Reviews on Recent Clinical Trials - Volume 12, Issue 1, 2017

Background: Recursive Partitioning Analysis (RPA) is a very flexible non parametric algorithm that allows classification of individuals according to certain criteria, particularly in clinical trials, the method is used to predict response to treatment or classify individuals according to prognostic factors. Objectives: In this paper we examine how often RPA is used in clinical trials and in meta-analysis. Methods: We reviewed abstracts published between 1990 and 2016, and extracted data regarding clinical trial phase, year of publication, type of treatment, medical indication and main evaluated endpoints. Results: One hundred and eighty three studies were identified; of these 43 were meta-analyses and 23 were clinical trials. Most of the studies were published between 2011 and 2016, for both clinical trials and meta-analyses of randomized clinical trials. The prediction of overall survival and progression free survival were the outcomes most evaluated, at 43.5% and 51.2% respectively. Regarding the use of RPA in clinical trials, the brain was the most common site studied, while for meta-analytic studies, other cancer sites were also studied. The combination of chemotherapy and radiation was seen frequently in clinical trials. Conclusion: Recursive partitioning analysis is a very easy technique to use, and it could be a very powerful tool to predict response in different subgroups of patients, although it is not widely used in clinical trials.

Type 2 Diabetes Mellitus (T2DM) is a chronic illness with high prevalence in Mexico, Latin- America, and the world and is associated to high morbidity, disability, and mortality rate, especially in developing countries. T2DM physiopathology is very complex; insulin resistance in the muscle, liver, and adipose tissue, a reduction in the production of incretins (mainly GLP-1) in the intestine, increased glucagon synthesis, an insufficient response of insulin generation, and increased glucose reabsorption in the kidney lead all together to an hyperglycemic state, which has been closely associated with the development of micro and macrovascular complications. Sodium Glucose Linked Transporter 2 inhibitors (SGLT2i) are the most recent therapeutic class available for treating T2DM. SGLT2i central effect is a glycosuric action, and they can reverse the deleterious effect of tubular reabsorption of glucose in the diabetic patient resulting in greater hyperglycemia. Because their mechanism of action is completely different to current drugs, they can be considered as monotherapy or in combination with any other oral or parenteral medication, including different types of insulin or its analogues. This therapeutic synergy accomplishes a greater percentage of patients achieving glycemic control goals.

Background: The Ewing sarcoma (ES) represents 10 to 15% malignant bone tumors and 40 to 45% pediatric malignant bone tumors. The aim of this review is to clarify the therapeutic results and prognostic factors of this entity. Methods: A systematic review of the literature was performed. Studies focused on the management of ES were considered for inclusion. Result: ES represents a model of multidisciplinary approach. The optimization of ES multimodality therapeutic strategies has resulted from the efforts of several national and international groups in Europe and North America and from cooperation between the pediatric and medical oncologists. The overall 5- year survival of Ewing localized tumors was 70% versus 30% in metastatic ES. Conclusion: The treatment of ES includes neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of the primary site and possible metastatic disease. The role of high-dose chemotherapy is still debated.

Background: Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. Aim: This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. Methods: RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson’s disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. Results and Conclusion: We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient’s life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient engagement in the intervention in order to clarify its specific role on health.

Background: Dyspepsia is one of the most frequent ailments in the Iranian community. Fuelled by a growing interest in understanding drugs and self-medication for common conditions such as dyspepsia, the public increasingly seeks health advice from professionals such as community pharmacists. The purpose of our study was to assess dyspepsia-related knowledge of pharmacists in Iran. Methods: This cross-sectional study has been done among 200 community pharmacists working in Tehran, Iran, and conducted through a survey questionnaire, which consisted of questions about demographic information and knowledge of dyspepsia. The validity and reliability of the questionnaire were also evaluated. The main results estimated the knowledge of pharmacists about dyspepsia, and the relationship between pharmacists’ demographic and practice characteristics and their knowledge of dyspepsia. Results: The mean (± SD) age of participants was 41.56 ± 13.90 years, and the mean score of knowledge was 9.32 ± 2.13 out of 17 points. Our results showed a statistically significant negative relationship between knowledge levels and both age and years of experience (p = 0.002 and p = 0.033, respectively). Conclusion: According to the research, the mean knowledge level of Iranian pharmacists, in terms of correct responses for dyspepsia questions, was just over half of the possible points. Thus it was concluded that improvement in the knowledge of dyspepsia among pharmacists would improve the quality of patient services, especially because of the high prevalence of dyspepsia among the public and their frequent referral to community pharmacists for taking over-the-counter medication.

Introduction: There are no reliable non-invasive markers of restenosis after Percutaneous Coronary Interventions (PCIs). The aim of our study was to measure changes incorrected QT interval (QTc), corrected QT dispersion (QTcd), corrected T wave peak to end interval (TPEc) and corrected TPE dispersion (TPEcd) after PCI and to determine whether restenosis subsequently affects these indices. Methods: From 211 patients, who underwent successful PCI, 202 patients were referred for repeated coronary angiography in order to exclusion of coronary restenosis and included in this analysis. QTc, QTcd, TPEc and TPEcd indices were calculated just before PCI and 24 hours later. Results: Comparing pre procedural with post procedural results, median QTc and median QTcd decreased significantly after PCI procedure (from 447 to 440 ms, p=0.017 and from 46 to 40 ms,p=0.005; respectively). Corresponding changes of TPEc and TPEcD were not statistically significant. Multivariate analysis showed higher amounts of QTcd changes [Exp(B): 1.033, 95% CI: 1.018-1.051; P=0.025] and younger age[Exp(B): 1.074, 95% CI: 1.038-1.112; P=0.023] as independent predictors of restenosis. Area under the ROC curve indicated good predictive performance of QTcd changes (ΔQTcd) [AUC: 0.71, 95% CI: 0.51-0.86, P = 0.03] and age [AUC 0.68, 95% CI 0.62-0.74, p = 0.04] for restenosis after PCI. The best cut-off point for ΔQTcd was 6 msec, and for age was 52 years. The sensitivity and specificity of ΔQTcd≥6 ms to detect coronary restenosis were 73.2% and 71.4% respectively. The diagnostic accuracy of age was also similar, the sensitivity and specificity of age≤ 52 years were 68.1% and 74.3% respectively. Conclusion: The Higher differences between pre and post PCI QTcd may be an inexpensive and simple predictor of restenosis after a previously successful coronary angioplasty. It seems that these findings encourage us to re-think about using QTcd as a simple ECG predictor for sustained coronary patency after angioplasty.

Background: HIV-infected patients may be at a greater risk of Hospital-Acquired Infections (HAIs) but risks factors for HAIs have not been well described in this population. Objective: The aim of this study was to examine the incidence, temporal trends and risk factors of HAIs among adult HIV positive patients. Methods: This was a retrospective cohort study carried out in an academic health system in New York City which included four hospitals over a 9-year period from 2006 to 2014. Simple and multiple logistic regression models were built to determine risk factors associated with site-specific HAIs such as Urinary Tract Infections (UTIs), Pneumonia (PNUs) and Bloodstream Infections (BSIs). Findings: There were 10,575 HIV positive discharges and 1,328 had HAIs: 697 UTIs, 555 BSIs and 192 PNUs. The incidence rate of HAIs decreased from 19.8 to 15.1 new infections per 1000 persondays between 2006 and 2014 (p value<0.001). In addition to the expected risk factors of urinary catheter use for UTI and central venous line use for BSI, symptomatic HIV and renal failure were significant risk factors for both UTIs (95% CI OR: (1.24, 2.27) and (1.46, 2.11) respectively) and BSIs (95% CIs OR: (2.28, 4.18) and (1.81, 2.71) respectively). Conclusion: HIV-infected patients had similar risk factors for HAIs as HIV-uninfected patients. Further research is required to address how patients’ CD4 counts and viral loads affect their susceptibility to HAIs.

Purpose: There has been a long-standing interest in the investigation of interactions in science. The objective of the study is to evaluate interaction between Epidermal Growth Factor Receptor (EGFR) mutation and treatment from randomized, phase II study of chemotherapy versus chemotherapy plus erlotinib in patients with progressive Non-Small Cell Lung Cancer (NSCLC) following clinical benefit from erlotinib. Materials and Methods: Forty-six patients with advanced stage NSCLC and progression from erlotinib were randomized to receive chemotherapy (pemetrexed or docetaxel) or chemotherapy plus erlotinib between 2008 and 2012. Patient characteristics at baseline including age, gender, tumor stage, race, smoking history and EGFR mutation status along with the clinical outcomes, namely response, Progression- Free Survival (PFS) and Overall Survival (OS) were obtained. The effects of treatment, EGFR mutation and interaction between the two on survival outcomes were evaluated using Cox proportional hazards model with first-order interaction. Results: For PFS, there was a significant interaction between treatment (arm B) and EGFR mutation (mutant EGFR+) (p = 0.018), although the main effects of treatment (arm B vs. arm A) and EGFR mutation (mutant vs. wild-type EGFR) were statistically significant (with p = 0.03 and p = 0.088, respectively) favoring arm B and mutant EGFR+. Thus when taking the interaction between treatment and EGFR into account, the hazard ratio comparing arm B to arm A when EGFR is positive was 1.49 (95% CI: 0.72, 3.11); and the hazard ratio comparing arm B to arm A when EGFR is negative was 0.17 (95% CI: 0.04 - 0.84). Similarly, for OS, there was a significant interaction between treatment and EGFR mutation (p = 0.02), with significant main effects of treatment and EGFR favoring arm B and mutant EFGR+. Taking together, the hazard ratio comparing arm B to arm A when EGFR is positive was 1.61 (95% CI: 0.68 - 3.82); and the hazard ratio comparing arm B to arm A when EGFR is negative was 0.16 (95% CI: 0.03 - 0.9). Conclusion: The interaction identified by Cox model shows there was an antagonistic effect between chemotherapy + erlotinib and EGFR mutation, a situation that the whole is less than the sum of the parts, despite the prolonging-survival main effect of each factor from Cox model. As a result, the continuing erlotinib beyond progression adds no benefit in survival outcomes but leads to an increase in adverse events.

Background: Antimicrobial prophylaxis should be used in circumstances where efficacy has been demonstrated and benefits outweigh the risk. Each hospital must have an antibiotic policy that is implementable and fully adhered to. Methods: A prospective observational study was conducted in 209 patients, admitted to wards of various surgical departments including surgery, obstetrics & gynaecology (O), otorhinolaryngology (ENT) and orthopaedics. Relevant antimicrobial use data of each patient was collected in a customized Case Record Form (CRF) from day one until patient was discharged. Results: Majority of the patients were young adults between 19-39 years of age. Preoperative antibiotics were given in 151 and postoperative antibiotics were prescribed in all. Third generation cephalosporins was the most frequently prescribed group. The selection of antibiotics by different departments varied greatly and many prescribed (n=85) two antibiotics for preoperative prophylaxis. Average duration of surgical prophylaxis was 6.25 days. In 90 patients, preoperative antibiotic was administered before 3 hours. Conclusion: Despite routine interactive academic activities, pattern of antibiotic used was not as per guidelines suggested by competent authorities. Interventions are warranted to promote the development, dissemination and adoption of evidence based antibiotic policy. The policy should be simple, clear, noncontroversial, clinically relevant and implementable. The constant monitoring with periodic audit to ensure adherence is warranted.