The four or more medicines (FOMM) support service:results from an evaluation of a new community pharmacy service aimed at over-65s

Background: 57% of all prescriptions dispensed in the UK in 2003 were for people aged ≥60, where ≥20% of them were prescribed ≥ five medicines. Inappropriate prescribing and non-adherence have a significant impact on hospital admissions and patient quality of life. The English government has identified that community pharmacy could make a significant contribution to reducing non-adherence and improving the quality of prescribing, reducing both hospital admissions and medicines wastage. Objective: To evaluate a community pharmacy service aimed at patients over the age of 65 years prescribed four or more medicines. Method: Patients were invited to participate in the service by the community pharmacy team. The pharmacist held regular consultations with the patient and discussed risk of falls, pain management, adherence and general health. They also reviewed the patient’s medication using STOPP/START criteria. Data wereas analysed for the first six months of participation in the service. Key findings: 620 patients were recruited with 441 (71.1%) completing the six month study period. Pharmacists made 142 recommendations to prescribers in 110 patients largely centred on potentially inappropriate prescribing of NSAIDs, PPIs or duplication of therapy. At follow-up there was a significant decrease in the total number of falls (mean -0.116 (-0.217 - -0.014)) experienced and a significant increase in medicines adherence (mean difference in MMAS-8: 0.513 (0.337 – 0.689)) and quality of life. Cost per QALY estimates ranged from £11,885 to £32,466 depending on the assumptions made. Conclusion: By focussing on patients over the age of 65 years with four or more medicines, community pharmacists can improve medicines adherence and patient quality of life

Type I interferon receptor deficiency in dendritic cells facilitates systemic murine norovirus persistence despite enhanced adaptive immunity

In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs) play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV) replicates in dendritic cells (DCs) and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance

Profile instabilities of the millisecond pulsar PSR J1022+1001

We present evidence that the integrated profiles of some millisecond pulsars exhibit severe changes that are inconsistent with the moding phenomenon as known from slowly rotating pulsars. We study these profile instabilities in particular for PSR J1022+1001 and show that they occur smoothly, exhibiting longer time constants than those associated with moding. In addition, the profile changes of this pulsar seem to be associated with a relatively narrow-band variation of the pulse shape. Only parts of the integrated profile participate in this process which suggests that the origin of this phenomenon is intrinsic to the pulsar magnetosphere and unrelated to the interstellar medium. A polarization study rules out profile changes due to geometrical effects produced by any sort of precession. However, changes are observed in the circularly polarized radiation component. In total we identify four recycled pulsars which also exhibit instabilities in the total power or polarization profiles due to an unknown phenomenon (PSRs J1022+1001, J1730-2304, B1821-24, J2145-0750). The consequences for high precision pulsar timing are discussed in view of the standard assumption that the integrated profiles of millisecond pulsars are stable. As a result we present a new method to determine pulse times-of-arrival that involves an adjustment of relative component amplitudes of the template profile. Applying this method to PSR J1022+1001, we obtain an improved timing solution with a proper motion measurement of -17 \pm 2 mas/yr in ecliptic longitude. Assuming a distance to the pulsar as inferred from the dispersion measure this corresponds to an one-dimensional space velocity of 50 km/s.Comment: 29 pages, 12 figures, accepted for publication in Ap

The Millisecond Pulsars in NGC 6760

We present the results of recent Arecibo and Green Bank observations of the globular cluster NGC 6760. Using Arecibo, a phase-coherent timing solution has been obtained for the previously known binary pulsar in this cluster, PSR J1911+0102A. We have also discovered a new millisecond pulsar in NGC 6760, PSR J1911+0101B, an isolated object with a rotational period of 5.38 ms and a dispersion measure DM = 196.7 cm-3 pc. Both pulsars are located within 1.3 core radii of the cluster center and have negative period derivatives. The resulting lower limits for the accelerations of the pulsars are within the range expected given a simple model of the cluster. A search for eclipses in the PSR J1911+0102A binary system using both telescopes yielded negative results. The corresponding limits on the extra gas column density at superior conjunction are consistent with the hypothesis that the observational properties of ultra-low-mass binary pulsars like PSR J1911+0102A are strongly affected by the inclination of the orbital plane of the system. Among globular cluster pulsar populations, that of NGC 6760 exhibits one of the largest known spreads in DM. This quantity seems to be roughly proportional to a cluster's central DM; this suggests that the observed spread is caused by a turbulent interstellar medium at spatial scales of 1 pc.Comment: 10 pages in referee format, 4 figures, one table, re-submitted to the Astrophysical Journa

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

The provision of non-needle/syringe drug injecting paraphernalia in the primary prevention of HCV among IDU: a systematic review

BACKGROUND: Sharing drug injecting paraphernalia other than needles and syringes (N/S) has been implicated in the transmission of Hepatitis C virus (HCV) among injecting drug users (IDU). We aimed to determine whether the provision of sterile non-N/S injecting paraphernalia reduces injecting risk behaviours or HCV transmission among IDU. METHODS: A systematic search of seven databases and the grey literature for articles published January 1989-February 2010 was undertaken. Thirteen studies (twelve observational and one non-randomized uncontrolled pilot intervention) were identified and appraised for study design and quality by two investigators. RESULTS: No studies examined the association between the provision of non-N/S injecting paraphernalia and incident HCV infection. One cross-sectional study found that individuals who frequently, compared to those who infrequently, used sterile cookers and water, were less likely to report prevalent HCV infection. Another found no association between the uptake of sterile non-N/S injecting paraphernalia and self-reported sharing of this paraphernalia. The remaining observational studies used attendance at needle and syringe exchange programmes (NSP) or safer injection facilities (SIF) that provided non-N/S injecting paraphernalia as a proxy measure. Eight studies presented adjusted odds ratios, ranging from 0.3 to 0.9, suggesting a reduced likelihood of self-reported sharing of non-N/S injecting paraphernalia associated with use of NSP or SIF. There was substantial uncertainty associated with these estimates however. Three unadjusted studies reported a reduction in the prevalence of sharing of non-N/S injecting paraphernalia over time among NSP users. Only one study reported an adjusted temporal trend in the prevalence of sharing non-N/S injecting paraphernalia, finding higher rates among non-NSP users than NSP users at each time point, and a greater reduction in sharing among non-NSP than NSP users over time. Study limitations included the use of convenience samples, self-reported exposure and outcome measures, flawed classification of the exposed and unexposed groups, and inadequate adjustment for potential confounding variables. CONCLUSIONS: The evidence to demonstrate that the provision of sterile non-N/S injecting paraphernalia reduces HCV transmission or modifies injecting risk behaviours is currently limited by an insufficient volume and quality of studies. Further research is required to inform practice and policy in this area

Acceptability of a Positive Parenting Programme on a Mother and Baby Unit: Q-Methodology with Staff

The Baby Triple P Positive Parenting Programme, a new addition to the established Triple P programmes, is currently being considered for a trial in a Mother and Baby Unit with the aim of exploring its benefits to mothers presenting with severe mental illness. The aim of the current study was to investigate staff views of the acceptability and feasibility of a parenting programme such as the Baby Triple P Positive Parenting Programme in a Mother and Baby Unit. Q-methodology, using an 88-item Q-sort, was employed to explore the opinions of 16 staff working in a Mother and Baby Unit in the North West of England. Results obtained from the Q-sort analysis identified two distinct factors: (1) staff qualified acceptance and (2) systemic approach/systemic results. Preliminary findings indicate that staff perceived Baby Triple P to be an acceptable and feasible intervention for the Mother and Baby Unit setting and that mothers on the unit would be open and receptive to the programme. Further research is required to expand these findings and assess the potential for this type of intervention to be used more widely across a number of Mother and Baby Unit settings