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Global obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus-based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two-round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence-based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.
Super-resolution (SR) microscopy is a cutting-edge method that can provide detailed structural information with high resolution. However, the thickness of the specimen has been a major limitation for SR methods, and large biological structures have posed a challenge. To overcome this, the key step is to optimise sample preparation to ensure optical homogeneity and clarity, which can enhance the capabilities of SR methods for the acquisition of thicker structures. Oocytes are the largest cells in the mammalian body and are crucial objects in reproductive biology. They are especially useful for studying membrane proteins. However, oocytes are extremely fragile and sensitive to mechanical manipulation and osmotic shocks, making sample preparation a critical and challenging step. We present an innovative, simple and sensitive approach to oocyte sample preparation for 3D STED acquisition. This involves alcohol dehydration and mounting into a high refractive index medium. This extended preparation procedure allowed us to successfully obtain a unique two-channel 3D STED SR image of an entire mouse oocyte. By optimising sample preparation, it is possible to overcome current limitations of SR methods and obtain high-resolution images of large biological structures, such as oocytes, in order to study fundamental biological processes. Lay Abstract: Super-resolution (SR) microscopy is a cutting-edge tool that allows scientists to view incredibly fine details in biological samples. However, it struggles with larger, thicker specimens, as they need to be optically clear and uniform for the best imaging results. In this study, we refined the sample preparation process to make it more suitable for SR microscopy. Our method includes carefully dehydrating biological samples with alcohol and then transferring them into a mounting medium that enhances optical clarity. This improved protocol enables high-resolution imaging of thick biological structures, which was previously challenging. By optimizing this preparation method, we hope to expand the use of SR microscopy for studying large biological samples, helping scientists better understand complex biological structures.
OBJECTIVE: From 1995, the European Association of Hospital Pharmacists (EAHP) has regularly investigated the progress of the hospital pharmacy profession in Europe, and identified key barriers and drivers of this. The most recent 'Investigation of the Hospital Pharmacy Profession in Europe' was conducted from November 2022 to March 2023. METHODS: The online questionnaire was sent to all hospital pharmacies in EAHP member countries. The investigation was drafted using the same questions as the 2015 baseline survey. Where possible and relevant, responses were compared with the data from previous surveys that monitored the implementation of the EAHP statements. Keele University, Centre for Medicines Optimisation, School of Pharmacy and Bioengineering, UK analysed the data. RESULTS: The overall number of responses was 653, with a better response rate of 19% compared with 14% in 2018 statements survey. The findings indicated that participating hospital pharmacies have similar characteristics to previous surveys. Section 1 (Introductory statements and governance), section 2 (Selection, procurement and distribution), section 3 (Production and compounding), section 5 (Patient safety and quality assurance) questions were generally answered positively, with results ranging from 52% to 90%. However, results for section 4 (Clinical pharmacy services) returned lower levels of positivity, with responses from 8 of the 15 questions being less than 60%. When asked what is preventing hospital pharmacists from achieving implementation of these activities, most answers were limited capacity, not considered to be a priority by managers, or other healthcare professionals do this. The last section focused on self-assessment and action planning, with fewer than 50% of positive responses; COVID-19 preparedness and vaccines with mixed positive and negative responses. Furthermore, implementation of the falsified medicines directive impacted the medication handling processes in 50% or more of the answers. Regarding sustainability, the majority (59%) of respondents felt a greater focus should be on sustainability from an organisational or management perspective. CONCLUSION: Results offer valuable insights into the hospital pharmacy profession throughout Europe. While there have been improvements in certain areas, challenges remain, particularly in implementing clinical pharmacy services. The findings provide a foundation for further dialogue, advocacy, and strategic planning to advance the role of hospital pharmacists and enhance patient care in Europe's healthcare systems.
- MeSH
- COVID-19 epidemiologie MeSH
- farmaceuti * trendy MeSH
- lidé MeSH
- nemocniční lékárny * trendy organizace a řízení statistika a číselné údaje normy MeSH
- průzkumy a dotazníky MeSH
- role odborníka * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
Background: Adverse drug reactions (ADRs), particularly in the context of polypharmacy, remain a persistent, unresolved problem for patients and healthcare professionals. The ADRe Profile identifies medicine-related harms, and supports their resolution, thereby improving care quality and preventing future problems. Objective: The objective of this study was to assess the validity and reliability of the ADRe Profile (https://www.swansea.ac.uk/adre/) in U.K. primary care general practices, building on assessments in other settings. Methods: The ADRe Profile's validity and reliability were investigated using complementary mixed methods: content validity index, contrast group construct validity, cognitive interviewing, and inter-rater reliability. Results: Cognitive interviews (n = 5) confirmed that the ADRe Profile needed only minor adjustments. The scale-level content validity index was 0.67 (n = 14), items ranging from 0.08 to 1. Significant differences in signs and symptoms associated with ADRs between service users taking different numbers of regular prescribed medicines confirmed construct validity (n = 68, U = 870.50, p < 0.001). Inter-rater reliability testing showed substantial agreement between service users and research nurse: 10 items had 100% agreement. Overall kappa mean was 0.71 (range: 0.31-1), (n = 42). Conclusions and Relevance: The ADRe Profile is suitable for use with older service users in primary care who live at home. Users understood the questions and provided meaningful answers. ADRe Profile responses were sufficiently reliable to be used as a basis for further investigations, prescriber referral and clinical actions. However, clinician judgement of content validity may depend on knowledge and experience, highlighting the importance of training. Clinicians acknowledged that the ADRe Profile was comprehensive but identified practical difficulties. Instruments to reduce ADRs should be validated before testing in feasibility studies and randomised controlled trials. Implications for Nursing Management: Managers need to optimise patient safety by introducing patient-centred symptom monitoring, with decision support. Before instruments are adopted, managers should check the reliability and validity data. Trial Registration: ClinicalTrials.gov identifier: NCT04663360.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- nežádoucí účinky léčiv * prevence a kontrola MeSH
- polypharmacy MeSH
- průzkumy a dotazníky MeSH
- psychometrie * přístrojové vybavení metody normy MeSH
- reprodukovatelnost výsledků MeSH
- senioři nad 80 let MeSH
- senioři 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
- randomizované kontrolované studie MeSH
- validační studie MeSH
- Geografické názvy
- Spojené království MeSH
Uroteliální karcinom (UC) představuje závažný onkologický problém s vysokou mortalitou, zejména u pokročilých stadií. Adjuvantní terapie, ať už chemoterapie, nebo imunoterapie, hraje klíčovou roli ve snižování rizika relapsu a zlepšení přežití po radikální operaci. Tento přehled shrnuje současné poznatky o využití adjuvantní léčby u UC a uroteliálního karcinomu horních cest močových (UTUC), včetně jeho histologických variant. Nejlépe etablovanou modalitou je chemoterapie na bázi cisplatiny, která prokázala přínos zejména u pacientů s vysokým rizikem relapsu (pT3-4, N+) bez předchozí neoadjuvantní chemoterapie. Významný průlom přinesla imunoterapie, zejména nivolumab, jehož účinnost byla potvrzena v randomizované studii CheckMate 274, přičemž největší benefit byl pozorován u pacientů s vysokou expresí PD-L1. Problematické zůstává postavení adjuvantní terapie u histologických variant UC, kde je potřeba dalšího výzkumu. Budoucí směřování adjuvantní léčby zahrnuje identifikaci prediktivních biomarkerů, včetně ctDNA, a vývoj personalizovaných strategií, které zohlední molekulární a imunitní charakteristiky nádoru. Optimalizace selekce pacientů pomocí tekutých biopsií a dalších biomarkerů je klíčem ke zlepšení dlouhodobých výsledků.
Urothelial carcinoma (UC) represents a significant oncological challenge with high mortality, particularly in advanced stages. Adjuvant therapy, whether chemotherapy or immunotherapy, plays a crucial role in reducing the risk of relapse and improving survival after radical surgery. This review summarises current knowledge on the use of adjuvant treatment in UC and upper tract urothelial carcinoma (UTUC), including its histological variants. The most established modality remains cisplatin-based chemotherapy, which has demonstrated benefits, particularly in patients at high risk of relapse (pT3-4, N+) without prior neoadjuvant chemotherapy. A major breakthrough has been the introduction of immunotherapy, especially nivolumab, whose efficacy was confirmed in the randomised CheckMate 274 trial, with the most significant benefit observed in patients with high PD-L1 expression. The role of adjuvant therapy in histological variants of UC remains unclear and requires further research. The future direction of adjuvant treatment involves the identification of predictive biomarkers, including circulating tumour DNA (ctDNA) and developing personalised strategies that consider the molecular and immune characteristics of the tumour. Optimising patient selection using liquid biopsies and other biomarkers is key to improving long-term outcomes.
- MeSH
- adjuvantní chemoterapie MeSH
- imunoterapie metody MeSH
- karcinom z přechodných buněk * farmakoterapie MeSH
- lidé MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- randomizované kontrolované studie jako téma MeSH
- urologické nádory farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
The design of MB327, a bispyridinium compound that ameliorates the nicotinic effects of acute organophosphorus nerve agent (NA) intoxication, followed an observation made by the German pharmacologist Klaus Schoene in the 1970s, who noted therapeutic activity in bispyridinium molecules missing the usual oxime group, CHNOH. Some of these compounds protected mice against soman. One structurally related to obidoxime called HY10 had this action. Its oxime moieties were capped by tert-butyl groups: CH=NOtBu. We modified HY10 by changing the bridge between the pyridinium units from a dimethylene ether to a trimethylene group (CH2OCH2 → CH2CH2CH2) and prepared a novel relative of trimedoxime, called LB1, whose synthesis and stereochemistry are described. Unlike obidoxime or trimedoxime, LB1 because of its capped oxime groups, cannot directly reactivate NA inhibited acetylcholinesterase. Its antidotal activity in mice is now reported. The therapeutic efficacy of LB1, atropine alone, atropine with LB1, atropine with an oxime (HI-6, obidoxime or trimedoxime), and atropine with an oxime and LB1, was studied by determining the LD50 values of the NAs soman, sarin, or tabun in mice treated with these compounds or mixtures. LB1 exceeded MB327 in toxicity and its activity was insufficient for a useful addition to the current standard antidotal treatment (protective ratio data are compared to those of MB327). Although this study produced largely negative biological results, the therapeutically beneficial mechanism of the effective bispyridinium non-oxime analogues is unclear, and has been demonstrated only in vivo. The present study points out directions in structural optimisation unlikely to yield the desired therapeutic outcomes and provides a literature review that could promote creative thinking for the design of widely-desirable non-oxime therapeutics for anticholinesterase inhibitors.
- MeSH
- acetylcholinesterasa metabolismus MeSH
- antidota * chemická syntéza chemie farmakologie terapeutické užití MeSH
- atropin terapeutické užití farmakologie MeSH
- cholinesterasové inhibitory toxicita MeSH
- myši MeSH
- nervová bojová látka * toxicita MeSH
- organofosforové sloučeniny * toxicita MeSH
- oximy chemie MeSH
- pyridinové sloučeniny * chemická syntéza chemie terapeutické užití farmakologie MeSH
- soman toxicita MeSH
- trimedoxim chemie chemická syntéza farmakologie terapeutické užití MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Background: The care provided to women during pregnancy, childbirth, and postpartum contributes to optimising well-being and health. Care for both the woman and the newborn should be individualised, supporting free choice in providing care. An essential part of childbirth is bonding, which supports the relationship between the woman and the newborn. Goal: This paper aims to inform about partial data and examine mutual connections regarding the experience of childbirth, midwife, and paediatric nurse care for women and newborns in the early postpartum period in South Bohemian obstetrics wards. Methods: This research used a quantitative method. The data were processed in SPSS and SASD programs. The research group consisted of 361 women; the selection criteria were at least 6 weeks and a maximum of 9 months after childbirth in South Bohemian obstetrics wards. Results: 73.4% of women perceived support from the midwife during childbirth, and 58.7% perceived childbirth as a natural process. Women with complications during childbirth were more likely to perceive the experience of childbirth as average. Women who had psychological difficulties during pregnancy perceived more fear during childbirth. Women who experienced bonding in the delivery room were most satisfied. Conclusion: Women should be informed and prepared for labour and delivery to know what to expect. Health professionals need to receive information from women so that they can provide holistic care and thus support their positive motherhood experience.
- MeSH
- lidé MeSH
- novorozenec MeSH
- poporodní období * psychologie MeSH
- porod MeSH
- porodní asistentky MeSH
- porodní sály MeSH
- průzkumy a dotazníky MeSH
- spokojenost pacientů * statistika a číselné údaje MeSH
- těhotné ženy MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Identification of real-time adverse drug reactions [ADRs] (as opposed to the risk of ADRs) in older poly-medicated people in primary care is a challenging task, often undertaken without an explicit strategy. This systematic review aims to evaluate replicable instruments and methods for identifying and addressing ADRs. METHODS: A systematic search was conducted in Medline, CINAHL, Scopus, Web of Science and Cochrane library, using controlled vocabulary (MeSH) and free-text terms. Randomised controlled trials (RCTs) implementing strategies to identify or resolve ADRs experienced by patients in primary care were included. Two reviewers independently screened studies, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias tool. Discrepancies were resolved by discussion. RESULTS: From 2,182 unique records, 49 studies were identified for full review. Eight papers reporting results from 6 RCTs were included. All six trials utilised a list of medicine-related unwanted symptoms to identify ADRs. Two of three studies using adverse drug reaction questionnaires reported statistically significant increased rates of ADR reporting. Two of three studies that combined symptom questionnaires with prescriber consultations reported reductions in the number of health problems. Overall, results suggest that the three studies that described multidisciplinary collaborations using lists of ADRs plus prescriber reviews enhanced patient safety. However, the RCTs were unblinded and reported suboptimal retention. When considered as a whole, findings are equivocal and the data are too heterogenous to warrant any firm conclusions, beyond the need for more research to optimise strategies to safeguard patient wellbeing. IMPLICATIONS: Adaptable and scalable instruments with decision support are needed in primary care to identify and mitigate medicine-related harm in older poly-medicated people. The effectiveness of adverse drug reaction identification instruments, the value of comprehensive instruments, and the optimum method of delivery should be explored in multicentre trials.
In less than a decade, immune checkpoint inhibitors (ICIs) have transformed the management of mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI) cancers. However, beyond colorectal cancer (CRC), much of the evidence is mostly derived from non-randomized phase II studies or post-hoc analyses of broader clinical trials. dMMR/MSI tumours represent a specific subgroup of gastro-esophageal adenocarcinomas (GEA), accounting for approximately 9 % of cases, with a higher prevalence in early-stage compared to advanced-stage disease and older female patients. These tumours are predominantly sporadic, often linked to MLH1 promoter methylation, and rarely exhibit HER2 overexpression/ERBB2 amplification or other oncogenic drivers. The treatment landscape for early stage dMMR/MSI GEA is likely to change substantially soon, as ICIs have shown high pathological complete response (pCR) rates in small phase II trials, raising questions on optimisation of neoadjuvant therapy, and paving the way for organ preservation. The standard of treatment for untreated patients with advanced dMMR/MSI GEA is chemotherapy + ICI irrespectively of PDL-1 status. However, the role of chemotherapy-free regimen consisting of CTLA-4 plus PD-1 inhibitors remains undetermined. This review addresses these and other emerging questions, offering expert opinions and insights into the future therapeutic landscape for dMMR/MSI GEA.
- MeSH
- adenokarcinom * farmakoterapie genetika patologie terapie MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- lidé MeSH
- mikrosatelitní nestabilita * MeSH
- nádory jícnu * farmakoterapie genetika patologie MeSH
- nádory žaludku * farmakoterapie genetika patologie terapie MeSH
- oprava chybného párování bází DNA * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The Satisfaction With Life Scale (SWLS) is a widely used self-report measure of subjective well-being, but studies of its measurement invariance across a large number of nations remain limited. Here, we utilised the Body Image in Nature (BINS) dataset-with data collected between 2020 and 2022 -to assess measurement invariance of the SWLS across 65 nations, 40 languages, gender identities, and age groups (N = 56,968). All participants completed the SWLS under largely uniform conditions. Multi-group confirmatory factor analysis indicated that configural and metric invariance was upheld across all nations, languages, gender identities, and age groups, suggesting that the unidimensional SWLS model has universal applicability. Full scalar invariance was achieved across gender identities and age groups. Based on alignment optimisation methods, partial scalar invariance was achieved across all but three national groups and across all languages represented in the BINS. There were large differences in latent SWLS means across nations and languages, but negligible-to-small differences across gender identities and age groups. Across nations, greater life satisfaction was significantly associated with greater financial security and being in a committed relationship or married. The results of this study suggest that the SWLS largely assesses a common unidimensional construct of life satisfaction irrespective of respondent characteristics (i.e., national group, gender identities, and age group) or survey presentation (i.e., survey language). This has important implications for the assessment of life satisfaction across nations and provides information that will be useful for practitioners aiming to promote subjective well-being internationally.
- MeSH
- dospělí MeSH
- faktorová analýza statistická MeSH
- genderová identita * MeSH
- jazyk (prostředek komunikace) MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- osobní uspokojení * MeSH
- průzkumy a dotazníky MeSH
- psychometrie metody MeSH
- senioři MeSH
- věkové faktory MeSH
- zpráva o sobě MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH