blood lipids, blood pressure control, exercise and taking of medication. RESULTS: 1757 patients were recruited in 64 hospitals and 1510 (762 in the intervention and 748 in the control group) attended the six-months follow-up visit. After adjustment for potentially important variables, there were, between the intervention and control group, differences in the mean reduction of body mass index (0.5 vs. 0.2; p < 0.001) and waist circumference (1.6 cm vs. 0.6 cm; p = 0.05), proportion of patients who exercise regularly and those with total cholesterol below 175 mg/dl (64.7% vs. 56.5%; p = 0.001). The reported intake of medications was high in both groups for all the drugs considered with no differences except for statins (98.1% vs. 95.9%; p = 0.029). CONCLUSIONS: At least in the short term, lifestyle changes among coronary heart disease patients are achievable by intensifying the responsibility of the patient himself by means of a simple and feasible intervention.