Revolucija v Šengalu Kavčič, Matej; ster, Marlene
Časopis za kritiko znanosti,
01/2023
288
Journal Article
Peer reviewed
Namen tega članka je predstaviti ljudstvo Ezidov in regijo Šengal (Sinjar) v Iraku, njegovo sodobno zgodovino in trenutne politične razmere s poudarkom na delovanju tamkajšnje samouprave oziroma ...Avtonomnega in demokratičnega sveta Šengala (MXDŞ). Večina podatkov je bila pridobljena z intervjuji v regiji Šengal v prvi polovici leta 2022. Avtorji na začetku članka orišejo zemljepis in zgodovino ter nadaljujejo z opisovanjem prebivalstva Šengala, kjer se globlje posvetijo kulturi in veri Ezidov ter njihovi zgodovini v odnosu do Iraka in iraškega Kurdistana. Šengal in Ezide je močno zaznamoval genocid, ki ga je nad njimi izvedla Daeš (islamska država) leta 2014, in tudi njihov odpor proti njej. Opisujejo razvoj odnosov po porazu Daeš v Šengalu med različnimi akterji, kot so iraška država, Demokratska stranka Kurdistana (KDP), Hašd al Šabi (ljudske mobilizacijske sile) in MXDŞ ter z vsakim od njih povezane oborožene sile. Podrobno pojasnjujejo sistem avtonomne uprave Šengala, njegovo vzpostavitev kot neposreden odgovor na genocid, načela delovanja in povezave celotnega ustroja. Prav tako obravnavajo delovanje njegovih posamičnih delov od komun do ljudskih svetov in odborov ter ustanov za izobraževanje, zdravstvo, komunalne službe, diplomacijo, oborožene sile ter ženske, mladinske in kulturne organizacije. Na koncu poskušajo orisati razsežnost »neosmanizma« in posledice napadov turške države z brezpilotnimi letali na Šengal. Članek zaključujejo s kratkim poročilom z zadnjega kongresa MXDŞ.
Background
The optimal duration of thromboprophylaxis after total hip or knee replacement, or hip fracture repair remains controversial. It is common practice to administer prophylaxis using ...low‐molecular‐weight heparin (LMWH) or unfractionated heparin (UFH) until discharge from hospital, usually seven to 14 days after surgery. International guidelines recommend extending thromboprophylaxis for up to 35 days following major orthopaedic surgery but the recommendation is weak due to moderate quality evidence. In addition, recent oral anticoagulants that exert effect by direct inhibition of thrombin or activated factor X lack the need for monitoring and have few known drug interactions. Interest in this topic remains high.
Objectives
To assess the effects of extended‐duration anticoagulant thromboprophylaxis for the prevention of venous thromboembolism (VTE) in people undergoing elective hip or knee replacement surgery, or hip fracture repair.
Search methods
The Cochrane Vascular Information Specialist searched the Specialised Register (last searched May 2015) and CENTRAL (2015, Issue 4). Clinical trials databases were searched for ongoing or unpublished studies.
Selection criteria
Randomised controlled trials assessing extended‐duration thromboprophylaxis (five to seven weeks) using accepted prophylactic doses of LMWH, UFH, vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) compared with short‐duration thromboprophylaxis (seven to 14 days) followed by placebo, no treatment or similar extended‐duration thromboprophylaxis with LMWH, UFH, VKA or DOACs in participants undergoing hip or knee replacement or hip fracture repair.
Data collection and analysis
We independently selected trials and extracted data. Disagreements were resolved by discussion. We performed fixed‐effect model meta‐analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random‐effects model when there was heterogeneity.
Main results
We included 16 studies (24,930 participants); six compared heparin with placebo, one compared VKA with placebo, two compared DOAC with placebo, one compared VKA with heparin, five compared DOAC with heparin and one compared anticoagulants chosen at investigators' discretion with placebo. Three trials included participants undergoing knee replacement. No studies assessed hip fracture repair.
Trials were generally of good methodological quality. The main reason for unclear risk of bias was insufficient reporting. The quality of evidence according to GRADE was generally moderate, as some comparisons included a single study, low number of events or heterogeneity between studies leading to wide CIs.
We showed no difference between extended‐duration heparin and placebo in symptomatic VTE (OR 0.59, 95% CI 0.35 to 1.01; 2329 participants; 5 studies; high quality evidence), symptomatic deep vein thrombosis (DVT) (OR 0.73, 95% CI 0.39 to 1.38; 2019 participants; 4 studies; moderate quality evidence), symptomatic pulmonary embolism (PE) (OR 0.61, 95% CI 0.16 to 2.33; 1595 participants; 3 studies; low quality evidence) and major bleeding (OR 0.59, 95% CI 0.14 to 2.46; 2500 participants; 5 studies; moderate quality evidence). Minor bleeding was increased in the heparin group (OR 2.01, 95% CI 1.43 to 2.81; 2500 participants; 5 studies; high quality evidence). Clinically relevant non‐major bleeding was not reported.
We showed no difference between extended‐duration VKA and placebo (one study, 360 participants) for symptomatic VTE (OR 0.10, 95% CI 0.01 to 1.94; moderate quality evidence), symptomatic DVT (OR 0.13, 95% CI 0.01 to 2.62; moderate quality evidence), symptomatic PE (OR 0.32, 95% CI 0.01 to 7.84; moderate quality evidence) and major bleeding (OR 2.89, 95% CI 0.12 to 71.31; low quality evidence). Clinically relevant non‐major bleeding and minor bleeding were not reported.
Extended‐duration DOAC showed reduced symptomatic VTE (OR 0.20, 95% CI 0.06 to 0.68; 2419 participants; 1 study; moderate quality evidence) and symptomatic DVT (OR 0.18, 95% CI 0.04 to 0.81; 2459 participants; 2 studies; high quality evidence) compared to placebo. No differences were found for symptomatic PE (OR 0.25, 95% CI 0.03 to 2.25; 1733 participants; 1 study; low quality evidence), major bleeding (OR 1.00, 95% CI 0.06 to 16.02; 2457 participants; 1 study; low quality evidence), clinically relevant non‐major bleeding (OR 1.22, 95% CI 0.76 to 1.95; 2457 participants; 1 study; moderate quality evidence) and minor bleeding (OR 1.18, 95% CI 0.74 to 1.88; 2457 participants; 1 study; moderate quality evidence).
We showed no difference between extended‐duration anticoagulants chosen at investigators' discretion and placebo (one study, 557 participants, low quality evidence) for symptomatic VTE (OR 0.50, 95% CI 0.09 to 2.74), symptomatic DVT (OR 0.33, 95% CI 0.03 to 3.21), symptomatic PE (OR 1.00, 95% CI 0.06 to 16.13), and major bleeding (OR 5.05, 95% CI 0.24 to 105.76). Clinically relevant non‐major bleeding and minor bleeding were not reported.
We showed no difference between extended‐duration VKA and heparin (one study, low quality evidence) for symptomatic VTE (OR 1.64, 95% CI 0.85 to 3.16; 1279 participants), symptomatic DVT (OR 1.36, 95% CI 0.69 to 2.68; 1279 participants), symptomatic PE (OR 9.16, 95% CI 0.49 to 170.42; 1279 participants), major bleeding (OR 3.87, 95% CI 1.91 to 7.85; 1272 participants) and minor bleeding (OR 1.33, 95% CI 0.64 to 2.76; 1279 participants). Clinically relevant non‐major bleeding was not reported.
We showed no difference between extended‐duration DOAC and heparin for symptomatic VTE (OR 0.70, 95% CI 0.28 to 1.70; 15,977 participants; 5 studies; low quality evidence), symptomatic DVT (OR 0.60, 95% CI 0.11 to 3.27; 15,977 participants; 5 studies; low quality evidence), symptomatic PE (OR 0.91, 95% CI 0.43 to 1.94; 14,731 participants; 5 studies; moderate quality evidence), major bleeding (OR 1.11, 95% CI 0.79 to 1.54; 16,199 participants; 5 studies; high quality evidence), clinically relevant non‐major bleeding (OR 1.08, 95% CI 0.90 to 1.28; 15,241 participants; 4 studies; high quality evidence) and minor bleeding (OR 0.95, 95% CI 0.82 to 1.10; 11,766 participants; 4 studies; high quality evidence).
Authors' conclusions
Moderate quality evidence suggests extended‐duration anticoagulants to prevent VTE should be considered for people undergoing hip replacement surgery, although the benefit should be weighed against the increased risk of minor bleeding. Further studies are needed to better understand the association between VTE and extended‐duration oral anticoagulants in relation to knee replacement and hip fracture repair, as well as outcomes such as distal and proximal DVT, reoperation, wound infection and healing.
Cilostazol for intermittent claudication Brown, Tamara; Brown, Tamara; Forster, Rachel B ...
Cochrane database of systematic reviews,
06/2021, Volume:
2021, Issue:
6
Journal Article
Peer reviewed
Open access
Background
Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent ...claudication (exercise‐induced lower limb pain relieved by rest). These patients have a three‐ to six‐fold increase in cardiovascular mortality. Cilostazol is a drug licensed for the use of improving claudication distance and, if shown to reduce cardiovascular risk, could offer additional clinical benefits. This is an update of the review first published in 2007.
Objectives
To determine the effect of cilostazol on initial and absolute claudication distances, mortality and vascular events in patients with stable intermittent claudication.
Search methods
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries, on 9 November 2020.
Selection criteria
We considered double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other drugs used to improve claudication distance in patients with stable intermittent claudication.
Data collection and analysis
Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We assessed the risk of bias with the Cochrane risk of bias tool. Certainty of the evidence was evaluated using GRADE. For dichotomous outcomes, we used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) and for continuous outcomes we used mean differences (MDs) and 95% CIs. We pooled data using a fixed‐effect model, or a random‐effects model when heterogeneity was identified. Primary outcomes were initial claudication distance (ICD) and quality of life (QoL). Secondary outcomes were absolute claudication distance (ACD), revascularisation, amputation, adverse events and cardiovascular events.
Main results
We included 16 double‐blind, RCTs (3972 participants) comparing cilostazol with placebo, of which five studies also compared cilostazol with pentoxifylline. Treatment duration ranged from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Cilostazol dose ranged from 100 mg to 300 mg; pentoxifylline dose ranged from 800 mg to 1200 mg. The certainty of the evidence was downgraded by one level for all studies because publication bias was strongly suspected. Other reasons for downgrading were imprecision, inconsistency and selective reporting.
Cilostazol versus placebo
Participants taking cilostazol had a higher ICD compared with those taking placebo (MD 26.49 metres; 95% CI 18.93 to 34.05; 1722 participants; six studies; low‐certainty evidence). We reported QoL measures descriptively due to insufficient statistical detail within the studies to combine the results; there was a possible indication in improvement of QoL in the cilostazol treatment groups (low‐certainty evidence). Participants taking cilostazol had a higher ACD compared with those taking placebo (39.57 metres; 95% CI 21.80 to 57.33; 2360 participants; eight studies; very‐low certainty evidence). The most commonly reported adverse events were headache, diarrhoea, abnormal stools, dizziness, pain and palpitations. Participants taking cilostazol had an increased odds of experiencing headache compared to participants taking placebo (OR 2.83; 95% CI 2.26 to 3.55; 2584 participants; eight studies; moderate‐certainty evidence).Very few studies reported on other outcomes so conclusions on revascularisation, amputation, or cardiovascular events could not be made.
Cilostazol versus pentoxifylline
There was no difference detected between cilostazol and pentoxifylline for improving walking distance, both in terms of ICD (MD 20.0 metres, 95% CI ‐2.57 to 42.57; 417 participants; one study; low‐certainty evidence); and ACD (MD 13.4 metres, 95% CI ‐43.50 to 70.36; 866 participants; two studies; very low‐certainty evidence). One study reported on QoL; the study authors reported no difference in QoL between the treatment groups (very low‐certainty evidence). No study reported on revascularisation, amputation or cardiovascular events. Cilostazol participants had an increased odds of experiencing headache compared with participants taking pentoxifylline at 24 weeks (OR 2.20, 95% CI 1.16 to 4.17; 982 participants; two studies; low‐certainty evidence).
Authors' conclusions
Cilostazol has been shown to improve walking distance in people with intermittent claudication. However, participants taking cilostazol had higher odds of experiencing headache. There is insufficient evidence about the effectiveness of cilostazol for serious events such as amputation, revascularisation, and cardiovascular events. Despite the importance of QoL to patients, meta‐analysis could not be undertaken because of differences in measures used and reporting. Very limited data indicated no difference between cilostazol and pentoxifylline for improving walking distance and data were too limited for any conclusions on other outcomes.
FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus ...and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity.
Megacities and other major population centres (MPCs) worldwide are major sources of air pollution, both locally as well as downwind. The overall assessment and prediction of the impact of MPC ...pollution on tropospheric chemistry are challenging. The present work provides an overview of the highlights of a major new contribution to the understanding of this issue based on the data and analysis of the EMeRGe (Effect of Megacities on the transport and transformation of pollutants on the Regional to Global scales) international project. EMeRGe focuses on atmospheric chemistry, dynamics, and transport of local and regional pollution originating in MPCs. Airborne measurements, taking advantage of the long range capabilities of the High Altitude and LOng Range Research Aircraft (HALO, https://www.halo-spp.de, last access: 22 March 2022), are a central part of the project. The synergistic use and consistent interpretation of observational data sets of different spatial and temporal resolution (e.g. from ground-based networks, airborne campaigns, and satellite measurements) supported by modelling within EMeRGe provide unique insight to test the current understanding of MPC pollution outflows.
Patient engagement is the active collaboration between patient partners and health system partners towards a goal of making decisions that centre patient needs-thus improving experiences of care, and ...overall effectiveness of health services in alignment with the Quintuple Aim. An important but challenging aspect of patient engagement is including diverse perspectives particularly those experiencing health inequities. When such populations are excluded from decision-making in health policy, practice and research, we risk creating a healthcare ecosystem that reinforces structural marginalisation and perpetuates health inequities.
Despite the growing body of literature on knowledge coproduction, few have addressed the role of power relations in patient engagement and offered actionable steps for engaging diverse patients in an inclusive way with a goal of improving health equity. To fill this knowledge gap, we draw on theoretical concepts of power, our own experience codesigning a novel model of patient engagement that is equity promoting, Equity Mobilizing Partnerships in Community, and extensive experience as patient partners engaged across the healthcare ecosystem. We introduce readers to a new conceptual tool, the Power Wheel, that can be used to analyse the interspersion of power in the places and spaces of patient engagement.
As a tool for ongoing praxis (reflection +action), the Power Wheel can be used to report, reflect and resolve power asymmetries in patient-partnered projects, thereby increasing transparency and illuminating opportunities for equitable transformation and social inclusion so that health services can meet the needs and priorities of all people.
Whole-genome and whole-exome sequencing of individual patients allow the study of rare and potentially causative genetic variation. In this study, we sequenced DNA of a trio comprising a boy with ...very-early-onset inflammatory bowel disease (veoIBD) and his unaffected parents. We identified a rare, X-linked missense variant in the NAPDH oxidase
gene (c.C721T, p.R241C) in heterozygous state in the mother and in hemizygous state in the patient. We discovered that, in addition, the patient was homozygous for a common missense variant in the
gene (c.T214C, p.Y72H).
encodes the p22phox protein, a cofactor for NOX1. Functional assays revealed reduced cellular ROS generation and antibacterial capacity of NOX1 and p22phox variants in intestinal epithelial cells. Moreover, the identified NADPH oxidase complex variants affected NOD2-mediated immune responses, and p22phox was identified as a novel NOD2 interactor. In conclusion, we detected missense variants in a veoIBD patient that disrupt the host response to bacterial challenges and reduce protective innate immune signaling via NOD2. We assume that the patient's individual genetic makeup favored disturbed intestinal mucosal barrier function.
The original version of this Article contained an error in the spelling of the author Robert Häsler, which was incorrectly given as Robert Häesler. This has now been corrected in both the PDF and ...HTML versions of the Article.
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