scholarly journals Long-Term Effects of AposTherapy in Patients with Osteoarthritis of the Knee: A Two-Year Followup

Arthritis ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Yaron Bar-Ziv ◽  
Eytan M. Debbi ◽  
Yuval Ran ◽  
Shaike Benedict ◽  
Nahum Halperin ◽  
...  
Keyword(s):  
Active Group ◽  
Long Term Effects ◽  
Control Groups ◽  
Knee Oa ◽  
Sf 36 ◽  
Physical Scale ◽  
And Function ◽  
And Control ◽  
Knee Society Function Score

Several biomechanics treatments for knee osteoarthritis (OA) have emerged with the goal of reducing pain and improving function. Through this, researchers have hoped to achieve a transition from the pathological gait patterns to coordinated motor responses. The purpose of the study was to determine the long-term effects of a therapy using a biomechanical device in patients with knee OA. Patients with knee OA were enrolled to active and control groups. The biomechanical device used in therapy (AposTherapy) was individually calibrated to each patient in the active group. Patients in the control group received standard treatment. Outcomes were the Western Ontario and McMaster Osteoarthritis Index (WOMAC), Aggregated Locomotor Function (ALF), Short Form 36 (SF-36), and Knee Society Score assessments. The active and control groups were similar at the baseline (group difference in all scores ). The active group showed a larger improvement over time between groups in all three WOMAC categories (, 21.7, and 18.1 for pain, stiffness, and function; all ), SF-36 Physical Scale (; ), Knee Society Knee Score (; ), and Knee Society Function Score (; ). At the two-year endpoint, the active group showed significantly better results (all ). The groups showed a difference of 4.9, 5.6, and 4.7 for the WOMAC pain, stiffness, and function scores, respectively, 10.8 s in ALF score, 30.5 in SF-36 Physical Scale, 16.9 in SF-36 Mental Scale, 17.8 in Knee Society Knee Score, and 25.2 in Knee Society Function Score. The biomechanical therapy examined was shown to significantly reduce pain and improve function and quality of life of patients with knee OA over the long term.

136 Effects of the homology direct repair enhancer RS-1 on pig embryo culture

2020 ◽  
Vol 32 (2) ◽  
pp. 194
Author(s):  
C. Gomes Lucas ◽  
B. Bauer ◽  
P. Chen ◽  
L. Spate ◽  
K. Wells ◽  
...  
Keyword(s):  
Embryo Development ◽  
Embryo Culture ◽  
Statistical Significance ◽  
Mineral Oil ◽  
Cell Number ◽  
Long Term Effects ◽  
Control Groups ◽  
Short Term Exposure ◽  
And Control

Advances in genome editing technologies, such as the CRISPR/Cas9 system, have facilitated gene manipulation and the generation of pigs resistant to disease, models for studying human diseases and for xenotransplantation. However, double-strand breaks generated by the CRISPR/Cas9 system are preferentially repaired by the non-homologous end joining (NHEJ) pathway compared with high-fidelity homology-directed repair (HDR). All reports of pigs created by zygote injection of the CRISPR/Cas9 system result from NHEJ rather than HDR. The molecule known as RS-1 was found to stimulate RAD51 and thus enhance HDR. Thus, our goals are to understand this pathway by evaluating the response, as well as dosage and temporal effects, of RS-1 on porcine embryo development, and to determine a safe concentration to achieve high HDR rates without affecting embryo development. As RS-1 was added to culture medium from a 7.5mM stock solution in DMSO, we also evaluated whether RS-1 in solution could have affinity and migrate to the mineral oil overlay placed in the media during embryo culture. After IVF, embryos were cultured without RS-1 (control groups) or in the presence of RS-1 at 7.5 and 15 µM. At 7.5 µM, RS-1 improved HDR in rabbits created by zygote injection of the CRISPR/Cas9. Based on that, we designed five experimental groups to evaluate short- (A, 20h) and long-term (B, 144 h) effects of RS-1: two groups in the presence of RS-1 at 7.5 µM (7.5 µM A and 7.5 µM B), two control groups (control A and control B), and a group in the presence of RS-1 at 15 µM A for short-term exposure only. First, embryos in the groups containing (7.5 µM A, 7.5 µM B, and 15 µM A) and without RS-1 (control A and control B) were cultured for 20h without the mineral oil overlay. Then, embryos from control A, 7.5 µM A, and 15 µM A groups were washed and cultured without RS-1 until Day 6 in the presence of the mineral oil overlay. To evaluate long-term effects of RS-1, embryos from control B and 7.5 µM B groups were washed and transferred to medium without or with RS-1 at 7.5 µM, respectively, and cultured until Day 6 with no mineral oil overlay. We report the mean values for each set of data±s.e.m., and the degree of statistical significance in all analyses was defined at P<0.05. We observed that the presence of RS-1 at 15 µM decreased cleavage rates (control A 79.1±2.7%; 7.5 µM A 83.6±1.6%; 15 µM 70.9±4.4%; control B 80.8±1.4%; 7.5 µM B 80.0±2.8%), and long-term exposure to RS-1 decreased development to the blastocyst stage (control A 46.5±3.0%; 7.5 µM A 42.7±3.4%; 15 µM 41.8±4.7%; control B 44.9±3.3%; 7.5 µM B 28.8±4.9%). In addition, RS-1 exposure decreased the total cell number compared with the controls (control A 61.4±2.8; 7.5 µM A 49.2±3.0; 15 µM 48.5±2.3; control B 59.9±3.4; 7.5 µM B 41.5±2.5), however no differences in apoptosis rates were observed between the treatments. Our work will serve as a basis to understand the effects of RS-1 and RAD51 during embryonic development and to improve the applicability of customizable nucleases for the production of genetically modified pigs.

scholarly journals POS0278 A MULTICENTER, OBSERVATIONAL, EXTENSION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND EFFICACY OF A SINGLE LORECIVIVINT INJECTION IN KNEE OA SUBJECTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 363.1-364
Author(s):  
I. Simsek ◽  
C. Swearingen ◽  
H. Ghandehari ◽  
S. Kennedy ◽  
J. Tambiah ◽  
...  
Keyword(s):  
Extension Study ◽  
Control Group ◽  
Womac Pain ◽  
Phase 2 ◽  
Control Groups ◽  
Knee Oa ◽  
Link Type ◽  
And Function ◽  
Post Hoc ◽  
And Control

Background:Lorecivivint (LOR), a novel intra-articular (IA) CLK2/DYRK1A inhibitor that modulates the Wnt pathway, is in development as a knee osteoarthritis (OA) treatment.Objectives:Subjects from two consecutive Phase 2 trials were followed up in a 5-year, pooled, observational study that evaluated the safety and exploratory efficacy of a single LOR injection that was previously administered into the target knee joint of subjects with moderate to severe knee OA. The study was terminated in its third year, as relevant long-term safety information became limited in the absence of repeated LOR administration. The primary objective evaluated the incidence of serious adverse events (SAEs). Safety data for all doses and a post hoc efficacy analysis for the pivotal dose (0.07 mg LOR) are reported.Methods:This was a Phase 3, multicenter, observational, extension study of completer subjects (OA-05; NCT02951026) from two Phase 2 trials of LOR: a 12-month Phase 2a trial (OA-02; NCT02536833)1 and a 6-month Phase 2b trial (OA-04; NCT03122860)2. Subjects received a single LOR or control (placebo or vehicle) injection at their parent-study baseline visit (OA-02 or OA-04 Visit 0 in this analysis). Pooled data from clinic visits at 6, 12, 24, and 36 months contributed to the extension-study (OA-05) analysis. SAEs, knee-related adverse events (AEs), and AEs of newly diagnosed conditions requiring treatment were collected as safety outcomes. Efficacy was assessed by target knee WOMAC Pain and Function subscores and radiographic medial joint space width (mJSW). A post hoc analysis was performed for 0.07 mg LOR versus control to assess responses in a subject subgroup (unilateral symptoms, no widespread pain, 18-month post-injection radiograph at study termination). Baseline-adjusted ANCOVA was performed using data from both the current and parent studies at 0, 3, 6, 12, and 18 months.Results:Of 703 subjects, 119 (17%) subjects discontinued prior to study termination. Subjects had a mean age of 60.7 years and mean BMI of 29.1 kg/m2, and 61% were female. The majority of subjects had KL 3 (61.2%) OA. The safety analysis set included 495 LOR-treated subjects and 208 control subjects. There were 169 AEs reported by 110 [15.6%] subjects. Four AEs were considered to be related to study drug and were reported by 3 (0.6%) subjects across LOR groups; no subjects withdrew from the study due to a treatment-related AE. The most common AEs were osteoarthritis (28 [4.0%] subjects) and arthralgia (25 [3.6%] subjects); incidence was similar between LOR and control groups. During the study, 68 SAEs were reported by 38 (5.4%) subjects, and no SAEs were considered to be related to treatment by investigator. One death occurred in the control group. Post hoc efficacy analyses demonstrated that subjects in the 0.07 mg LOR group (n=59) showed greater improvements from baseline in both WOMAC Pain and Function at 6 and 12 months versus subjects in the control group (n=70) (Figure 1; Day 0):6 months:Pain: -8.16, 95% CI [-15.60, -0.71], P=0.032Function: -9.47, 95% CI [-17.09, -1.84], P=0.01512 months:Pain: -8.51, 95% CI [-15.17, -1.85], P=0.013Function: -9.62, 95% CI [-16.83, -2.42], P=0.009No mJSW progression was observed in any group over 18 months.Limitations to this analysis include 1) subjects from LOR and control groups were “completers,” therefore, more likely to be responders, and 2) subjects could have been on any medication or treatment in the extension study.Conclusion:From these data, LOR appeared to be safe and well tolerated. A post hoc-analyzed subset of completer subjects treated with a single 0.07 mg LOR injection reported durable symptom improvements in WOMAC Pain and Function for up to at least 12 months versus control subjects.References:[1]Yazici Y, et al. Arthritis Rheumatol. 2020.[2]Yazici Y, et al. ACR meeting. 2019. Abstract L03.Disclosure of Interests:Ismail Simsek Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Christopher Swearingen Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Heli Ghandehari Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Sarah Kennedy Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Jeyanesh Tambiah Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Yusuf Yazici Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Nebojsa Skrepnik Consultant of: Pfizer, Regeneron, Orthofix, Grant/research support from: Samumed, LLC

scholarly journals ¬Long-Term Effects of CIPS-based Training Module on Professional Elementary School Teachers

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Erni Munastiwi
Keyword(s):  
Elementary School ◽  
Elementary School Teachers ◽  
Long Term Effects ◽  
Training Module ◽  
Control Groups ◽  
School Teachers ◽  
Significant Difference ◽  
And Control ◽  
Experimental Group

CIPS-based Training Module has been developed to encourage teachers to improve their personal skills. Hence, the aim of this study is to investigate the long-term effects of the CIPS-based Training Module on the elementary school teachers. This study used the quasi-experimental design that involved 63 elementary school teachers. The teachers were divided into the experimental and control groups to test the objective of this study. The indicators of data analysis used in this study are mean score, standard deviation and independent sample t-test. The results show that there is a significant difference between the experimental and control groups. The experimental group obtained a higher mean score than the control group, which indicates that the CIPS-based Training Module has a positive long-term effect on the elementary school teachers from the experimental group. Hence, it is recommended the CIPS-based Training Module be implemented in the training of teachers, as their thinking and teaching skills will improve, which in turn will benefit the students in attaining high achievement.

A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma.

1991 ◽  
Vol 9 (5) ◽  
pp. 736-740 ◽  
Author(s):  
L E Spitler
Keyword(s):  
Malignant Melanoma ◽  
Adjuvant Therapy ◽  
Randomized Trial ◽  
Control Groups ◽  
Disease Free Interval ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
And Control

We conducted a long-term follow-up (median, 10.5 years) of patients included in a randomized trial of levamisole versus placebo as surgical adjuvant therapy in 203 patients with malignant melanoma. Of the patients randomized, 104 received levamisole, and 99 received placebo. The results show that there is no difference between the treatment and control groups with regard to any of the three end points analyzed. These included disease-free interval, time to appearance of visceral metastasis, and survival. Moreover, there was no significant difference between the treatment and control groups after adjusting for age, sex, or stage of disease.

Abstract P138: Long-term Effects Of Severe Caloric Restriction To The Heart Function

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Aline M De Souza ◽  
Jonathas Almeida ◽  
Nataliia Shults ◽  
Hong Ji ◽  
Kathryn Sandberg
Keyword(s):  
Cardiovascular Disease ◽  
Caloric Restriction ◽  
Heart Function ◽  
Left Ventricular ◽  
Structure And Function ◽  
Long Term Effects ◽  
Isolated Hearts ◽  
Ad Libitum ◽  
And Function

Severe caloric restriction (sCR) increases the risk for acute cardiovascular disease. Less understood are the long-term effects on cardiovascular disease risk after the sCR period has ended. We investigated the effects of sCR on heart structure and function months after refeeding (sCR-Refed). Female Fischer rats (3-months-old) were maintained on (CT) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received ad libitum chow for 3 months and they were analyzed by precision ultrasound to assess their heart function. After imaging, the animals were sacrificed and the hearts were subjected to ischemia-reperfusion (I/R) using a Langendorff preparation. After 2 weeks of sCR, rats lost 15% of their initial body weight (BW) [% (100*(Final-Initial/Initial)): CT, 1.5±0.8 vs sCR, -15.4±1.1; p<0.001;n=8]. After 3 months of refeeding, there was no detectable difference in BW between CT and sFR-Refed groups. Isolated hearts from the sCR-Refed rats exhibited worse myocardial pathology after I/R compared to CT rats. The parallel orientation of myofibers and striations normally present in cardiomyocytes was lost in sCR-Refed rats. Further analysis revealed uneven blood-filling of the microcirculatory vessels and prominent interstitial edema of the myocardium. Hearts from sCR-Refed rats had more atrophied cardiomyocytes than CT [Atrophied/Total (%): CT, 0.2±0.1 vs sCR-Refed, 50.6±1.1; p<0.001; n=5]. The number of arrhythmic events during a 30 min ischemic interval in isolated hearts doubled after 2 weeks on the sCR diet ( data not shown ) and remained doubled 3 months later [Arrhythmias (% of time): CT, 34±8 vs sCR-Refed, 68±9; p=0.02; n=8]. Ultrasound imaging showed no difference in stroke volume, coronary perfusion pressure and left ventricular mass. However, the thickness of the left ventricular posterior wall was significantly reduced in sCR-Refed rats [(mm): CT, 2.55 ±0.03 vs sCR-Refed, 2.10±0.04; p=0.002; n=4]. These findings indicate heart structure and function remained damaged months after the sCR period ended and BW was restored. These studies have adverse cardiovascular risk implications for who are subjected either voluntarily (crash diets) or involuntarily (very low food security) to periods of inadequate caloric intake.

Abstract 2211: Statin Therapy May Increase the Risk of Intracerebral Hemorrhage: A Meta-analysis of 26 Randomized Controlled Trials

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
James S McKinney ◽  
William J Kostis ◽  
John B Kostis
Keyword(s):  
Statin Therapy ◽  
Meta Analysis ◽  
Active Group ◽  
Controlled Trials ◽  
Control Groups ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Group A ◽  
The Difference ◽  
And Control

Introduction--- Statin therapy decreases the risk of myocardial infarction and ischemic stroke. However, an increased risk of intracerebral hemorrhage (ICH) has been observed in some studies. To investigate this issue we performed a meta-analysis of all randomized controlled trials (RCTs) using statins that reported ICH. Methods--- We performed a Medline literature search through March 18, 2011 and identified additional RCTs by reviewing reference lists of retrieved studies and prior meta-analyses. All RCTs of statin therapy versus placebo or high dose versus low dose statin therapy that reported ICH or hemorrhagic stroke were included. The primary outcome variable was ICH. 26 RCTs were included. All analyses used random effects models and heterogeneity was not observed in any of the analyses. Results--- 84 831 subjects were included in the Active group, and 84 851 in the Control group. A trend towards a higher incidence of ICH was observed in the Active treatment group compared to Control (OR = 1.15; 95% CI = 0.91 to 1.45, p =0.24) (Figure). Significant relationships were not observed between the log OR for ICH with achieved LDL in the Active group (slope = 0.0002; 95% CI = -0.0098 to 0.0101, p =0.96) or with the difference in LDL drop between the Active and Control groups (slope = 0.0030; 95% CI = -0.0089 to 0.0149, p =0.62). Total stroke (OR = 0.84; 95% CI = 0.78 to 0.91, p <0.001) and all-cause mortality (OR = 0.91; 95% CI = 0.86 to 0.96, p <0.001) were significantly reduced in the Active group. A significant relationship between all-cause mortality and the difference in LDL drop between the Active and Control groups was observed (slope = -0.0030; 95% CI = -0.0009 to -0.0051, p<0.005). There was not evidence of publication bias in this meta-analysis. Conclusions--- Active therapy was associated with a trend towards increased ICH in this meta-analysis of 26 RCTs of statin therapy. However, this risk does not appear to be related to the degree of decline or achieved LDL. The risk of ICH is offset by a significant reduction in ischemic stroke and all-cause mortality and should not dissuade practitioners from prescribing statins in otherwise appropriate patients.

Long-term effects of group exercise intervention on maximal step-up height in middle-aged female primary care patients with obesity and other cardio-metabolic risk factors

2020 ◽  
Author(s):  
Lillemor Amanda Nyberg ◽  
Carl Johan Sundberg ◽  
Per Wändell ◽  
Jan Kowalski ◽  
Mai-Lis Hellenius
Keyword(s):  
Physical Activity ◽  
Waist Circumference ◽  
Exercise Intervention ◽  
Metabolic Risk ◽  
Group Exercise ◽  
Long Term Effects ◽  
Sf 36 ◽  
Primary Care Patients

Abstract Background: Low physical performance is a predictor of morbidity and mortality. This study looks at long-term effects of an exercise intervention on maximal step-up height (MSH) in individuals with low physical function. Furthermore, we studied correlates to changes in MSH. Methods: Female patients (n=101), mean(SD) age of 52(11) years, were recruited for a 3-month group exercise intervention including 2-3 sessions/week of mixed aerobic fitness and strength training. MSH, weight, body mass index (BMI), waist circumference, maximal oxygen consumption (VO₂-max), self-reported health (SF-36) and physical activity (PA) were measured at baseline (T0), after 3 months (T1) and after 14-30(mean 22) months (T2). Relationships between changes in MSH (cm) and age, baseline MSH, time to follow-up, changes in anthropometric measurements, VO₂-max, SF-36 and PA were studied with regression analyses. Results: MSH, significantly, increased from T0 to T1, 27.2(5.7) to 29.0(5.5) cm and decreased to 25.2(5.5) cm at T2. Time to follow-up (B=-0.42, p<0.001) and change in BMI (B=-0.29, p=0.012) correlated significantly to changes in MSH. Waist circumference, VO₂-max, PF and exercise/physical activity levels were significantly improved at T2, while BMI did not change. In a univariate logistic regression model, maintenance of MSH correlated to the extent of mixed training (OR 3.33, 95% CI 1.25-8.89). In a multivariate logistic regression model adjusted for important factors the correlation was not significant. However, MSH was significantly higher in individuals participating in 2-3 session per week compared to one session. Conclusions: A 3-month group exercise intervention increased MSH, improved fitness, decreased risk in female patients with elevated cardio-metabolic risk. After an average of 22 months MSH was reduced while positive effects remained for waist circumference, VO₂-max, physical function and physical activity. However, regular group exercise 2-3 times per week with mixed aerobic fitness and strength training was associated with maintenance of MSH in a subgroup of patients. We suggest that such an intervention including regular support from healthcare professionals is a successful approach for maintaining improved leg-muscle strength among primary care patients.

scholarly journals EEG Based Classification of Long-Term Stress Using Psychological Labeling

Sensors ◽  
2020 ◽  
Vol 20 (7) ◽  
pp. 1886 ◽  
Author(s):  
Sanay Muhammad Umar Saeed ◽  
Syed Muhammad Anwar ◽  
Humaira Khalid ◽  
Muhammad Majid ◽  
Ulas Bagci
Keyword(s):  
Objective Measure ◽  
Machine Learning Algorithms ◽  
Support Vector ◽  
Eeg Signal ◽  
Expert Evaluation ◽  
Clinical Practices ◽  
Control Groups ◽  
Alpha Asymmetry ◽  
And Control

Stress research is a rapidly emerging area in the field of electroencephalography (EEG) signal processing. The use of EEG as an objective measure for cost effective and personalized stress management becomes important in situations like the nonavailability of mental health facilities. In this study, long-term stress was classified with machine learning algorithms using resting state EEG signal recordings. The labeling for the stress and control groups was performed using two currently accepted clinical practices: (i) the perceived stress scale score and (ii) expert evaluation. The frequency domain features were extracted from five-channel EEG recordings in addition to the frontal and temporal alpha and beta asymmetries. The alpha asymmetry was computed from four channels and used as a feature. Feature selection was also performed to identify statistically significant features for both stress and control groups (via t-test). We found that support vector machine was best suited to classify long-term human stress when used with alpha asymmetry as a feature. It was observed that the expert evaluation-based labeling method had improved the classification accuracy by up to 85.20%. Based on these results, it is concluded that alpha asymmetry may be used as a potential bio-marker for stress classification, when labels are assigned using expert evaluation.

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