Reviews on Recent Clinical Trials - Volume 14, Issue 1, 2019

Background: The need for immune suppressive strategies in the control of chronic inflammatory bowel diseases originated in the 1960s following the perception of a relative inefficacy of salazopyrin and its derivatives. In some 50 years upon an anecdotal claim, the indication for thiopurines in the management of inflammatory bowel diseases has come of age. Objective: The aim of this minireview is to give an overview, after the historical premises, of the current use of thiopurines in the context of inflammatory bowel diseases. Method: Through MEDLINE searches, we reviewed the literature of the last two decades. Results: For Crohn's disease, the 1980 trial of 6-mercaptopurine for steroid sparing and fistula closure proved pivotal. The analysis of withdrawal experiments and of numerous open trials has established the efficacy of thiopurines for ulcerative colitis. In this indication, cutting-edge data are now showing that because targeting dysplasia, thiopurines can induce mucosal/histological healing, thus abolishing or delaying the need for pre-emptive (tumor prophylactic) colectomy. Conclusion: In UC thiopurines may be recognized to effect a treat-to-target strategy, joining the modern algorithms of rheumatologic disorders.

Background: A clinical data management system is a software supporting the data management process in clinical trials. In this system, the effective support of clinical data management dimensions leads to the increased accuracy of results and prevention of diversion in clinical trials. The aim of this review article was to investigate the dimensions of data management in clinical data management systems. Methods: This study was conducted in 2017. The used databases included Web of Science, Scopus, Science Direct, ProQuest, Ovid Medline and PubMed. The search was conducted over a period of 10 years from 2007 to 2017. The initial number of studies was 101 reaching 19 in the final stage. The final studies were described and compared in terms of the year, country and dimensions of the clinical data management process in clinical trials. Results: The research findings indicated that none of the systems completely supported the data management dimensions in clinical trials. Although these systems were developed for supporting the clinical data management process, they were similar to electronic data capture systems in many cases. The most significant dimensions of data management in such systems were data collection or entry, report, validation, and security maintenance. Conclusion: Seemingly, not sufficient attention has been paid to automate all dimensions of the clinical data management process in clinical trials. However, these systems could take positive steps towards changing the manual processes of clinical data management to electronic processes.

Background: Malignant pleural effusion, which is a common clinical problem in patients with cancer, may be due to both primary thoracic tumours or to a metastatic spread in the chest and constitutes the first sign of disease in approximately 10% of patients. Almost all cancers can potentially produce a pleural effusion. The presence of malignant tumour cells in the pleural fluid is generally indicative of advanced disease and is associated with high morbidity and mortality with reduced therapeutic options. Dyspnoea during mild physical activity or at rest is generally the typical sign of restrictive respiratory failure. Methods: This is a systematic review of all the main articles in the English language on the topic of malignant pleural effusion and reported by the Pubmed database from 1959 to 2018. I reviewed the literature and guidelines with the aims to focus on what is known and on future pathways to follow the diagnosis and treatment of malignant pleural effusions. Results: The main goal of palliation of a malignant pleural effusion is a quick improvement in dyspnoea, while thoracentesis under ultrasound guidance is the treatment of choice for patients with a limited life expectancy or who are not candidates for more invasive procedures such as drainage using an indwelling small pleural catheter, chemical pleurodesis with sclerosing agents, pleurectomy or pleuro-peritoneal shunt. Conclusion: Despite progress in therapeutic options, the prognosis remains severe, and the average survival is 4-9 months from the diagnosis of malignant pleural effusion. Moreover, mortality is higher for patients with malignant pleural effusion compared with those with metastatic cancer but no malignant pleural effusion. Therefore, the prognosis of these patients primarily depends on the underlying disease and the extension of a primary tumour. This review focuses on the most relevant updates in the management of malignant pleural effusion.

Background & Aims: Evaluating the effect of Kangaroo Mother Care (KMC) on breastfeeding success shows conflicting results. Regarding the importance of breastfeeding and uncertainties about its effect, this study intended to conduct a systematic review and meta-analysis of randomised controlled trials on the effect of KMC on success of breastfeeding. Methods: In this systematic review and meta-analysis study, required data were collected by searching the following keywords: breastfeeding, Breast-Feeding, “skin-to-skin”, “Kangaroo Mother Care”, randomized clinical trial. The following databases were searched: Google Scholar, PubMed, EMBASE, Scopus, and Cochrane Central Register of Controlled Trials. Two authors independently extracted the data. To estimate the Breast-Feeding outcome variables, CMA2 software was used. The risk of bias of studies was assessed with the criteria developed in the Cochrane Handbook. Results: Twenty articles were included. In the KMC and CNC groups, 1,432 and 1,410 neonates were examined. Breastfeeding success rate was higher in the KMC group within different time slots, however this difference was not statistically significant (RR=1.11(95CI, 0.93-1.34) and RR=1.13(95%CI, 0.92-1.34) based on the time slot and birth weight, respectively). The inter-groups differences in the mean scores of Infant Breast-Feeding Assessment Tool (IBFAT) were statistically significant (P<0.05). Breastfeeding was initiated very sooner in the KMC group, suggesting a statistically significant inter-groups difference -0.72(95%CI, from -0.92 to -0.53) (P<0.05). Majority of the studies had a high risk of bias. Conclusion: Findings indicated a superiority of KMC over CNC in terms of breastfeeding success. Assessment of the complications and costs of KMC implementation is recommended.

Background: Although not well established; gender may play a role in the incidence, clinical manifestations, and atherosclerotic burden of Coronary Artery Anomalies (CAAS). Our aim is to investigate the impact of gender on coronary artery anomalies. Methods: All coronary angiograms performed at the University Heart Center Zurich, Switzerland, between January 2000 and December 2016 were investigated. Those of anomalous origin, course and termination (fistula) were included in the analysis with the exclusion of coronary artery aneurysms and myocardial bridges. Results: Out of the original 39577 angiographic studies that included 28550 males and 11026 females, Coronary Artery Anomalies (CAAS) were documented in 130 (0.32%) patients of whom 69.2% (n=90) and 30.8%(n=40) were males and females respectively. However, the overall prevalence of coronary anomalies amongst both genders did not differ (0.32% vs 0.36%, P = 1) and so were the basic characteristics except for hypertension, which was more prevalent in females (P = 0.03644). The most prevalent anomaly overall was (left circumflex artery from right coronary artery/sinus), which was present in (n=47, 36.2%). No impact of gender on the incidence of individual anomalies except for Right Coronary Artery (RCA) originating from Left Circumflex Artery (LCX), which was only documented in men (P = 0.0000116). On the other hand malignant CAAS presented equally with a proportion of 10% for both genders (P = 1). Although males outnumbered females in terms of atherosclerotic burden in CAAS this was statistically not significant (P = 0.331). Conclusion: Both genders have a similar impact on the overall prevalence, clinical manifestations and atherosclerotic burden of CAAs. Anomaly of RCA originating from LCX occurred more frequently in males than females.

Background: The use of indwelling Central Venous Access Devices (CVADs) is associated with the development of bloodstream infections. When CVADs are used to administer systemic antibiotics, particularly second- or higher-generation cephalosporins, there is a particular risk of developing Clostridium difficile infection. The overall bloodstream infection rate is estimated to be around 1.74 per 1000 Central Venous Catheter (CVC)-days. Objective: We hypothesised that daily oral administration of the anion-binding resin colestyramine (cholestyramine) would help prevent infections in those receiving intravenous antibiotic treatment via CVADs. Method: A small case series is described of adult patients who received regular intravenous antibiotic treatment (ceftriaxone, daptomycin or vancomycin) for up to 40 weeks via indwelling CVADs; this represented a total of 357 CVC-days. In addition to following well-established strategies to prevent C. difficile infection, during the course of the intravenous antibiotic treatment the patients also received daily oral supplementation with 4 g colestyramine. Results: There were no untoward infectious events. In particular, none of the patients developed any symptoms or signs of C. difficile infection, whereas approximately one case of a bloodstream infection would have been expected. Conclusion: It is suggested that oral colestyramine supplementation may help prevent such infection through its ability to bind C. difficile toxin A (TcdA) and C. difficile toxin B (TcdB); these toxins are able to gain entry into host cells through receptor-mediated endocytosis, while anti-toxin antibody responses to TcdA and TcdB have been shown to induce protection against C. difficile infection sequelae.

Background: Blood cytokines affect the development of inflammatory processes in both normal and pathological states. We have studied changes in the concentration of interleukins (ILs) - 1β, IL-4, IL-10, IL-12B p40, transforming growth factor β (TGF β), tumor necrosis factor (TNF-α) in acute carrageenan-induced inflammation and degenerative-dystrophic changes of knee joint caused by monoiodoacetate-induced Osteoarthritis (OA) in experimental models on rats. We also investigated the change in the cytokine profile during prophylactic and therapeutic administration of chondroitin sulfate to animals under experimental conditions. Methods: The concentration of the cytokines was measured in blood serum by enzyme-linked immunosorbent assay. Results: The manifestation of articular lesions was characterized by a disturbance in the balance between proinflammatory (IL-1β, IL-12B p40, TNF-α) and anti-inflammatory (IL-4, IL-10, TGF -β) cytokines. Conclusion: A reduction in the concentration of proinflammatory cytokines in blood serum after prophylactic and therapeutic administration of chondroitin sulfate to the rat with experimental models of acute inflammation of the hind limb and degenerative-dystrophic changes in the knee joint with OA is associated with anti-inflammatory and regenerative properties of the drug.

Introduction: This study was done to review the association of pulmonary hypertension (PH) with Transcatheter Aortic Valve Replacement (TAVR) procedures done in the US for years 2010 to 2012. Methods: We used Nationwide Inpatient Sample (NIS) data to extract data for patients who were hospitalized with a primary/secondary diagnosis of TAVR as specified by International Classification of Disease (ICD-9) codes 35.05 and 35.06. PH was identified with ICD-9 codes 416.0 and 416.8. Logistic regression models were used to analyze the association between PH and clinical outcomes of TAVR. Results: A total of 8,824 weighted discharges were identified with a primary/secondary diagnosis of TAVR, of which 1,976 (22.4%) also had PH. Mean age of patients undergoing TAVR with and without PH was 81.4 and 81.1 years, respectively. More females had a diagnosis of PH with TAVR when compared to males, (56.9% vs. 43.1). When controlling for demographics, diabetes and hypertension; the association between PH and TAVR was statistically significant (p<.0001). Estimated odds of TAVR with PH was 5.46 (95% CI: 4.63, 6.41) times greater than for TAVR without PH. Similarly, the estimated odds for a length of stay greater than 1 week for TAVR with PH was 1.43 (95% CI: 1.12, 1.82; p=.0034) times greater than odds for TAVR without PH. PH was not statistically significant for in-hospital mortality in patients receiving TAVR (p=0.7067). Conclusion: This study suggests that underlying PH does not influence the immediate mortality of patients underlying TAVR. Further studies are needed to delve into the bearing of PH on TAVR.

Background: Human Immunodeficiency Virus (HIV) prevalence rates in refugee camps are inconclusive in current literature, with some studies highlighting the increased risk of transmission due to poor living conditions and lower levels of education. With the increasing number of refugees from HIV endemic countries, it is important to assess the programs established to support patients upon arrival. Refugees have been reported to have a lower health literacy and face disease-related stigmatization, which must be overcome for the lifelong treatment of HIV. Case Presentation: 31-year-old female arrived in Canada as a refugee from Sudan with her 5 children in July of 2017. She was diagnosed with HIV and severe dental carries during her initial medical evaluation and referred to our centre. A lack of social support has resulted in severe psychological stress. The first being stigmatization which has led to her not disclosing the diagnosis to anyone outside her medical care team. Her level of knowledge about HIV is consistent with literature reporting that despite HIV prevention programs in refugee camps, compliance with risk reduction behaviors, especially in females, is low. Lastly, her major concern relates to the cost of living and supporting her children. Conclusion: Assessment of current HIV programs is necessary to recognize and resolve gaps in the system. Focusing on programs which increase both risk reduction behaviors in refugee camps and integration of refugees in a new healthcare system can facilitate an easier transition for patients and aid in the quest for global 90-90-90 targets for HIV.

Background: The most effective agents in the treatment of breast cancer have a common side effect, the hair loss. Some studies reported a reduction of hair loss with the use of the scalp cooling device. Indeed, it decreases the drug accumulation in the hair follicles. We report our preliminary experience with a scalp cooling device in reducing chemotherapy-induced alopecia and related distress in breast cancer patients undergoing adjuvant chemotherapy. Methods: Hair loss grading and treatment tolerability were evaluated during chemotherapy every 21 days and 3 weeks after the last cycle of chemotherapy via Dean's scale by patients and operators and a comfort analogic scale by patients. We administered the Hospital Anxiety and Depression Scale questionnaire at the baseline and at the end of treatment to assess the distress related to chemotherapy- induced alopecia. Results: Among the 46 patients identified, 27 accepted the device. The eligible chemotherapy regimens included docetaxel+cyclophosphamide (TC), doxorubicin+cyclophosphamide (AC) and paclitaxel (P) weekly+trastuzumab (T). 24 pts (89%) completed the treatment; 3 pts (11%) treated with AC prematurely interrupted use of the scalp-cooling device due to inefficacy. After the last cycle of chemotherapy, the number of patient who perceived a HL < grade 2 was 16 (59%). The hair retention reported by operators has been higher (78%). 81.5% of patients well tolerated the treatment. Conclusion: In our study, the scalp-cooling device reduced chemotherapy-induced alopecia in taxane- based chemotherapy. Furthermore, it suggests a discordance in hair loss perception between patients and operators.

Introduction: The early suspension of Altitude trial in recent years has induced most nephrologists and cardiologists to abandon Aliskiren use. Consequently, the potential usefulness of the direct renin inhibition in IgA glomerulonephritis remained an under-investigated therapeutic option. Case Report: We report the case of a 53 years old IgA GMN patient unresponsive to all conventional anti-angiotensin-2 agents, steroids and immunosuppressants, in which the administration of Aliskiren permitted to achieve and maintain a complete proteinuria remission in the absence of any adverse event. Conclusion: Aliskiren might represent a valid and safe therapeutic option in IgA GMN, although further investigations would be needed to confirm this conclusion.