Patients In Clinical Research Research Articles

Volume Navigation with Fusion of RealTime Ultrasound and CT Images to Guide Posterolateral Transforaminal Puncture in Percutaneous Endoscopic Lumbar Discectomy

The use of percutaneous endoscopic lumbar discectomy (PELD) is increasing in the treatment of lumbar disc herniations (LDH). Nerve and vessel injury may happen during the establishment of the transforaminal working channel. Also, there is usually exposure to intraop radiation when the C-arm is used to help establish the location of the transforaminal working channel. To evaluate the accuracy and safety of the volume navigation technique for guiding transforaminal puncture in cadaver and clinical patient treatment. Cadaver experiment and comparative clinical research. Changhai Hospital, the Second Military Medical University. Volume navigation guided transforaminal puncture was performed in 15 cadavers. The registration error, time of overall puncture, ultrasound (US) observed distance between needle tip and target (DNT), and puncture error were recorded. Clinical research was performed in 63 patients who had undergone PELD. Comparative research was done between 2 groups: Those who had transforaminal puncture carried out under C-arm guidance (n = 30), and those patients whose transforaminal puncture was carried out under volume navigation guidance (n = 33). Puncture times and frequency of fluoroscopy were recorded. Both groups were evaluated with Oswestry Disability Index (ODI), and visual analog scale (VAS) before surgery at 1, 3, and 6 months, and 1 year post-surgery. In the cadaver experiment, mean registration error was 2.66 ± 1.10 mm; DNT 20.08 ± 1.32 mm; puncture error 2.91 ± 1.29 mm; overall time of puncture 22.10 ± 5.20 min. In the clinical patient research, puncture times and frequency of fluoroscopy were significantly lower in the volume navigation group compared with the C-arm group (P < 0.001). There were no significant differences between the 2 groups in ODI and VAS scores (P > 0.05) at different time points. The correlation between the registration errors and the puncture errors requires further analysis. Also, due to the relatively small number of cases studied, additional cases need to be collected to obtain reliable results. The volume navigation technique can be used for PELD because it helps to guide percutaneous posterolateral transforaminal puncture accurately with reduced puncture times and intraop radiation. Lumbar disc herniation (LDH), ultrasound volume navigation (US VNav), percutaneous endoscopic lumbar discectomy (PELD), foramen, puncture.

Establishing minimally important differences for the American Shoulder and Elbow Surgeons score and the Western Ontario Rotator Cuff Index in patients with full-thickness rotator cuff tears

The American Shoulder and Elbow Surgeons (ASES) score and the Western Ontario Rotator Cuff Index (WORC) are frequently used measures in clinical research for patients with rotator cuff tears (RCTs). The minimally important differences (MIDs) for these measures have not been established in patients with RCTs. The purpose of this study was to establish the MIDs for patients with known RCTs treated both surgically or nonsurgically. We included 222 subjects with full-thickness RCTs. The WORC and ASES were collected at baseline and at 4, 8, 16, 32, 48, and 64 weeks, as was an end of study form with questions about change in the condition after treatment. We calculated anchor-based and distribution-based MIDs. We used regression modeling to determine change in MIDs as predicted by several variables. For the anchor-based method, we found an MID of 21.9 for the ASES and -282.6 for the WORC. When using the distribution-based method of ½ and ⅓ the standard deviation, we arrived at an MID of 26.9 and 17.9 points for the ASES and -588.7 and -392.5 points for the WORC. No variables predicted MID changes. This is the first study to report MIDs for the ASES and WORC in a population of patients with only full-thickness RCTs. This information will directly improve our ability to determine when patients with RCTs are changing in a meaningful manner and accurately power clinical studies using these outcome measures.

Ethics of clinical research in patients with ALS: is there a risk of exploitation?

Amyotrophic lateral sclerosis is the most common degenerative disease of the motor neuron network. Due to its inevitably fatal outcome, numerous attempts have been made to ameliorate its course. The emergence of every new technology has spurred research to see if it might benefit patients with ALS (PALS). This paper suggests a detailed road map to be followed when performing clinical research in PALS to satisfy the ethics requirements of the Declaration of Helsinki, expressed using the terminology of Beauchamp and Childress. The ethics principles that need to be satisfied are arranged in a hierarchical manner, each having to be satisfied before the next is approached: Justice; Beneficence, Nonmaleficence, Professional-Patient Relationship, and Respect for Autonomy. Study participants’ autonomy can be respected only when all other principles have been addressed before PALS are approached to participate. Five ‘red flags’ are identified, which, if present, might indicate a risk that PALS may be exploited. PALS who are contemplating new treatments or clinical trials and their families will be assured that their best interests are the only ones that matter whenever adherence to established ethics principles and avoidance of known pitfalls are made explicit.

Favorable Outcomes in Blunt Chest Injury with Noninvasive Bi-Level Positive Airway Pressure Ventilation

Recent clinical research in patients with blunt chest injury has focused on the benefits of surgical fixation of rib fractures. Noninvasive ventilation (NIV) has been demonstrated to prevent the need for intubation and ventilation in posttraumatic respiratory failure. The preemptive use of NIV in patients with rib fractures has not been extensively studied. Our study evaluated the outcomes of patients with ≥3 rib fractures and hospitalized for ≥ 4 days. Seventy-one patients treated with NIV were compared with 270 patients without NIV. NIV patients were older (65.8 vs 56.5 years) had more rib fractures (6.25 vs 5.32) and a higher body mass index (31 vs 27.8) than the comparison group, P < 0.05, but did not have an increased mortality or incidence of respiratory failure. NIV patients did have a statistically significant increase in length of stay compared to control (12.8 vs 8.8, P < 0.05). In the total sample, worse clinical outcomes were associated with older age, increased number of and bilateral rib fractures, higher Injury Severity Score, lower Glasgow Coma Scale, and higher body mass index. Outcomes in the most severely injured group of patients treated with NIV were comparable to other studies using surgical fixation of rib fractures and epidural pain control.

Promoting Gait Recovery and Limiting Neuropathic Pain After Spinal Cord Injury

Most persons living with a spinal cord injury experience neuropathic pain in the months following their lesion, at the moment where they receive intensive gait rehabilitation. Based on studies using animal models, it has been proposed that central sensitization in nociceptive pathways (maladaptive plasticity) and plasticity related to motor learning (adaptive plasticity) share common neural mechanisms and compete with each other. This article aims to address the discrepancy between the growing body of basic science literature supporting this hypothesis and the general belief in rehabilitation research that pain and gait rehabilitation represent two independent problems. First, the main findings from basic research showing interactions between nociception and learning in the spinal cord will be summarized, focusing both on evidence demonstrating the impact of nociception on motor learning and of motor learning on central sensitization. Then, the generalizability of these findings in animal models to humans will be discussed. Finally, the way potential interactions between nociception and motor learning are currently taken into account in clinical research in patients with spinal cord injury will be presented. To conclude, recommendations will be proposed to better integrate findings from basic research into future clinical research in persons with spinal cord injury.

Neuroethics and Disorders of Consciousness: Discerning Brain States in Clinical Practice and Research

Decisions about end-of-life care and participation in clinical research for patients with disorders of consciousness begin with diagnostic discernment. Accurately distinguishing between brain states clarifies clinicians' ethical obligations and responsibilities. Central to this effort is the obligation to provide neuropalliative care for patients in the minimally conscious state who can perceive pain and to restore functional communication through neuroprosthetics, drugs, and rehabilitation to patients with intact but underactivated neural networks. Efforts to bring scientific advances to patients with disorders of consciousness are reviewed, including the investigational use of deep brain stimulation in patients in the minimally conscious state. These efforts help to affirm the civil rights of a population long on the margins.

The detection and clinical significance of homocysteine in patients with coronary atherosclerotic heart disease

In recent years, high plasma homocysteine (HHcy) as an independent risk factor for coronary atherosclerotic heart disease (CHD) has been widely received clinical attention. Some detection methods and clinical research for patients with CHD are constantly developing. Enzymatic cycling assay, the most commonly used method at present, represents important application value in the aspects of disease occurrence, severity prediction and therapeutic monitoring for CHD.(Chin J Lab Med, 2016, 39: 726-728) Key words: Coronary disease; Homocysteine; Severity of illness index

High field MRI: What are the special safety risks at higher fields?

In the last 10 years the use of MR-scanners with a magnetic field stronger than 3 Tesla (“Ultra-high field MRI”, i.e. UHF-MRI, defined as 7–9.4 Tesla in this presentation) has increased sharply, mainly driven by the fact that the three main manufacturers decided to develop 7 Tesla MRI scanners for research purposes. More recently, also human 9.4 Tesla research MRI scanners are offered commercially. Over the last 10 years, important improvements in hardware and imaging sequences at 7 Tesla have led to a quality of fMRI, anatomical neuroimaging, cerebral angiography and spectroscopy clearly surpassing the quality routinely obtained at 3 Tesla. This improved performance has resulted in the use of UHF-MRI not only in normal, young volunteers but also for clinical research in patients. When using UHF-MRI scanners in patient populations the amount of subjects having implants or a history of surgery increases sharply, resulting in a more urgent need of safety testing of common implants as well as a strong local implementation of safety procedures. In this presentation the safety aspects of UHF-MRI, regarding normal volunteers, patients and workers, will be discussed.

QL-25 * THE SYMPTOM BURDEN OF PRIMARY BRAIN TUMORS: EVIDENCE FOR A CORE SET OF TUMOR AND TREATMENT-RELATED SYMPTOMS

BACKGROUND: A set of common cancer and treatment-related symptoms has been proposed to enhance both quality of care and clinical research in patients with a variety of solid tumors. These symptoms include anorexia, anxiety, constipation, depression, diarrhea, dyspnea, fatigue, insomnia, nausea, pain, neuropathy, and vomiting. Using data from several prospective studies, this study evaluated the impact of tumor grade, disease stage and treatment in patients with primary brain tumors on the reporting of symptoms. METHODS: Aggregate symptom report data using the MD Anderson Symptom Instrument -Brain Tumor (MDASI-BT) from 617 patients enrolled in 8 clinical studies was used. Descriptive statistics were used to report the prevalence and severity of symptoms as they relate to tumor grade, treatment stage (newly diagnosed, on active treatment, on surveillance, at recurrence), and KPS. RESULTS: The sample was primarily white(83%) males(59%), with high grade gliomas(75%) with KPS ≥ 90(71%). Over 50% of patients reported at least 10 concurrent symptoms, and 40% of patients reporting at least 3 moderate-severe symptoms. Fatigue, drowsiness, difficulty remembering, difficulty with sleep, and distress were the most severe symptoms reported by all tumor grades. Patients with either grade 4 tumors or tumor recurrence reported weakness and difficulty speaking as severe. Newly diagnosed patients or on active treatment also reported irritability and problems concentrating as most severe. Functional interference of symptoms with ability to work, perform activities, walk, and enjoy life was reported by more than 25% of patients. Low KPS was associated with more severe symptoms and functional impact. CONCLUSIONS: These results support a core set of symptoms that are common across brain tumor patients that may impact clinical care, and assessment of treatment benefit. Although some symptoms overlap with those reported in patients with other solid tumors, the additional symptoms and functional limitations underscore the clinical complexity of patients with brain tumors.

Preliminary results of preoperative FOLFOX chemotherapy for locally advanced colon cancer patients with therapeutic drug monitoring of 5-FU.

579 Background: Preoperative chemotherapy is an alternative approach undergoing active clinical research in patients (pts) with locally advanced colon cancer (LACC). The aim of this study was to assess the feasibility and preliminary evidence of activity of a direct monitoring of 5-FU levels based on pharmacokinetically (PK) guided dose adjustments. Methods: LACC pts (T4 or T3 with extramural depth &gt;5mm) diagnosed after a colonoscopy and spiral CT were scheduled to receive 4 cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and then tailored according to PK monitoring to reach an area under the curve (AUC) between 25-30 mg·h·L-1). Surgery was planned 4 to 6 weeks after the completion of chemotherapy treatment. All pts were staged at baseline and before surgery. Pathological tumor regression was graded according to the MSKCC classification. Toxicity was reported according to the NCI-CTCAE 4.0. Results: From March 2011 to April 2013, 16 pts (M/F: 10/6; median age 56) with LACC were evaluated. Median dose of 5-FU was 4750 mg. 70.6% pts required a 5-FU dose increase to reach the target AUC. Median 5-Fu plasma clearance was 199,58 L/h. Side effect profile included G3 neutropenia (6 pts), G2 diarrhea (5 pts), G2 nausea (3 pts) and G2 asthenia (4 pts). Neoadjuvant treatment was discontinued in 2 pts due to small bowell obstruction requiring surgery. No progressive disease was observed during preoperative chemotherapy. A radiological dowstaging was achieved in 9 pts (56.25%). All pts underwent surgery (laparoscopy-assisted 50%) with an R0 resection rate of 93.75%. There were no treatment-related deaths. Pathological responses (MSKCC score) included grades 4, 3+ and 3 in 12.5%, 12.5% and 25% of pts, respectively. Median number of harvested nodes was 23.5 (7-51) with a ypN0 rate of 75%. Median time to hospital discharge was 7 days. After a median follow-up of 7 months (3-27), the 2-year actuarial median PFS and OS were 67.5% and 100%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts achieves major pathological responses in almost 50% the pts and a remarkable R0 resection rate. Further research seems warranted.

Clinical research of patients with multiple organ dysfunction syndrome induced by severe heat stroke: nine case reports and literature review

The objective was to analyze the clinical features of multiple organ dysfunction syndrome (MODS) induced by severe heat stroke, and to investigate the pathogenesis, diagnosis and prevention strategies in patients with MODS caused by severe heat stroke.

Quantitative MRI techniques of cartilage composition.

Due to aging populations and increasing rates of obesity in the developed world, the prevalence of osteoarthritis (OA) is continually increasing. Decreasing the societal and patient burden of this disease motivates research in prevention, early detection of OA, and novel treatment strategies against OA. One key facet of this effort is the need to track the degradation of tissues within joints, especially cartilage. Currently, conventional imaging techniques provide accurate means to detect morphological deterioration of cartilage in the later stages of OA, but these methods are not sensitive to the subtle biochemical changes during early disease stages. Novel quantitative techniques with magnetic resonance imaging (MRI) provide direct and indirect assessments of cartilage composition, and thus allow for earlier detection and tracking of OA. This review describes the most prominent quantitative MRI techniques to date-dGEMRIC, T2 mapping, T1rho mapping, and sodium imaging. Other, less-validated methods for quantifying cartilage composition are also described-Ultrashort echo time (UTE), gagCEST, and diffusion-weighted imaging (DWI). For each technique, this article discusses the proposed biochemical correlates, as well its advantages and limitations for clinical and research use. The article concludes with a detailed discussion of how the field of quantitative MRI has progressed to provide information regarding two specific patient populations through clinical research-patients with anterior cruciate ligament rupture and patients with impingement in the hip. While quantitative imaging techniques continue to rapidly evolve, specific challenges for each technique as well as challenges to clinical applications remain.

Awareness and attitude of cancer patients about participation in clinical research (CR) in Saudi Arabia.

e17528 Background: Enrollment of patients in CR may be impacted by their levels of awareness and attitude toward participation. Our study aims at assessing the awareness and willingness to participate in CR and identifying the barriers and influencing factors for participation. Methods: A cross-sectional study was performed using an interview-based questionnaire composed of close-ended questions conducted by trained research coordinators. Descriptive statistics, univariate and multivariate analyses were applied. Results: A total of 300 patients were enrolled in the study with a median age of 53.6 (42.2 - 64.0), and 188 patients (62.67%) were females. The majority of patients 289 (97.31%) were not aware of what is institutional review board. On the other hand, 226 (75.33%) showed interest in CR participation, if offered. The trust in treating physician (88.33 %) and the belief that participation in CR offers a better chance of cure (73.14%) were the two most important influencing factors to participate, while the preference of receiving standard treatment (43.13%) and the unknown efficacy of treatment (40.32%) were the top two barriers to participate. In univarate analyses, patients younger than 45 years (p&lt;0.015) and those with higher education (more than middle school) (p&lt;0.022) were significantly more interested in CR participation. However; in a multivariate analysis, higher education was the only significant predictor of interest to participate (p&lt;0.023). Conclusions: There is an apparent gap in cancer patients’ awareness about CR. However, there is an obvious interest in participation in CR especially in patients with higher education level. Enhancing public awareness is crucial to improve CR participation.

Bevacizumab and Subtype-Adapted Chemotherapy Backbone in Neuroendocrine Tumors

mide in combination with bevacizumab in 34 patients with locally advanced or metastatic neuroendocrine tumors (NETs) treated in four institutions in Boston, MA. This chemotherapy regimen led to a 15% response rate (RR) and 65% stable disease overall, with a better outcomeforpatientswithpancreaticNETs(pNETs;RR,33%;median progression-free survival [PFS], 14.3 months) than patients with carcinoid tumors (RR, 0%; median PFS, 7.3 months). We agree with the authors’ main conclusions, in particular with the importance of the role of antiangiogenic therapy in this disease. We think that this study highlights some important issues in clinical research for patients with NETs. First,aspointedoutbytheauthors,thesmallnumberofaccrued patientsinthisstudywasanissue,makingitdifficulttodrawdefinitive statistical conclusions. Neuroendocrine tumors are rare, with an ageadjustedannualincidenceoffive/100,000patientsintheUnitedStates (SEER 17 registry 2000-2004) for all stages and 1.03/100,000 for metastatic disease. 2 Thus, it is important to conduct multicenter clinical trials for this disease to achieve sufficient enrollment. Therefore, nationwide networks dedicated to treatment and clinical research in neuroendocrine tumors are of particular importance. For example, the Reseau National des Tumeurs Endocrines (RENATEN), a neuroendocrine tumors network in France, gathers data from 17 tertiary care centers all over the country and has several goals: to increase the qualityofcare,toorganizeacentralexpertpathologicreviewforevery

Clinical Research for Patients

Clinical Research for Patients

Ethical Challenges in Conducting Research on Dying Patients and Those at High Risk of Dying

Clinical research to improve care across the broad spectrum of health care has led to better quantity and quality of life for many patients. However, imposing arbitrary restrictions that might result in the exclusion from clinical research of patients who are at the end of life, or patients with a high risk of dying, is undesirable. Such exclusions may violate the principle of justice, by denying these patients a valid opportunity to make an important socio-medical contribution, and could make it difficult or impossible to advance clinical knowledge about the care of these patients. This article reviews issues relevant to the conduct of research on dying patients and those who are at high risk of dying, and outlines special considerations for ensuring that such research is ethical. In particular, precautions should be taken to ensure that informed consent is obtained from patients who are capable (or their substitute decision maker if the patient is not capable), free from coercion, and not harboring false expectations about the likelihood of benefiting from the study intervention. The unique circumstances surrounding the timing of this research (at the end of life or potentially there) may warrant that some patients be considered vulnerable, requiring special protective measures. Adhering to these principles will help ensure that dying patients or patients at high risk of dying can still participate in research that has the potential to advance knowledge and improve future care.

Exposure to and Understanding of Technical Terms in Informed Consent Forms for Biomedical Research

This cross-sectional survey with 432 patients and 158 nurses investigated the exposure to and understanding of technical terms used in informed consent forms (ICFs) for biomedical research in the Republic of Korea. The percentage of positive responses, when asked if ever exposed to the study-related terms, ranged from 4.9% to 80.8% for patients and 22.8% to 99.4% for nurses. The term phase III was least recognized by both patients and nurses. The percentage of positive responses to “understanding the study-related terms well” ranged from 0.9% to 56.2% for patients and 5.1% to 70.9% for nurses. The average number of positive respondents, when asked if they understood each term well, statistically differed by age group, education, and exposure to clinical research for patients and by education and exposure to biomedical research for nurses. The low level of understanding of technical terms in ICFs should be improved by ensuring that sufficient explanations are provided to patients while obtaining informed consent and by replacing terms with more common and easily understandable words.

Probing basal ganglia functions by saccade eye movements

The basal ganglia (BG) are a group of subcortical structures involved in diverse functions, such as motor, cognition and emotion. However, the BG do not control these functions directly, but rather modulate functional processes occurring in structures outside the BG. The BG form multiple functional loops, each of which controls different functions with similar architectures. Accordingly, to understand the modulatory role of the BG, it is strategic to uncover the mechanisms of signal processing within specific functional loops that control simple neural circuits outside the BG, and then extend the knowledge to other BG loops. The saccade control system is one of the best-understood neural circuits in the brain. Furthermore, sophisticated saccade paradigms have been used extensively in clinical research in patients with BG disorders as well as in basic research in behaving monkeys. In this review, we describe recent advances of BG research from the viewpoint of saccade control. Specifically, we account for experimental results from neuroimaging and clinical studies in humans based on the updated knowledge of BG functions derived from neurophysiological experiments in behaving monkeys by taking advantage of homologies in saccade behavior. It has become clear that the traditional BG network model for saccade control is too limited to account for recent evidence emerging from the roles of subcortical nuclei not incorporated in the model. Here, we extend the traditional model and propose a new hypothetical framework to facilitate clinical and basic BG research and dialogue in the future.

9 The added value of quality-of-life and other patient-reported outcomes in clinical research of patients with myelodysplastic syndromes

European senior programme (ESP) is well known for acceptable outcomes using expanded criteria donor (ECD) kidneys from donors older than 65 years for recipients older than 65 years. The incidence of end-stage renal disease (ESRD) is 229/million in India with a mean age of 45 years. We performed a retrospective analysis of transplantation of ECD versus standard criteria donor (SCD) kidneys into younger recipients.Forty-three ECD transplantations among 158 deceased donor organ transplantation (DDOT) were performed between January 2006 and December 2009. Among 43 transplantation from 30 donors, 14 were dual kidney transplantations (DKT) performed based upon biopsy evaluation. All recipients received thymoglobulin (rATG) induction followed by immunosuppression with a steroid, mycophenolate mofetil (MMF), and a calcineurin inhibitor. Statistical analysis used chi-square test and unpaired Student t test. Kaplan-Meier curves were used for survival analysis.For ECD the mean donor age was 64 ± 11 years. Cerebrovascular accidents (CVA) were the cause of death among 60% of donors, 73.13% of whom were hypertensive and 23.13% diabetic.Mean DKT donor age was 75 ± 9.17 years versus 60 ± 8.0 years for single kidney transplantation (SKT). Mean recipient age of DKT versus SKT was 44 ± 12.4 years versus 43 ± 14 years. Mean serum creatinine (SCr; mg/dL) of SKT patients was 1.64 ± 0.75 versus 1.68 ± 0.46 in DKT. Mean follow-up was 455 ± 352 days. Mean SCr of 43 ECD recipients of mean age, 43.4 ± 14.2 years was 1.61 ± 0.61 mg/dL. Among 43 recipients, 23.25% were diabetic, 41.86% displayed delayed graft function (DGF), and 23.25% experienced biopsy-proven acute rejection (BPAR). Patient survival rate was 72.09% and graft survival rate was 67.44%. For SCD transplantations (n = 115), the mean donor age was 36 ± 14 years and recipient mean age was 32.8 ± 14.07 years. Mean SCr was 1.32 ± 0.46 mg/dL with 26.95% recipients displaying DGF, whereas 20.86% had BPAR. In the SCD group the patient survival rate was 79.13% and the graft survival rate was 72.17%. Thus, although the ECD group showed poor graft function (P = .042), they had acceptable patient and graft survivals (P = .34 and P = .56, respectively).Because of the organ shortage, DDOT using ECD transplants for younger recipients is a feasible option with acceptable outcomes.

Toronto Alexithymia Scale (TAS-20): A Study of Patients with Schizophrenia Spectrum Disorders

researches demonstrate emotion disturbances in schizophrenia and schizophrenia spectrum disorders including deficits in emotional expression and recognition. Schizophrenia and schizophrenia spectrum disorders is typically regarded as a neurocognitive disorder, which suggests that emotional disturbances reflect abnormalities in brain areas important for emotion processing. The aim of this research was to investigate factor structure of alexithymia in patients with schizophrenia spectrum disorders. The research sample consisted of 180 patients with schizophrenia spectrum disorders from inpatients and outpatients of Mostafa Khomeini and Hazrat Rasoul hospitals. Toronto Alexithymia Scale (TAS-20) was used for collecting of data. Confirmatory factor analysis and structural equation model confirmed that alexuthymia has three different components in patients with schizophrenia spectrum disorders. The results suggest that this instrument has acceptable construct validity in the diagnosis and clinical research for patients with schizophrenia spectrum disorders.