Effectiveness of an early mobility protocol for stroke patients in Intensive Care Unit

Objectives:To evaluate the effectiveness of an early mobility protocol for stroke patients in the intensive care unit.Methods:Participants were patients with first or recurrent stroke (n=60, age=49.02±6.36 years, body mass index=32.95±5.67 kg/m²) admitted to the intensive care stroke unit in general hospitals, Riyadh during October and December 2016. Single group pretest-posttest design involving an early mobility protocol was started within first 24 hours admission. Pre and post measurements of muscle strength, pulmonary function and quality of life were carried out.Results:There were significant improvements in muscle strength of upper and lower extremities´ muscles after treatment (p<0.05), pulmonary functions including Forced Vital Capacity, Forced Expiratory Volume 1 (p<0.05) and quality of life, namely, Barthel Index and modified Rankin Scale (p<0.01).Conclusion:This study demonstrates that initiating an early mobility protocol is safe and effective for intensive care unit stroke patients and supports introducing the current protocol as a standard protocol in neurogenic Intensive Care Units.

Stroke is a life-threatening condition caused by interruption of the blood supply to any part of the brain. Stroke causes acute neurological disorders and long-term disabilities and imposes economic, social and health impacts on individuals and their families.1 Survivors of stroke are left with mental and physical disabilities that cause social and economic burdens and impair quality of life (QOL). In Saudi Arabia stroke is becoming a rapidly increasing problem and a primary cause of morbidity and mortality.2 Worldwide the incidence of first-time stroke was 17 million during 1990-2000.3 Cerebrovascular diseases including stroke is a leading cause of mortality,4 and stroke is the fifth leading cause of death, but it remains the first cause of disability in the USA.5 By 2030 there will be almost 12 million stroke deaths and 70 million stroke survivors globally.6 Stroke has an adverse influence on the QOL of patients. The onset of stroke is sudden, and unlike other disabling conditions, it leaves patients and their family’s ill prepared for its sequelae.7 Stroke may create unique conditions that affect the patients’ QOL, involving dysfunctions in physical, emotional, memory, thinking, and social interactions.8Stroke is an urgent health care issue. It is a common cause of the hospital admissions. Immediate admission to the neuro-intensive care unit can facilitate early stroke treatment strategies.9 Stroke patients in the intensive care unit (ICU) experience a decrease in physical activity that represents a significant stress on the body and leads to a considerable decrease in functional status, increases morbidity, mortality rate, and duration of hospital stay and cost of care.10 In addition to comorbid diseases, patients on mechanical ventilation have many barriers to mobility because they are surrounded by tubes, catheters, life support and monitoring equipment. Additionally, other factors besides weakness, such as sleep loss, lack of social communication, nutritional status, sedation, and an ICU culture that encourages bed rest further contribute to functional deterioration.11 There is considerable loss of the muscle mass during the initial weeks of immobility in the ICU, therefore its management is inherently related to QOL after discharge.12 Considerable published evidence indicates that patients in ICUs have high morbidity and mortality, high costs of care and a marked decline in functional status.13,14Early and progressive mobilization program has been described as a key component for patients in the ICU. It may decrease post stroke complications such as infections, deep venous thrombosis, pneumonia, pressure ulcers, falls and de-conditioning with bed rest.15 It has been recognized that mobilization of post stroke patients is essential to prevent hospital-associated complications, functional decline and facilitate recovery.16 Moreover, the benefits of early mobilization include decreased ICU-acquired weakness, improved functional recovery within hospital,17 Effective stroke intervention begins the day the patient has a stroke.18 It has a positive effect on patient functional ability, promotes positive psychological effects and improves walking at hospital discharge and reduces hospital length of stay.19 While on the other hand, long term inactivity may affect the patients’ physical, social, emotional, behavioral, and psychological pattern.20 In addition, secondary changes associated with stroke-related inactivity include muscle atrophy, a shift in muscle fiber type to a greater predominance of fast-fatigable, insulin-resistant fibers, loss of cardiovascular fitness, and increased intramuscular fat.21 Therefore, early mobilization program which is a complex intervention that needs crucial patient assessment and management, as well as interdisciplinary team collaboration and training.22,23 The early mobilization may improve patient outcomes and recovery.24 Few studies have investigated the role of increased mobility in ICU patients. Therefore, this prospective intervention trial evaluated the effectiveness of an early mobility program administered by physical therapists and nursing personnel for stroke patients admitted in ICU.     

Skin deep: from dermal fibroblasts to pancreatic beta cells

Immunologic Research - Type I diabetes (T1D) is a chronic autoimmune disease caused by pancreatic β-cell destruction induced by autoantibodies and autoreactive T cells. After significant...     

A controlled study of MRI signal hyperintensities in older depressed patients with and without hypertension

OBJECTIVES: To compare the frequency/severity of signal hyperintensities--likely markers of cerebrovascular disease--in the subcortical gray and deep white matter on magnetic resonance imaging (MRI) scans of brains of hypertensive and normotensive older depressed and nondepressed comparison subjects. DESIGN: Between-groups comparison of cross-sectional MRI data employing analyses of covariance controlling for the effects of age, gender, and height. SETTING: A comprehensive inpatient-outpatient geriatric psychiatry service in a university hospital. PARTICIPANTS: Nondemented older depressed (n = 81) and nondepressed comparison (n = 70) subjects divided into four groups (hypertensive depressed (n = 40), hypertensive normals (n = 21), normotensive depressed (n = 41), normotensive normals (n = 49)). MEASUREMENTS: Signal hyperintensities were rated on T-2 weighted MRI scans blind to patient diagnoses employing two standardized hyperintensity rating systems (Fazekas, Boyko). RESULTS: Hypertensive depressives had significantly more- severe hyperintensity ratings in both subcortical gray and deep white matter than did normotensive depressives and controls (P < .05) and significantly more-severe hyperintensity ratings only in subcortical gray matter (P < .05) than did hypertensive controls. Hypertensive controls had significantly more-severe ratings in deep white matter than either normotensive group (P < .05). CONCLUSIONS: Findings suggest a relationship between deep white matter hyperintensities and hypertension (regardless of depressive state), and a particular role of subcortical gray matter hyperintensities (possibly interacting with more-severe deep white matter lesions) in older depressed hypertensives, as compared with older depressed normotensives of similar ages and severity of depression. These data support possible heterogeneous pathogenic contributions in late-life depression subgroups, one of which appears to be influenced by cerebrovascular disease.     

Diabetes mellitus,metabolic syndrome,and physical activity among Ethiopians: A systematic review

Background and aimsThe incidence of diabetes mellitus (DM) is increasing worldwide, and there is growing appreciation for the impact of limited physical activity on the disease. This study aimed to determine whether the current research on DM in Ethiopia has sufficiently identified and focused on the importance of limited physical activity according to the Global Physical Activity Questionnaire (GPAQ) in the disease etiology.MethodsThis was a systematic review, performed according to the PRISMA checklist. We searched primary studies of diabetes, diabetes-related complications, determinants, and magnitude of related morbidities in Ethiopia in PubMed, Medline, and ISI Web of Science databases. Reviews, editorial communications, reports, and letters were excluded.ResultsAmong 363 articles that were identified from all databases, 28 were included. It was found that 39% of the studies measured and included limited physical activity as a predisposing lifestyle factor in diabetes, while 17.86% either did not report or did not include this variable at all. Although 42.86% of the studies identified limited physical activity as an etiological factor in diabetes, it was not measured according to the GPAQ guidelines.ConclusionsThese data suggest that Ethiopian researchers do not give sufficient attention to the role of physical activity and its definition per GPAQ as a preventative factor for reducing the severity of diabetes symptoms. We suggest that physical activity research and promotion should be advocated in Ethiopia, and that researchers should seek advice on how to re-frame their work in the future.     

Application of Lipid Blend-Based Nanoparticulate Scaffold for Oral Delivery of Antihypertensive Drug: Implication on Process Variables and In Vivo Absorption Assessment

Purpose

The aim of the present study was to formulate and optimize lipid blend-based olmesartan medoxomil (OLM) loaded nanoparticulate scaffolds (NLCs) for enhanced oral bioavailability.

Method

The OLM-NLCs were formulated using dependent variables in different concentrations of solid lipid, liquid lipid, surfactant, and co-surfactant by using melt emulsification combined with ultrasonication technique. The formulations were experimentally optimized using a three-factor, three-level statistical design approach. The formulated OLM-NLCs were evaluated for various pharmaceutical quality evaluation parameters and further optimized formulation (OLM-NLCopt) was assessed for release kinetics, thermal behavior, and in vivo absorption assessment.

Result

The optimized formulation (OLM-NLCopt) showed particle size (138.7 nm), PDI (0.18), and entrapment efficiency (83.65%). The comparative in vitro release study revealed OLM-NLCopt showed significantly higher (p?<?0.05) drug release compare to OLM-susp. The in vivo study showed the OLM-NLCopt indicated nearly 3-fold improvement in oral bioavailability vis-a-vis OLM-susp in mice model.

Conclusion

The results of the release study and pharmacokinetic study suggest the potential of OLM-NLCs for improved oral delivery.

     

Interferon-beta in pediatric multiple sclerosis patients: safety in short-term prescription

None of the approved immunomodulatory drugs in adults Multiple Sclerosis (MS) patients have been officially approved for the pediatric patients and are currently used off-label in this population. In this study, we evaluated the effectiveness and tolerability of intramuscular interferon beta1-a (Avonex(?)) and subcutaneously injected interferon beta1-b (Betaferon(?)) in children with definite relapsing-remitting MS (RRMS). Thirteen patients aged younger than 16, who were recently diagnosed with definite RRMS according to the McDonald's criteria, were enrolled in this study. Six patients were treated with Avonex(?) 30 μg, intramuscularly every week, and seven patients were treated with Betaferon(?) 250 μg, subcutaneously every other day. All patients were treated with adult doses; initially interferon-beta was prescribed with half dose, and it was increased to full adult dose steadily. Eleven girls and two boys, mean (SD) age of 14.7 (1.9) years, were studied. Following nine months of using interferon-beta, nine patients (69.2%) had no relapses and the remaining four, experienced only one relapse. The mean EDSS score was decreased significantly after the study period. The present study provides reasonable data for the use of interferon-beta in Pediatric MS due to lack of short-term complications and safety. Studies with larger sample size and longer follow up duration are required to shed light on the long term impact of the interferon-beta therapy in children.     

Meier-Gorlin syndrome mutations disrupt an Orc1 CDK inhibitory domain and cause centrosome reduplication

Like DNA replication, centrosomes are licensed to duplicate once per cell division cycle to ensure genetic stability. In addition to regulating DNA replication, the Orc1 subunit of the human origin recognition complex controls centriole and centrosome copy number. Here we report that Orc1 harbors a PACT centrosome-targeting domain and a separate domain that differentially inhibits the protein kinase activities of Cyclin E-CDK2 and Cyclin A-CDK2. A cyclin-binding motif (Cy motif) is required for Orc1 to bind Cyclin A and inhibit Cyclin A-CDK2 kinase activity but has no effect on Cyclin E-CDK2 kinase activity. In contrast, Orc1 inhibition of Cyclin E-CDK2 kinase activity occurs by a different mechanism that is affected by Orc1 mutations identified in Meier-Gorlin syndrome patients. The cyclin/CDK2 kinase inhibitory domain of Orc1, when tethered to the PACT domain, localizes to centrosomes and blocks centrosome reduplication. Meier-Gorlin syndrome mutations that disrupt Cyclin E-CDK2 kinase inhibition also allow centrosome reduplication. Thus, Orc1 contains distinct domains that control centrosome copy number and DNA replication. We suggest that the Orc1 mutations present in some Meier-Gorlin syndrome patients contribute to the pronounced microcephaly and dwarfism observed in these individuals by altering centrosome duplication in addition to DNA replication defects.