Combining intensive practice nurse counselling or brief general practitioner advice with varenicline for smoking cessation in primary care: study protocol of a pragmatic randomized controlled trial

Introduction: Combining behavioural support and pharmacotherapy is most effective for smoking cessation and recommended in clinical guidelines. Despite that smoking cessation assistance from the general practitioner can be effective, dissemination of clinical practice guidelines and efforts on upskilling has not lead to the routine provision of smoking cessation advice among general practitioners. Intensive counselling from the practice nurse could contribute to better smoking cessation rates in primary care. However, the effectiveness of intensive counselling from a practice nurse versus usual care from a general practitioner in combination with varenicline is still unknown. Materials and methods: A pragmatic randomized controlled trial was conducted comparing: (a) intensive individual counselling delivered by a practice nurse and (b) brief advice delivered by a general practitioner; both groups received 12-weeks of open-label varenicline. A minimum of 272 adult daily smoking participants were recruited and treated in their routine primary care setting. The primary outcome was defined as prolonged abstinence from weeks 9 to 26, biochemically validated by exhaled carbon monoxide. Data was analysed blinded according to the intention-to-treat principle and participants with missing data on their smoking status at follow-up were counted as smokers. Secondary outcomes included: one-year prolonged abstinence, short-term incremental cost-effectiveness, medication adherence, and baseline predictors of successful smoking cessation. Discussion: This trial is the first to provide scientific evidence on the effectiveness, cost-effectiveness, and potential mechanisms of action of intensive practice nurse counselling combined with varenicline under real-life conditions. This paper explains the methodology of the trial and discusses the pragmatic and/or explanatory design aspects

AIDS knowledge and sexual activity among Flemish secondary school students: a multilevel analysis of the effects of type of education

<p>Abstract</p> <p>Background</p> <p>The behavior of adolescents puts them at an increased risk for HIV and other STIs, and their knowledge about HIV/AIDS is often inadequate. An understanding of how AIDS knowledge and sexual activity co-vary among Flemish secondary school students and of how education type, specifically, affects these students is limited. This study addresses the question of whether the effects of education type on HIV/AIDS knowledge and sexual activity are independent of the socio-demographic characteristics of the students.</p> <p>Methods</p> <p>Data from the Flemish Educational Assessment survey, which collected data from a large representative sample of third- and fifth-grade high school students (<it>N </it>= 11,872), were used. Data were analyzed using multilevel logistic and Poisson regression techniques.</p> <p>Results</p> <p>There is an indication that type of education affects both an adolescent's sexual activity and his/her AIDS knowledge; these effects prove robust for differences in socio-economic backgrounds. Students in lower status education types are more likely to be sexually active and to have poorer AIDS knowledge. The relationship between AIDS knowledge and sexual activity is, however, more complex. Although students in education types with poorer AIDS knowledge are more sexually active, within each of these groups the sexually active have better AIDS knowledge than the non-sexually active. There is also evidence of active information seeking by sexually active students, which leads to improved AIDS knowledge.</p> <p>Conclusion</p> <p>These findings are consistent with the literature on the role of the educational system in the reproduction of social inequalities. Students from lower status education types are at increased sexual risk compared to those from higher status types. There is also evidence of active information seeking by sexually active students, which leads to improved AIDS knowledge.</p

Assessing effects of a media campaign on HIV/AIDS awareness and prevention in Nigeria: results from the VISION Project

BACKGROUND: In response to the growing HIV epidemic in Nigeria, the U.S. Agency for International Development (USAID) initiated the VISION Project, which aimed to increase use of family planning, child survival, and HIV/AIDS services. The VISION Project used a mass-media campaign that focused on reproductive health and HIV/AIDS prevention. This paper assesses to what extent program exposure translates into increased awareness and prevention of HIV/AIDS. METHODS: This analysis is based on data from the 2002 and 2004 Nigeria (Bauchi, Enugu, and Oyo) Family Planning and Reproductive Health Surveys, which were conducted among adults living in the VISION Project areas. To correct for endogeneity, two-stage logistic regression is used to investigate the effect of program exposure on 1) discussion of HIV/AIDS with a partner, 2) awareness that consistent condom use reduces HIV risk, and 3) condom use at last intercourse. RESULTS: Exposure to the VISION mass media campaign was high: 59%, 47%, and 24% were exposed to at least 1 VISION radio, printed advertisement, or TV program about reproductive health, respectively. The differences in outcome variables between 2002 baseline data and the 2004 follow-up data were small. However, those with high program exposure were almost one and a half (Odds Ratio [O.R.] = 1.47, 95% Confidence Interval [C.I.] 1.01–2.16) times more likely than those with no exposure to have discussed HIV/AIDS with a partner. Those with high program exposure were over twice (O.R. = 2.20, C.I. 1.49–3.25) as likely as those with low exposure to know that condom use can reduce risk of HIV infection. Program exposure had no effect on condom use at last sex. CONCLUSION: The VISION Project reached a large portion of the population and exposure to mass media programs about reproductive health and HIV prevention topics can help increase HIV/AIDS awareness. Programs that target rural populations, females, and unmarried individuals, and disseminate information on where to obtain condoms, are needed to reduce barriers to condom use. Improvements in HIV/AIDS prevention behaviour are likely to require that these programmatic efforts be continued, scaled up, done in conjunction with other interventions, and targeted towards individuals with specific socio-demographic characteristics

Lentiviral gene therapy corrects platelet phenotype and function in patients with Wiskott-Aldrich syndrome

BACKGROUND: Thrombocytopenia is a serious issue for all patients with classical Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) because it causes severe and life-threatening bleeding. Lentiviral gene therapy (GT) for WAS has shown promising results in terms of immune reconstitution. However, despite the reduced severity and frequency of bleeding events, platelet counts remain low in GT-treated patients. OBJECTIVE: We carefully investigated platelet defects in terms of phenotype and function in untreated patients with WAS and assessed the effect of GT treatment on platelet dysfunction. METHODS: We analyzed a cohort of 20 patients with WAS/XLT, 15 of them receiving GT. Platelet phenotype and function were analyzed by using electron microscopy, flow cytometry, and an aggregation assay. Platelet protein composition was assessed before and after GT by means of proteomic profile analysis. RESULTS: We show that platelets from untreated patients with WAS have reduced size, abnormal ultrastructure, and a hyperactivated phenotype at steady state, whereas activation and aggregation responses to agonists are decreased. GT restores platelet size and function early after treatment and reduces the hyperactivated phenotype proportionally to WAS protein expression and length of follow-up. CONCLUSIONS: Our study highlights the coexistence of morphologic and multiple functional defects in platelets lacking WAS protein and demonstrates that GT normalizes the platelet proteomic profile with consequent restoration of platelet ultrastructure and phenotype, which might explain the observed reduction of bleeding episodes after GT. These results are instrumental also from the perspective of a future clinical trial in patients with XLT only presenting with microthrombocytopenia

All-sky search for time-integrated neutrino emission from astrophysical sources with 7 years of IceCube data

Since the recent detection of an astrophysical flux of high energy neutrinos, the question of its origin has not yet fully been answered. Much of what is known about this flux comes from a small event sample of high neutrino purity, good energy resolution, but large angular uncertainties. In searches for point-like sources, on the other hand, the best performance is given by using large statistics and good angular reconstructions. Track-like muon events produced in neutrino interactions satisfy these requirements. We present here the results of searches for point-like sources with neutrinos using data acquired by the IceCube detector over seven years from 2008--2015. The discovery potential of the analysis in the northern sky is now significantly below $E_\nu^2d\phi/dE_\nu=10^{-12}\:\mathrm{TeV\,cm^{-2}\,s^{-1}}$, on average $38\%$ lower than the sensitivity of the previously published analysis of four years exposure. No significant clustering of neutrinos above background expectation was observed, and implications for prominent neutrino source candidates are discussed.Comment: 19 pages, 17 figures, 3 tables; ; submitted to The Astrophysical Journa

Searches for sterile neutrinos with the IceCube detector

The IceCube neutrino telescope at the South Pole has measured the atmospheric muon neutrino spectrum as a function of zenith angle and energy in the approximate 320 GeV to 20 TeV range, to search for the oscillation signatures of light sterile neutrinos. No evidence for anomalous nu(mu) or (nu) over bar (mu) disappearance is observed in either of two independently developed analyses, each using one year of atmospheric neutrino data. New exclusion limits are placed on the parameter space of the 3 + 1 model, in which muon antineutrinos experience a strong Mikheyev-Smirnov-Wolfenstein-resonant oscillation. The exclusion limits extend to sin(2)2 theta(24) <= 0.02 at Delta m(2) similar to 0.3 eV(2) at the 90% confidence level. The allowed region from global analysis of appearance experiments, including LSND and MiniBooNE, is excluded at approximately the 99% confidence level for the global best-fit value of vertical bar U-e4 vertical bar(2)

Lowering IceCube’s energy threshold for point source searches in the southern sky

Observation of a point source of astrophysical neutrinos would be a "smoking gun" signature of a cosmic-ray accelerator. While IceCube has recently discovered a diffuse flux of astrophysical neutrinos, no localized point source has been observed. Previous IceCube searches for point sources in the southern sky were restricted by either an energy threshold above a few hundred TeV or poor neutrino angular resolution. Here we present a search for southern sky point sources with greatly improved sensitivities to neutrinos with energies below 100 TeV. By selecting charged-current nu(mu) interacting inside the detector, we reduce the atmospheric background while retaining efficiency for astrophysical neutrino-induced events reconstructed with sub-degree angular resolution. The new event sample covers three years of detector data and leads to a factor of 10 improvement in sensitivity to point sources emitting below 100 TeV in the southern sky. No statistically significant evidence of point sources was found, and upper limits are set on neutrino emission from individual sources. A posteriori analysis of the highest-energy (similar to 100 TeV) starting event in the sample found that this event alone represents a 2.8 sigma deviation from the hypothesis that the data consists only of atmospheric background

Observation and Characterization of a Cosmic Muon Neutrino Flux from the Northern Hemisphere using six years of IceCube data

The IceCube Collaboration has previously discovered a high-energy astrophysical neutrino flux using neutrino events with interaction vertices contained within the instrumented volume of the IceCube detector. We present a complementary measurement using charged current muon neutrino events where the interaction vertex can be outside this volume. As a consequence of the large muon range the effective area is significantly larger but the field of view is restricted to the Northern Hemisphere. IceCube data from 2009 through 2015 have been analyzed using a likelihood approach based on the reconstructed muon energy and zenith angle. At the highest neutrino energies between 191 TeV and 8.3 PeV a significant astrophysical contribution is observed, excluding a purely atmospheric origin of these events at $5.6\,\sigma$ significance. The data are well described by an isotropic, unbroken power law flux with a normalization at 100 TeV neutrino energy of $\left(0.90^{+0.30}_{-0.27}\right)\times10^{-18}\,\mathrm{GeV^{-1}\,cm^{-2}\,s^{-1}\,sr^{-1}}$ and a hard spectral index of $\gamma=2.13\pm0.13$. The observed spectrum is harder in comparison to previous IceCube analyses with lower energy thresholds which may indicate a break in the astrophysical neutrino spectrum of unknown origin. The highest energy event observed has a reconstructed muon energy of $(4.5\pm1.2)\,\mathrm{PeV}$ which implies a probability of less than 0.005% for this event to be of atmospheric origin. Analyzing the arrival directions of all events with reconstructed muon energies above 200 TeV no correlation with known $\gamma$-ray sources was found. Using the high statistics of atmospheric neutrinos we report the currently best constraints on a prompt atmospheric muon neutrino flux originating from charmed meson decays which is below $1.06$ in units of the flux normalization of the model in Enberg et al. (2008).Comment: 20 pages, 21 figure