Multicentre Controlled Clinical Trial Research Articles

Rehabilitation of traumatic spinal cord injury with lower limb exoskeleton

In recent years, several technological innovations have emerged to improve the rehabilitation of traumatic spinal cord injury (SCI). Among them, robotic orthosis, also known as human exoskeletons, are prominent devices for lower limb therapy. Since the early 2000s, numerous clinical studies have begun to investigate the efficacy of these devices, demonstrating the beneficial effects of exoskeletons regarding the prevention and deceleration of the progression of complications following spinal cord injury and subsequent immobilization. Previous works also deal with physiological, psycho-social and social effects, and presents possible risk factors following SCI. In this paper, the main results of the relevant international research is reviewed, the structure and operation of the first devices (ReWalkTM P6.0) in Hungary are presented, also, the main modalities of robotic assisted rehabilitation activity at international level are demonstrated. Based on the international results, the training protocol for a multicentre controlled clinical trial, involving the University of Pécs and the National Institute for Medical Rehabilitation is presented in this work. According to our hypothesis, high intensity exoskeleton-assisted complex rehabilitation induces positive changes in bone density, in the urogenital and gastrointestinal tract. Changes are quantified by objective urodynamic and defecative parameters. The difference in bone density is assessed with DEXA scan, and the effects on mental status are evaluated by questionnaires. The aim of this research is to promote a complementary therapeutic procedure based on validated results for SCI patients with paraplegia, also to establish recommendations for home use of the robotic exoskeletons, and to conceivably join to international scientific research projects. Orv Hetil. 2020; 161(29): 1200-1207.

CADASIL: Treatment and Management Options.

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

Factors associated with pain and disability reduction following exercise interventions in chronic whiplash

Some studies support the prescription of exercise for people with whiplash-associated disorders (WAD); however, the response is highly variable. Further research is necessary to identify factors which predict response. This is a secondary analysis of a randomized, multicentre controlled clinical trial of 202 volunteers with chronic WAD (grades 2 and 3). They received either neck-specific exercise with, or without a behavioural approach, or prescription of physical activity for 12 weeks. Treatment response, defined as a clinical important reduction in pain or disability, was registered after 3 and 12 months, and factors associated with treatment response were explored using logistic regression. Participation in the neck-specific exercise group was the only significant factor associated with both neck pain and neck disability reduction both at 3 and 12 months. Patients in this group had up to 5.3 times higher odds of disability reduction and 3.9 times higher odds of pain reduction compared to those in the physical activity group. Different baseline features were identified as predictors of response depending on the time point examined and the outcome measure selected (pain vs. disability). Factors associated with treatment response after exercise interventions differ in the short and long term and differ depending on whether neck pain or disability is considered as the primary outcome. Participation in a neck-specific exercise intervention, in contrast to general physical activity, was the only factor that consistently indicated higher odds of treatment success. These results support the prescription of neck-specific exercise for individuals with chronic WAD.

Safety and efficacy evaluation of a human acellular nerve graft as a digital nerve scaffold: a prospective, multicentre controlled clinical trial

This study developed a human acellular nerve graft (hANG) as an alternative to autogenous nerve and reports on its safety and efficacy. There were two groups comprised of 72 patients that received digital nerve repair with hANG (test) and 81 that received conventional direct tension-free suture repair of the nerve defect (control). The efficacy of the treatment was evaluated by static 2-point discrimination (s2PD) and Semmes-Weinstein monofilament testing. Safety was evaluated by local wound response and laboratory testing. Mean age of patients in the test group was 33.0 ± 11.1 years (range 18-61 years) and in the control group 36.9 ± 13.4 years (range 15-77 years) (p = 0.0470). Mean time from injury to repair in the test group was 23.7 ± 52 days (range 0-200 days) and in the control group 1.5 ± 10.4 days (range 0-91 days) (p = 0.0005). Mean length of nerve graft was 1.80 ± 0.82 cm (range 1-5 cm). All surgeries were performed successfully and without complications. The excellent and good rate of s2PD in the test group was 65.28% and 95% CI was 51.98-78.93%. s2PD in the test group improved over time and average distance was 12.81 ± 5.99 mm at 6 months postoperatively. No serious adverse or product-related events were reported. These results indicate that hANG is a safe and effective for the repair of nerve defects of 1-5 cm in size.

Design of the BRISC study: a multicentre controlled clinical trial to optimize the communication of breast cancer risks in genetic counselling

BackgroundUnderstanding risks is considered to be crucial for informed decision-making. Inaccurate risk perception is a common finding in women with a family history of breast cancer attending genetic counseling. As yet, it is unclear how risks should best be communicated in clinical practice. This study protocol describes the design and methods of the BRISC (Breast cancer RISk Communication) study evaluating the effect of different formats of risk communication on the counsellee's risk perception, psychological well-being and decision-making regarding preventive options for breast cancer.Methods and designThe BRISC study is designed as a pre-post-test controlled group intervention trial with repeated measurements using questionnaires. The intervention-an additional risk consultation-consists of one of 5 conditions that differ in the way counsellee's breast cancer risk is communicated: 1) lifetime risk in numerical format (natural frequencies, i.e. X out of 100), 2) lifetime risk in both numerical format and graphical format (population figures), 3) lifetime risk and age-related risk in numerical format, 4) lifetime risk and age-related risk in both numerical format and graphical format, and 5) lifetime risk in percentages. Condition 6 is the control condition in which no intervention is given (usual care). Participants are unaffected women with a family history of breast cancer attending one of three participating clinical genetic centres in the Netherlands.DiscussionThe BRISC study allows for an evaluation of the effects of different formats of communicating breast cancer risks to counsellees. The results can be used to optimize risk communication in order to improve informed decision-making among women with a family history of breast cancer. They may also be useful for risk communication in other health-related services.Trial registrationCurrent Controlled Trials ISRCTN14566836.

Effects of montelukast compared to double dose budesonide on airway inflammation and asthma control

Many patients with asthma remain symptomatic with impaired airway function on inhaled steroids. This study investigates the relationship between the clinical effect seen in response to additional treatment and the effect on airway inflammatory indices. Seventy-five adult asthmatic patients, incompletely controlled on 800 mcg budesonide/day, were randomised following a 4 week run-in period, to a double-blind, multi-centre controlled clinical trial of doubling inhaled corticosteroid (budesonide 1600 mcg/day) or adding 10mg montelukast for 12 weeks. Induced sputum was collected at baseline and end of treatment and analysed for eosinophil and neutrophil percentages, leukotrienes C4, D4 and E4, IL-8, Eosinophil Cationic Protein (ECP) and histamine. Sputum evidence of inflammation (2.0% eosinophils) was seen in only 29% of these patients and the percentage of eosinophils and other markers of airway inflammation did not change over the study period in either treatment group. There were significant improvements in am PEF (montelukast: 31.7 L/min, budesonide: 32.3 L/min) and quality of life with both treatments. We conclude that while both treatments showed similar improvements in lung function and quality of life, there was no evidence from these sputum markers measured that the effects were mediated via a reduction in airway inflammation or that the level of pre-treatment markers was associated with outcome.

A web-based data collection system for clinical studies using Java.

Data collection in multi-centre controlled clinical trials is a major problem. We describe a web-based documentation system for data collection via the Internet we have developed in Java. It keeps both the platform independent program (a Java applet) and the database on a single server to which the participating centres have access at any time. It is based on a three-tier model where client requests are handled and monitored by an application server (a Java application). We show the advantages such a system has over the HTML/CGI combination which is often used for database access, as well as possible extensions, e.g. connection to a data dictionary. Finally, we discuss the security problems which arise by the use of the Internet for data collection.

Why don't cancer patients get entered into clinical trials? Experience of the Sheffield Lymphoma Group's collaboration in British National Lymphoma Investigation studies

By standardising treatment, often in collaboration with specialised centres, multicentre controlled clinical trials offer higher survival rates, particularly for less common cancers.1 Patients are generally willing to take part in...

Immunotherapy of Immune-mediated Diseases

Owing to advances in knowledge of the basic mechanisms of the immune response, pathogenetic mechanisms in animal models of human disease and genetic and pathogenetic processes in human disease itself, it is now possible not only to speculate on but to apply novel immunotherapeutic treatments to immune-mediated human diseases. Some of these regimens have already shown therapeutic promise but in order to assess their effectiveness, optimum mode of administration and possible short- and long-term side-effects, multicentre controlled clinical trials are clearly required. Such work is already underway.

The relative roles of surgery and radiotherapy in the management of soft tissue sarcomas of adults: A personal appraisal

The literature of the last 25 years pertaining to the treatment of sarcomas of the soft somatic tissues by surgery and radiotherapy, both separately and in combination, has been reviewed. Surgery alone, if it is to be successful in an appreciable proportion of cases, must be radical. There is a growing body of evidence which suggests that less-than-radical surgery in combination with postoperative radiotherapy may give results equal or superior to those of radical surgery alone. There is need for a multicentre controlled clinical trial to compare the results of the two modes of treatment.

Diabetic retinopathy: management update

The objective of the study is to review the current knowledge and management of diabetic retinopathy. Current information from multi-centre controlled clinical trials and epidemiological studies in different parts of the world were used to review the epidemiology, pathophysiology, classification, clinical features and management of diabetic retinopathy. Diabetes mellitus affects all ocular tissues. Retinopathy, its most devastating ocular complication, presents with similar clinical picture in both types 1 and 2 diabetes. In Nigeria, diabetic retinopathy has an incidence of 33%; accounts for 16.7% of retinal diseases and leads to bilateral blindness in 22.2% of diabetics. Its incidence depends on both the duration of diabetes and the level of glycaemic control. Hypertension, dyslipaemia, hyperglycaemia and cigarette smoking aggravate retinopathy and adversely affect its response to treatment. Strict blood sugar control delays the onset of retinopathy and retards the progression of established disease. Timely laser and vitrectomy surgeries obviate severe visual loss in diabetic retinopathy. The role of medical therapy for diabetic retinopathy is still experimental. Diabetes occurs worldwide; diabetic retinopathy is increasing in incidence. Developed countries have clear guidelines on the care of diabetes and its complications. The need for similar guidelines in Nigeria is urgent.

POTASSIUM, GLUCOSE, AND INSULIN TREATMENT FOR ACUTE MYOCARDIAL INFARCTION: REPORT BY THE MEDICAL RESEARCH COUNCIL WORKING-PARTY ON THE TREATMENT OF MYOCARDIAL INFARCTION

In a multicentre controlled clinical trial of potassium, glucose, and insulin in the treatment of acute myocardial infarction no significant benefit was shown to be derived from the regimen, the mortality-rate at twenty-eight days in the treated group being 23·9% (98 of 410 patients) and in the control group 25·3% (109 of 430 patients). The incidence of cardiac arrhythmias also was not significantly altered by the treatment.