Compliance and persistence with osteoporosis medications: A critical review of the literature

It is widely acknowledged that compliance and persistence with oral osteoporosis medications, particularly with bisphosphonates, is poor. Several excellent reviews have been written on compliance and persistence with osteoporosis medications and have discussed improvements seen with extended dosing intervals. This review begins with studies on extended dosing intervals to examine the limitations of administrative claims data. It also looks at compliance and persistence across multiple medical conditions, examining the importance of prescription fulfillment, intentional choice, causation and possible interventions

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates

Background Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. Methods The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. Results Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and three months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. Conclusions If a significant decrease is observed the treatment can continue but if no decrease occurs the clinician should reassess to identify problems with the treatment, mainly low adherence</p

Improvement in health-related quality of life in osteoporosis patients treated with teriparatide

<p>Abstract</p> <p>Background</p> <p>Individuals with osteoporosis and recent vertebral fractures suffer from pain and impaired health-related quality of life (HRQL). To determine whether patients with osteoporosis treated with teriparatide experienced improvement in HRQL and pain symptoms after several months of therapy.</p> <p>Methods</p> <p>We retrospectively studied a sample of osteoporosis patients treated with teriparatide in a Canadian rheumatology practice. We included patients that received teriparatide therapy with baseline and follow-up Mini-Osteoporosis Quality of Life Questionnaire (OQLQ) data. Follow-up data was measured at three or six months. We used a paired Student's t-test to compare baseline and follow-up measurements for each of the questionnaire's ten questions (five domains). Statistical analysis was also repeated to only include patients who suffered a prior vertebral fracture.</p> <p>Results</p> <p>57 patients were included in the study, including 47 women. The mean age was 63.8 years (standard deviation 12.1 years). About sixty five percent (37/57) had previously sustained one or more osteoporotic fractures and about 38.6% (22/57) had suffered a prior vertebral fracture. About 44% (25/57) of individuals were taking one or more types of pain medications regularly prior to starting therapy. At follow-up, significant improvements were observed in the OQLQ domains of pain symptoms. This was seen when all patients on teriparatide were included, and also when only patients with prior vertebral fractures were included. There was also an improvement in emotional functioning, relating to fear of falling at 3 months follow-up (p = 0.019). Respondents also reported improvement in the domain of activities of daily living, relating to vacuuming at 6 months follow-up (p = 0.036), and an improvement in the leisure domain, relating to ease of traveling in the prior vertebral fracture population at 3 months follow-up (p = 0.012). However, there was no significant improvement observed in the domains of physical functioning. Participants also reported a decrease in need for pain medications, with 26% (15/57) requiring analgesics at the time of follow-up.</p> <p>Conclusion</p> <p>Teriparatide use may be associated with improvements in HRQL in osteoporosis patients, in particular alleviation of pain symptoms. These results were especially evident in patients with a history of vertebral fractures. These findings should be confirmed in larger prospective studies with a suitable control group.</p

Vertebral body stenting: a new method for vertebral augmentation versus kyphoplasty

Vertebroplasty and kyphoplasty are well-established minimally invasive treatment options for compression fractures of osteoporotic vertebral bodies. Possible procedural disadvantages, however, include incomplete fracture reduction or a significant loss of reduction after balloon tamp deflation, prior to cement injection. A new procedure called “vertebral body stenting” (VBS) was tested in vitro and compared to kyphoplasty. VBS uses a specially designed catheter-mounted stent which can be implanted and expanded inside the vertebral body. As much as 24 fresh frozen human cadaveric vertebral bodies (T11-L5) were utilized. After creating typical compression fractures, the vertebral bodies were reduced by kyphoplasty (n = 12) or by VBS (n = 12) and then stabilized with PMMA bone cement. Each step of the procedure was performed under fluoroscopic control and analysed quantitatively. Finally, static and dynamic biomechanical tests were performed. A complete initial reduction of the fractured vertebral body height was achieved by both systems. There was a significant loss of reduction after balloon deflation in kyphoplasty compared to VBS, and a significant total height gain by VBS (mean ± SD in %, p < 0.05, demonstrated by: anterior height loss after deflation in relation to preoperative height [kyphoplasty: 11.7 ± 6.2; VBS: 3.7 ± 3.8], and total anterior height gain [kyphoplasty: 8.0 ± 9.4; VBS: 13.3 ± 7.6]). Biomechanical tests showed no significant stiffness and failure load differences between systems. VBS is an innovative technique which allows for the possibly complete reduction of vertebral compression fractures and helps maintain the restored height by means of a stent. The height loss after balloon deflation is significantly decreased by using VBS compared to kyphoplasty, thus offering a new promising option for vertebral augmentation

INvestigational Vertebroplasty Efficacy and Safety Trial (INVEST): a randomized controlled trial of percutaneous vertebroplasty

Background: The treatment of painful osteoporotic vertebral compression fractures has historically been limited to several weeks of bed rest, anti-inflammatory and analgesic medications, calcitonin injections, or external bracing. Percutaneous vertebroplasty (the injection of bone cement into the fractured vertebral body) is a relatively new procedure used to treat these fractures. There is increasing interest to examine the efficacy and safety of percutaneous vertebroplasty and to study the possibility of a placebo effect or whether the pain relief is from local anesthetics placed directly on the bone during the vertebroplasty procedure. Methods/Designs: Our goal is to test the hypothesis that patients with painful osteoporotic vertebral compression fractures who undergo vertebroplasty have less disability and pain at 1 month than patients who undergo a control intervention. The control intervention is placement of local anesthesia near the fracture, without placement of cement. One hundred sixty-six patients with painful osteoporotic vertebral compression fractures will be recruited over 5 years from US and foreign sites performing the vertebroplasty procedure. We will exclude patients with malignant tumor deposit (multiple myeloma), tumor mass or tumor extension into the epidural space at the level of the fracture. We will randomly assign participants to receive either vertebroplasty or the control intervention. Subjects will complete a battery of validated, standardized measures of pain, functional disability, and health related quality of life at baseline and at post-randomization time points (days 1, 2, 3, and 14, and months 1, 3, 6, and 12). Both subjects and research interviewers performing the follow-up assessments will be blinded to the randomization assignment. Subjects will have a clinic visit at months 1 and 12. Spine X-rays will be obtained at the end of the study (month 12) to determine subsequent fracture rates. Our co-primary outcomes are the modified Roland score and pain numerical rating scale at 1 month. Discussion: Although extensively utilized throughout North America for palliation of pain, vertebroplasty still has not undergone rigorous study. The study outlined above represents the first randomized, controlled study that can account for a placebo effect in the setting of vertebroplasty. Trial Registration: Current Controlled Trials ISRCTN81871888.The source of funding for the study and all authors for this publication was National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Oral bisphosphonate compliance and persistence: a matter of choice?

Compliance to oral bisphosphonates is suboptimal, with negative consequences of increased healthcare utilization and less effective fracture risk reduction. Extending dose interval increased adherence only moderately. We used literature derived from multiple chronic conditions to examine the problem of noncompliance with osteoporosis medication. We reviewed the literature on adherence to osteoporosis medication as well as that across multiple chronic conditions to understand what is known about the cause of the poor adherence. Poor compliance to oral medications is due mostly, not to forgetfulness, but to deliberate choice. Gender differences and style of healthcare management also play a role. Preliminary data suggest psychobehavioral interventions may help to improve motivation. We need to understand better reasons for poor compliance before effective interventions can be developed. Forgetfulness is only a small part of poor compliance. Patient preferences must be considered in medication decision making

IgTM: An algorithm to predict transmembrane domains and topology in proteins

<p>Abstract</p> <p>Background</p> <p>Due to their role of receptors or transporters, membrane proteins play a key role in many important biological functions. In our work we used Grammatical Inference (GI) to localize transmembrane segments. Our GI process is based specifically on the inference of Even Linear Languages.</p> <p>Results</p> <p>We obtained values close to 80% in both specificity and sensitivity. Six datasets have been used for the experiments, considering different encodings for the input sequences. An encoding that includes the topology changes in the sequence (from inside and outside the membrane to it and vice versa) allowed us to obtain the best results. This software is publicly available at: <url>http://www.dsic.upv.es/users/tlcc/bio/bio.html</url></p> <p>Conclusion</p> <p>We compared our results with other well-known methods, that obtain a slightly better precision. However, this work shows that it is possible to apply Grammatical Inference techniques in an effective way to bioinformatics problems.</p

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse