Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials.

PURPOSE: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy. PATIENTS AND METHODS: All patients were included in the Intergroupe Francophone du Myelome 99-02 and 99-04 trials and treated with vincristine, doxorubicin, and dexamethasone (VAD) induction therapy followed by double autologous stem-cell transplantation (ASCT). Best post-ASCT response assessment was available for 802 patients. RESULTS: With a median follow-up of 67 months, median event-free survival (EFS) and 5-year EFS were 42 months and 34%, respectively, for 405 patients who achieved at least VGPR after ASCT versus 32 months and 26% in 288 patients who achieved only partial remission (P = .005). Five-year overall survival (OS) was significantly superior in patients achieving at least VGPR (74% v 61% P = .0017). In multivariate analysis, achievement of less than VGPR was an independent factor predicting shorter EFS and OS. Response to VAD had no impact on EFS and OS. The impact of VGPR achievement on EFS and OS was significant in patients with International Staging System stages 2 to 3 and for patients with poor-risk cytogenetics t(4;14) or del(17p). CONCLUSION: In the context of ASCT, achievement of at least VGPR is a simple prognostic factor that has importance in intermediate and high-risk MM and can be informative in more patients than CR.

Long-term data from the swiss pulmonary hypertension registry.

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

The Relevance of Long-Term Adherence to Non Pharmacological and Pharmacological Treatment of Hypertension

Current hypertension guidelines point to the necessity of achieving sustained and strict blood pressure control in every hypertensive patient. To reach this goal the patient should comply both with hygienic measures and pharmacologic treatment. This remains a difficult task, particularly since hypertension is generally asymptomatic and since any therapeutic intervention might adversely alter the patient's quality of life. Long-term persistence with antihypertensive therapy is facilated when the treatment is initiated with well tolerated antihypertensive agents, especially blockers of the renin-angiotensin system. Having a normal blood pressure during treatment is also an important determinant of persistence. This explains the growing interest for fixed-dose combinations, which have the main advantage to be at the same time efficient and well tolerated. These simple to use preparations have even gained acceptance as first-line drug regimen.

Iowa Department on Aging Office of the State Long-Term Care Ombudsman Annual Report 2009, (Federal Fiscal Year October 1, 2008 through September 30, 2009), January 2010.

The State Long-Term Care Ombudsman program operates as a unit within the Iowa Department on Aging. Duties of all long-term care ombudsmen are mandated by the Older Americans Act. This office serves people living in nursing facilities, skilled nursing facilities, residential care facilities, nursing facilities in hospitals, elder group homes and assisted living programs. In order to carry out all of the mandates of the Older Americans Act this office recommends to increase the number of staff and create a volunteer ombudsman program. NOTE: The second file includes a correction to the report on page 8.

Immunohistochemical and flow cytometric analysis of long-term label-retaining cells in the adult heart.

Cardiac-resident stem/progenitor cells have been identified based on expression of stem cell-associated antigens. However, no single surface marker allows to identify a definite cardiac stem/progenitor cell entity. Hence, functional stem cell markers have been extensively searched for. In homeostatic systems, stem cells divide infrequently and therefore retain DNA labels such as 5-bromo-2'-deoxyuridine, which are diluted with division. We used this method to analyze long-term label-retaining cells in the mouse heart after 14 days of 5-bromo-2'-deoxyuridine administration. Labeled cells were detected using immunohistochemical and flow-cytometric methods after varying chasing periods up to 12 months. Using mathematical models, the observed label dilution could consistently be described in the context of a 2-population model, whereby a population of rapidly dividing cells accounted for an accelerated early decline, and a population of slowly dividing cells accounted for decelerated dilution on longer time scales. Label-retaining cells were preferentially localized in the atria and apical region and stained negative for markers of the major cell lineages present in the heart. Most cells with long-term label-retention expressed stem cell antigen-1 (Sca-1). Sca-1(+)CD31(-) cells formed cell aggregates in culture, out of which lineage-negative (Lin(-))Sca-1(+)CD31(-) cells emerged, which could be cultured for many passages. These cells formed cardiospheres and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. In conclusion, recognition of slow-cycling cells provides functional evidence of stem/progenitor cells in the heart. Lin(-)Sca-1(+)CD31(-) cardiac-derived progenitors have a potential for differentiation into cardiomyogenic and mesenchymal cell lineages.

Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice

Background: Prionopathies are characterized by spongiform brain degeneration, myoclonia, dementia, and periodic electroencephalographic (EEG) disturbances. The hallmark of prioniopathies is the presence of an abnormal conformational isoform (PrP(sc)) of the natural cellular prion protein (PrP(c)) encoded by the Prnp gene. Although several roles have been attributed to PrP(c), its putative functions in neuronal excitability are unknown. Although early studies of the behavior of Prnp knockout mice described minor changes, later studies report altered behavior. To date, most functional PrP(c) studies on synaptic plasticity have been performed in vitro. To our knowledge, only one electrophysiological study has been performed in vivo in anesthetized mice, by Curtis and coworkers. They reported no significant differences in paired-pulse facilitation or LTP in the CA1 region after Schaffer collateral/commissural pathway stimulation. Principal Findings: Here we explore the role of PrP(c) expression in neurotransmission and neural excitability using wild-type, Prnp -/- and PrP(c)-overexpressing mice (Tg20 strain). By correlating histopathology with electrophysiology in living behaving mice, we demonstrate that both Prnp -/- mice but, more relevantly Tg20 mice show increased susceptibility to KA, leading to significant cell death in the hippocampus. This finding correlates with enhanced synaptic facilitation in paired-pulse experiments and hippocampal LTP in living behaving mutant mice. Gene expression profiling using Illumina microarrays and Ingenuity pathways analysis showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission were co-regulated in Prnp -/- and Tg20 mice. Lastly, RT-qPCR of neurotransmission-related genes indicated that subunits of GABA(A) and AMPA-kainate receptors are co-regulated in both Prnp -/- and Tg20 mice. Conclusions/Significance: Present results demonstrate that PrP(c) is necessary for the proper homeostatic functioning of hippocampal circuits, because of its relationships with GABA(A) and AMPA-Kainate neurotransmission. New PrP(c) functions have recently been described, which point to PrP(c) as a target for putative therapies in Alzheimer's disease. However, our results indicate that a "gain of function" strategy in Alzheimer's disease, or a "loss of function" in prionopathies, may impair PrP(c) function, with devastating effects. In conclusion, we believe that present data should be taken into account in the development of future therapies.

Radioimmunotherapy confers long-term survival to lymphoma patients with acceptable toxicity: registry analysis by the international radioimmunotherapy network.

The Radioimmunotherapy Network (RIT-N) is a Web-based, international registry collecting long-term observational data about radioimmunotherapy-treated patients with malignant lymphoma outside randomized clinical studies. The RIT-N collects unbiased data on treatment indications, disease stages, patients' conditions, lymphoma subtypes, and hematologic side effects of radioimmunotherapy treatment. Methods: RIT-N is located at the University of Gottingen, Germany, and collected data from 14 countries. Data were entered by investigators into a Web-based central database managed by an independent clinical research organization. Results: Patients (1,075) were enrolled from December 2006 until November 2009, and 467 patients with an observation time of at least 12 mo were included in the following analysis. Diagnoses were as follows: 58% follicular lymphoma and 42% other B-cell lymphomas. The mean overall survival was 28 mo for follicular lymphoma and 26 mo for other lymphoma subtypes. Hematotoxicity was mild for hemoglobin (World Health Organization grade II), with a median nadir of 10 g/dL, but severe (World Health Organization grade III) for platelets and leukocytes, with a median nadir of 7,000/mu L and 2.2/mu L, respectively. Conclusion: Clinical usage of radioimmunotherapy differs from the labeled indications and can be assessed by this registry, enabling analyses of outcome and toxicity data beyond clinical trials. This analysis proves that radioimmunotherapy in follicular lymphoma and other lymphoma subtypes is a safe and efficient treatment option.

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer. The SWIss Venous ThromboEmbolism Registry (SWIVTER) II.

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

Willigness to pay for long-term care coverage: the role of private information and self-insurance

Both public and private insurance for long-term care is undeveloped in some European countries such as in Spain and empirical evidence is still limited. This paper aims at exmining the determinants of the demand for Long Term Care (LTC) coverage in Spain using contingent valuation techniques. Our findings indicate that only one-fifth of the population is willing to pay to assure coverage decisions are significantly affected by private information asymmetry and housing tenure in giving rise to self-insurance reduces the probability of insurance being hypothetically purchased.

Iowa Department on Aging, Office of the State Long-Term Care Ombudsman, Annual Report 2012 (Federal Fiscal Year October 1, 2010 through September 30, 2011), January 2012.

The State Long-Term Care Ombudsman program (SLTCOP)operates as a unit within the Iowa Department on Aging. Duties of all long-term care ombudsmen are mandated by the Older Americans Act. This office serves people living in nursing, skilled nursing, residential care, and nursing facilities in hospitals as well as elder group homes and assisted living facilities. In order to carry out all of the mandates of the Older Americans Act this office recommends to establish a fully functioning volunteer ombudsman program that meets the criteria set forth in the Federal Older Americans Act as well as to strengthen family & resident councils, and to increase collaboration between the SLTCOP and Iowa’s Aging Network.

External beam radiotherapy ± chemotherapy in the treatment of anal canal cancer: a single-institute long-term experience on 100 patients.

One-hundred patients treated with curative radiotherapy (RT) ± chemotherapy (CT) for an anal canal carcinoma (T1-4N0-3M0) were retrospectively analyzed. Five- and 10-year local control (LC) rates were 73% and 67%, respectively. Acute and late G3-G4 toxicity rates were 32% and 12%, respectively. Two patients underwent a colostomy for a G4 anal toxicity. This study confirms the outcomes of RT ± CT in the treatment of anal canal cancer. Concomitant CT and LC statistically influenced Overall Survival and Colostomy-Free Survival. CT also statistically reduced the risk of nodal relapse. High rates of acute skin toxicity impose tailored volumes and techniques of irradiation.

State of Iowa Long-Term Economic Recovery Strategy Prepared for the Economic Development Administration, U.S. Department of Commerce, October 2010

The Rebuild Iowa Office (RIO) continues to coordinate the state‘s recovery effort from the storms, tornadoes and floods of 2008. Much has been accomplished since the Office‘s last quarterly report was issued in July 2010. State funding has been disbursed to help Iowans with unmet needs and housing. Local governments and entities are utilizing millions of federal dollars so thousands of disaster-impacted homeowners can be offered a buyout. More infrastructure projects are under construction and new neighborhoods are being built with mitigation efforts in mind. However, as Iowa continues to celebrate many successes along the road to recovery, it must also address the numerous challenges that are encountered along the path. Recovering from the state‘s largest disaster must be looked at as a marathon, not a sprint. Over the past three months, the RIO has especially remained focused on helping small business owners impacted by the 2008 disasters. Many disaster-affected businesses have reopened their doors, however their debt load continues to be overwhelming and many still struggle with the timeliness of the disbursement of funds. This report describes how programs and recent modifications are working to assist recovering businesses. This report contains updates on housing progress while outlining the complexities behind certain programs and the bottlenecks communities are facing due to strict federal guidelines for implementation. This following pages also describe how Iowa is implementing Smart Planning principles, publicizing flood awareness through outreach efforts and preparing a blueprint for the state to follow when future disasters occur. As always, the RIO recognizes and thanks the countless leaders and front-line workers from local, regional, state and federal government, businesses, non-profit organizations and private citizens that have provided input, support and leadership. Their dedication to Iowa‘s disaster recovery has made the plans and projects on the following pages possible.

What factors influence long-term antidepressant use in primary care? Findings from the Australian diamond cohort study.

BACKGROUND: Antidepressants are one of the most commonly prescribed drugs in primary care. The rise in use is mostly due to an increasing number of long-term users of antidepressants (LTU AD). Little is known about the factors driving increased long-term use. We examined the socio-demographic, clinical factors and health service use characteristics associated with LTU AD to extend our understanding of the factors that may be driving the increase in antidepressant use. METHODS: Cross-sectional analysis of 789 participants with probable depression (CES-D≥16) recruited from 30 randomly selected Australian general practices to take part in a ten-year cohort study about depression were surveyed about their antidepressant use. RESULTS: 165 (21.0%) participants reported <2 years of antidepressant use and 145 (18.4%) reported ≥2 years of antidepressant use. After adjusting for depression severity, LTU AD was associated with: single (OR 1.56, 95%CI 1.05-2.32) or recurrent episode of depression (3.44, 2.06-5.74); using SSRIs (3.85, 2.03-7.33), sedatives (2.04, 1.29-3.22), or antipsychotics (4.51, 1.67-12.17); functional limitations due to long-term illness (2.81, 1.55-5.08), poor/fair self-rated health (1.57, 1.14-2.15), inability to work (2.49, 1.37-4.53), benefits as main source of income (2.15, 1.33-3.49), GP visits longer than 20min (1.79, 1.17-2.73); rating GP visits as moderately to extremely helpful (2.71, 1.79-4.11), and more self-help practices (1.16, 1.09-1.23). LIMITATIONS: All measures were self-report. Sample may not be representative of culturally different or adolescent populations. Cross-sectional design raises possibility of "confounding by indication". CONCLUSIONS: Long-term antidepressant use is relatively common in primary care. It occurs within the context of complex mental, physical and social morbidities. Whilst most long-term use is associated with a history of recurrent depression there remains a significant opportunity for treatment re-evaluation and timely discontinuation.

Follow-up care amongst long-term childhood cancer survivors: a report from the Swiss Childhood Cancer Survivor Study.

In the Swiss Childhood Cancer Survivor Study, we aimed to assess the proportion of long-term survivors attending follow-up care, to characterise attendees and to describe the health professionals involved. We sent a questionnaire to 1252 patients, of whom 985 (79%) responded, aged in average 27 years (range 20-49). Overall, 183 (19%) reported regular, 405 (41%) irregular and 394 (40%) no follow-up. For 344, severity of late effects had been classified in a previous medical examination. Only 17% and 32% of survivors with moderate and severe late effects respectively had made regular visits a decade later. Female gender, after a shorter time since diagnosis, had radiotherapy, and having suffered a relapse predicted follow-up. In the past year, 8% had seen a general practitioner only, 10% a paediatric or adult oncologist and 16% other health specialists for a cancer related problem. These findings underline the necessity to implement tailored national follow-up programmes.