Effectiveness and safety of glimepiride and iDPP4, associated with metformin in second line pharmacotherapy of type 2 diabetes mellitus: systematic review and meta-analysis

Objective: Our review analyses the studies that have specifically compared the association iDPP4/metformin with glimepiride/metformin, both in second line pharmacotherapy of type 2 diabetes mellitus (DM2). Methods: Systematic literature review with a meta-analysis of clinical trials comparing glimepiride with any iDPP4, both used together with metformin as a second line treatment of DM2. The effectiveness variables used were as follows: %HbA1c variation, fasting plasma glucose variation, patients achieving the therapeutic objective of HbA1c <7%, treatment dropouts due to lack of effectiveness and rescue treatments needed. The safety variables included were as follows: weight variation at the end of treatment; presentation of any type of adverse event; presentation of serious adverse events; patients who experienced any type of hypoglycaemia; patients who experienced severe hypoglycaemia; treatments suspended due to adverse effects; and deaths for any reason. Results: Four studies met the inclusion criteria. The group treated with glimepiride showed better results in all effectiveness variables. Regarding safety variables, the main differences observed were in the greater number of cases with hypoglycaemia in the group treated with glimepiride, and the serious adverse events or treatment discontinuations due to these which occurred in slightly over 2% more cases in this group compared to the iDPP4 group. The remaining adverse events, including mortality, did not show any differences between both groups. The variation in the weight difference between groups (2.1 kg) is not considered clinically relevant. Conclusions: A greater effectiveness is seen in the glimepiride/metformin association, which should not be diminished by slight differences in adverse effects, with absence of severe hypoglycaemia in over 98% of patients under treatment. The association of glimepiride/metformin, both due to cost as well as effectiveness and safety, may be the preferential treatment for most DM2 patients, and it offers a potential advantage in refractory hyperglycemic populations, tolerant to treatment.S

Psycho-oncological support for breast cancer patients: A brief overview of breast cancer services certification schemes and national health policies in Europe.

Psycho-oncology addresses the psychological, social, behavioural, and ethical aspects of cancer. Identification and proper management of the patients' psychosocial needs, as well as the needs of their caregivers and family are essential for a person-centred concept of breast cancer care. The aim of this overview is to describe how psychosocial support in breast cancer is incorporated in cancer-related policy documents, such as national cancer plans and breast cancer care certification schemes.post-print163 K

Prospects for Pulsar Studies at MeV Energies

Enabled by the Fermi Large Area Telescope, we now know that pulsars fill the gamma-ray sky, and we are beginning to understand their emission mechanism and their distribution throughout the Galaxy. To address key questions calls for a sensitive, wide-field MeV telescope, which can detect the population of MeV-peaked pulsars hinted at by Fermi

Monitoring and evaluation of breast cancer screening programmes : Selecting candidate performance indicators

In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality

Fermi-LAT Search for Pulsar Wind Nebulae around gamma-ray Pulsars

The high sensitivity of the Fermi-LAT (Large Area Telescope) offers the first opportunity to study faint and extended GeV sources such as pulsar wind nebulae (PWNe). After one year of observation the LAT detected and identified three pulsar wind nebulae: the Crab Nebula, Vela-X and the PWN inside MSH 15-52. In the meantime, the list of LAT detected pulsars increased steadily. These pulsars are characterized by high energy loss rates from ~3 \times 10^{33} erg s$^{-1}$ to 5 \times 10$^{38}$ erg s$^{-1}$ and are therefore likely to power a PWN. This paper summarizes the search for PWNe in the off-pulse windows of 54 LAT-detected pulsars using 16 months of survey observations. Ten sources show significant emission, seven of these likely being of magnetospheric origin. The detection of significant emission in the off-pulse interval offers new constraints on the gamma-ray emitting regions in pulsar magnetospheres. The three other sources with significant emission are the Crab Nebula, Vela-X and a new pulsar wind nebula candidate associated with the LAT pulsar PSR J1023-5746, coincident with the TeV source HESS J1023-575. We further explore the association between the H.E.S.S. and the Fermi source by modeling its spectral energy distribution. Flux upper limits derived for the 44 remaining sources are used to provide new constraints on famous PWNe that have been detected at keV and/or TeV energies.Comment: Accepted for publication in Astrophysical Journal, 42 pages, 17 figure

Search for gamma-ray emission from magnetars with the Fermi Large Area Telescope

We report on the search for 0.1-10 GeV emission from magnetars in 17 months of Fermi Large Area Telescope (LAT) observations. No significant evidence for gamma-ray emission from any of the currently-known magnetars is found. The most stringent upper limits to date on their persistent emission in the Fermi-LAT energy range are estimated between ~10^{-12}-10^{-10} erg/s/cm2, depending on the source. We also searched for gamma-ray pulsations and possible outbursts, also with no significant detection. The upper limits derived support the presence of a cut-off at an energy below a few MeV in the persistent emission of magnetars. They also show the likely need for a revision of current models of outer gap emission from strongly magnetized pulsars, which, in some realizations, predict detectable GeV emission from magnetars at flux levels exceeding the upper limits identified here using the Fermi-LAT observations.Comment: ApJ Letters in press; Corresponding authors: Caliandro G. A., Hadasch D., Rea N., Burnett

Fermi LAT Observations of the Supernova Remnant W28 (G6.4-0.1)

We present detailed analysis of the two gamma-ray sources,1FGL J1801.3-2322c and 1FGL J1800.5-2359c,that have been found toward the supernova remnant(SNR) W28 with the Large Area Telescope(LAT) on board the Fermi Gamma-ray Space Telescope.1FGL J1801.3-2322c is found to be an extended source within the boundary of SNR W28,and to extensively overlap with the TeV gamma-ray source HESS J1801-233,which is associated with a dense molecular cloud interacting with the supernova remnant.The gamma-ray spectrum measured with LAT from 0.2--100 GeV can be described by a broken power-law function with a break of ~1GeV,and photon indices of 2.09$\pm$0.08(stat)$\pm$0.28(sys) below the break and 2.74$\pm$0.06(stat)$\pm$0.09(sys) above the break.Given the clear association between HESS J1801-233 and the shocked molecular cloud and a smoothly connected spectrum in the GeV--TeV band,we consider the origin of the gamma-ray emission in both GeV and TeV ranges to be the interaction between particles accelerated in the SNR and the molecular cloud.The decay of neutral pions produced in interactions between accelerated hadrons and dense molecular gas provide a reasonable explanation for the broadband gamma-ray spectrum. 1FGL J1800.5-2359c, located outside the southern boundary of SNR W28, cannot be resolved.An upper limit on the size of the gamma-ray emission was estimated to be ~16$'$ using events above ~2GeV under the assumption of a circular shape with uniform surface brightness. It appears to coincide with the TeV source HESS J1800-240B,which is considered to be associated with a dense molecular cloud that contains the ultra compact HII region W28A2(G5.89-0.39).We found no significant gamma-ray emission in the LAT energy band at the positions of TeV sources HESS J1800-230A and HESS J1800-230C.The LAT data for HESS J1800-230A combined with the TeV data points indicate a spectral break between 10GeV and 100GeV.Comment: 23 pages, 6 figures. Accepted for publication in the Astrophysical Journal. Corresponding authors: H. Katagiri, H. Tajima, T. Tanaka, and Y. Uchiyam

GeV Gamma-ray Flux Upper Limits from Clusters of Galaxies

The detection of diffuse radio emission associated with clusters of galaxies indicates populations of relativistic leptons infusing the intracluster medium. Those electrons and positrons are either injected into and accelerated directly in the intracluster medium, or produced as secondary pairs by cosmic-ray ions scattering on ambient protons. Radiation mechanisms involving the energetic leptons together with decay of neutral pions produced by hadronic interactions have the potential to produce abundant GeV photons. Here, we report on the search for GeV emission from clusters of galaxies using data collected by the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope (Fermi) from August 2008 to February 2010. Thirty-three galaxy clusters have been selected according to their proximity and high mass, X-ray flux and temperature, and indications of non-thermal activity for this study. We report upper limits on the photon flux in the range 0.2-100 GeV towards a sample of observed clusters (typical values 1-5 x 10^-9 ph cm^-2 s^-1) considering both point-like and spatially resolved models for the high-energy emission, and discuss how these results constrain the characteristics of energetic leptons and hadrons, and magnetic fields in the intracluster medium. The volume-averaged relativistic-hadron-to-thermal energy density ratio is found to be < 5-10% in several clusters.Comment: 9 pages, 3 tables, 1 figure, accepted for publication in ApJ Letter

Periodic Emission from the Gamma-ray Binary 1FGL J1018.6-5856

Gamma-ray binaries are stellar systems containing a neutron star or black hole with gamma-ray emission produced by an interaction between the components. These systems are rare, even though binary evolution models predict dozens in our Galaxy. A search for gamma-ray binaries with the Fermi Large Area Telescope (LAT) shows that 1FGL J1018.6-5856 exhibits intensity and spectral modulation with a 16.6 day period. We identified a variable X-ray counterpart, which shows a sharp maximum coinciding with maximum gamma-ray emission, as well as an O6V((f)) star optical counterpart and a radio counterpart that is also apparently modulated on the orbital period. 1FGL J1018.6-5856 is thus a gamma-ray binary, and its detection suggests the presence of other fainter binaries in the Galaxy.Comment: Contact authors: R.H.D. Corbet, M. Kerr, C.C. Cheun