This article reviews the concept of locomotor rehabilitation index (LRI) from the principle of dynamical similarities and the theory of mechanism minimizing the energy expenditure in pathological walking. This index is defined as the percentage ratio between self-selected speed and optimum speed (algebraically LRI = 100 × self-selected speed/optimum walking speed). First, we analyze the mechanical foundations of human walking especially focusing on general size effects. Then, we discuss the descriptive physiology of pendular mechanism, evidencing the path that leads to the view of reductionist and extremely descriptive view of pathological gait. Integrative models, generated by the first evidence presented in our previous papers around the LRI, represent a crucial change of perspective. This model is discussed in details and criticized concerning the ensuing experimental findings. Finally, we discuss the case of Parkinson's disease using the Nordic walking as a neat example of application of LRI on pathological locomotion. To conclude , the concept of LRI is reinforced by the substantial evidence, showing that this new proposal for assessing the gait functionality is extremely promising and should be stimulated in studies that examine the effects of therapies on gait functionality in degenerative diseases.

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Background and objectives: According to Chinese White Paper on Osteoporosis Prevention (2009), an estimated number of 69 million Chinese people are experiencing osteoporosis caused by loss and deterioration of bone mineral density (BMD). Middle-aged women have a greater possibility in developing osteoporosis in comparison with men because of a decreased estrogen level and degeneration in physical fitness level. A Tai Chi-based intervention in the present study will be created based on four components consisting of fall-prevention/balance training, stretching/flexibility training, resistance training (Tai Chi push hand), and strength training. Design: A prospective three-arm parallel randomized controlled trial. Methods: This study will take place in ten community centers in southeast China, and postmenopausal women aged 50–65 years and without menses for 6–12 months will be recruited and randomly assigned into three groups with the allocation ratio of 1:1:1 (n = 50 for each group), including two experimental groups (a traditional Tai Chi group and a modified Tai Chi-based intervention group) and a control group. Participants in the control group will be asked to maintain their original lifestyle during the 12-month intervention period. Participants in the traditional Tai Chi and modified Tai Chi-based intervention groups will experience the traditional Yang-style Tai Chi and receive the modified Tai Chi-based intervention, respectively. The modified Tai Chi-based intervention contains four components: 1) eight Tai Chi based fall-prevention movements; 2) ten Qigong-based stretching/flexibility movements; 3) eight resistance training-based Tai Chi push hand movements; 4) eight Chen style-based Tai Chi movements. For both the experimental groups, study participants will experience four 60-minute Tai Chi training sessions weekly for 12 months. Outcome measures: BMD at multiple musculoskeletal regions is primary outcome measure. Secondary outcome measures include low limb muscle strength, physical function, and reaction time at both upper and low limbs, which will be measured at baseline and 12 months (at the end of the intervention). Discussion: Results of this study will provide preliminary evidence regarding the value of Tai Chi movement as an intervention for attenuating BMD loss in postmenopausal women. Ethics and dissemination: This study protocol was approved by the Institution Review Board of Shanghai Sports University (approval No. 11290502800) and will be performed in accordance with the principles of the Declaration of Helsinki. Patient recruitment started in August 2017. The analysis of primary outcome measures will be completed in October 2018. The estimated study completion date is June 2019. Dissemination plans include presentations at scientific conferences and scientific publications. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR-IOR-15005887) on 27 January 2015.

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Background and objectives: Previous studies have shown that deep brain stimulation can improve clinical symptoms in patients with mild Alzheimer’s disease, but the therapeutic effect in patients with moderate-to-severe Alzheimer’s disease remains unclear. Therefore, we intend to assess the therapeutic effect of deep brain stimulation on moderate-to-severe Alzheimer’s disease through a 24-month follow-up visit. Design: A prospective single-center, self-controlled study. Methods: This trial will be performed at the 101^st Hospital of PLA, Wuxi, China. We will include 20 patients with moderate-to-severe Alzheimer’s disease who will be given bilateral deep brain stimulation via an implant located beside the fornical column. Outcome measures: The primary outcome measure is the percent of patients whose scores on the Mini Mental State Examination have improved after 24 months. The secondary outcome measures include the percent of patients whose scores on the Mini Mental State Examination Scale have improved at other visits, their Montreal Cognitive Assessment-Basic score, Rey-Osterrieth Complex Figure Test score, score on the delayed recall of the Rey-Osterrieth Complex Figure Test, trail making test score, Hamilton Rating Scale for Depression score, functional magnetic resonance imaging results, functional PET imaging results at each visit point, and the incidence of adverse events. Discussion: This trial will provide feasible, objective, and quantifiable evidence for deep brain stimulation in the clinical treatment of moderate-to-severe Alzheimer’s disease. Ethics and dissemination: This study protocol was approved by the Institution Review Board of the 101^st Hospital of PLA in China (approval No. L2017002) in December 2016. Design of the study was finished in October 2016, and registered in August 2017. Participant recruitment was started at October 2017, and was expected to be finished within 12 months. Data analysis will be completed until October 2020. The results of the study will be disseminated through presentations at peer-reviewed publications. Trial registration: This trial was registered in the Chinese Clinical Trial Registry with registration No. ChiCTR-ONC-17012311 (version 2.0).

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Background and objectives: The Wharton’s jelly of the umbilical cord tissue contains a high density of mesenchymal stromal cells (MSCs). Wharton’s jelly derived mesenchymal stromal cells have immunosuppressive potential that can be utilized for treatment of autoimmune diseases such as type 1 diabetes (T1D). The objectives of this study are to assess the safety and efficacy of allogeneic Wharton’s Jelly derived MSCs (WJMSCs) in the treatment of T1D from the viewpoints of changes in beta-cell function, metabolic control, and diabetes treatment satisfaction during one year study period. Design: A two stage design. An open, non-randomized, dose-escalation scheme will be used in the first stage of the study, and a randomized, double-blinded, parallel, placebo-controlled scheme in the second stage of the study. Methods: The study population will consist of adult patients with T1D for < 2 years, 18–40 years of age (inclusive at both ends), only male in the first stage and both sexes in the second stage. In the first stage, a dose-escalation scheme with three doses will be evaluated for safety. The second stage will not be started until all patients in the first stage will have completed the 1-month follow-up visit. The second stage will recruit 15 patients who will be randomized to active treatment or placebo (2:1 ratio). Both patients and investigators will be blinded to the study protocol used in the second stage. Outcome measures: The primary outcome measure of this study will be safety. The secondary outcome measure will be efficacy of treatment, i.e., preservation of endogenous insulin production. This will be evaluated as delta change in C-peptide concentration in response to a mixed meal tolerance test, compared with before treatment. Discussion: By combining the first part (dose-escalation scheme) with the second part (double-blinded, parallel, placebo-controlled scheme), this study will provide both safety and efficacy data for the use of WJMSCs in the treatment of T1D. Obtained findings will guide on how to pursue this concept and indicate what dose of cells will be optimal for future trials. Ethics and dissemination: This study protocol was approved by the Ethics Committee Stockholm (approval number: 2017/1533-31/2) and the Swedish Medicinal Product Agency (EudraCT number: 2017-002766-50), and will be performed in accordance with the Declaration of Helsinki. Dissemination plans include presentations at scientific conferences and scientific publications. Patient recruitment was initiated in January 2018, and the first stage of the trial, the dose escalation, is expected to be completed for 1-month follow-up safety data, in the fourth quarter of 2018. Primary outcome measure will be estimated in 2020. Trial registration: ClinicalTrials.gov identifier: NCT03406585.

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Since it was initially described by and named after Strumpell and Lorrain in the late 1800s, hereditary spastic paraplegia (HSP) or familial spastic paraplegia, has remained a source of interest and study for the medical community. This rare disease, or rather spectrum of neurological diseases, is undergoing a fresh wave of unveiling as molecular and genetic techniques have bolstered our understanding of HSP. HSP is a neurodegenerative disease with a wide range of effects on patients. The mainstays of lower extremity spasticity, urinary urgency and impairment of lower extremity vibratory sensation can present alone or accompanied by a list of additional symptoms such as: epilepsy, dementia and peripheral neuropathy. In this review, some of the more recent studies are discussed, in which pathophysiology, imaging, and genetics are investigated. The review of these studies may not only help to advance our knowledge and management of HSP, but may serve as a future paradigm for similar groups of diseases that experience a wide spectrum of clinical symptoms.

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Background: A large number of approximately 600 known neurological diseases have no or limited medical interventions; many treatments are temporizing or only marginally effective and have changed little over decades. The Neurologic Stem Cell Treatment Study (NEST) utilizes bone marrow derived stem cells (BMSCs) for neurological diseases and injuries to nervous tissue. Methods/Design: Administration of BMSCs is an established approach for the treatment of neurological diseases and injury with its effectiveness verified in the pre-clinical and clinical studies. BMSCs and the associated bone marrow fraction are posited to have a number of different mechanisms by which they may potentially improve neurological function. The circumventricular organs which lie in the wall of the third ventricle are noteworthy for a minimized or absent blood-brain barrier (BBB) facilitating entry of intravenously provided BMSCs. There is documentation in the literature that intranasal delivery of BMSCs may follow the pathways of the trigeminal nerves, facilitating their entry into the pons, brain parenchyma and cerebral spinal fluid (CSF) for effects on the CNS. The NEST is an open label, non-randomized, efficacy study with two arms. Arm 1 consists of intravenous autologous BMSCs alone; Arm 2 combines intravenous with intranasal application of BMSCs to the lower 1/3 of the nasal mucosa. There will be a total of 300 patients in the study. Endpoints include at least a 10% improvement in neurological function. Discussion: There have been a number of preclinical studies establishing the utility of intravenous and intranasal methods in providing access to the CNS for certain drugs, proteins and cellular elements. Preclinical and clinical studies utilizing BMSCs have shown positive effects in various neurological diseases. It is anticipated that combining these two administration methods for BMSCs delivery to the brain may provide a greater therapeutic response. Trial registration: ClinicalTrials.gov identifier NCT02795052; registered on June 6, 2016. Ethics: This study protocol has been Institutional Review Board (IRB) approved and will be performed in accordance with principles of research ethics set forth in the Belmont Report. Informed consent: Signed informed consent will be obtained from the patients or their guardians.

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Background and objectives: Middle cerebral artery trunk occlusion can cause large infarctions. Clinically, thrombolytic therapy, defibrillation, vasodilation, and surgery are often used to treat these large infarctions. However, the therapeutic efficacy of these therapeutic interventions in promoting prognosis remains controversial. Nalmefene, an opioid receptor antagonist, exhibits a neuroprotective effect. Few clinical studies have reported on the therapeutic efficacy of nalmefene in the treatment of large cerebral infarctions. In this study, we investigated the therapeutic efficacy of nalmefene in restoring the neurologic function of patients with middle cerebral artery trunk infarction while using conventional treatment as a control. Design: A randomized, controlled, prospective trial. Methods: Two hundred and thirty-six patients with middle cerebral artery trunk infarction who will receive treatment at the First Hospital of Jilin University in China will be randomly divided into a control group (n = 116) and a nalmefene group (n = 120). Patients in the control group will receive conventional treatment. Patients in the nalmefene group will receive 10 successive days of intravenous nalmefene hydrochloride injection based on conventional treatment. Outcome measures and preliminary results: The primary outcome of this study is the efficacy rate at 20 days (i.e., 10 days after treatment). The secondary outcomes of this study include (1) the National Institutes of Health Stroke Scale (NIHSS) score at 20 days, which is used to evaluate neurologic function deficits; (2) Glasgow Coma Scale scores at 0 days (before treatment) and 10 days; (3) serum level of matrix metalloproteinase-9 at 0, 5, and 10 days (i.e., before treatment and 5 and 10 days of treatment); and (4) magnetic resonance imaging perfusion images of the head at 0 and 10 days. The results of a preliminary experiment involving participants receiving the same treatment as in the present study revealed that compared with the control group, the NIHSS score was significantly decreased, the efficacy rate was increased, Glasgow Coma Scale score was significantly increased, serum level of matrix metalloproteinase-9 was significantly decreased, cerebral blood flow and cerebral blood volume on the lesion side were significantly increased, and the mean transit time of contrast agent on the lesion side was significantly shortened in the nalmefene group. Discussion: Findings from this study will provide clinical evidence for use of nalmefene in combination with conventional treatment for large cerebral infarctions and data to support this combined therapy, which can improve the prognosis in patients with large cerebral infarctions. Ethics and dissemination: This study was designed in December 2011. Clinical ethics approval was received in November 2017. This trial was registered in December 2017. Patient recruitment will begin in January 2018 and end in January 2019. Data analysis will be completed in December 2019. Results will be disseminated for publication in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-IOR-17013871).

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Robotic-assisted gait training is becoming an important component of the rehabilitation strategy when working with patients diagnosed with a stroke. To date, research has largely focused on the effect of using robotic-assisted devices on lower limb function through the assessment of gait and balance parameters in sub-acute and chronic stroke patients, in a clinical setting. However, there may be significant benefit of implementing robotic-assisted gait training devices in the acute hospital setting soon after stroke diagnosis, but also with chronic stroke patients as a home-based rehabilitation tool. This article concludes that further research is needed when considering the influence of robotic-assisted technology on the early mobilisation (i.e., ability to stand and walk with and/or without the support from a therapist) of stroke patients in the hospital setting, their implementation in a home-based environment, and the need to incorporate more robust, quantifiable and scientific techniques to evaluate stroke patient progress through a variety of biomechanical assessment parameters.

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The microtubule-associated protein 'tau' is primarily expressed within axons in the central nervous system where it stabilizes microtubules and aids in cargo transport. While basal phosphorylation of tau is normal, tau modifications, predominantly hyperphosphorylation, are critical in the pathogenesis of numerous neurodegenerative disorders known as the tauopathies. Over the years, tau has been shown to be a valuable and elusive target for the treatment of neurodegenerative diseases. Targeting tau via genetic, biological, and pharmacological approaches in vitro and in vivo may prevent degenerative pathologies. However, to date none of these approaches have been successful in human studies, albeit some promising studies are currently underway. This review aims to briefly discuss the biology and pathology of tau and summarize current treatment strategies in clinical trials.

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Background: The activity of "caregiving" for people affected with Alzheimer's disease (AD) is associated with an augmentation in health problems (anxiety, depression, stress, increased mortality), as well as in social and financial problems. Different methods of counselling, to reduce caregiver anxiety and depression, have been shown to be effective. Methods/Design: This study will be a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) controlled superiority trial with two parallel groups. Two hundred and sixty-four caregivers of AD patients will be randomly allocated to the modified Mittelmann psychosocial intervention or an educational intervention. The treatment will consist of 6 hours of counselling and psychosocial support to caregivers, administered by psychologists, along with a specific telephone support service, whereas the active control treatment will be 6 hours of general information about AD. The primary endpoint is change in caregiver burden measured with the Zarit Burden Interview. Secondary endpoints comprise caregiver depression, anxiety and quality of life. All endpoints will be measured at baseline, 6, 12 and 24 months post treatment. Discussion: The results of this trial will be helpful to supply the efficacy of early counselling and psychosocial support for AD caregivers and offer in-depth useful information for stakholders and policy makers to implement strategies for caregivers. Trial registration: Clinical Trials.gov identifier: NCT02685787; registered on 6 February 2016. Ethics: This trial has been approved by Umbria Ethical Review Committee, Italy and will be performed in accordance with the norms on Good Clinical Practice and the Helsinki Declaration. Informed consent: Written informed consent will be obtained from the caregivers.

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Millions of people around the world are suffering from various types of degenerative diseases. Most of these diseases also classified as chronic diseases are of longer duration and slow progression. Most of these disorders are incurable but are manageable with presently available therapies. Chronic degenerative disorders such as heart disease, cancer, asthma, arthritis, diabetes, kidney failure etc. are responsible for over 70% mortality world over. For managing a number of degenerative diseases, single molecule drugs have played a major role. However, issues of unavailability of curative therapeutics, suboptimal response, treatment resistance and adverse drug reactions remain problematic and pose a serious concern. Under such circumstances, botanical drugs can play an important role in changing the health care scenario worldwide. Investigators should focus on development of newer botanical drugs to provide holistic health to masses in safe, economic and effective manner.

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Background and objectives: Cooled radiofrequency (RF) for neurotomy of genicular nerves has been proved to be efficient in short-term (12 weeks) to relieve the knee pain in severe osteoarthritis (OA) and total knee arthroplasty (TKA). This study is aimed to analyze the results of cooled radiofrequency in patients with chronic knee pain after one year of follow-up. Design: A retrospective case-series study. Methods: Forty patients underwent cooled RF of genicular nerves. We evaluated results of 36-Item Short Form Survey (SF-36), Knee Society Score (KSS) and Visual Analogue Scale (VAS) preoperatively and after one-year follow-up. Results: Regarding SF-36, a significant improvement in pain, general health and overall outcome was obtained. Preoperative average VAS score was 8.5; 1 year after surgery this score was 5.3. Significant differences were found at the knee score (KS) in KSS but not in the function score (FS) in KSS. Conclusion: Cooled RF for neurotomy of genicular nerves is still effective after 1 year of the procedure in the treatment of chronic knee pain due to osteoarthritis. The rate of conversion to arthroplasty is low. This technique could be a good alternative for chronic pain management in patients in whom TKA is not the first option of treatment.

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Background and objectives: Percutaneous transforaminal endoscopic discectomy (PTED) is a major minimally invasive surgical method for the treatment of degenerative lumbar disc herniation. The choice of posture for patients undergoing PTED is controversial. Surgeons tend to perform PTED with the patient in the prone position rather than in the lateral position. Little is documented on which posture has higher efficacy and safety. This study will be performed to investigate the efficacy and safety of the prone position versus lateral position for older adult patients undergoing PTED for the treatment of degenerative lumbar disc herniation. Design: A prospective, single-center, open-label, randomized controlled trial. Methods: This study will include 168 older adult patients with degenerative lumbar intervertebral disc herniation who receive treatment in the Department of Spine Surgery, Dalian Municipal Central Hospital Affiliated to Dalian Medical University, China. These patients will be randomized to undergo PTED in either the prone or lateral position (n = 84 patients in each surgical position). After surgery, all patients will be followed up for 2, 6, and 12 months. Outcome measures and preliminary results: The primary outcome is the Oswestry Disability Index at 12 months postoperatively. This index is used to evaluate the improvement in low back pain. The secondary outcomes are the Oswestry Disability Index preoperatively (at baseline) and at 2 and 6 months postoperatively; X-ray morphology of the lumbar spine, Visual Analog Scale score, and Japanese Orthopaedic Association score preoperatively and at 2, 6, and 12 months postoperatively; modified MacNab grade at 2, 6, and 12 months postoperatively; partial pressures of oxygen and carbon dioxide preoperatively, intraoperatively, and 1 hour postoperatively; mean arterial pressure, Likert score, and times and doses of vasopressor used intraoperatively; and the incidence of recurrent lumbar intervertebral disc herniation and incidence of adverse reactions 12 months postoperatively. The results of 54 patients included in a pilot study of PTED showed that regardless of use of the prone position (n = 24) or lateral position (n = 28), the Visual Analog Scale score and Oswestry Disability Index at 2 months postoperatively were significantly lower than those before surgery (P < 0.05). Intraoperative arterial blood gas analysis revealed that the partial pressures of oxygen and carbon dioxide were significantly different between patients in the prone and lateral positions (P < 0.05). Discussion: Based on the pilot study, future studies involving larger sample sizes are needed to investigate the short- and medium-term efficacy and safety of the prone versus lateral position for patients undergoing PTED for degenerative lumbar intervertebral disc herniation and to identify a better surgical posture suitable for older adult patients. Ethics and dissemination: This study was approved by Medical Ethics Committee of Dalian Municipal Central Hospital Affiliated to Dalian Medical University, China in May 2018 (approval No. 2018-012-01). This study protocol will be performed in strict accordance with the Declaration of Helsinki. Written informed consent will be obtained from the participants. The study protocol was designed in December 2017. Patient recruitment will begin in August 2018 and end in August 2019. Data analysis will begin in October 2020 and end in November 2020. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800016399). Protocol version: 1.0.

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Background and objectives: Incidence of diabetes mellitus is increasing due to genetic predisposition, high body fat, and insulin resistance. Though multiple oral hypoglycaemic agents and insulin are available, these are associated with side effects, primary and secondary failure. Hence, evaluation of antidiabetic potential of medicines described in traditional health sciences such as Ayurveda (Indian system of medicine) is also important. This study aimed to assess the efficacy and safety of Vidangadi Yoga (ayurvedic polyherbal medicine) and metformin in the management of type 2 diabetes mellitus (T2DM) based on biochemical parameters and adverse events. Methods: In this prospective, randomized, open-label, active-controlled, two-arm study, 61 patients with T2DM were included and randomly divided two groups. Patients in the Vidangadi Yoga group received Vidangadi Yoga tablet 500 mg thrice daily before food with water, while patients in the metformin group received metformin 500 mg after food twice daily for 90 days. Subjects were asked to undergo follow-up at the interval of 15 days until the completion of 90 days. Assessment was done on changes observed in fasting and postprandial blood glucose, glycosylated haemoglobin, lipid profile, haemogram, hepatic, renal profile, and clinical symptoms. Results: After 90 days of medication, fasting and postprandial blood glucose levels in both groups were significantly decreased when compared with baseline (P < 0.001). There were no significant differences in fasting and postprandial blood glucose levels between both groups. After 90 days of medication, haemogram, and hepatic and renal profiles (safety parameters) in the two groups were not significantly different from baseline. No adverse events were related with the use of the studied medicine. Conclusion: Vidangadi Yoga exhibits equivalent efficacy to metformin and is safe in lowering fasting and postprandial blood glucose levels. Ethics and trial registration: This study was approved by the institutional ethics committee of PDEA’s College of Ayurved and Research Centre, Pune, Maharashtra, India (approval number 6833) on March 22, 2014 and was registered with Clinical Trials Registry- India (CTRI) (No. CTRI/2015/04/005719) on April 25, 2015.

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Hypertension refers to increased arterial blood pressure and can be divided into two categories: primary and secondary. Primary hypertension caused by angiogenic degenerative changes is a degenerative disease. With liberalization of China’s reproduction policy and increases in maternal age, the prevalence of pregnancy-induced hypertension (PIH) in China has increased gradually. PIH is not a type of primary hypertension, but there are differences in the treatment of these two types of hypertension. Here, we review the choice and use of drugs for PIH management using drugs for the management of primary hypertension as a reference. First-line drugs such as labetalol, nifedipine, or methyldopa should be taken via the oral route if blood pressure is ≥ 150/90 mmHg. For chronic hypertension, other drugs should be added after the first drug at the highest concentration has been revealed to be ineffective. If the blood pressure of patients with acute hypertension is ≥ 160/110 mmHg, maternal stroke or eclampsia can result. If PIH patients are about to deliver, they can be given labetalol (i.v.), hydralazine (i.v.) or nifedipine (p.o.). Moreover, all anti-hypertensive treatments should be based on considerations of maternal and fetal safety.

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Periodontal diseases are microbial induced chronic inflammatory conditions characterized by infiltration of leukocytes, loss of connective tissue, alveolar bone resorption, and formation of periodontal pockets. In response to periodontal pathogens, leukocytes elaborate destructive oxidants, proteinases and other factors. Periodontal disease is a chronic inflammatory disease, which leads to alteration of the micronutrient levels such as zinc, selenium, iron and copper. The imbalance of the micronutrient levels leads to increased susceptibility to oxidative damage of tissues. These micronutrients play a role in both health and disease. The vitality of the periodontal tissues in both health and disease depends on the adequate source of essential nutrients being available to the host. Micronutrients are imperative for optimum host response. Populations worldwide are prone to their insufficiency due to lifestyle changes or poor nutritional intake. Balanced levels of these trace minerals such as iron, zinc, selenium and copper are essential to prevent progression of chronic conditions like periodontitis. Their excess as well as deficiency is detrimental to periodontal health. Selenium, zinc and copper are integral components of antioxidant enzymes and prevent reactive oxygen species induced destruction of tissues. Their deficiency can worsen periodontitis associated with systemic conditions like diabetes mellitus. This review focused on the role of micronutrients, namely, iron, zinc, selenium and copper in periodontal health and their association with chronic periodontitis.

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Background: Progressive disability in activities of daily living (ADL) is inevitable for people with Alzheimer's disease and related dementias (ADRD). Attempts to slow or prevent ADL disability have been unsuccessful despite making progress in behavioral training methods. Missing from this research is an emphasis on how we maximize a patient's engagement during training and the rigorous examination of implementation protocols (dosing and training methods) which may advantage learning in people with ADRD. Our team addressed this gap with the development of the Skill-building through Task-Oriented Motor Practice (STOMP) intervention which creates methods for obtaining ADL goals that support "personhood" and tests high-intensity protocols that appear to advantage learning and sustained learning over time. Through this study, we aim to evaluate differential outcomes in activities of daily living by two different dose levels of the STOMP intervention. Secondarily, we will assess the moderating effects of participant attention to task during training. Methods/Design: A randomized, single blinded, controlled trial with 32 eligible patients with dementia assigned to either the original, intensive STOMP protocol (3 hours per day, 5 days per week for 2 weeks) or a less-intensive STOMP protocol (1 hour per day, 2 days per week for 2 weeks) delivered by an occupational therapy assistant in the home. ADL training is delivered using motor learning theory techniques of blocked practice, continuous verbal praise, errorless learning and intense dosing schedules. Blinded occupational therapists will complete baseline, post-intervention and 3-month follow-up assessments in the home. Primary outcomes will be examiner and caregiver rated ADL performance. Secondary outcomes will be the amount of time the participant is engaged in the task (e.g., attention to training). Discussion: Through this protocol, we will examine differential ADL outcomes by dose for the STOMP ADL intervention. Our results will inform dosing parameters for future intervention studies for people with ADRD. Trial registration: ClinicalTrials.gov identifier: NCT02356055 Ethics: This study protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#4648) and will be performed in accordance with the Declaration of Helsinki. Informed consent: Written consent will be obtained by the participant's legally-authorized representative as older adults with dementia are considered a vulnerable population. However, in all cases, assent of the participant will also be obtained at the time of consent.

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In the last few years numerous evidences have shown an increased prevalence of “Potential Inappropriate Prescriptions (PPIs)” in the elderly (>/=65 years) and have estimated that more than 10% of all hospitalizations in this population are hospitalized for problems consequent to drugs given. The predictive factors more strongly related to the inappropriate use of drugs are polytherapy (>/= 5 drugs contemporary), uncritical application of guidelines in many cases inadequate and built with data from young subjects-adults affected by a single pathology, recommend drug regimens that do not consider the changes in the pharmacokinetics and pharmacodynamics parameters, exposing to significant risks. Considering that polytherapy is any case necessary (due to the effect of comorbidity and longer life expectancy), is unavoidable not acknowledge the impossibility, as much for clinicians as for any guideline all interactions: in this perspective the application of evaluation scientifically based criteria and information technology tools could represent a resource for to tend to prescriptive appropriateness, still a challenge for researchers, clinicians, manager, third-payers. The application of explicit criteria (ex. Beers and STOPP & START) to the administrative data base of pharmaceutical prescriptions could represent a screening too, not only to qualitatively and quantitatively asses PPIs, given immediate availability of information, but above all to create practical support for the clinician’s work by crating “adaptive database” for interactive research for specific conditions. However, regardless of more or less functional software applications, more multidimensional and multidisciplinary efforts (ex. geriatric counseling) are needed to take on problems related to polypharmacy in elderly patients: the most appropriate therapeutic regimen should combine guidelines, geriatric assessment, social and economic considerations, the patient’s will and should be periodically reviewed, especially as the presence of multiple comorbidities increases the risk of adverse reactions.

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Multiple sclerosis (MS) is a complex inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltrates lead to damage of myelin and axons. Often this seems associated with a type of autoimmune and inflammatory disorder which is transient, with attempted remyelination that is not durable. Neurological disorders appear somewhat randomly, seem to improve and demonstrate recovery. Progression is variable, but over time, seems to become more widespread with microglial activation associated with extensive chronic neurodegeneration and persistent disability. Magnetic resonance imaging (MRI), with and without contrast, has become the standard metric of finding and following lesions and axonal loss. The traditional methods of treatment include medications, diet, exercises, and neurological supportive care. The medications are limitedly effective, and often have very undesirable side effects. Medications seem to reduce the frequency of new episodes, but are not yet able to reverse acquired deficits or long-term progression. Clinical trials exploring cellular therapy are currently underway, and showing some interesting progress with management of many with the MS disorder. What has been needed is a reliable and affordable metric to track the patient's clinical progress, both from a location of lesion and volumetric changes on MRI. PIXYL software offers a major improvement in providing tracking capability of outcomes in use of medications or cellular therapy. Time consuming, limited accuracy, and costs of having serial MRI segmented and analyzed make standing neuroradiological interpretations difficult to standardize. This software offers a new ability to resolve much of these issues, including taking manual (human) interpretation out of potential bias or different interpreters, and offers volumetric and lesional changes over time in serial studies. This paper introduces the functions and values of use of sophisticated software analytics in the evaluation and management of this ongoing disease process.

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Incretin-related drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) analogues, have been clinically available and widely used to treat patients with type 2 diabetes mellitus. Accumulating evidence indicates that these agents exert glycemic control and have various other favorable effects, including prevention of atherosclerosis. It is important to assess and manage early-phase atherosclerosis, but whether diabetic therapeutics including incretin-related drugs improve or maintain vascular endothelial cell function has not been fully determined. We previously published prospective clinical trials focused on flow-mediated dilation in patients with type 2 diabetes, who did not have severe atherosclerosis, using two different incretin-related drugs: a DPP-4 inhibitor and a GLP-1 analogue. These trials showed that these therapeutic agents did not improve endothelial cell function. In this article, we discuss how incretin-related drugs contribute, if at all, to vascular endothelial cell function, atherosclerosis, and beta-cell function, based on our clinical trials and previous evidence.

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Background: Cardiotoxicity is a toxic side effect of trastuzumab-based therapy. Current guidelines for cardiac monitoring (every 3 months) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving trastuzumab-based therapy have been dictated by the increased risk of cardiotoxicity observed in clinical trials. However, the majority of these patients are at a low risk of cardiac complications and may not require such frequent monitoring. Objective: This randomized controlled clinical trial will be performed to demonstrate that cardiac monitoring (echocardiography (ECHO)/multiple gated acquisition scan (MUGA) every 4 months is not inferior to every 3 months in the detection of cardiac dysfunction (decrease in left ventricular ejection fraction (LVEF)) in patients receiving trastuzumab-based therapy for early-stage HER2-positive breast cancer. Study period: From June 2016 to December 2018. Study location: The Ottawa Hospital Cancer Centre. Principal investigator: Dr. Olexiy Aseyev and Dr. Susan Dent at Department of Medicine, Division of Medical Oncology, The Ottawa Hospital, University of Ottawa, Canada. Study design: A prospective, single-center, randomized controlled non-inferiority clinical trial. Study population: A total of 200 patients with early-stage HER2-positive breast cancer (n = 100 in each group) receiving trastuzumab-based therapy will be enrolled. Inclusion criteria: Patients with histologically confirmed early-stage HER2-positive breast cancer receiving trastuzumab-based therapy, who are over 18 years of age, have a normal baseline LVEF (> 53%) and are able to provide verbal consent will be included in this study. Exclusion criteria: Patients will be excluded if they have any contraindication to transthoracic echocardiography or MUGA. Randomization: Eligible and consented patients will be randomized using a permuted block design to receive cardiac evaluation (by either transthoracic echocardiography or MUGA) every 3 months, or every 4 months while on treatment, 100 patients for each type of cardiac evaluation. Primary outcome measure: The rate of changes in LVEF diagnosed by ECHO or MUGA throughout trastuzumab-based therapy in both groups. Secondary outcome measures: Rates of trastuzumab delay/discontinuation, referral to cardiology, rate of cardiac events. Human specimen collection: Not involved. Ethical approval: This study was approved by the Ottawa Health Science Network Research Ethics Board. Trial registration: ClinicalTrials.gov identifier: NCT02696707 on February 18, 2016. Study status: This study is currently recruiting participants. Study enrolment is expected to be completed by July 2018 and analysis of primary outcome measure will be completed by October 2018 and the study will be completed by December 2018. Discussion: This study will present data on the cardiac safety of less frequent cardiac monitoring in patients with early-stage HER2-positive breast cancer. Future trials will explore cardiac monitoring strategies using composite data including baseline cardiac risk factors, baseline cardiac imaging and cardiac biomarkers. Health care economics will be explored.

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Background: Shared decision making is an emerging approach through which physicians and patients can reach health care decisions based on mutual agreement. Scientific physician-patient shared decision making can facilitate selection of optimized treatments, improvement in curative effects, postoperative prognosis, and short-term and long-term rehabilitation in patients with coronary heart disease. However, there have been no studies on Chinese physicians' and patients' attitude to shared decision making. Methods/Design: This is a multicenter, large sample, cross-sectional, open-label, clinical survey. Participants are 1,000 Chinese patients with coronary heart disease and 200 medical staff members of both sexes over 18 years old. The primary survey index is the satisfaction of medical staff members and coronary heart disease patients with shared decision making. The secondary survey indices include staff and patient satisfaction with a clinical decision-making aid, patients' awareness of disease risk and curative benefits, and physician-patient trust. Discussion: This study is the first to investigate the attitude of Chinese medical staff members and coronary heart disease patients to clinical shared decision making and to examine the feasibility of using this approach. This study provides an evidence-based foundation for investigating the problems and solutions of clinical shared decision making and strengthening the adherence to statin medication in patients with coronary heart disease. Trial registration: This study protocol was registered at Chinese Clinical Trial Registry (registration number: ChiCTR-OCS-14004646). Ethics: This study protocol has been approved by Ethics Committee, The First Affiliated Hospital of Dalian Medical University (approval number: LCKY2014-14) and will be performed in strict accordance with the Declaration of Helsinki, formulated by the World Medical Association. Informed consent: Signed informed consent will be obtained from each included subject.

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Background and objectives: Hypoxia is an important factor that affects bone formation and regulates bone growth. Therefore, many older adult patients living in high-altitude hypoxic areas exhibit osteoporosis. Oxidative stress-related hypoxia-inducible factors can induce abnormal expression of various factors including vascular endothelial growth factor (VEGF), insulin-like growth factor, and endothelin. However, it remains unclear whether these factors influence changes in bone metabolic markers. This study protocol aimed to investigate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude hypoxic area of China. Design: A prospective, single-center, non-randomized, controlled trial. Methods: One hundred and twenty older adult male patients with degenerative osteoporosis residing in the high-altitude area of China who receive treatment at the Affiliated Hospital of Qinghai University of China between January 2015 and February 2018 are being included in the osteoporosis group. One hundred and twenty healthy older adult males who concurrently received physical examination are being included in the control group. One day after admission, serum levels of hypoxia-inducible factor 1-alpha (HIF-1α), HIF-2α, VEGF, osteocalcin, and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured using an enzyme-linked immunosorbent assay. Bone mineral density in L1–4 segments, right femoral neck, and the greater trochanter of the femur was detected using dual-energy X-ray absorptiometry. Outcome measures: The primary outcome measure of this study is serum HIF-1α levels at 1 day after admission. Secondary outcome measures include serum levels of HIF-1α, HIF-2α, VEGF, osteocalcin, and TRACP 5b at 1 day after admission, as well as the correlation between serum levels of oxidative stress indicators (HIF-1α, HIF-2α, and VEGF) and bone metabolic markers (osteocalcin and TRACP 5b) at 1 day after admission. Discussion: Findings from this study aim to validate the correlation between oxidative stress-related factors and bone metabolic markers in older adult male patients with degenerative osteoporosis who reside in the high-altitude area of China. Ethics and dissemination: This study was approved by the Ethics Committee of the Affiliated Hospital of Qinghai University of China (approval No. QHY1402G). The study was performed in accordance with the Declaration of Helsinki. Participants are informed of the study protocol and procedures, and sign an informed consent. Participant recruitment, blood sampling, and data collection began in January 2015 and will be ended in February 2018. Outcome measure analysis and trial completion will be in March 2018. Results will be disseminated through presentations at scientific meetings and/or by publication in peer-reviewed journals. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-ROC-17012848).

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Background and objectives: The main treatment goals for degenerative knee osteoarthritis are to relieve pain, restore knee function, improve quality of life, delay knee replacement, and reduce the number of revisions. Knee replacement is currently the most common treatment for degenerative knee osteoarthritis; however, the cost is high, and the procedure is often associated with prosthesis loosening and shedding and many adverse reactions. Therefore, we hypothesize that knee-preserving arthroscopic debridement for treatment of knee degenerative osteoarthritis in elderly patients is lower-cost, effective, safe, and reliable. Design: Prospective, single-center, open-label, non-randomized controlled trial. Methods: In total, 212 elderly patients (knees) with degenerative knee osteoarthritis who receive treatment in the Second Hospital of Chaoyang (Liaoning Province, China) will be included in this study. These patients will be assigned to two groups according to each patient’s condition and wishes (n = 106/group). In the control group, intra-articular injection of sodium hyaluronate will be performed, followed by oral administration of nonsteroidal anti-inflammatory drugs, conventional physiotherapy, and quadriceps functional exercise. In the arthroscopic debridement group, arthroscopic debridement will be performed, followed by oral administration of nonsteroidal anti-inflammatory drugs, conventional physiotherapy, and quadriceps functional exercise. All patients will be followed up at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years. Outcome measures: The primary outcome measure is the percentage of patients with a Hospital for Special Surgery (HSS) knee score of ≥ 85 points at 2 years after surgery, which will be used to evaluate knee function recovery. The secondary outcome measures are the percentage of patients with an HSS knee score of ≥ 85 points before surgery and at 1 week, 1 month, 3 months, 6 months, and 1 year after surgery; the HSS score, visual analog scale score, Western Ontario and McMaster Universities Osteoarthritis Index, knee range of motion, hospitalization costs, and knee X-ray morphology before surgery and 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery; medical costs after 2 years of treatment; and incidence of adverse reactions at 1 week, 1 month, 3 months, 6 months, 1 year, and 2 years after surgery. Discussion: The findings from this study will reveal whether arthroscopic debridement for the treatment of degenerative knee osteoarthritis in elderly patients has the advantages of fewer adverse reactions and lower treatment costs with effective restoration of knee function. Ethics and dissemination: This study was approved by Medical Ethics Committee of Second Hospital of Chaoyang of China (approval No. 2017-08-01). The study will be performed in accordance with the Declaration of Helsinki. Participants provided signed informed consent regarding the study protocol prior to participation in the study. This study was designed in June 2017. Patient recruitment and data collection will begin in June 2018. Patient recruitment will end in December 2018. Data analysis will be performed in June 2021. The study will be completed in August 2021. Results will be disseminated through presentations at scientific meetings and/or by publication in a peer-reviewed journal. Trial registration: This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800015208). Protocol version (1.0).

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