Characteristics of patients initiating teriparatide for the treatment of osteoporosis

Summary The demographic and clinical characteristics of patients initiating teriparatide were compared with those of patients initiating bisphosphonates for the treatment of osteoporosis. In these samples of commercially insured, Medicare, and Medicaid patients, patients initiating teriparatide were older, in poorer health, and appeared to have more severe osteoporosis than patients initiating bisphosphonates. Introduction The demographic and clinical characteristics of patients initiating teriparatide are compared with those of patients initiating bisphosphonates. Methods Beneficiaries (45 years and older) with at least one claim for teriparatide or a bisphosphonate from 2003 to 2005 and continuous enrollment in the previous 12 months and subsequent 6 months were identified from commercial, Medicare, and Medicaid administrative claims databases. Patients initiating teriparatide (commercial/Medicare (N = 2,218); Medicaid (N = 824)) were compared to patients initiating bisphosphonates (commercial/Medicare (N = 97,570); Medicaid (N = 77,526)) in terms of age, provider specialty, comorbidities, prior use of osteoporosis medications, fractures, BMD screening, health status, and resource utilization. Results Teriparatide patients were older and in poorer health than bisphosphonate patients. Approximately 38% of teriparatide patients in both groups had fractured in the pre-period compared to 16% of commercial/Medicare and 15% of Medicaid bisphosphonate patients. Teriparatide patients were more likely to have used osteoporosis medications in the pre-period (79.9% versus 32.1% (commercial/Medicare); 82.2% versus 19.6% (Medicaid)). Conclusions In these samples of patients, those initiating teriparatide differed from those initiating bisphosphonates. Teriparatide patients were older, in poorer health, and appeared to have more severe osteoporosis than bisphosphonate patients. Comparisons of treatment outcomes should take these differences in patient characteristics into consideration.     

Electrocardiograms of an unusual type in right bundle-branch block

There are certain cases of intraventricular block in which the ventricular complexes of the electrocardiograms show the following characteristics: In Lead I all the ventricular deflections are small. There is a conspicuous S deflection, and T is usually flat or upright. In Leads II and III the ventricular deflections are similar in all respects to those seen in bundle-branch block of the common variety.Precordial leads have been employed in three cases in which the standard electrocardiograms were of this kind. In these leads the ventricular complexes are like those that are recorded in dogs with right branch block and in patients with diphasic ventricular complexes of the rare type. It is thought that the curves referred to represent right branch block. Some additional factor that modifies the form of the electrocardiogram may be present.     

Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins: vector design strategies for improved vaccine efficacy

A live virus vaccine vector has been constructed from a molecularly cloned attenuated strain of Venezuelan equine encephalitis virus (VEE). High levels of foreign protein expression are regulated by an additional copy of the 26 S viral subgenomic RNA promoter. The position of this additional promoter and foreign gene in the VEE genome was predicted to have a major influence on expression level of the heterologous protein. Two sites in the genome were tested to determine the optimal site for expression of the matrix/capsid (MA/CA) coding region of human immunodeficiency virus (HIV-1). One vector contained the additional promoter and the MA/CA genes immediately downstream of the VEE E1 gene at the 3' end of the genome. In the second vector, the additional promoter was introduced immediately upstream from the authentic 26 S subgenomic promoter. Significantly higher levels of MA/CA were expressed from the downstream vector compared to the upstream vector. However, the stability of expression for both vectors was similar following passage in baby hamster kidney cells (BHK) cells. In BALB/c mice, the two vectors elicited similar levels of cellular immune responses to MA/CA as determined by bulk cytotoxic T-lymphocyte assays and precursor frequency analysis, but the humoral response induced by the downstream vector was significantly stronger. At 11 months post boosting with the downstream vector, serum antibody levels against HIV MA/CA were undiminished, and MA/CA specific CTLp were detectable in all mice tested. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins.     

Templated Open Flocs of Anisotropic Particles for Pulmonary Delivery with Pressurized Metered Dose Inhalers

The challenges in forming stable drug suspensions in hydrofluoroalkane (HFA) propellants have limited drug dosages and efficiency of drug delivery with pressurized metered dose inhalers (pMDI). Herein, stable suspensions of weakly flocculated particles, in the shape of thin plates or needles, of a poorly water-soluble drug, itraconazole (Itz), are efficiently delivered by pMDI at high doses, up to 2.4 mg/actuation. These anisotropic particles pack inefficiently and form low-density flocs that stack upon each other to prevent settling. In contrast, spherical particles formed dense aggregates that settled within minutes. Upon actuation of the pMDI, atomized propellant droplets shear apart and thus template the highly friable flocs. Evaporation of the HFA compacts the flocs to yield porous particles with optimal aerodynamic properties. High fine particle fractions (49–64%) were achieved with the stable suspensions for drug loadings up to 50mg/mL. Furthermore, the micron-sized particles, ideal for pulmonary delivery, are composed of nanoparticles that dissociate and facilitate rapid dissolution of poorly water-soluble drugs. Pulmonary delivery of stable suspensions of templated, open flocs is broadly applicable to a range of anisotropic particle morphologies for poorly water-soluble drugs and proteins for efficient delivery of high doses, up to several milligrams, using minimal amounts of excipients.     

HIV risk and the overlap of injecting drug use and high-risk sexual behaviours among men who have sex with men in Zanzibar (Unguja), Tanzania

BackgroundMen who have sex with men and inject drugs (MSM-IDU) are particularly vulnerable to HIV infection and have the potential to transmit HIV across multiple populations through their male and female sexual partners and injection drug-using partners.MethodsRespondent-driven sampling was used to recruit men who reported engaging in anal sex with another man in the past 3 months, aged ≥15 years, and living in Unguja, Zanzibar. Participants responded to a face-to-face interview about their HIV and injecting risk behaviours and were tested for HIV, Hepatitis B (HBV) and C (HCV) and syphilis.ResultsAmong the 509 MSM who enrolled in the survey, 14% (n = 66) reported injecting drugs in the past 3 months among which 66% used heroin, 60% used a needle after someone else had and 68% passed a needle to someone else after using it. MSM-IDU were significantly more likely to have two or more non-paying male receptive sex partners and to have engaged in group sex in the past month, to have symptoms of a sexually transmitted infection in past 6 months, to have been arrested or beaten in the past 12 months and to be infected with HIV and co-infected with HIV and HCV compared to MSM who did not inject drugs. MSM-IDU were less likely to have used a condom at last sex with a non-paid female partner, to know where to get a confidential HIV test and to have ever been tested for HIV compared to MSM who did not inject drugs.ConclusionMSM-IDU, and MSM in general, in Unguja practice multiple high-risk behaviours that put them at risk for blood-borne and sexual transmission of HIV and HCV infection. Targeted interventions for MSM-IDU must account for the overlap of high-risk sexual and drug-using networks and integrate injection drug use and HIV services.     

Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism.

We investigated long-term potentiation (LTP) at mossy fiber synapses on CA3 pyramidal neurons in the hippocampus. Using Ca2+ imaging techniques, we show here that when postsynaptic Ca2+ was sufficiently buffered so that [Ca2+]i did not rise during synaptic stimulation, the induction of mossy fiber LTP was prevented. In addition, induction of mossy fiber LTP was suppressed by postsynaptic injection of a peptide inhibitor of cAMP-dependent protein kinase. Finally, when ionotropic glutamate receptors were blocked, LTP depended on the postsynaptic release of Ca2+ from internal stores triggered by activation of metabotropic glutamate receptors. These results support the conclusion that mossy fiber LTP and LTP at other hippocampal synapses share a common induction mechanism involving an initial rise in postsynaptic [Ca2+].