Reviews on Recent Clinical Trials - Volume 14, Issue 4, 2019

About 10 years ago, the so-called chronic cerebrospinal venous insufficiency syndrome was discovered. This clinical entity, which is associated with extracranial venous abnormalities that impair venous outflow from the brain, was initially found exclusively in multiple sclerosis patients. Currently, we know that such venous lesions can also be revealed in other neurological pathologies, including Alzheimer’s and Parkinson’s diseases. Although direct causative role of chronic cerebrospinal venous insufficiency in these neurological diseases still remains elusive, in this paper, we suggest that perhaps an abnormal venous drainage of the brain affects functioning of the glymphatic system, which in turn results in the accumulation of pathological proteins in the cerebral tissue (such as β-synuclein, β-amyloid and α-synuclein) and triggers the venous outflow from the cranial cavity and circulation of the cerebrospinal fluid in the settings of neurodegenerative disease.

Background: Many of the clinical trials remain inefficient owing to the low retention rate, and an impact on the power of the study. In addition, regulatory bodies recommend including the patients’ experience, especially, patient-reported outcomes, while making clinical decisions, and approvals. Introduction: Patient centricity has reached the stage where patients are both willing and required to participate in clinical trial designs, regulatory review and experts on other panels. Efforts are being made in the right direction and there are multiple aspects that have been or are being addressed. Objective: The current article focuses on how to include patients in clinical trial designs, the benefits, challenges, and solutions. This means patients who were merely the participants until now, they will be the drivers of trials now, and hence the clinical trials will be more efficient and productive. Key Findings: There is a drive to enhance patients’ participation in clinical trial designs, especially, visits, efficacy outcomes and their expectations with the treatment. Patients want to remain informed, right from before participation to the completion of the trial. Patients are now an important part of regulatory review, as apparent from recent initiatives by the FDA and EMA. This will enhance patients’ awareness, and bring ownership and transparency. Various patient organizations, advocacy groups have made some great suggestions and taken initiatives in this direction. Clinical Trials Transformation Initiative, European Patient’s Academy on Therapeutic Innovation, and Patient- Centered Outcomes Research Institute are a few key initiatives. However, there is a set of challenges emanating from the complexity of trials, associated with unique mechanism of action of drugs, their efficacy and safety profiles, which has to be dealt with properly. Conclusion: Overall, the pharma domain is at the verge of putting the patient in the spotlight, to achieve a near-real democracy, where the clinical research is the by the patient, for the patient, and, of the patient.

Background: High-Flow through Nasal Cannula (HFNC) is a system delivering heated humidified air-oxygen mixture at a flow up to 60 L/min. Despite increasing evidence in hypoxemic acute respiratory failure, a few is currently known in chronic obstructive pulmonary disease (COPD) patients. Objective: To describe the rationale and physiologic advantages of HFNC in COPD patients, and to systematically review the literature on the use of HFNC in stable and exacerbated COPD patients, separately. Methods: A search strategy was launched on MEDLINE. Two authors separately screened all potential references. All (randomized, non-randomized and quasi-randomized) trials dealing with the use of HFNC in both stable and exacerbated COPD patients in MEDLINE have been included in the review. Results: Twenty-six studies have been included. HFNC: 1) provides heated and humidified airoxygen admixture; 2) washes out the anatomical dead space of the upper airway; 3) generates a small positive end-expiratory pressure; 4) guarantees a more stable inspired oxygen fraction, as compared to conventional oxygen therapy (COT); and 5) is more comfortable as compared to both COT and non-invasive ventilation (NIV). In stable COPD patients, HFNC improves gas exchange, the quality of life and dyspnea with a reduced cost of muscle energy expenditure, compared to COT. In exacerbated COPD patients, HFNC may be an alternative to NIV (in case of intolerance) and to COT at extubation or NIV withdrawal. Conclusion: Though evidence of superiority still lacks and further studies are necessary, HFNC might play a role in the treatment of both stable and exacerbated COPD patients.

Background: Several studies report that practicing Yoga may lead to numerous psychophysiological benefits in patients undergoing treatment for cancer. Moreover, it may result in an effective alternative for coping with sleep disturbances, anxiety, depression and fatigue symptoms. A study based on the “Yoga in Oncology” project of the Foundation Poliambulanza was carried out, and it was designed to explore the benefits of Yoga, therefore corroborating Yoga as a therapeutic activity that can have a beneficial impact on patients diagnosed with cancer. Methods: Seventy patients were recruited, of whom 20% were males and 80% were females 18 years of age and older. All patients were being treated at the oncology department for gastrointestinal, mammary or genital carcinoma, and the disease was metastatic in 80% of patients. Data were collected between April 2013 and May 2017. The protocol consisted of a weekly 90-minute Yoga lesson for 8 consecutive weeks, and the data collection was carried out in 2 phases: (T0) preprotocol assessment and (T1) postprotocol assessment. Psychophysiological assessment was carried out with the following scales: the (BFI) Brief Fatigue Inventory, (HADS) Hospital Anxiety and Depression Scale and (PSQI) Pittsburgh Sleep Quality Index. Results: Data analysis showed a significant difference between the (T0) and (T1) HADS (Hospital Anxiety and Depression Scale) scores. The constructs of this scale consist of psychological variables for the assessment of anxiety and depression. In contrast, scores from the (BFI) Brief Fatigue Inventory and (PSQI) Pittsburgh Sleep Quality Index did not show significant differences between (T0) and (T1): such scales are relative to psychophysiological variables for an assessment of the perception of fatigue and quality of sleep. Conclusion: It is noteworthy that the data, once analyzed, showed a significant difference between preprotocol and postprotocol levels of anxiety and depression but not for the perception of fatigue or the quality of sleep. In accordance with the scientific literature, data from this study highlight that practicing Yoga may promote changes in the levels of perceived anxiety and depression in patients undergoing treatment for cancer, thus positively affecting their (QoL). It is clear that the difference in significance between the psychological and physiological variables considered here and the statistical significance found only in levels of anxiety and depression encourage further studies to account for the nature of fatigue and sleep disturbances and how to address these symptoms in oncological patients. Moreover, other points of interest for future clinical research regard the evaluation of the reason for the possible denial to participate to this kind of study, as well as the social-cultural differences in patients’ behavior.

Background: Shoulder joint dislocation is the most common dislocation of joints in the body. To reduce the anterior shoulder dislocation, it is necessary to have analgesia and sedation. Methods: In this randomized clinical trial, patients were divided into two equal groups. Group I received midazolam-fentanyl (0.05 mg/kg fentanyl at a dose of 1 μg/kg) for 10 minutes and group II received dexmedetomidine (1 μg/kg in the initial dose and then 0.2 μg/kg/h) for 10 minutes. The levels of analgesia according to VAS criteria and the time to reach desired sedation were compared between the two groups. Results: A total of 60 patients participated in this study. The time to reach the desired sedation was 8.60 ± 2.3 minutes in the dexmedetomidine group and 11.27 ± 3.57 minutes in the midazolamfentanyl group (p= 0.001). Also, the VAS score in both midazolam-fentanyl and dexmedetomidine groups was 3.3 ± 1.24 and 2.57 ± 0.9, respectively. The differences were statistically significant (p=0.015). There was significant relationship between the time to reach desired sedation and the level of analgesia. Moreover, there was no significant difference between patient age and the time to reach the desired level of analgesia. During this study, no side effect was observed. Conclusion: The findings of this study show that dexmedetomidine provides a higher level of analgesia than midazolam-fentanyl. Moreover, it was also shown that dexmedetomidine causes quicker procedural sedation than midazolam-fentanyl.

Background: Atelectasis and hypoxemia are frequently reported after coronary artery bypass graft surgery (CABG). Some studies confirm the benefits of breathing exercises on pulmonary complications, but the efficacy of preoperative breathing exercises in patients undergoing CABG is controversial. In this study, the effect of preoperative breathing exercises on the incidence of atelectasis and hypoxemia in patients candidate for CABG was examined. Methods: In a single-blinded randomized clinical trial, 100 patients who were undergoing coronary artery bypass graft surgery were randomly allocated into two groups of experimental and control, each consisted of 50 patients. Before the operation, experimental group patients were enrolled in a protocol including deep breathing, cough and incentive spirometer. In the control group, hospital routine physiotherapy was implemented. All the patients received the hospital routine physiotherapy once a day for 2 to 3 minutes in the first four days postoperatively. Arterial blood gases and atelectasis were compared between groups. Results: There was no significant difference between groups in terms of atelectasis and hypoxemia (p Value>0.05). Conclusion: Preoperative breathing exercise does not reduce pulmonary complications in patients undergoing CABG.

Background: The effective relief of renal colic patients with low complications is one of the important concerns of emergency physicians. The aim of this study was to investigate the use of injectable ketamine as an alternative to routine drugs in the relief of pain in patients with renal colic. Methods: This double-blind clinical trial was conducted on patients who had suffered kidney pain due to kidney stones in 2017, referred to Ahvaz Imam Khomeini Hospital. Patients were divided into 2 groups: the first group received intravenous ketamine (0.3 mg/kg) and the second group received intravenous morphine (0.1 mg/kg) in a double-blind form. Finally, the mean pain was evaluated before injection, after 10, 20, 30, and 60 minutes as the initial result while the side effects were considered as secondary results. Results: In this study, 135 patients with renal colic participate in this study. The mean pain at the time of referral to the hospital in the group receiving morphine and ketamine was 9.2 and 9.2, respectively, which did not show any significant difference. Based on these findings, there was no significant difference between the factors evaluated during the study of the two groups. Only in the ketamine group, there were 3 cases of nausea and 1 of vomiting. However, there was a significant increase in the need for additional doses of fentanyl in the morphine recipient group (p = 0.02). Conclusion: The findings suggest that the use of ketamine can produce a more rapid relief effect, and decrease the use of opioids which create various complications, including nausea and vomiting in patients, especially patients with renal colic.

Background: Recovery of patients with traumatic brain injury largely depends on the reduction in secondary brain damage. The present study aims at investigating the effect of Tranexamic Acid (TXA) administration within the first hours of brain trauma in the emergency department (ED). Methods: This randomized, double-blind, placebo-controlled clinical trial was carried out in patients with subdural and epidural hemorrhage. Patients with any type of bleeding were assigned into two groups of TXA and 0.9% normal saline as placebo. The rate of intracranial hemorrhage after surgery was assessed by CT-scan and amount of hemoglobin (Hb) was measured immediately before surgery and after 6 hours of surgery. Results: A total of 80 participants were randomly assigned into four groups of 20 people. There was a significant difference in the mean of intraoperative bleeding during surgery in patients receiving TXA and placebo in both SDH (Subdural hematoma) and EDH (Epidural Hemorrhage) groups (P= 0.012). The Hb drop amount had no significant difference with placebo (P< 0.0001). No complications were observed in any of the intervention and control groups during the study as well. Conclusion: The use of TXA may reduce bleeding, however, based on the results of this study, such effect was not statistically significant in controlling the epidural and subdural hemorrhage, but clinical trials with a higher sample size are suggested for further investigation in this regard.

Background: Coronary calcified lesions may limit optimal stent deployment resulting in stent underexpansion, increasing the risk of thrombosis. The Shockwave Lithoplasty System, a new technology combining a balloon angioplasty catheter with the use of sound waves, it is able to break calcium deposits without affecting vascular soft tissue. Case Presentation: An 80-year-old Caucasian man with ST elevation myocardial infarction underwent emergent coronary angiography showing complete intrastent thrombosis at the proximal trait of LAD. After thrombus removal, it was evident that stent under-expansion at its proximal edge was caused by vascular calcification. Coronary shockwave lithoplasty was chosen to treat this lesion. After calcium deposits disruption we were able to obtain complete stent expansion. Conclusion: Our case demonstrates the usefulness and safety of the lithoplasty system in the context of ST elevation myocardial infarction.