Five-Year Denosumab Treatment of Postmenopausal Women with Osteoporosis: Results from the first two Years of the Freedom Trial Extension

Objectives : The FREEDOM trial1 open-label extension is designed to evaluate the long-term efficacy and safety of denosumab for up to 10 years. We report the results from the first 2 years of the extension, representing up to 5 years of denosumab exposure.Materials/Methods : Postmenopausal women enrolled in the extension previously completed FREEDOM. During the extension, all women receive denosumab (60 mg) every 6 months and calcium and vitamin D daily. For the FREEDOM denosumab group, the data reflect 5 years of denosumab treatment (long-term group). For the FREEDOM placebo group, the data reflect 2 years of denosumab treatment (de novo group). P-values are descriptive.Results : There were 4550 (70.2%) FREEDOM women enrolled in the extension (2343 long-term; 2207 de novo). During the 4th and 5th years of denosumab treatment, the long-term group had further 1.9% and 1.7% increases in lumbar spine BMD and further 0.7% and 0.6% increases in total hip BMD (all P<0.0001 compared with extension baseline). Total BMD increases with 5-year denosumab treatment were 13.7% (lumbar spine) and 7.0% (total hip). In the de novo group, BMD increased during the first 2 years of denosumab treatment by 7.9% (lumbar spine) and 4.1% (total hip) (all P<0.0001 compared with extension baseline). After denosumab administration, serum CTX was rapidly and maximally reduced in both groups with the characteristic attenuation observed at the end of the dosing interval, as previously reported.2 Incidences of new vertebral and nonvertebral fractures were low and below rates observed in the FREEDOM placebo group. Adverse event reports were similar for both groups: in the long-term group, 83.4% reported AEs and 18.9% were serious. In the de novo group, the percentages were 82.8% and 19.4%, respectively. In FREEDOM, the respective percentages were 92.8% and 25.8% in the denosumab group and 93.1% and 25.1% in the placebo group. Two subjects in the de novo group had AEs adjudicated to ONJ which healed without further complications ; one resolved within the 6-month dosing interval and denosumab was continued. There were no atypical femoral fractures.Conclusions : Denosumab treatment for 5 years was well-tolerated and continued to significantly reduce CTX and significantly increase BMD. Reference: 1)Cummings;NEJM;2009;361:756, 2)Eastell;JBMR;2010; doi-10.1002/jbmr.251 Disclosure of Interest: This study was funded by Amgen; S Papapoulos: Consulting fees from Amgen, Merck, Novartis, Procter & Gamble, GSK, and Wyeth; R Chapurlat: Research grants and/or consulting fees from Amgen, Merck, Novartis, sanofi-aventis, Roche, Servier, and Warner Chilcott;ML Brandi: Research grants and/or consulting fees from Amgen, Eli Lily, GSK, MSD, NPS, Nycomed, Roche, Servier, and Stroder; JP Brown: Research grants and/or consulting or speaking fees from Abott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Novartis, Merck, and Warner Chilcott; E Czerwinski: Research grants from Amgen, Astrazeneca, Danone Research, Eli Lilly, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche, SantoSolve AS, and Servier; N Daizadeh, A Grauer, C Libanati: Employed by Amgen and own Amgen stocks or stock options; M-A Krieg, D Mellstrom, H Resch: None; S Radominski: Research grants from Amgen, Pfizer, Novartis, Bristol-Myers Squibb, Roche, and Aventis; Z Man: Lecture fees and/or consulting fees from Merck, Novartis, Roche, and sanofi-aventis. Novartis steering committee member; JA Roman: Research grants from Roche; J-Y Reginster: Research grants, consulting fees, and/or lecture fees from Amgen, Analis, Bristol Myers Squibb, Ebewee Pharma, Genevrier, GSK, IBSA, Lilly, Merck Sharp & Dhome, Negma, Novartis, Novo-Nordisk, Nycomed, NPS, Roche, Rottapharm, Servier, Teijin, Teva, Theramex, UCB, Wyeth, and Zodiac; C Roux: Research grants and/or consulting fees from Amgen, MSD, Novartis, Servier, and Roche; SR Cummings: Research grants and/or consulting fees from Amgen, Eli Lilly, Novartis, and Merck; HG Bone: Research grants and/or consulting or speaking fees from Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda, and Zelos

FRAX® International Task Force of the 2010 Joint International Society for Clinical Densitometry & International Osteoporosis Foundation Position Development Conference.

Osteoporosis is a serious worldwide epidemic. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors and femoral neck BMD and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. The International Society for Clinical Densitometry (ISCD) in conjunction with the International Osteoporosis Foundation (IOF) assembled an international panel of experts that ultimately developed joint Official Positions of the ISCD and IOF advising clinicians regarding FRAX® usage. As part of the process, the charge of the FRAX® International Task Force was to review and synthesize data regarding geographic and race/ethnic variability in hip fractures, non-hip osteoporotic fractures, and make recommendations about the use of FRAX® in ethnic groups and countries without a FRAX® calculator. This synthesis was presented to the expert panel and constitutes the data on which the subsequent Official Positions are predicated. A summary of the International Task Force composition and charge is presented here.

Iowa Sex Offender Treatment and Supervision Task Force Report to the Iowa General Assembly, January 15, 2006

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.

Expectations of elderly people on the nurse-client relationship and interaction in home care : "When I see the nurse's smiling face it feels likes sunshine on a rainy and gloomy day"

The purpose of the thesis was to explore expectations of elderly people on the nurse-client relationship and interaction in home care. The aim is to improve the quality of care to better meet the needs of the clients. A qualitative approach was adopted. Semi-structured theme interviews were used for data collection. The interviews were conducted during spring 2006. Six elderly clients of a private home care company in Southern Finland acted as informants. Content analysis was used as the method of data analysis. The findings suggest that clients expect nurses to provide professional care with loving-kindness. Trust and mutual, active interaction were expected from the nurse-client relationship. Clients considered it important that the nurse recognizes each client's individual needs. The nurse was expected to perform duties efficiently, but in a calm and unrushed manner. A mechanic performance of tasks was considered negative. Humanity was viewed as a crucial element in the nurse-client relationship. Clients expressed their need to be seen as human beings. Seeing beyond the illness was considered important. A smiling nurse was described to be able to alleviate pain and anxiety. Clients hoped to have a close relationship with the nurse. The development of a close relationship was considered to be more likely if the nurse is familiar and genuine. Clients wish the nurses to have a more attending presence. Clients suggested that the work areas of the nurses could be limited so that they would have more time to transfer from one place to another. Clients felt that they would benefit from this as well. The nurses were expected to be more considerate. Clients wished for more information regarding changes that affect their care. They wished to be informed about changes in schedules and plans. Clients hoped for continuity from the nurse-client relationship. Considering the expectations of clients promotes client satisfaction. Home care providers have an opportunity to reflect their own care behaviour on the findings. To better meet the needs of the clients, nurses could apply the concept of loving-kindness in their work, and strive for a more attending presence.

Non-Quasi-Competitiveness and Stability in Cournot's Model

This paper retakes previous work of the authors, about the relationship between non-quasi-competitiveness (the increase in price caused by an increase in the number of oligopolists) and stability of the equilibrium in the classical Cournot oligopoly model. Though it has been widely accepted in the literature that the loss of quasi-competitiveness is linked, in the long run as new firms entered the market, to instability of the model, the authors in their previous work put forward a model in which a situation of monopoly changed to duopoly losing quasi-competitiveness but maintaining the stability of the equilibrium. That model could not, at the time, be extended to any number of oligopolists. The present paper exhibits such an extension. An oligopoly model is shown in which the loss of quasi-competitiveness resists the presence in the market of as many firms as one wishes and where the successive Cournot's equilibrium points are unique and asymptotically stable. In this way, for the first time, the conjecture that non-quasi- competitiveness and instability were equivalent in the long run, is proved false.

Motive-oriented therapeutic relationship in brief psychodynamic intervention for patients with depression and personality disorders.

Motive-Oriented Therapeutic Relationship (MOTR, also called Complementary Therapeutic Relationship) has already shown itself to be related to therapeutic outcome in several studies. The present study aims to test MOTR in a 4-session Brief Psychodynamic Intervention for patients presenting with major depressive disorder (MDD) and comorbid personality disorder (PD). In total, N = 20 patients were selected; n = 10 had MDD, n = 10 had MDD with comorbid PD. The first therapy session was videotaped and analyzed by means of Plan Analysis and the MOTR scale. Results suggest a differential effect on outcome: only the nonverbal component of MOTR is related to symptomatic change in patients presenting with MDD and comorbid PD; no such effect was found for patients with MDD alone. These results are discussed in line with the generalization and refinement of the conclusions of previous findings on the MOTR. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1-11, 2011.

On Globalization and the Growth of Governments

This paper investigates the relationship between trade openness and the size of government, both theoretically and empirically. We show that openness can increase the size of governments through two channels: (1) a terms of trade externality, whereby trade lowers the domestic cost of taxation and (2) the demand for insurance, whereby trade raises risk and public transfers. We provide a unified framework for studying and testing these two mechanisms. First, we show how their relative strength depends on a key parameter, the elasticity of substitution between domestic and foreign goods. Second, while the terms of trade externality leads to inefficiently large governments, the increase in public spending due to the demand for insurance is optimal. We show that large volumes of trade may result in welfare losses if the terms of trade externality is strong enough while small volumes of trade are always beneficial. Third, we provide new evidence on the positive association between openness and the size of government and test whether it is consistent with the terms of trade externality or the demand for insurance. Our findings suggest that the positive relationship is remarkably robust and that the terms of trade externality may be the driving force behind it, thus raising warnings that globalization may have led to inefficiently large governments.

The relationship between depressive symptoms and family functioning in institutionalized elderly

The present study aimed to investigate the relationship between family functioning and depressive symptoms among institutionalized elderly. This is a descriptive, cross-sectional study of quantitative character. A total of 107 institutionalized elderly were assessed using a sociodemographic questionnaire, the Geriatric Depression Scale (to track depressive symptoms) and the Family APGAR (to assess family functioning). The correlation coefficient of Pearson’s, the chi-square test and the crude and adjusted logistic regression were used in the data analysis with a significance level of 5 %. The institutionalized elderly with depressive symptoms were predominantly women and in the age group of 80 years and older. Regarding family functioning, most elderly had high family dysfunctioning (57 %). Family dysfunctioning was higher among the elderly with depressive symptoms. There was a significant correlation between family functioning and depressive symptoms. The conclusion is that institutionalized elderly with dysfunctional families are more likely to have depressive symptoms.

Relationship between time of day and periprocedural myocardial infarction after elective angioplasty.

Objectives: To test if the time of day significantly influences the occurrence of type 4A myocardial infarction in elective patients undergoing percutaneous coronary intervention (PCI). Background: Recent studies have suggested an influence of circadian rhythms on myocardial infarction size and mortality among patients with ST-elevation myocardial infarction. The aim of the study is to investigate whether periprocedural myocardial infarction (PMI) is influenced by the time of day in elective patients undergoing PCI. Methods: All consecutive patients undergoing elective PCI between 2007 and 2011 at our institutions with known post-interventional troponin were retrospectively included. Patients (n = 1021) were divided into two groups according to the starting time of the PCI: the morning group (n = 651) between 07:00 and 11:59, and the afternoon group (n = 370) between 12:00 and 18:59. Baseline and procedural characteristics as well as clinical outcome defined as the occurrence of PMI were compared between groups. In order to limit selection bias, all analyses were equally performed in 308 pairs using propensity score (PS) matching. Results: In the overall population, the rate of PMI was statistically lower in the morning group compared to the afternoon group (20% vs. 30%, p < 0.001). This difference remained statistically significant after PS-matching (21% vs. 29%, p = 0.03). Multivariate analysis shows that being treated in the afternoon independently increases the risk for PMI with an odds ratio of 2.0 (95%CI: 1.1-3.4; p = 0.02). Conclusions: This observational PS-matched study suggests that the timing of an elective PCI influences the rate of PMI.

Psychological distress in health sciences college students and its relationship with academic engagement

Objective: To determine the prevalence of psychological distress and its relationship with academic engagement (absorption, dedication and vigor), sex and degree among students from four public universities. Method: A non-experimental,comparative correlational, quantitative investigation without intervention. Study population: 1840 nursing and physical therapy students. The data collection tool used was a questionnaire. Results: A 32.2% prevalence of psychological distress was found in the subjects; a correlation between vigor and psychological distress was found for all of the subjects and also for women. High absorption and dedication scores and low psychological distress scores predicted higher vigor scores. Conclusion: The risk of psychological distress is high, especially for women. Women seem to have a higher level of psychological distress than men. Vigor, energy and mental resilience positively influence psychological distress and can be a vehicle for better results during the learning and studying process.







Iowa's Adult Literacy Program State Plan Extension, 2005

The major purposes of Iowa’s Adult Literacy Program State Plan Extension for Program Year 2005 are: • provide a comprehensive blue print for implementation of Title II of the Act; • serve as a basis for both immediate and long-range planning and continuous, systematic evaluation of program effectiveness; • provide basis for common understanding among Iowa’s literacy partners, other interested entities and the U.S. Department of Education. The plan extension is designed to update Iowa’s Adult Literacy State Plan for Program Year 2005 in line with the guidelines provided by the United States Department of Education: Division of Adult Education and Literacy (USDE:DAEL).

Iowa's Adult Literacy Program State Plan Extension, 2006

The passage of the Workforce Investment Act of 1998 (WIA) [Public Law 105-220] by the 105th Congress has ushered in a new era of collaboration, coordination, cooperation and accountability. The overall goal of the Act is “to increase the employment, retention, earnings of participants, and increase occupational skill attainment by participants, and, as a result improve the quality of the workforce, reduce welfare dependency, and enhance the productivity and competitiveness of the Nation.” The key principles inculcated in the Act are: • streamlining services; • empowering individuals; • universal access; • increased accountability; • new roles for local boards; • state and local flexibility; • improved youth programs. The purpose of Title II, The Adult Education and Family Literacy Act (AEFLA) of the Workforce Investment Act of 1998, is to create a partnership among the federal government, states, and localities to provide, on a voluntary basis, adult education and literacy services in order to: • assist adults to become literate and obtain the knowledge and skills necessary for employment and self-sufficiency; • assist adults who are parents obtain the educational skills necessary to become full partners in the educational development of their children; • assist adults in the completion of a secondary school education. The major purposes of Iowa’s Adult Literacy Program State Plan Extension for Program Year 2006 are: • provide a comprehensive blue print for implementation of Title II of the Act; • serve as a basis for both immediate and long-range planning and continuous, systematic evaluation of program effectiveness; • provide basis for common understanding among Iowa’s literacy partners, other interested entities and the U.S. Department of Education. The plan extension is designed to update Iowa’s Adult Literacy State Plan for Program Year 2006 in line with the guidelines provided by the United States Department of Education: Division of Adult Education and Literacy (USDE:DAEL).