Comparative assessment of onabotulinumtoxinA and mirabegron for overactive bladder: an indirect treatment comparison

CONTEXT: OnabotulinumtoxinA and mirabegron have recently gained marketing authorisation to treat symptoms of overactive bladder (OAB). OBJECTIVE: To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA in patients with idiopathic OAB. DESIGN: Network meta-analysis. DATA SOURCES: A search of 9 electronic databases, review documents, guidelines and websites. METHODS: Randomised trials comparing any licensed dose of onabotulinumtoxinA or mirabegron with each other, anticholinergic drugs or placebo were eligible (19 randomised trials were identified). 1 reviewer extracted data from the studies and a second reviewer checked the data. Candidate trials were assessed for similarity and networks were developed for each outcome. Bayesian network meta-analysis was conducted using both fixed-effects and random-effects models. When there were differences in mean baseline values between mirabegron and onabotulinumtoxinA trials they were adjusted for using network meta-regression (NMR). RESULTS: No studies directly comparing onabotulinumtoxinA to mirabegron were identified. A network was created for each of the 7 outcomes, with 3-9 studies included in each individual network. The trials included in the networks were broadly similar. Patients in the onabotulinumtoxinA trials had more urinary incontinence and urgency episodes at baseline than patients in the mirabegron trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA and mirabegron were more efficacious than placebo at reducing the frequency of urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was more efficacious than mirabegron (50 and 25 mg) in completely resolving daily episodes of urinary incontinence and urgency and in reducing the frequency of urinary incontinence, urgency and urination. NMR supported the results of the network meta-analysis. CONCLUSIONS: In the absence of head-to-head trials comparing onabotulinumtoxinA to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be superior to mirabegron in improving symptoms of urinary incontinence, urgency and urinary frequency in patients with idiopathic OAB

Measuring the impact of health policies using Internet search patterns: the case of abortion

<p>Abstract</p> <p>Background</p> <p>Internet search patterns have emerged as a novel data source for monitoring infectious disease trends. We propose that these data can also be used more broadly to study the impact of health policies across different regions in a more efficient and timely manner.</p> <p>Methods</p> <p>As a test use case, we studied the relationships between abortion-related search volume, local abortion rates, and local abortion policies available for study.</p> <p>Results</p> <p>Our initial integrative analysis found that, both in the US and internationally, the volume of Internet searches for abortion is inversely proportional to local abortion rates and directly proportional to local restrictions on abortion.</p> <p>Conclusion</p> <p>These findings are consistent with published evidence that local restrictions on abortion lead individuals to seek abortion services outside of their area. Further validation of these methods has the potential to produce a timely, complementary data source for studying the effects of health policies.</p

Tobacco smoking changes during the first pre-vaccination phases of the COVID-19 pandemic: A systematic review and meta-analysis

Background: Globally, tobacco smoking remains the largest preventable cause of premature death. The COVID-19 pandemic has forced nations to take unprecedented measures, including ‘lockdowns’ that might impact tobacco smoking behaviour. We performed a systematic review and meta-analyses to assess smoking behaviour changes during the early pre-vaccination phases of the COVID-19 pandemic in 2020. Methods: We searched Medline/Embase/PsycINFO/BioRxiv/MedRxiv/SSRN databases (January–November 2020) for published and pre-print articles that reported specific smoking behaviour changes or intentions after the onset of the COVID-19 pandemic. We used random-effects models to pool prevalence ratios comparing the prevalence of smoking during and before the pandemic, and the prevalence of smoking behaviour changes during the pandemic. The PROSPERO registration number for this systematic review was CRD42020206383. Findings: 31 studies were included in meta-analyses, with smoking data for 269,164 participants across 24 countries. The proportion of people smoking during the pandemic was lower than that before, with a pooled prevalence ratio of 0·87 (95%CI:0·79–0·97). Among people who smoke, 21% (95%CI:14–30%) smoked less, 27% (95%CI:22–32%) smoked more, 50% (95%CI:41%-58%) had unchanged smoking and 4% (95%CI:1–9%) reported quitting smoking. Among people who did not smoke, 2% (95%CI:1–3%) started smoking during the pandemic. Heterogeneity was high in all meta-analyses and so the pooled estimates should be interpreted with caution (I2\u3e91% and p-heterogeneity\u3c0·001). Almost all studies were at high risk of bias due to use of non-representative samples, non-response bias, and utilisation of non-validated questions. Interpretation: Smoking behaviour changes during the first phases of the COVID-19 pandemic in 2020 were highly mixed. Meta-analyses indicated that there was a relative reduction in overall smoking prevalence during the pandemic, while similar proportions of people who smoke smoked more or smoked less, although heterogeneity was high. Implementation of evidence-based tobacco control policies and programs, including tobacco cessation services, have an important role in ensuring that the COVID-19 pandemic does not exacerbate the smoking pandemic and associated adverse health outcomes

Measurement of the branching ratio of the decay KL -> pi e nu and extraction of the CKM parameter |Vus|

We present a new measurement of the branching ratio R of the decay KL -> pi e nu (Ke3), relative to all charged KL decays with two tracks, based on data taken with the NA48 detector at the CERN SPS. We measure R = 0.4978 +- 0.0035. From this we derive the Ke3 branching fraction and the weak coupling parameter |Vus| in the CKM matrix. We obtain |Vus|f+(0) = 0.2146 +- 0.0016, where f+(0) is the vector form factor in the Ke3 decay.Comment: 18 pages, 8 figures. accepted by Phys Lett.

Measurement of K^0_e3 form factors

The semileptonic decay of the neutral K meson, KL -> pi e nu (Ke3), was used to study the strangeness-changing weak interaction of hadrons. A sample of 5.6 million reconstructed events recorded by the NA48 experiment was used to measure the Dalitz plot density. Admitting all possible Lorentz-covariant couplings, the form factors for vector (f_+(q^2)), scalar (f_S) and tensor (f_T) interactions were measured. The linear slope of the vector form factor lambda_+ = 0.0284+-0.0007+-0.0013 and values for the ratios |f_S/f_+(0)| = 0.015^{+0.007}_{-0.010}+-0.012 and |f_T/f_+(0)| = 0.05^{+0.03}_{-0.04}+-0.03 were obtained. The values for f_S and f_T are consistent with zero. Assuming only Vector-Axial vector couplings, lambda_+ = 0.0288+-0.0004+-0.0011 and a good fit consistent with pure V-A couplings were obtained. Alternatively, a fit to a dipole form factor yields a pole mass of M = 859+-18 MeV, consistent with the K^*(892) mass.Comment: 16 pages, 7 figures. submitted to Phys. Lett.

Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines

We characterize the breadth, function and phenotype of innate and adaptive cellular responses in a prevention of Mycobacterium tuberculosis infection trial. Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guerin (BCG, a live attenuated vaccine) or placebo (n = ~30 per group). H4:IC31 vaccination induces Ag85B and TB10.4-specific CD4 T cells, and an unexpected NKTlike subset, that expresses IFN-γ, TNF and/or IL-2. BCG revaccination increases frequencies of CD4 T cell subsets that either express Th1 cytokines or IL-22, and modestly increases IFNγ-producing NK cells. In vitro BCG re-stimulation also triggers responses by donor-unrestricted T cells, which may contribute to host responses against mycobacteria. BCG, which demonstrated efficacy against sustained Mycobacterium tuberculosis infection, modulates multiple immune cell subsets, in particular conventional Th1 and Th22 cells, which should be investigated in discovery studies of correlates of protection

What we talk about when we talk about "global mindset": managerial cognition in multinational corporations

Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as “global mindset” that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research

The significance of opthalmologic evaluation in the early diagnosis of inborn errors of metabolism: the Cretan experience

BACKGROUND: The Inborn Errors of Metabolism (IEM) are far from the rare systemic diseases that mainly affect the neural tissue. There are very few written reports on ocular findings in subjects with IEM, thus it was interesting to study the frequency of ocular findings in the studied population and explore their contribution to the early diagnosis of IEM. METHODS: Our study involved the evaluation of IEM suspected cases, which had been identified in a rural population in Crete, Greece. Over a period of 3 years, 125 patients, who fulfilled the inclusion criteria of this study, were examined. Analytical physical examination, detailed laboratory investigation as well as a thorough ocular examination were made. RESULTS: A diagnosis of IEM was established in 23 of the 125 patients (18.4%). Ten (43.5%) of the diagnosed IEM had ocular findings, while 8 of them (34.8%) had findings which were specific for the diagnosed diseases. One patient diagnosed with glycogenosis type 1b presented a rare finding. Of the 102 non-diagnosed patients, 53 (51.96 %) presented various ophthalmic findings, some of which could be related to a metabolic disease and therefore may be very helpful in the future. CONCLUSIONS: The ocular investigation can be extremely useful for raising the suspicion and the establishment of an early diagnosis of IEM. It could also add new findings related to these diseases. The early management of the ocular symptoms can improve the quality of life to these patients