The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes

Metformin is, if not contraindicated and if tolerated, usually preferred over other antidiabetic drugs for the first line treatment of type-2 diabetes. The particular decision on which antidiabetic agent to use is based on variables such as efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia, risk, and patient preferences. However, there is no guidance how to consider these in the selection of antidiabetic drug treatment. In this work, we aimed to summarize available evidence and tried to give pragmatic treatment recommendations from a clinical practice perspective. There are clear contraindications for some drugs in those with impaired renal and liver function and precautions in those with heart failure for the use of metformin (NYHA III-IV) and glitazones. On the other hand, GLP-1 analogs, DPP-4 inhibitors and acarbose are generally less critical and can be used in the majority of patients. We identified the following gaps with respect to the selection of antidiabetic drug treatment in patients with co-morbid disease conditions: 1) Guidelines fail to give advice on the use of specific antidiabetic drugs in patients with co-morbidity. 2) The literature is deficient in studies documenting antidiabetic drug use in patients with severely impaired renal function, diabetic retinopathy, cerebrovascular disease and systolic heart failure. 3) Further there are no specific data on patients with multiple of these co-morbid disease conditions. We postulate that differential use of antidiabetic drugs in patients with co-morbid disease constellations will help to reduce treatment related complications and might improve prognosis

Self-adjustment mechanisms and their application for orthosis design

Medical orthoses aim at guiding anatomical joints along their natural trajectories while preventing pathological movements, especially in case of trauma or injuries. The motions that take place between bone surfaces have complex kinematics. These so-called arthrokinematic motions exhibit axes that move both in translation and rotation. Traditionally, orthoses are carefully adjusted and positioned such that their kinematics approximate the arthrokinematic movements as closely as possible in order to protect the joint. Adjustment procedures are typically long and tedious. We suggest in this paper another approach. We propose mechanisms having intrinsic self-aligning properties. They are designed such that their main axis self-adjusts with respect to the joint’s physiological axis during motion. When connected to a limb, their movement becomes homokinetic and they have the property of automatically minimizing internal stresses. The study is performed here in the planar case focusing on the most important component of the arthrokinematic motions of a knee joint

Fixation strength of biocomposite wedge interference screw in ACL reconstruction: effect of screw length and tunnel/screw ratio. A controlled laboratory study

<p>Abstract</p> <p>Background</p> <p>Primary stability of the graft is essential in anterior cruciate ligament surgery. An optimal method of fixation should be easy to insert and provide great resistance against pull-out forces.</p> <p>A controlled laboratory study was designed to test the primary stability of ACL tendinous grafts in the tibial tunnel. The correlation between resistance to traction forces and the cross-section and length of the screw was studied.</p> <p>Methods</p> <p>The tibial phase of ACL reconstruction was performed in forty porcine tibias using digital flexor tendons of the same animal. An 8 mm tunnel was drilled in each specimen and two looped tendons placed as graft. Specimens were divided in five groups according to the diameter and length of the screw used for fixation. Wedge interference screws were used. Longitudinal traction was applied to the graft with a Servohydraulic Fatigue System. Load and displacement were controlled and analyzed.</p> <p>Results</p> <p>The mean loads to failure for each group were 295,44 N (Group 1; 9 × 23 screw), 564,05 N (Group 2; 9 × 28), 614,95 N (Group 3; 9 × 35), 651,14 N (Group 4; 10 × 28) and 664,99 (Group 5; 10 × 35). No slippage of the graft was observed in groups 3, 4 and 5. There were significant differences in the load to failure among groups (ANOVA/P < 0.001).</p> <p>Conclusions</p> <p>Longer and wider interference screws provide better fixation in tibial ACL graft fixation. Short screws (23 mm) do not achieve optimal fixation and should be implanted only with special requirements.</p

Biomechanics and anterior cruciate ligament reconstruction

For years, bioengineers and orthopaedic surgeons have applied the principles of mechanics to gain valuable information about the complex function of the anterior cruciate ligament (ACL). The results of these investigations have provided scientific data for surgeons to improve methods of ACL reconstruction and postoperative rehabilitation. This review paper will present specific examples of how the field of biomechanics has impacted the evolution of ACL research. The anatomy and biomechanics of the ACL as well as the discovery of new tools in ACL-related biomechanical study are first introduced. Some important factors affecting the surgical outcome of ACL reconstruction, including graft selection, tunnel placement, initial graft tension, graft fixation, graft tunnel motion and healing, are then discussed. The scientific basis for the new surgical procedure, i.e., anatomic double bundle ACL reconstruction, designed to regain rotatory stability of the knee, is presented. To conclude, the future role of biomechanics in gaining valuable in-vivo data that can further advance the understanding of the ACL and ACL graft function in order to improve the patient outcome following ACL reconstruction is suggested

Numerical Simulation of Asymmetrically Altered Growth as Initiation Mechanism of Scoliosis

The causes of idiopathic scoliosis are still uncertain; buckling is mentioned often, but never proven. The authors hypothesize another option: unilateral postponement of growth of MM Rotatores or of ligamentum flavum and intertransverse ligament. In this paper, both buckling and the two new theories of scoliotic initiation are studied using a new finite element model that simulates the mechanical behavior of the human spine. This model was validated by the stiffness data of Panjabi et al. (J. Biomech. 9:185–192, 1976). After a small correction of the prestrain of some ligaments and the MM Rotatores the model appeared to be valid. The postponement in growth was translated in the numerical model in an asymmetrical stiffness. The spine was loaded axially and the resulting deformation was analyzed for the presence of the coupling of lateral deviation and axial rotation that is characteristic for scoliosis. Only unilateral postponement of growth of ligamentum flavum and intertransverse ligament appeared to initiate scoliosis. Buckling did not initiate scoliosis

Description of the attachment geometry of the anteromedial and posterolateral bundles of the ACL from arthroscopic perspective for anatomical tunnel placement

The anterior cruciate ligament (ACL) consists of an anteromedial bundle (AMB) and a posterolateral bundle (PLB). A reconstruction restoring the functional two-bundled nature should be able to approximate normal ACL function better than the most commonly used single-bundle reconstructions. Accurate tunnel positioning is important, but difficult. The purpose of this study was to provide a geometric description of the centre of the attachments relative to arthroscopically visible landmarks. The AMB and PLB attachment sites in 35 dissected cadaver knees were measured with a 3D system, as were anatomical landmarks of femur and tibia. At the femur, the mean ACL centre is positioned 7.9 ± 1.4 mm (mean ± 1 SD) shallow, along the notch roof, from the most lateral over-the-top position at the posterior edge of the intercondylar notch and from that point 4.0 ± 1.3 mm from the notch roof, low on the surface of the lateral condyle wall. The mean AMB centre is at 7.2 ± 1.8 and 1.4 ± 1.7 mm, and the mean PLB centre at 8.8 ± 1.6 and 6.7 ± 2.0 mm. At the tibia, the mean ACL centre is positioned 5.1 ± 1.7 mm lateral of the medial tibial spine and from that point 9.8 ± 2.1 mm anterior. The mean AMB centre is at 3.0 ± 1.6 and 9.4 ± 2.2 mm, and the mean PLB centre at 7.2 ± 1.8 and 10.1 ± 2.1 mm. The ACL attachment geometry is well defined relative to arthroscopically visible landmarks with respect to the AMB and PLB. With simple guidelines for the surgeon, the attachments centres can be found during arthroscopic single-bundle or double-bundle reconstructions

On species delimitation: Yet another lemur species or just genetic variation?

<p>Abstract</p> <p>Background</p> <p>Although most taxonomists agree that species are independently evolving metapopulation lineages that should be delimited with several kinds of data, the taxonomic practice in Malagasy primates (Lemuriformes) looks quite different. Several recently described lemur species are based solely on evidence of genetic distance and diagnostic characters of mitochondrial DNA sequences sampled from a few individuals per location. Here we explore the validity of this procedure for species delimitation in lemurs using published sequence data.</p> <p>Results</p> <p>We show that genetic distance estimates and <it>Population Aggregation Analysis </it>(PAA) are inappropriate for species delimitation in this group of primates. Intra- and interspecific genetic distances overlapped in 14 of 17 cases independent of the genetic marker used. A simulation of a fictive taxonomic study indicated that for the mitochondrial D-loop the minimum required number of individuals sampled per location is 10 in order to avoid false positives via PAA.</p> <p>Conclusions</p> <p>Genetic distances estimates and PAA alone should not be used for species delimitation in lemurs. Instead, several nuclear and sex-specific loci should be considered and combined with other data sets from morphology, ecology or behavior. Independent of the data source, sampling should be done in a way to ensure a quantitative comparison of intra- and interspecific variation of the taxa in question. The results of our study also indicate that several of the recently described lemur species should be reevaluated with additional data and that the number of good species among the currently known taxa is probably lower than currently assumed.</p

Resistive Exercise for Arthritic Cartilage Health (REACH): A randomized double-blind, sham-exercise controlled trial

<p>Abstract</p> <p>Background</p> <p>This article provides the rationale and methodology, of the first randomised controlled trial to our knowledge designed to assess the efficacy of progressive resistance training on cartilage morphology in women with knee osteoarthritis.</p> <p>Development and progression of osteoarthritis is multifactorial, with obesity, quadriceps weakness, joint malalignment, and abnormal mechanical joint forces particularly relevant to this study. Progressive resistance training has been reported to improve pain and disability in osteoarthritic cohorts. However, the disease-modifying potential of progressive resistance training for the articular cartilage degeneration characteristic of osteoarthritis is unknown. Our aim was to investigate the effect of high intensity progressive resistance training on articular cartilage degeneration in women with knee osteoarthritis.</p> <p>Methods</p> <p>Our cohort consisted of women over 40 years of age with primary knee osteoarthritis, according to the American College of Rheumatology clinical criteria. Primary outcome was blinded measurement of cartilage morphology via magnetic resonance imaging scan of the tibiofemoral joint. Secondary outcomes included walking endurance, balance, muscle strength, endurance, power, and velocity, body composition, pain, disability, depressive symptoms, and quality of life.</p> <p>Participants were randomized into a supervised progressive resistance training or sham-exercise group. The progressive resistance training group trained muscles around the hip and knee at 80% of their peak strength and progressed 3% per session, 3 days per week for 6 months. The sham-exercise group completed all exercises except hip adduction, but without added resistance or progression. Outcomes were repeated at 3 and 6 months, except for the magnetic resonance imaging scan, which was only repeated at 6 months.</p> <p>Discussion</p> <p>Our results will provide an evaluation of the disease-modifying potential of progressive resistance training for osteoarthritis.</p> <p>Trial Registration</p> <p>ANZCTR Reference No. 12605000116628</p