interventional causality
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People worldwide are confronted with environmental and sociopolitical stressors that act as potent sources of subjective uncertainty. The uncertainty arising in response to the volatility and unpredictability of adversities is amplified by their representation or misrepresentation in media news. While the causal effect of media news on vicarious traumatization has been well established, we argue that the impact of negative media news is principally related to distress and anxiety stemming from the uncertainty-inducing effect of media representations of the state of the world. As a growing body of research suggests, minimizing uncertainty related to global stressors is a significant driver of media news use. However, extensive media exposure perpetuates stress and is associated with symptoms of psychopathology. The self-perpetuating vicious circle of worry and excessive media consumption has been amply confirmed by new research related to the COVID-19 pandemic. Furthermore, attempts to alleviate stress and anxiety stemming from uncertainties often result in maladaptive strategies. In particular, the adoption of rigid behavioral patterns may prompt various forms of socially detrimental behavior. Critical factors in prevention and remediation include limiting media overexposure and implementing therapeutic interventions that focus on increasing tolerance to uncertainty.
- MeSH
- COVID-19 psychologie MeSH
- duševní zdraví * MeSH
- hromadné sdělovací prostředky * MeSH
- lidé MeSH
- nejistota MeSH
- psychický stres * psychologie etiologie MeSH
- úzkost psychologie etiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis). There is an expanding array of treatment options, but high-quality data are sparse. Diagnostic accuracy is important and needs collaboration between hematologists and neuromuscular specialists to determine the sequence and intensity of investigations. Appropriate causal attribution to the IgM disorder is essential to enable the correct therapeutic intervention. The aims of treatment intervention should be clear and realistic. Consistent and clinically meaningful measures are needed to capture treatment success. Despite therapeutic advances, many patients experience persistent disability, highlighting the need for further research.
- MeSH
- imunoglobulin M * imunologie MeSH
- lidé MeSH
- management nemoci MeSH
- nemoci periferního nervového systému * terapie diagnóza etiologie imunologie MeSH
- Waldenströmova makroglobulinemie * terapie komplikace diagnóza imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
BACKGROUND: Immune checkpoint inhibitors (ICIs) are an important therapeutic pillar in metastatic urothelial carcinoma (mUC). The occurrence of immune-related adverse events (irAEs) appears to be associated with improved outcomes in observational studies. However, these associations are likely affected by immortal time bias and do not represent causal effects. The aim of this study was to assess the effect of irAEs on outcomes while correcting for immortal time bias, using target trial emulation (TTE). METHODS: TTE was contrasted to adjusted naïve and time-updated Cox models. We performed a multi-institutional retrospective study involving mUC patients under ICI. The primary objective was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Secondary endpoints included the influence of irAEs on objective response rates (ORRs) to ICI and the influence of systemic corticosteroids on outcomes. RESULTS: Among 335 patients (median age: 69 yrs), 69.6% received ICI in the second line or further lines. During a median follow-up of 21.1 months, 122 (36.4%) patients developed irAEs of any grade (grade ≥ 3: 14.9%). Hazard ratios (HRs) for PFS ranged from 0.37 for naïve adjusted Cox model to 0.88 (95% confidence interval (CI), 0.59-1.30) with time-updated covariates, and from 0.41 to 1.10 (95% CI, 0.69-1.75) for OS. TTE accounting for immortal time bias yielded a HR of 1.02 (95% CI, 0.72-1.44) for PFS, and 0.90 (95% CI, 0.62-1.30) for OS. In contrast to the naïve Cox model (HR = 2.26, 95% CI 1.26-4.05), the presence of irAEs was no longer a predictive factor for improved ORR in time-updated Cox models (HR = 1.27, 95% CI 0.68-2.36) and TTE (HR = 1.43, 95% CI 0.89-2.29). In patients with irAEs, systemic corticosteroids did not negatively impact survival. CONCLUSION: Using TTE, we were able to show that the occurrence of irAEs is no longer associated with better survival or improved response rates to ICI in mUC patients, in contrast to the naïve analysis. These findings demonstrate that TTE is a suitable formal framework to avoid immortal time bias in studies with time-dependent non-interventional exposures.
- MeSH
- inhibitory kontrolních bodů * škodlivé účinky terapeutické užití MeSH
- karcinom z přechodných buněk farmakoterapie mortalita imunologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory močového měchýře farmakoterapie mortalita imunologie patologie MeSH
- nežádoucí účinky léčiv etiologie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- urologické nádory farmakoterapie mortalita imunologie patologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: The interaction between joint kinematics and kinetics is usually assessed by linear correlation analysis, which does not imply causality. Understanding the causal links between these variables may help develop landing interventions to improve technique and create joint-specific strengthening programs to reduce reaction forces and injury risk. OBJECTIVE: Therefore, the aim of this study was to analyze the causal interaction between lower limb sagittal kinematics and vertical ground reaction force (VGRF) during single-leg jump landing in children who are jumpers (volleyball and gymnastics) and non-jumpers, using the causal empirical decomposition method. Our hypothesis is that children who participate in jumping sports, compared to those who do not, employ a different joint strategy to regulate ground reaction forces during landing, particularly at the ankle level. METHODS: Two groups were compared: the jumpers group (n = 14) and the non-jumpers (control group, n = 11). The causal interaction between sagittal kinematics and VGRF was assessed using ensemble empirical mode decomposition (EEMD) and time series instantaneous phase dependence in bi-directional causality. The relative causal strength (RCS) between the time series was quantified as the relative ratio of absolute cause strength between kinematics and VGRF. RESULTS: A significant interaction between joint and group was found for RCS (p = 0.035, η2p = 0.14). The post-hoc analysis showed the jumpers group had higher ankle-to-VGRF RCS than the control group (p = 0.017, d = 1.03), while in the control group the hip-to-VGRF RCS was higher than the ankle-to-VGRF RCS (p = 0.004, d = 0.91). CONCLUSION: Based on the causal decomposition approach, our results indicate that practicing jumping sports increases the causal effect of ankle kinematics on ground reaction forces in children. While non-jumper children rely more on the hip to modulate reaction forces, jumper children differ from non-jumpers by their greater use of the ankle joint. These findings could be used to develop specific training programs to improve landing techniques according to practice level, potentially helping to reduce the risk of injury in both athletes and non-athletes.
- MeSH
- biomechanika fyziologie MeSH
- dítě MeSH
- dolní končetina fyziologie MeSH
- gymnastika * fyziologie MeSH
- hlezenní kloub fyziologie MeSH
- lidé MeSH
- volejbal fyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Health literacy is a core public health issue in relation to children and adolescents associated with multiple health behaviours and health outcomes. The aim of the study is to test the direct associations between health literacy, physical activity behaviour, health outcomes of body composition and cardiorespiratory fitness among Slovak adolescents and possible indirect effect of health literacy on health outcomes of body composition and cardiorespiratory fitness mediated by adolescents' physical activity behaviour. METHODS: Data from the Slovak Health Behaviour in School-aged Children (HBSC) study conducted in 2022 were used. For the purposes of this study, a subsample of the adolescents (n = 508; mean age = 14.50; SD = 0.82; 54.3% boys) which provided HBSC questionnaire data on health literacy, moderate-to-vigorous physical activity and vigorous physical activity and participated in body composition (InBody 230) and cardiorespiratory fitness (20-m shuttle run test) measurements. Data were analysed using linear regression analysis. RESULTS: The findings showed that higher health literacy of the adolescents was directly associated with higher frequency of physical activity represented by moderate-to-vigorous physical activity and vigorous physical activity and only with the visceral fat area in the crude model. Furthermore, there was an indirect effect of health literacy on cardiorespiratory fitness and most of the body composition variables (except the Body Mass Index) which was mediated by physical activity of the respondents. CONCLUSIONS: Health literacy is indirectly associated to body composition and cardiorespiratory fitness through higher frequency of physical activity. It seems that health literacy as cognitive and social competencies need behavioural components to be involved in the proposed causal pathway between health literacy and health outcomes. Our findings may contribute to the process of creating a framework for future health literacy interventions in adolescents.
- MeSH
- cvičení * fyziologie MeSH
- kardiorespirační zdatnost * fyziologie MeSH
- lidé MeSH
- mladiství MeSH
- průzkumy a dotazníky MeSH
- složení těla * MeSH
- zdravotní gramotnost * statistika a číselné údaje MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
Malformace vena magna Galeni je velmi vzácná, život ohrožující vrozená vada mozkových cév. Velikost a typ malformace má zásadní vliv na klinické projevy, především na hemodynamiku. V novorozeneckém věku se nejčastěji setkáváme s choroidálním typem, který způsobuje srdeční selhání novorozence krátce po narození, nebo dokonce již prenatálně. Pacienti vyžadují multioborový přístup. Kauzální terapie náleží do rukou intervenčních radiologů. Vzhledem k metodám a vysoce specializované péči na novorozeneckých jednotkách intenzivní péče již není mortalita pacientů 100% tak, jako tomu bylo ve 20. století. Přesto se stále jedná o onemocnění s vysokou mortalitou i morbiditou. Článek je doplněn krátkým přehledem našich pacientů z posledních 12 let.
Vein of Galen aneurysmal malformation is a rare life threatening congenital malformation of cerebral vessels. Size and type of malformation has a major influence on clinical manifestations especially on hemodynamics. In the neonatal period the most common type is choroidal which causes heart failure in the newborn shortly after birth or even prenatally. Patients need multidisciplinary approach. Causal therapy belongs to the hands of interventional radiologists. Thanks to these methods and highly specialized care in neonatal intensive care units the mortality of these patients is no longer 100% as in the 20th century. Nevertheless, it is still a disease with high mortality and morbidity. The article is supplemented with a short overview of our patients from the last 12 years.
- MeSH
- diagnostické zobrazování klasifikace MeSH
- intervenční radiologie metody MeSH
- lidé MeSH
- malformace Galenovy žíly * diagnostické zobrazování klasifikace patofyziologie terapie MeSH
- novorozenec MeSH
- postnatální péče MeSH
- statistika jako téma MeSH
- terapeutická embolizace metody MeSH
- ukazatele zdravotního stavu MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
Jsou shrnuty poznatky o rizikových faktorech a biomarkerech Alzheimerovy nemoci (AD), které jsou základem pro poznání patofyziologie onemocnění a pro rozpoznání buněčných cílů nových léčiv. Hlavními cíli nových léčiv pro AD jsou procesy spojené s neurotoxicitou amyloidu beta (A?) a tau proteinu, narušenou neurotransmisí, metabolickou dysregulací, mitochondriální dysfunkcí, oxidačním stresem, neurozánětem, neuroplasticitou, proteostází a proteinopatií. Některá nová léčiva jsou zaměřena na více asociovaných buněčných procesů, jako je cholinergní deplece, toxicita glutamátu, agregace A?, hyperfosforylace tau, oxidační stres a aktivita mitochondriálních proteinů. Farmakologická intervence při AD s potenciálem být kauzální zahrnuje regulaci produkce, eliminace, šíření a vzájemné interakce oligomerů a agregátů A? (k prevenci nástupu onemocnění), oligomerů tau a neurofibrilárních klubek (k eliminaci progrese onemocnění) a mitochondriální dysfunkce (ke snížení progrese neurodegenerace). Účinnost farmakoterapie lze zvýšit vhodnou kombinací s jinými lékovými i nelékovými intervencemi a doplňky stravy.
Knowledge about risk factors and biomarkers of Alzheimer ́s disease (AD), which are the basis for understanding the pathophysiology of the disease and for identifying the cellular targets for new drugs, is summarized. The main targets of new AD drugs are processes associated with amyloid beta (A?) and tau neurotoxicity, impaired neurotransmission metabolic dysregulation, mitochondrial dysfunction, oxidative stress, neuroinflammation, neuroplasticity, proteostasis, and proteinopathy. Some new drugs target multiple associated cellular processes, such as cholinergic depletion, glutamate toxicity, A? aggregation, tau hyperphosphorylation, oxidative stress, and mitochondrial protein activity. Pharmacological intervention in AD with the potential to be causal includes targeting the production, elimination, distribution, and interactions of A? oligomers and aggregates (to prevent disease onset), tau oligomers and neurofibrillary tangles (to prevent disease progression), and mitochondrial dysfunction (to reduce neurodegeneration progression). The effectiveness of pharmacotherapy may be enhanced by appropriate combination with other drug and non-drug interventions and nutritional supplements.
BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) β, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.
- MeSH
- celogenomová asociační studie * MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory * genetika epidemiologie MeSH
- lidé MeSH
- mendelovská randomizace * MeSH
- rizikové faktory MeSH
- studie případů a kontrol MeSH
- věk při počátku nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
OBJECTIVES: Higher-than-recommended sugar consumption (< 10% of total energy intake; WHO) leads to negative health impacts and the development of serious diseases. Sugar-sweetened beverages (SSBs) proved to be among the leading sources of free sugar intake, as they contain large amounts of added sugar. Our article aims to propose tax measures that will help change consumer behaviour and reduce SSBs consumption. METHODS: For a comparison of the forms of taxation, the experience of seven countries (Denmark, France, Hungary, Italy, Poland, Catalonia - Spain, and the UK) were analysed. The evolution of sugar consumption, consumption of sweetened drinks and obesity before and after the introduction and/or abolition of the sugar tax were reviewed. RESULTS: States that implemented a tax on SSBs were able to reduce SSBs consumption in the first year after the tax was introduced when states with a sugar-content-based tax have implemented it more effectively than states with a volume-based tax. Based on this finding, we propose basic design assumptions for the tax that can be used in European countries that have not yet introduced the tax. Progressive taxation divides beverages into 3 bands. The basic assumption is to encourage the desired consumer behaviour, i.e., consumption of SSBs with lower sugar content. The proposed tax design is applied to the conditions of the Czech Republic as a model case study. CONCLUSIONS: The results of our study suggest that SSBs taxation could be an effective policy intervention to improve population health by reducing the health impacts of SSBs among children and adolescents, although further studies are needed to prove the causality of the described associations.
- MeSH
- cukrem slazené nápoje * ekonomika MeSH
- daně * MeSH
- Evropská unie * MeSH
- lidé MeSH
- obezita prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Pozadí: Izolace infekčních nebo imunosuprimovaných pacientů je běžnou intervencí v nemocnicích. Důkazy zdůrazňují různé dopady v důsledku izolace. Cíl: Prozkoumat zkušenosti dospělých hospitalizovaných pacientů s izolací na jednolůžkovém pokoji. Metodika: Byla provedena integrační revize. Proto bylo provedeno systematické vyhledávání v Cochrane, CINAHL, MEDLINE a GeroLit, stejně jako dodatečné ruční vyhledávání a zpětné vyhledávání v letech 2021 a 2023. Screening a extrakci dat prováděli nezávisle dva recenzenti. Syntéza výsledků studie byla provedena konstantním porovnáváním. Výsledky: Z 5 975 zjištění bylo zahrnuto 20 studií (9 kvalitativních, 9 kvantitativních, 2 smíšené) obsahujících 58 534 účastníků. Zkušenosti pacientů závisí na různých kontextových faktorech. Studie popisují mnohostrannou zkušenost s izolací na jednolůžkovém pokoji. Izolace je vnímána jako ochrana před hrozbami; pacienti zažívají klid a soukromí, ale jsou také konfrontováni s omezeními ve vztahu k mobilitě a kontaktu. Studie zmiňují, že izolace má různé psychologické a sociální dopady a také vliv na vnímání poskytované péče. Ačkoli je to často vnímáno jako velká zátěž, studie zdůrazňují příležitost k sebereflexi a nalezení vnitřní síly. Diskuse: Pacienti uváděli komplexní, multidimenzionální a nekonzistentní zkušenost. Je zapotřebí dalšího výzkumu, aby se řešily diferencované kauzální vztahy mezi ovlivňujícími faktory a různými zkušenostmi.
Background: Isolation of infectious or immunosuppressed patients is a common intervention in hospitals. Evidence highlights various impacts due to isolation. Aim: To explore adult inpatients' experience of single room isolation. Methods: An integrative review was performed. Therefore, a systematic search was conducted in Cochrane, CINAHL, MEDLINE, and GeroLit, as well as an additional handsearch and a reverse search in 2021 and 2023. Screening and data extraction were carried out independently by two reviewers. Synthesis of study results was performed by constant comparison. Results: Of the 5,975 findings, 20 studies (9 qualitative, 9 quantitative, 2 mixed) containing 58,534 participants were included. Patients' experience depends on various context factors. The studies describe a multifaceted experience of single room isolation. Isolation is perceived as a protection against threats; patients experience peace and privacy but are also confronted with restrictions in relation to mobility and contact. The studies mention that isolation has various psychological and social impacts, as well as effects on the perception of received care. Although often perceived as a heavy burden, the studies highlight the opportunity for self-reflection and to find inner strength. Discussion: Patients reported a complex, multidimensional, and inconsistent experience. Further research is needed to address differentiated causal relationships between the influencing factors and different experiences.