The Impact of Vitamin K2 (Menaquionones) in Children’s Health and Diseases: A Review of the Literature

Vitamin K2 activates vitamin K-dependent proteins that support many biological functions, such as bone mineralization, the inhibition of vascular stiffness, the improvement of endothelial function, the maintenance of strong teeth, brain development, joint health, and optimal body weight. Due to the transformation of food habits in developed countries over the last five decades, vitamin K and, specifically, vitamin K2 intakes among parents and their offspring have decreased significantly, resulting in serious health implications. The therapeutics used in pediatric practice (antibiotics and glucocorticoids) are also to blame for this situation. Low vitamin K status is much more frequent in newborns, due to both endogenous and exogenous insufficiencies. Just after birth vitamin K stores are low, and since human milk is relatively poor in this nutrient, breast-fed infants are at particular risk of a bleeding disorder called vitamin K deficiency bleeding. A pilot study showed that better vitamin K status is associated with lower rate of low-energy fracture incidence. An ongoing clinical trial is intended to address whether vitamin K2 and D3 supplementation might positively impact the biological process of bone healing. Vitamin K2 as menaquinone-7 (MK-7) has a documented history of safe and effective use. The lack of adverse effects of MK-7 makes it the ideal choice for supplementation by pregnant and nursing women and children, both healthy and suffering from various malabsorptions and health disorders, such as dyslipidemia, diabetes, thalassemia major (TM), cystic fibrosis (CF), inflammatory bowel diseases (IBD), and chronic liver diseases. Additionally, worthy of consideration is the use of vitamin K2 in obesity-related health outcomes.

The Perceptions and knowledge of Physiotherapist regarding exercise and joint health in India

BACKGROUND: A physiotherapist plays a key role in assessing, monitoring, educating and prescribing exercise for RA. A few previous surveys across the goble emphasized on the lack of evidence to guide physiotherapist recognizing the early signs of RA, in knowledge of disease course, and in evidence-based interventions and therefore the ability to manage an individual with RA over the course of the disease. The study aims to investigate physiotherapists’ current practice in specific disease-related Knowledge and clinical skills required managing people with RA and extent to which they promote physical activity and exercise. METHOD: A cross-sectional national e-survey was sent to physiotherapists regarding their confidence in managing RA patients. Questionnaire Data developed from previous literatures included the following details: years of clinical experience, current RA clinical caseload, and professional qualifications, primary clinical area of practice, relevant treatment options in established or newly diagnosed cases and management goals. RESULT: A total of 478 physiotherapist responses were received.84% agreed to the fact that exercises does play an important role in joint health promotion. Almost 70% strongly agreed to factor that FIIT principal has to be taken in consideration while prescribing exercises. Approximately 48% were familiar with Index that measures disease activity and ACR-preferred tools for functional status assessment in RA. Moreover, 98% were having a clear perspective of different guidelines of management in RA and Osteoarthritis (OA).While considering the choice of treatment physical activity and educational advice were more preferred as compared to the modalities or manual therapy. CONCLUSION: The present practices are in lines with the current guidelines for RA management, but still most of them never prescribed high-intensity exercise and lacked knowledge of when to advice appropriate splints/orthoses. Even the recommendations regarding splints were not clear. So, there's a requirement to develop education and training for constantly upgrading physiotherapists within for the promotion of physical activity in rheumatoid arthritis patients.

Influence of Menisci on Tibiofemoral Contact Mechanics in Human Knees: A Systematic Review

Purpose: Menisci transfer axial loads, while increasing the load-bearing tibiofemoral contact area and decreasing tibiofemoral contact pressure (CP). Numerous clinical and experimental studies agree that an increased CP is one predominant indicator for post-traumatic osteoarthritis (PTOA) of the knee joint. However, due to the immense variability in experimental test setups and wide range of treatment possibilities in meniscus surgery, it is difficult to objectively assess their impact on the CP determination, which is clearly crucial for knee joint health. Therefore, the aim of this systematic review is to investigate the influence of different meniscal injuries and their associated surgical treatments on the CP. Secondly, the influence of different test setups on CP measurements is assessed. On the basis of these results, we established the basis for recommendations for future investigations with the aim to determine CPs under different meniscal states.Methods: This review was conducted in accordance with the PRISMA guidelines. Studies were identified through a systematic literature search in Cochrane, PubMed and Web of Science databases. Literature was searched through pre-defined keywords and medical subject headings.Results: This review indicates a significant increase of up to 235% in peak CP when comparing healthy joints and intact menisci with impaired knee joints, injured or resected menisci. In addition, different test setups were indicated to have major influences on CP: The variety of test setups ranged from standard material testing machines, including customized setups via horizontal and vertical knee joint simulators, through to robotic systems. Differences in applied axial knee joint loads ranged from 0 N up to 2,700 N and resulted unsurprisingly in significantly different peak CPs of between 0.1 and 12.06 MPa.Conclusion: It was shown that untreated traumatic meniscal tears result in an increased CP. Surgical repair intervention were able to restore the CP comparable to the healthy, native condition. Test setup differences and particularly axial joint loading variability also led to major CP differences. In conclusion, when focusing on CP measurements in the knee joint, transparent and traceable in vitro testing conditions are essential to allow researchers to make a direct comparison between future biomechanical investigations.

Efficacy and tolerability of Native CT-II® on modulating knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled trial

Background Osteoarthritis (OA) of the knee is the most common type of arthritis, increasing with advancing age and external factors such as obesity. Joint health has historically relied on nutritional supplements derived from herbs and other natural products. Undenatured collagen type II demonstrated positive results with substantially lower therapeutic doses. Hence, the present study was designed to determine the efficacy and safety of Native CT-II®, an undenatured type II collagen, on the symptomatic effects in individuals having joint pain due to OA. Methods A randomized, double-blinded, placebo-controlled, parallel study was conducted on 101 slightly overweight volunteers, whose knee joint pain VAS score was ≥ 60 had been included in the study for at least three months. The participants were divided into three groups, with similar demographic and baseline characteristics. The test product containing Native CT-II®, positive control containing G+C, and the placebo were taken six tablets per day for 84 consecutive days (Three capsules to be taken post-breakfast and three capsules post-dinner). Improvement in overall joint health in each participant from baseline to end of the study was measured by WOMAC, self-administered questionnaire in Native CT-II® as compared to G+C and placebo group. Results This study demonstrated that Native CT-II® had an effective impact on the symptomatic effects of knee impairment associated with OA and in the quality of life of the participants. After 84 days, participants receiving Native CT-II® and G+C had significant improvement in overall joint health as compared to participants receiving placebo. Conclusion Native CT-II® was shown to be effective in relieving symptoms and improving quality of life for patients with knee joint pain associated with OA. Trial registration: The trial was registered with the clinical trial registry of the U.S. National Library of Medicine under National Institutes of Health (NIH) (https://clinicaltrials.gov/) with the National Clinical Trial (NCT) No: NCT04470336, Date of first registration: 14/07/2020.

Artificial intelligence-based automatic assessment of lower limb torsion on MRI

Abnormal torsion of the lower limbs may adversely affect joint health. This study developed and validated a deep learning-based method for automatic measurement of femoral and tibial torsion on MRI. Axial T2-weighted sequences acquired of the hips, knees, and ankles of 93 patients (mean age, 13 ± 5 years; 52 males) were included and allocated to training (n = 60), validation (n = 9), and test sets (n = 24). A U-net convolutional neural network was trained to segment both femur and tibia, identify osseous anatomic landmarks, define pertinent reference lines, and quantify femoral and tibial torsion. Manual measurements by two radiologists provided the reference standard. Inter-reader comparisons were performed using repeated-measures ANOVA, Pearson’s r, and the intraclass correlation coefficient (ICC). Mean Sørensen-Dice coefficients for segmentation accuracy ranged between 0.89 and 0.93 and erroneous segmentations were scarce. Ranges of torsion as measured by both readers and the algorithm on the same axial image were 15.8°–18.0° (femur) and 33.9°–35.2° (tibia). Correlation coefficients (ranges, .968 ≤ r ≤ .984 [femur]; .867 ≤ r ≤ .904 [tibia]) and ICCs (ranges, .963 ≤ ICC ≤ .974 [femur]; .867 ≤ ICC ≤ .894 [tibia]) indicated excellent inter-reader agreement. Algorithm-based analysis was faster than manual analysis (7 vs 207 vs 230 s, p < .001). In conclusion, fully automatic measurement of torsional alignment is accurate, reliable, and sufficiently fast for clinical workflows.

The depoliticization of health and safety committees and representation: The Ontario case

Studies in several national jurisdictions have highlighted the limitations of joint health and safety committees and worker representatives in affecting change in working conditions. Using Canadian data, this article focuses on the argument that many health and safety committees and worker representatives have been captured or substantially controlled through the State’s promotion of an internal responsibility system framed around a technocratic partnership. The historical development of this framing is first understood within a political economic framework which highlights several major influences, followed by a field theory analysis which explains how these control relations are established by management within workplace settings.

The Implications of Being “In it Together”: Relationship Satisfaction and Joint Health Behaviors Predict Better Health and Stronger Concordance Between Partners

Background Extensive evidence shows that satisfying marriages boost physical health and longevity. A separate literature reveals strong concordance in couples’ health, but the relationship processes that contribute to health concordance remain poorly understood. Purpose The current study examined whether relationship satisfaction and joint health behaviors—the extent to which couples eat, sleep, and exercise together—are associated simultaneously with better health and greater health similarity between partners. Methods Heterogeneous variance multilevel models were applied to data from 234 married couples (Mage = 46, Range = 20–84) reporting on their relationship satisfaction, joint health behaviors, and four health indicators—health satisfaction, depressive symptoms, comorbidities, and medication use. Results More satisfied couples engaged in more joint health behaviors than less satisfied counterparts. When joint health behaviors and relationship satisfaction were examined as separate fixed effects, both predicted greater health satisfaction and fewer depressive symptoms. More joint health behaviors were also associated with less medication use. When both were modeled together, only relationship satisfaction predicted depressive symptoms. By contrast, in random effects, joint health behaviors predicted greater similarity in health satisfaction, depressive symptoms, and comorbidities. Relationship satisfaction only predicted more similar depressive symptoms. Conclusions Although more satisfied couples engaged in more joint health behaviors. relationship satisfaction and joint health behaviors uniquely predicted couples’ health quality and concordance, suggesting that distinct mechanisms may drive better health and stronger health resemblance.

Real-World Experience with Emicizumab Prophylaxis in the Milan Cohort: A Single-Center Experience

INTRODUCTION: Emicizumab is a humanised bispecific monoclonal antibody, which replaces the function of factor VIII (FVIII) by bridging activated factor IX and factor X. Emicizumab is approved for prophylaxis of patients with Hemophilia A (HA), both with and without inhibitors. Real-world data on the efficacy and safety of emicizumab were recently reported from a few hemophilia treatment centers, but more data are needed to assess the efficacy and safety of emicizumab in comparison to standard prophylactic treatment. OBJECTIVE: To evaluate the safety and efficacy of emicizumab prophylaxis in a single cohort of patients with HA, with and without inhibitors. METHODS: We performed an observational prospective study including patients affected with HA, with and without inhibitors, switched to emicizumab prophylaxis in the post-marketing era. Data regarding inhibitor status, Annualized Bleeding Rate (ABR), cause of bleeding, type and location of bleeds, Emicizumab Plasmatic Concentration [Emi] and activated partial thromboplastin time (aPTT) were collected for each patient. Hemophilia Joint Health Scores (HJHS) and General Health Visual Analogue Scale (GH-VAS) were collected by trained physiotherapists before switching to emicizumab and 12 months after treatment start. RESULTS: A total of 22 patients, 21 with severe and 1 with moderate HA, were enrolled. Twenty patients were without inhibitor against FVIII and 2 adults with inhibitor were previously treated with bypassing agents. All patients started emicizumab prophylaxis with a loading dose of 3 mg/kg once weekly for 4 weeks, followed by a maintenance dosage of 1.5 mg/kg weekly. Within the children cohort, 3 were Previously Untreated Patients (PUPs) and 2 were previously treated with FVIII without developing inhibitor. The ABR showed a reduction of 74% in the entire cohort, as reported in Table 1. When stratifying for age groups, the ABR reduction was 70% for adults and 100% for children. Within the adults, the zero-bleeding patients increased from 2 to 11 patients (from 12 to 64%, respectively). In the adult cohort, 6 patients experienced 11 bleeding events over a mean follow-up of 300 days. Five out of 11 events were experienced in 6 months by a single patient who developed anti-drug antibodies (ADA) against emicizumab around the 5 th week ([Emi] 31.7 ug/ml). The prophylaxis with emicizumab was interrupted due to the treatment failure, which occurred despite spontaneous ADA clearance. Another patient developed ADA around the 9 th week ([Emi] 28.3 ug/ml), but without associated bleedings in up to 14 weeks of follow-up (minimum [Emi] 17 ug/ml). Of the remaining 5 adults who experienced bleedings during emicizumab prophylaxis, one patient developed spontaneous soft tissue bleeding, another one developed a spontaneous hemarthrosis in his target joint and the remaining 3 patients experienced post-traumatic joint bleedings, 2 out of 3 bleedings were in target joints. The analysis of the number of total joint bleedings before and after switching stratified for spontaneous and post-traumatic, revealed a reduction in target joint bleedings of 73% and a reduction of spontaneous and post-traumatic bleeding of 80% and 43%, respectively. All events were managed in outpatient clinic and required only a single infusion of FVIII concentrate. The plasmatic concentrations of emicizumab at steady state were within previous reported normal range for all patients, with exception of the two patients who developed ADA. Interestingly, steady state concentration was higher in children than in adults (median [Emi] 64.9 ug/ml and 49.85, respectively). The HJHS and GH-VAS scores at baseline and after 12 months of emicizumab prophylaxis available in 6 adults showed improvement in joint health and self-perceived global health, as shown in Figures 2 and 3. No thrombotic events were reported in the entire cohort. DISCUSSION: We report our Milan single center experience on the use of emicizumab prophylaxis in children and adults with HA, with and without inhibitors. Our experience shows a good efficacy of emicizumab both in children and adults, with few post-traumatic bleedings occurring mainly in target joints of adult patients. In addition, physician's and self-assessed scores revealed an improvement of patient's joint health after 12 months of emicizumab prophylaxis. Figure 1 Figure 1. Disclosures Peyvandi: Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sobi: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria.