Factors Associated with Persistence with Teriparatide Therapy: Results from the DANCE Observational Study

Purpose. Determine patient-reported reasons for discontinuation with teriparatide. Methods. Patients taking teriparatide in a multicenter, prospective, and observational study were given three questionnaires: baseline, follow-up questionnaire 1 (QF1, 2 to 6 months), and follow-up questionnaire 2 (QF2, 12 months). Discontinuation reported at QF1 and QF2 was defined as “early” and “late,” respectively, and remaining patients were considered persistent. Cochran-Armitage trend test was used to identify factors associated with discontinuation. Results. Side effects, concern about improper use, injection difficulties, and several patient-perceived physician issues were associated with early discontinuation. Low patient-perceived importance of continuing treatment, side effects, difficulty paying, and low patient-perceived physician knowledge were associated with late discontinuation. The most common specific reasons selected for discontinuing treatment were “concerns about treatment outweighing the benefits” (n = 53) and “difficulty paying” (n = 47). Conclusions. Persistence with teriparatide is dependent on managing side effects, addressing financial challenges, proper training, and obtaining support from the healthcare provider

Human Innate Mycobacterium tuberculosis–Reactive αβTCR+ Thymocytes

The control of Mycobacterium tuberculosis (Mtb) infection is heavily dependent on the adaptive Th1 cellular immune response. Paradoxically, optimal priming of the Th1 response requires activation of priming dendritic cells with Th1 cytokine IFN-γ. At present, the innate cellular mechanisms required for the generation of an optimal Th1 T cell response remain poorly characterized. We hypothesized that innate Mtb-reactive T cells provide an early source of IFN-γ to fully activate Mtb-exposed dendritic cells. Here, we report the identification of a novel population of Mtb-reactive CD4− αβTCR+ innate thymocytes. These cells are present at high frequencies, respond to Mtb-infected cells by producing IFN-γ directly ex vivo, and display characteristics of effector memory T cells. This novel innate population of Mtb-reactive T cells will drive further investigation into the role of these cells in the containment of Mtb following infectious exposure. Furthermore, this is the first demonstration of a human innate pathogen-specific αβTCR+ T cell and is likely to inspire further investigation into innate T cells recognizing other important human pathogens

Access to

properly cited. Purpose. Determine patient-reported reasons for discontinuation with teriparatide. Methods. Patients taking teriparatide in a multicenter, prospective, and observational study were given three questionnaires: baseline, follow-up questionnaire 1 (QF1, 2 to 6 months), and follow-up questionnaire 2 (QF2, 12 months). Discontinuation reported at QF1 and QF2 was defined as "early" and "late," respectively, and remaining patients were considered persistent. Cochran-Armitage trend test was used to identify factors associated with discontinuation. Results. Side effects, concern about improper use, injection difficulties, and several patient-perceived physician issues were associated with early discontinuation. Low patient-perceived importance of continuing treatment, side effects, difficulty paying, and low patient-perceived physician knowledge were associated with late discontinuation. The most common specific reasons selected for discontinuing treatment were "concerns about treatment outweighing the benefits" (n = 53) and "difficulty paying" (n = 47). Conclusions. Persistence with teriparatide is dependent on managing side effects, addressing financial challenges, proper training, and obtaining support from the healthcare provider

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

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Protein Signature of Lung Cancer Tissues

Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment

Association between two distinct executive tasks in schizophrenia: a functional transcranial Doppler sonography study

BACKGROUND: Schizophrenia is a severe mental disorder involving impairments in executive functioning, which are important cognitive processes that can be assessed by planning tasks such as the Stockings of Cambridge (SOC), and tasks of rule learning/abstraction such as the Wisconsin Card Sorting Test (WCST). We undertook this study to investigate the association between performance during separate phases of SOC and WCST, including mean cerebral blood flow velocity (MFV) measurements in chronic schizophrenia. METHODS: Functional transcranial Doppler sonography (fTCD) was used to assess bilateral MFV changes in the middle (MCA) and anterior (ACA) cerebral arteries. Twenty-two patients with chronic schizophrenia and 20 healthy subjects with similar sociodemographic characteristics performed SOC and WCST during fTCD measurements of the MCA and the ACA. The SOC was varied in terms of easy and difficult problems, and also in terms of separate phases, namely mental planning and movement execution. The WCST performance was assessed separately for maintaining set and set shifting. This allowed us to examine the impact of problem difficulty and the impact of separate phases of a planning task on distinct intervals of WCST. Simultaneous registration of MFV was carried out to investigate the linkage of brain perfusion during the tasks. RESULTS: In patients, slowing of movement execution during easy problems (SOC) was associated with slowing during maintaining set (WCST) (P < 0.01). In healthy subjects, faster planning and movement execution during predominantly difficult problems were associated with increased performance of WCST during set shifting (P < 0.01). In the MCA, patients showed a significant and positive correlation of MFV between movement execution and WCST (P < 0.01). CONCLUSION: The results of this study demonstrate performance and brain perfusion abnormalities in the association pattern of two different tasks of executive functioning in schizophrenia, and they support the notion that executive functions have a pathological functional correlate predominantly in the lateral hemispheres of the brain. This study also underpins the scientific potential of fTCD in assessing brain perfusion in patients with schizophrenia