Reviews on Recent Clinical Trials - Volume 13, Issue 1, 2018

Background: Women with gestational diabetes mellitus (GDM) are at an increased risk for developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. In this review, we will discuss postpartum cardiovascular and diabetes risk in women with a history of GDM and different ways to improve postpartum screening. Methods: This review involves a comprehensive literature review on gestational diabetes and postpartum risk for cardiovascular disease and diabetes mellitus as well as post-partum screening methods. Results: Cardiovascular risk post-partum is potentiated by increased inflammatory markers leading to worsening atherosclerosis and cardiovascular events downstream. Decreased insulin sensitivity and β cell compensation, recurrent GDM, maternal factors such as pre and post-partum weight gain and lactation may contribute to T2DM risk. Postpartum glucose testing is essential in screening women as hyperglycemia in pregnancy has long term effects on both cardiovascular disease and diabetes risk on the mother. Conclusion: Long and short term improvement to post-partum glucose testing is essential to decreasing cardiometabolic and diabetes risk in women with gestational diabetes mellitus.

Background: Lung ultrasound is increasingly being used by the bedside physicians to complement the findings of physical examination. Lung ultrasound is non-invasive, devoid of radiation exposure and can be performed rapidly and repeatedly as needed at bedside. This review aims to elucidate the evidence base and the future directions for bedside point-of-care lung ultrasound in critically ill patients. Methods: Research articles, review papers and online contents related to point-of-care ultrasound in critically ill patients were reviewed. Results: The diagnostic accuracy of lung ultrasound for common conditions like pleural effusion, pneumothorax, pulmonary edema and pneumonia is superior to chest radiograph and is comparable to chest CT scan. Lung ultrasound is helpful to evaluate the progress of lung pathology and response to treatment, over time. Ultrasound guidance for thoracocentesis decreases the complication rates. Conclusion: Bedside lung ultrasound in critically ill patients can serve as a tool to diagnose common lung pathologies, monitor its course and guide clinical management.

Background: Endoscopic Ultrasound has been used in the clinical arena for almost 35 years and it is now well-integrated in everyday hospital practice. Method: We conducted a systematic review of the available English-language articles. Objective: The purpose of this review is to summarize all the relevant indications to endoscopic ultrasound and analyze its relevant data in terms of accuracy and clinical outcomes. Results: More than 5000 scientific papers published in the literature have demonstrated its high accuracy for the diagnosis and staging of a variety of benign and malignant conditions. Staging indications include gastroesophageal and rectal cancers. Diagnostic, staging and therapeutic indications include diseases of the pancreaticobiliary area. Finally, differential diagnosis of submucosal tumors represents another important indication to this technique.

Background: Schizophrenia is a chronic and debilitating mental disorder that affects the patient's and their family's life. The disease remains a complicated disorder that is challenging to treat, despite there being a large antipsychotic armamentarium. Brexpiprazole acts both as a partial agonist at the serotonin 5-HT1A and dopamine D2 receptors and as an antagonist at the serotonin 5- HT2A and noradrenaline alpha1B and alpha2C receptors, all with similar potency. This balanced receptor profile may produce promising antipsychotic effects on positive, negative and cognitive symptoms in schizophrenia with minimal adverse effects. Methods: This review summarizes the pharmacodynamics and pharmacokinetic profile of brexpiprazole and the clinical trial information pertaining to its effectiveness and safety and tolerability, discusses its best clinical use, and compares its clinical profile to those of other widely used antipsychotic agents. Results: Brexpiprazole demonstrated significant clinical efficacy and had good safety and tolerability in well-designed trials with patients with schizophrenia. This agent may be a useful treatment alternative. Conclusion: However, it will be valuable to consider a long-term observational study that includes an active comparator, especially other second-generation antipsychotics (SGAs), to further evaluate the efficacy and safety of brexpiprazole in the treatment of schizophrenia.

Introduction: Aortic valve surgery is no exception to the general rule that history is a cycle in many fields. This manuscript aims to assist readers in transitioning from past to present and on into the future within the field of aortic valve surgery. Methods: The existing literature has been examined, including old and modern articles published on pubmed, old articles non visible on pubmed, old and recent books on the history of medicine, looking for similarities and repetitions in techniques and surgical approaches to the aortic valve in the past and the current times. Results: Steps of evolution included a blind approach, plasty procedures under direct visualization of the valve without the aid of cardiopulmonary bypass, prosthetic valve replacements via sternotomies with cardiopulmonary bypass, minimally-invasive access routes, trans-catheter aortic valve implants (TAVI), suture-less prostheses, mini-thoracotomies incorporating suture-less prostheses, and finally, totally-endoscopic aortic valve replacements. Conclusion: After the advent of CPB and several decades of open-heart surgery with full sternotomies, the minimally-invasive approach has re-emerged. Supported by a commitment to smaller incisions and shorter bypass times, the concept is now being aggressively developed. The cycling of science, including the field of aortic valve surgery, means that ingenious theories and concepts that have fallen by the wayside can be brought back and explored again with current tools and enhanced knowledge.

Background: Every phase of a clinical trial should be designed in compliance with good clinical practices by following all relevant regulatory guidelines. Patient safety, data integrity and ethics are an integral part of a successful clinical trial which must be considered. Therefore, risk monitoring is an essential tool to identify the risks associated with conduct of any trial. This article is a result of extensive research conducted by a reputed pharmaceutical company to identify the potential stages of risks associated with the conduct phase of trial that could impact the overall quality and safety of a trial. Methods: The skillful and experienced team members of a reputed pharmaceutical company involved in conducting clinical trials underwent brainstorming sessions to assess and categorize the risks associated with each stage of conduct phase of a clinical trial. They also developed a mitigation plan based on their experiences, best practices and applicable guidance documents. Results: During conduct phase, risks are associated with preparation of site master and trial master file, courier of study supply to site(s) including investigational product prior to site initiation visit, patient recruitment, telephonic monitoring, adverse or serious adverse event monitoring, site monitoring visit(s), collected case report form pages forward to data management vendor, data query clarification and site close-out visit. Conclusion: A close working relationship with all the persons associated with the clinical trial, timely monitoring and prospective mitigation planning is required for the conduct of a high quality trial.

Background: An intricate network of reciprocal interactions between adipose tissue and immune system have been largely demonstrated, leading to the well-accepted concept of insulin resistance as a low grade inflammatory state and, conversely, chronic high-grade inflammation as a dysmetabolic condition. Immune homeostasis is regulated by several players including the complement system, a complex protein network at the crossroad between the innate and adaptive arms of the human defences against pathogens. Objective: Complement C3 represents the nodal point of the complement cascade independently of the pathway recruited. Aim of this review is to collect the evidence supporting the role of complement C3 as a candidate biomarker of insulin resistance and other metabolic disorders. Methods: We reviewed the available evidence pointing to a role of complement system, and in particular complement C3, in insulin resistance and other cardiometabolic diseases including diabetes (T2D), hypertension, non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Results: Compelling preclinical evidence demonstrated a role of adipose-tissue C3 and its cleavage products C3a and acylation stimulating protein (ASP) in adipose tissue inflammation and insulin resistance. To further support this hypothesis, several clinical studies, both cross-sectional and longitudinal, confirmed this association in independent cohorts. Moreover, preliminary evidence support a role of complement C3 in other cardiometabolic diseases such as hypertension, NAFLD and atherosclerosis. Conclusion: Future studies are needed to fully confirm the usefulness of C3 as a clinical biomarker and to establish accurate cut-off values. Moreover, the therapeutic potential of C3 modulation in either cardiometabolic and inflammatory diseases need to be investigated.

Objective: The current clinical trial was aimed at evaluating the safety and beneficial effect of Cassia tora (C. tora) supplementation in healthy adults. Design: A randomized, double blind, placebo controlled study with a crossover design was done on 60 healthy normal weight adults (age range: 20-55 yrs). The study consisted of 2 treatment phases of 24 weeks each with a washout period of 4 weeks between the phases. 30 subjects randomly allocated to the ‘Placebo first’ group and 30 to ‘C. tora first’ group and assigned to receive a dose of C. tora (330 mg) or matched placebo three times a day. Safety markers were measured at base line and at the end of both the treatment phases. Body mass index, blood pressure, fasting blood sugar, glycated hemoglobin, lipid profile and antioxidants were measured at baseline and at every three months interval. Repeated measures analysis was applied to assess the period and carryover effects of the drug over placebo on biochemistries. Results: C. tora supplementation was well tolerated and no apparent changes were observed in safety markers. The net effect of C. tora in natural units over placebo was 0.83 [0.57, 1.09]- high density lipoprotein cholesterol; 27.63 [24.39, 30.88]- superoxide dismutase; 0.32 [0.28, 0.36]- catalase; 0.68 [0.56, 0.80]- glutathione peroxidase; 0.25 [0.22, 0.29]- glutathione s-transferase; 0.32 [0.29, 0.36]- glutathione and -1.08 [-1.63, -0.54]- low density lipoprotein cholesterol. Conclusion: The findings advocate that C. tora supplementation is safe and beneficial in elevating high density lipoprotein cholesterol and antioxidants and hence advised for consumption.

Introduction: Amyloidosis is a group of diseases pathohistologically diagnosed by characteristic extracellular deposition of an abnormal fibrillary protein (i.e. amyloid) into organs, leading to organ dysfunction secondary to destruction of normal tissue architecture. Methods: Case-report of a 44 year-old female, presenting with massive abdominal distension clinically suspected of ascites. Results: On admission, the patient was complaining of nausea, vomiting, abdominal pain, distension and bloating associated with weight loss and diarrhoea. Her prior medical history revealed a treatment naïve viral hepatitis C (HCV) infection with normal liver tests. She was on long term haemodialysis due to end-stage renal disease. Based on clinical, laboratory and radiology findings we established the diagnosis of light chain amyloidosis associated with multiple myeloma, complicated with amyloid bowel depositions and intestinal pseudo-obstruction. On imaging, diffuse liver enlargement was seen. Liver biopsy could have rendered the possible cause of hepatomegaly, but patient's noncompliance hindered the answer whether liver involvement was the consequence of a chronic hepatitis due to HCV infection or amyloid accumulation. Unfortunately, consequent patient's death prevented specific treatment implementation. Conclusion: Patients with multiple myeloma and obscure abdominal complaints should be worked up for amyloidosis. Intestinal pseudo-obstruction due to amyloidosis can imitate in certain instances ascites hence complicating diagnostic algorithm. In such complex clinical cases, close collaboration between surgeon, gastroenterohepatologist and haematologist is necessary.