New treatments and therapeutic approaches repeatedly emerged in the field of inflammatory bowel disease.
to update the French treatment algorithms for Crohn's disease (CD) and ulcerative colitis ...(UC).
A formal consensus method was used to determine changes to the treatment algorithms for various situations of CD and UC. Thirty-seven experts voted on questions that had been drafted by the steering committee ahead of time. Consensus was defined as at least 66% of experts agreeing on a response.
Anti-TNF were reinforced as a first-line therapy rather than the use of immunosuppressant alone. Vedolizumab for UC, ustekinumab for CD took place as second-line maintenance therapy and potentially as a first-line therapy in the setting of unrestricted reimbursement for vedolizumab. Tofacitinib was recommended by the experts in case of vedolizumab failure for UC. Algorithms for complicated CD with abscess, intestinal and complex anal fistula were updated according to recent prospective cohort studies.
The changes incorporated to the algorithms provide up-to-date and easy-to-use guidelines to treat patients with IBD.
Summary
Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, ...retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty‐eight (74 36–100 years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow‐up (7 0·2–48.7 months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) 0·36–0·80, P < 0·05}. Bleeding onset during follow‐up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29–100) and a specificity of 86% (95% CI: 57–98, P = 0·02). Kaplan–Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: 0·67–97, P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow‐up are both associated with bleeding in patients with AFVI.
•By 2015, over half of the 53 countries interrupted endemic transmission of measles and rubella.•Measles and rubella cases have declined, as has the number of measles genotypes.•All countries in the ...Region are committed to the goal of eliminating measles and rubella.•Several challenges in vaccination and surveillance performance still remain.•Critical programmatic issues need to be addressed to achieve regional elimination.
Despite availability of safe and cost-effective vaccines to prevent it, measles remains one of the significant causes of death among children under five years of age globally. The World Health Organization (WHO) European Region has seen a drastic decline in measles and rubella cases in recent years, and a few of the once common measles genotypes are no longer detected. Buoyed by this success, all Member States of the Region reconfirmed their commitment in 2010 to eliminating measles and rubella, and made this a central objective of the European Vaccine Action Plan 2015–2020 (EVAP). Nevertheless, sporadic outbreaks continue, recently affecting primarily adolescents and young adults with no vaccination or an incomplete vaccination history. The European Regional Verification Commission for Measles and Rubella Elimination was established in 2011 to evaluate the status of measles and rubella elimination based on documentation submitted annually by each country’s national verification committee.
Each country’s commitment to eliminate measles and rubella is influenced by competing health priorities, and in some cases lack of capacity and resources. All countries need to improve case-base surveillance for both measles and rubella, ensure documentation of each outbreak and strengthen the link between epidemiology and laboratory data. Achieving high coverage with measles- and rubella-containing vaccines will require a multisectoral approach to address the root causes of lower uptake in identified communities including service delivery challenges or vaccine safety concerns caused by circulating myths about vaccination.
The WHO European Region has made steady progress towards eliminating measles and rubella and over half of the countries interrupted endemic transmission of both diseases by 2015. The programmatic challenges in disease surveillance, vaccination service delivery and communication in the remaining endemic countries should be addressed through periodic evaluation of the strategies by all stakeholders and exploring additional opportunities to accelerate the ongoing elimination activities.
This paper considers natural Lapwood convection in a shallow porous cavity filled with a binary fluid. The investigation is mainly focused on the nonlinear behaviour of subcritical convection and the ...bistability phenomenon caused by the combined effects of porous medium form drag and double-diffusive convection. The Dupuit–Darcy model, which includes the effect of the form drag at high Reynolds flow, is used to describe the convective flow in the porous matrix. The enclosure is subject to vertical temperature and concentration gradients. The governing parameters of the problem under study are the Rayleigh number,
$R_{T}$
, the buoyancy ratio,
$\unicodeSTIX{x1D711}$
, the Lewis number,
$Le$
, the form drag coefficient, (
$1/P_{r}^{\ast }$
), where
$P_{r}^{\ast }$
is a modified Prandtl number, and the aspect ratio of the cavity,
$A$
. An analytical solution, valid for shallow enclosures (
$A\gg 1$
), is derived on the basis of the parallel flow approximation. Among other things, this work focuses on the effects of the form drag parameter on the convective flows that occur when the thermal and solutal buoyancy forces are opposing each other. For this situation, in the absence of the form drag effect, the onset of motion is known to occur at a subcritical Rayleigh number,
$R_{TC}^{sub}$
, which depends upon
$\unicodeSTIX{x1D711}$
and
$Le$
only. The effects of
$P_{r}^{\ast }$
on
$R_{TC}^{sub}$
and on the subsequent convective heat and mass transfer rates are found to be significant. A new bistability phenomenon arises when the onset of subcritical convection is shifted close to or beyond the threshold of supercritical convection, whether heating or cooling isothermally or upon applying constant heat and solute fluxes, regardless of the enclosure aspect ratio value. It is demonstrated, on the basis of linear stability theory, that the form drag parameter has a stabilizing effect and considerably affects the threshold for Hopf bifurcation,
$R_{TC}^{Hopf}$
, which characterizes the transition from steady to unsteady convection. In the range of governing parameters considered in this study, the heat, solute and flow characteristics predicted by the analytical model are found to agree well with the numerical study of the full governing equations.
Zusammenfassung
Hintergrund
Die Maserninzidenz in den 53 Mitgliedstaaten der Europäischen Region der Weltgesundheitsorganisation (WHO) ist in den vergangenen Jahrzehnten drastisch zurückgegangen. Die ...Verifizierungskommission der Europäischen Region für die Eliminierung der Masern und Röteln (RVC) stellte fest, dass Ende 2017 in 43 Mitgliedstaaten eine endemische Übertragung der Masern seit zwölf Monaten oder länger nicht mehr stattgefunden hatte. Allerdings nahm die Maserninzidenz in der Region 2018 im Vergleich zu 2017 stark zu. Dieser Beitrag bewertet den aktuellen Stand in Bezug auf das Ziel, Masern in der Region zu eliminieren. Es werden Überlegungen zu Herausforderungen und Maßnahmen dieses Ziel zu erreichen angestellt.
Methodik
Die hier vorgestellten Daten für 2017 und 2018 (Stand: 01.02.2019) wurden von den 53 Mitgliedstaaten vorgelegt. Der Eliminierungsstand der Masern in den Ländern wurde aus dem Bericht von 2018 über die 7. Sitzung der RVC entnommen.
Ergebnisse
Für das Jahr 2017 meldeten 44 Länder in der Europäischen Region insgesamt 25.863 Masernfälle. Für 2018 wurden aus 47 Ländern 82.596 Masernfälle gemeldet. Davon stammen die meisten Fälle aus der Ukraine (64 %) und aus Serbien (6 %). Das Alter war in 82.588 Fällen bekannt: 8 % der Infizierten waren <1 Jahr alt, 17 % 1–4 Jahre, 38 % 5–19 Jahre und 37 % waren 20 Jahre oder älter. Daten zum Impfstatus lagen für 76 % der Infizierten vor, von denen 62 % nicht geimpft worden waren. Zehn Länder meldeten insgesamt 72 Sterbefälle im Zusammenhang mit Masernerkrankungen.
Schlussfolgerungen
Für die Eliminierung der Masern in der Europäischen Region sind eine hohe Immunitätsrate in der Bevölkerung und eine genaue epidemiologische Überwachung weiterhin von wesentlicher Bedeutung. Um dieses Ziel zu erreichen, müssen sich alle Mitgliedsstaaten langfristig politisch engagieren.
•Form drag effect on double diffusive and Soret convection within tall porous layers.•Form drag shifts drastically the onset of subcritical convection.•The form drag has a stabilising effect and ...delay the onset of subcritical convection and Hopf bifurcation.•The drag from leads to bistability phenomena below and above the threshold of supercritical convection.•Form drag induce traveling waves within the overstable regime.
This paper reports a numerical study of natural convection in at all porous enclosure filled with a binary fluid. The Darcy–Dupuis model, which includes effects of the form drag force, is adopted to describe the flow in the porous medium. The two vertical walls of the cavity are subject to constant gradients of temperature while the two horizontal ones are kept adiabatic and impermeable. Concentration gradients are assumed to be induced either by the imposition of constant gradients of solute on the vertical walls of the system (a=0; double diffusive convection) or by the Soret effect (a=1). Governing parameters of the problem under study are the thermal Rayleigh number RT, form drag parameter G, buoyancy ratio φ, Lewis number. Le, normalized porosity ε, and aspect ratio of the cavity A. The case of equal and opposing thermal and solutal buoyancy forces, φ=-1, is considered. For this situation, an equilibrium solution corresponding to the rest state is possible and the resulting onset of motion can be either supercritical or subcritical. A semi-analytical solution, valid for an infinite layer (A≫1) assuming parallel flow, is derived. Based on the linear stability theory, the onset of motion from the rest state is predicted for both double diffusive and Soret convection. The onset of Hopf bifurcation, characterizing the transition from a convective steady state to oscillatory state, is also studied. The influence of the governing parameters on the onset of motion and the resulting fluid flow, temperature and concentration fields is discussed in detail. The existence of supercritical, subcritical and oscillatory convective modes is demonstrated. A good agreement is found between the predictions of the parallel flow approximation and the numerical results obtained by solving the full governing equations. The existence of multiple solutions and traveling waves for a given set of the governing parameter is demonstrated and leads to the existence of a bistability phenomenon. Overall, the form drag behaves as a stabilizing effect and is seen to affect considerably the onset of subcritical convection and Hopf bifurcation.
In 2005, the Regional Committee of the World Health Organization (WHO) European Region (EUR) passed a resolution calling for the regional elimination of measles, rubella, and congenital rubella ...syndrome (CRS) (1). In 2010, all 53 countries in EUR* reaffirmed their commitment to eliminating measles, rubella, and CRS (2); this goal was included in the European Vaccine Action Plan 2015-2020 (3,4). Rubella, which typically manifests as a mild febrile rash illness, is the leading vaccine-preventable cause of birth defects. Rubella infection during pregnancy can result in miscarriage, fetal death, or a constellation of malformations known as CRS, which usually includes one or more visual, auditory, or cardiac defects (5). The WHO-recommended measles and rubella elimination strategies in EUR include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine (MRCV) through routine immunization services; 2) providing measles and rubella vaccination opportunities, including supplementary immunization activities (SIAs), to populations susceptible to measles or rubella; 3) strengthening surveillance by conducting case investigations and confirming suspected cases and outbreaks with laboratory results; and 4) improving the availability and use of evidence to clearly communicate the benefits and risks of preventing these diseases through vaccination to health professionals and the public (6). This report updates a previous report and describes progress toward rubella and CRS elimination in EUR during 2005-2019 (7). In 2000, estimated coverage with the first dose of a rubella-containing vaccine (RCV1) in EUR was 60%, and 621,039 rubella cases were reported (incidence = 716.9 per 1 million population). During 2005-2019, estimated regional coverage with RCV1 was 93%-95%, and in 2019, 31 (58%) countries achieved ≥95% coverage with the RCV1. During 2005-2019, approximately 38 million persons received an RCV during SIAs in 20 (37%) countries. Rubella incidence declined by >99%, from 234.9 cases per 1 million population (206,359 cases) in 2005 to 0.67 cases per 1 million population (620 cases) by 2019. CRS cases declined by 50%, from 16 cases in 2005 to eight cases in 2019. For rubella and CRS elimination in EUR to be achieved and maintained, measures are needed to strengthen immunization programs by ensuring high coverage with an RCV in every district of each country, offering supplementary rubella vaccination to susceptible adults, maintaining high-quality surveillance for rapid case detection and confirmation, and ensuring effective outbreak preparedness and response.
In 2010, all 53 countries* in the World Health Organization (WHO) European Region (EUR) reconfirmed their commitment to eliminating measles and rubella and congenital rubella syndrome (1); this goal ...was included as a priority in the European Vaccine Action Plan 2015-2020 (2). The WHO-recommended elimination strategies in EUR include 1) achieving and maintaining ≥95% coverage with 2 doses of measles-containing vaccine (MCV) through routine immunization services; 2) providing measles and rubella vaccination opportunities, including supplementary immunization activities (SIAs), to populations susceptible to measles or rubella; 3) strengthening surveillance by conducting case investigations and confirming suspected cases and outbreaks with laboratory results; and 4) improving the availability and use of evidence for the benefits and risks associated with vaccination (3). This report updates a previous report (4) and describes progress toward measles elimination in EUR during 2009-2018. During 2009-2017, estimated regional coverage with the first MCV dose (MCV1) was 93%-95%, and coverage with the second dose (MCV2) increased from 73% to 90%. In 2017, 30 (57%) countries achieved ≥95% MCV1 coverage, and 15 (28%) achieved ≥95% coverage with both doses. During 2009-2018, >16 million persons were vaccinated during SIAs in 13 (24%) countries. Measles incidence declined to 5.8 per 1 million population in 2016, but increased to 89.5 in 2018, because of large outbreaks in several EUR countries. To achieve measles elimination in EUR, measures are needed to strengthen immunization programs by ensuring ≥95% 2-dose MCV coverage in every district of each country, offering supplemental measles vaccination to susceptible adults, maintaining high-quality surveillance for rapid case detection and confirmation, and ensuring effective outbreak preparedness and response.
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