BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.
OBJECTIVES: To determine the safety and oncological advantages of en bloc resection of bladder tumour (ERBT) vs conventional transurethral resection of bladder tumour (cTURBT) in terms of resection quality, staging quality, and safety. PATIENTS AND METHODS: We conducted a single-blinded randomised controlled trial at seven European hospitals with the following inclusion criteria: first diagnosis of non-muscle-invasive bladder cancer, no singular carcinoma in situ, and tumour size >4.3 mm. Patients were randomised intraoperatively in a 1:1 ratio to either the ERBT or cTURBT group. Outcome analysis was performed using the chi-square test, t-test, and multivariate regression analysis. RESULTS: A total of 97 patients were randomised into the study (cTURBT = 40, ERBT = 57). A switch to cTURBT was necessary in two patients (3.5%) and 11.5% of the screened patients were preoperatively excluded for ERBT. There was no difference in the specimen presence of detrusor muscle with 73.7% in cTURBT and 67.3% in ERBT specimens (P = 0.69). There were no significant differences in mean operative time (ERBT 27.6 vs cTURBT 25.4 min, P = 0.450) or mean resection time (ERBT 16.3 vs cTURBT 15.5 min, P = 0.732). Overall the complication rate did not differ significantly (ERBT 18.2% vs cTURBT 7.5%, P = 0.142). Bladder perforations occurred significantly more often in the ERBT group (ERBT seven vs cTURBT none, P = 0.020). R0 status was reported more often after ERBT, whilst a second resection was significantly less frequent after ERBT (P = 0.018). Recurrence rates were comparable for both techniques after 6 months of follow-up. CONCLUSION: The feasibility of ERBT is higher than previously reported. Whereas other perioperative and safety parameters are comparable to cTURBT, bladder perforations occurred significantly more often in the ERBT group and raised safety concerns. This is why this trial was terminated.
- MeSH
- Cystectomy * methods adverse effects MeSH
- Single-Blind Method MeSH
- Carcinoma, Transitional Cell surgery pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Urinary Bladder Neoplasms * surgery pathology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Transurethral Resection of Bladder MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
BACKGROUND: The actions required to achieve higher-quality and harmonised global surveillance of child and adolescent movement behaviours (physical activity, sedentary behaviour including screen time, sleep) are unclear. OBJECTIVE: To identify how to improve surveillance of movement behaviours, from the perspective of experts. METHODS: This Delphi Study involved 62 experts from the SUNRISE International Study of Movement Behaviours in the Early Years and Active Healthy Kids Global Alliance (AHKGA). Two survey rounds were used, with items categorised under: (1) funding, (2) capacity building, (3) methods, and (4) other issues (e.g., policymaker awareness of relevant WHO Guidelines and Strategies). Expert participants ranked 40 items on a five-point Likert scale from 'extremely' to 'not at all' important. Consensus was defined as > 70% rating of 'extremely' or 'very' important. RESULTS: We received 62 responses to round 1 of the survey and 59 to round 2. There was consensus for most items. The two highest rated round 2 items in each category were the following; for funding (1) it was greater funding for surveillance and public funding of surveillance; for capacity building (2) it was increased human capacity for surveillance (e.g. knowledge, skills) and regional or global partnerships to support national surveillance; for methods (3) it was standard protocols for surveillance measures and improved measurement method for screen time; and for other issues (4) it was greater awareness of physical activity guidelines and strategies from WHO and greater awareness of the importance of surveillance for NCD prevention. We generally found no significant differences in priorities between low-middle-income (n = 29) and high-income countries (n = 30) or between SUNRISE (n = 20), AHKGA (n = 26) or both (n = 13) initiatives. There was a lack of agreement on using private funding for surveillance or surveillance research. CONCLUSIONS: This study provides a prioritised and international consensus list of actions required to improve surveillance of movement behaviours in children and adolescents globally.
- MeSH
- Capacity Building MeSH
- Screen Time * MeSH
- Global Health MeSH
- Exercise * MeSH
- Delphi Technique * MeSH
- Child MeSH
- Consensus MeSH
- Humans MeSH
- Adolescent MeSH
- Sedentary Behavior * MeSH
- Sleep MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
PURPOSE: The International Study of Movement Behaviors in the Early Years (SUNRISE) was conducted in Tunisia to assess the proportion of preschoolers who met the World Health Organization guidelines for physical activity, sedentary behavior, and sleep. The study also evaluated the feasibility of the methods for the SUNRISE study. METHODS: Five kindergartens were recruited from urban and rural areas in Tunisia. Physical activity and sleep duration were assessed using a waist-worn ActiGraph. Screen time and sleep quality were assessed via an interview-administered parent questionnaire. The NIH Toolbox was used. RESULTS: A total of 112 preschoolers were assessed (50 boys, age = 4.1 [0.58]). Only 18% of children met all recommendations of the World Health Organization guidelines, while 53% met the sedentary screen time (in minutes per day), and 41% met physical activity recommendation (in minutes per day). Eighty-one percent of children met the sleep duration recommendation (in minutes per day). There was good compliance with the ActiGraph protocol. CONCLUSIONS: This pilot study provided important insights into the feasibility of the study and the movement behaviors of Tunisian preschool children. The results suggest there is a need to promote healthy levels of physical activity and sedentary screen time in children, which should be a priority in public health initiatives, including preschool curricula, in Tunisia.
- MeSH
- Actigraphy MeSH
- Screen Time MeSH
- Exercise * MeSH
- Humans MeSH
- Pilot Projects MeSH
- Child, Preschool MeSH
- Surveys and Questionnaires MeSH
- Sedentary Behavior * MeSH
- Sleep * MeSH
- Feasibility Studies MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Tunisia MeSH
INTRODUCTION: The main goal of placenta accreta spectrum (PAS) screening is to enable delivery in an expert center in the presence of an experienced team at an appropriate time. Our study aimed to identify independent risk factors for emergency deliveries within the IS-PAS 2.0 database cohort and establish a multivariate predictive model. MATERIAL AND METHODS: A retrospective analysis of prospectively collected PAS cases from the IS-PAS database between January 2020 and June 2022 by 23 international expert centers was performed. All PAS cases (singleton and multiple pregnancies) managed according to local protocols were included. Individuals with emergent delivery were identified and compared to those with scheduled delivery. A multivariate analysis was conducted to identify the possible risk factors for emergency delivery and was used to establish a predictive model. Maternal outcomes were compared. RESULTS: Overall, 315 women were included in the study. Of these, 182 participants (89 with emergent and 93 with scheduled delivery) were included in the final analysis after exclusion of those with unsuspected PAS antenatally or who lacked information about the urgency of delivery. Gestational age at delivery was higher in the scheduled group (34.7 vs. 32.9, p < 0.001). Antenatal bleeding (OR 2.9, p = 0.02) and a placenta located over a uterine scar (OR 0.38, p = 0.001) were the independent predictive factors for emergent delivery (AUC 0.68). Ultrasound (US) markers: loss of clear zone (p = 0.001), placental lacunae (p = 0.01), placental bulge (p = 0.02), and presence of bridging vessels (p = 0.02) were more frequently documented in the scheduled group. None of these markers improved the predictive values of the model. Higher PAS grades were identified in the scheduled group (p = 0.01). There were no significant differences in maternal outcomes. CONCLUSIONS: Antenatal bleeding and the placental location away from the uterine scar remained the most significant predictors for emergent delivery among patients with PAS, even when combining more predictive risk factors, including US markers. Based on these results, patients who bleed antenatally may benefit from transfer to an expert center, as we found no differences in maternal outcomes between groups delivered in expert centers. Earlier-scheduled delivery is not supported due to the low predictive value of our model.
- MeSH
- Cesarean Section * statistics & numerical data MeSH
- Adult MeSH
- Humans MeSH
- Emergencies MeSH
- Placenta Accreta * diagnosis MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Pregnancy MeSH
- Delivery, Obstetric * statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Purine de novo purine synthesis involves 10 reactions catalysed by six enzymes, including phosphoribosylformyglycinamidine synthase (PFAS). To date, genetic defects of three of these enzymes, namely ATIC, ADSL and PAICS, have been characterised in humans. Here, we report for the first time two individuals with PFAS deficiency. Probands were identified through metabolic and genetic screening of neurologically impaired individuals. The pathogenicity of the variants was established by structural and functional studies. Probands C1 and C2 presented with prematurity, short stature, recurrent seizures and mild neurological impairment. C1 had elevated urinary levels of formylglycineamide riboside (FGAr) and bi-allelic PFAS variants encoding the NP_036525.1:p.Arg811Trp substitution and the NP_036525.1:p.Glu228_Ser230 in-frame deletion. C2 is a 20-year-old female with a homozygous NP_036525.1:p.Asn264Lys substitution. These amino acid changes are predicted to affect the structural stability of PFAS. Accordingly, C1 skin fibroblasts showed decreased PFAS content and activity, with impaired purinosome formation that was restored by transfection with pTagBFP_PFAS_wt. The enzymatic activities of the corresponding recombinant mutant PFAS proteins were also reduced, and none of them, after transfection, corrected the elevated FGAR/r levels in PFAS-deficient HeLa cells. While genetic defects in purine de novo synthesis are typically considered in patients with severe neurological impairment, these disorders, especially PFAS deficiency, should also be considered in milder phenotypes.
- MeSH
- Humans MeSH
- Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor * genetics deficiency metabolism MeSH
- Young Adult MeSH
- Mutation MeSH
- Purine-Pyrimidine Metabolism, Inborn Errors * genetics MeSH
- Child, Preschool MeSH
- Purines * biosynthesis MeSH
- Check Tag
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
BACKGROUND: Severe combined immunodeficiency (SCID) is a fatal but treatable inborn error of immunity (IEI). Newborn screening (NBS) using T-cell receptor excision circles (TREC) has been adopted globally, with very few countries incorporating kappa recombination excision circles (KREC) to also detect early B-cell development disorders, such as X-linked agammaglobulinemia (XLA). OBJECTIVE: To evaluate the effectiveness of a 2-year pilot SCID NBS program in the Czech Republic, emphasising the utility of combined TREC/KREC screening. METHODS: Between January 2022 and December 2023, a dual TREC/KREC NBS pilot was conducted across the Czech Republic, alongside spinal muscular atrophy (SMA) screening. Approximately 200,000 newborns were screened using quantitative real-time PCR on dried blood spots collected 48-72 h after birth. RESULTS: The pilot referred 58 newborns, identifying 21 cases of IEI, including two SCID cases, with an overall incidence of TREC/KREC screenable IEI of 10.5/100,000 newborns. SCID incidence was 1/100,000. KREC screening proved invaluable, detecting 10 cases of congenital agammaglobulinemia including novel non-XLA forms, which increased the estimated incidence of agammaglobulinemia in the Czech Republic sixfold. Over one-third of low KREC results were linked to maternal immunosuppression. CONCLUSION: The Czech pilot demonstrated the effectiveness of integrated TREC/KREC NBS in detecting both T- and B-cell immunodeficiencies. As of 2024, SCID and SMA screening are included in the nationwide NBS, with KREC screening significantly improving early detection of B-cell disorders.
- MeSH
- Agammaglobulinemia diagnosis MeSH
- B-Lymphocytes immunology MeSH
- Genetic Diseases, X-Linked MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Neonatal Screening * methods MeSH
- Pilot Projects MeSH
- Receptors, Antigen, T-Cell * genetics MeSH
- Severe Combined Immunodeficiency * diagnosis genetics epidemiology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
Multidisciplinární tým Pneumologické kliniky 2. LF UK a FN Motol v roce 2024 projednal 454 případů nemocných s plicním karcinomem; odoperovaných bylo v tom roce 70 (16 %). Mezi operovanými převažovali nemocní s adenokarcinomem (52 %) ve stadiích I–IIIB podle klasifikace TNM (rozsah primárního nádoru T, postižení mízních uzlin N a přítomnost vzdálených metastáz M). 18 operovaným jsme podali imunochemoterapii jako neoadjuvantní léčbu, u 61 % z nich došlo ke kompletní patologické regresi. Z operačních výkonů převažovaly významně lobektomie (86 %), pouze 1 výkon skončil explorativní thorakotomií. Shody mezi stadiem určeným klinicky a patologem jsme dosáhli v 55 %. Do 30 dnů po operaci nikdo nezemřel. Současné výsledky operativy plicního karcinomu jsme srovnali s podobnými sestavami nemocných z ambulantního i klinických pracovišť z posledních 45 let. Během této doby se počet indikací k resekční léčbě nezvýšil. Změnilo se zastoupení morfologických typů plicního karcinomu (nárůst adenokarcinomů), provedené výkony u operovaných (jednoznačně dnes převažují lobektomie) a mírně se zvýšil počet operovaných ve stadiích IIIA a IIIB. Shoda mezi klinicky zhodnoceným rozsahem nádoru a jeho skutečnou velikostí stanovenou patologem zůstává jako v minulosti na velmi dobré úrovni, a je srovnatelná s výsledky nejvyspělejších center ve světě. Počet indikací k resekci je závislý na včasnosti diagnostiky. V současnosti diagnostikujeme ve stadiích TNM I a II méně než 20 % nemocných s plicním karcinomem. Možné zlepšení vidíme ve zvýšení počtu účastníků screeningu karcinomu plic pomocí nízkodávkového CT, které je u nás dobře organizované a dostupné všem zájemcům od roku 2022. Dosud známé výsledky tohoto screeningu potvrzují 57% zastoupení I. a II. stadia TNM u takto zjištěných pacientů.
In 2024, the multidisciplinary team of the Department of Pulmonology, 2nd Faculty of Medicine, Charles University and Motol University Hospital discussed 454 cases of patients with lung cancer; There were 70 (16%) operated on that year. Patients with adenocarcinoma (52%) in TNM stages I to IIIB prevailed among the operated patients. We administered immunochemotherapy as neoadjuvant treatment to 18 of the operated patients, and 61% of them experienced complete pathological regression. Lobectomies (86%) were significantly more prevalent among surgical procedures, only once the procedure ended with exploratory thoracotomy. We have achieved a 55% agreement between cTNM and pTNM. No one died within 30 days after the operation. We compared the current results of lung cancer surgery with similar groups of patients from outpatient and clinical departments from the last 45 years. During this time, the number of indications for resection treatment did not increase. The proportion of morphological types of lung carcinoma has changed (increase in adenocarcinomas), procedures performed in patients (lobectomies clearly predominate today) and the number of patients operated on in stages IIIA and IIIB has increased slightly. The agreement between the clinically evaluated extent of the tumor and its actual size determined by the pathologist remains at a very good level, as in the past, and is comparable to the results of the most advanced centers in the world. The number of indications for resection depends on the timeliness of diagnosis. At present, less than 20% of patients with lung cancer are diagnosed in TNM stages I and II. We see a possible improvement in the increase in the number of participants in lung cancer screening using low-dose CT, which is well organized and available to all interested parties from 2022. The results of this screening known so far confirm a 57% representation of stages I and II of TNM in patients detected in this way.
- MeSH
- Chemoradiotherapy, Adjuvant MeSH
- Middle Aged MeSH
- Humans MeSH
- Lung Neoplasms surgery diagnosis therapy MeSH
- Neoadjuvant Therapy MeSH
- Observational Studies as Topic MeSH
- Retrospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: The effect of human papillomavirus (HPV) vaccination on cervical intraepithelial neoplasia grade 2 or worse (CIN2+) recurrence with respect to cone margin positivity is unknown. Most studies assessed this effect beyond two months post-conisation. We aimed to determine both the duration and early onset of effect in women who had been prophylactically vaccinated or vaccinated after conisation, considering cone margin status. METHODS: This cohort study used data from one of the central laboratories in the Czech Republic, covering approximately 33% of women undergoing national cervical cancer screening. It included women treated for CIN2+ between 2010 and 2024 who had received either prophylactic HPV vaccination (available through the national immunisation program since 2011) or post-conisation vaccination (recommended by the Czech Gynaecological and Obstetrical Society since 2008). The vaccination effect was estimated using the incidence rate ratio (IRR) from a Poisson regression model, calculated as 100 × (1-IRR). FINDINGS: Of the 10,054 women enrolled, 919 were vaccinated after conisation, 502 prophylactically, and 169 had undetermined timing of vaccination. Throughout the follow-up period, CIN2+ recurrence was observed in 513 unvaccinated women, with a rate of 14·61 per 1000 person-years (py), in 14 prophylactically vaccinated women, with a rate of 5·84 (54% reduction; 95% confidence interval [CI]: 22-73%), and in 15 women vaccinated post-excision, with a rate of 3·37 (74% reduction; 95% CI: 57-85%). The high recurrence rate of 58·59 per 1000 py within six months of conisation was reduced by 80% (95% CI: 19-95%) with prophylactic vaccination and by 89% (95% CI: 57-97%) with incomplete post-excision vaccination. Among a total of 1771 women with a positive cone margin, recurrence was identified in 272 of 1568 unvaccinated women, corresponding to a recurrence rate of 51·62 per 1000 py. A reduction was observed in 84 prophylactically vaccinated and in 119 women vaccinated post-excision, with only 6 recurrence cases documented in each group. This corresponded to recurrence rates of 14·94 (62% reduction; 95% CI: 14-83%) and 9·78 per 1000 py (79% reduction; 95% CI: 52-90%), respectively. INTERPRETATION: Regardless of timing, HPV vaccination has a beneficial long-term effect in lowering the risk of CIN2+ recurrence. Despite the greater reduction in relapse achieved by post-excision vaccination, the difference compared with the prophylactic one was not statistically significant. The most pronounced benefit was observed within the first six months post-conisation, particularly in women with a positive cone margin. FUNDING: Cooperatio 31 fund, Health Sciences, Charles University, Prague, Czech Republic.
- Publication type
- Journal Article MeSH
A series of triterpenoids of the lupane, taraxastane, friedelane and baccharane type were oxidized using selenium dioxide (SeO2) and benzeneseleninic anhydride (BSA) under various conditions. Depending on the reaction conditions, different reaction pathways were observed, including dehydrogenation, allylic oxidation, and 1,2-diketone formation. In this way, derivatives functionalized in the triterpene core (especially in rings A, D, and E), difficult to obtain by other methods, can be easily prepared. In some cases, rarely observed α-phenylseleno-ketones were isolated. An unexpected reaction involving the cleavage of the carbon-carbon double bond was observed in the presence of stoichiometric amounts of osmium tetroxide. Further transformations of selected intermediates facilitated the synthesis of new, functionally enriched derivatives. The key reaction pathways were investigated using density functional theory (DFT), focusing on bond length variations and transition states, revealing energetically favored pathways and critical transition structures, including covalent and noncovalent interactions. Solvent and isomerization equilibrium effects were proposed to explain the experimentally observed discrepancies. Cytotoxic activity of selected derivatives was investigated. Derivatives 4 and 38 showed strongest cytotoxicity in cancer cells and fibroblasts (IC50 2.6-26.4 μM); some compounds were selective for G-361 or HeLa cells. These results suggest that they may find application in pharmaceuticals.
- MeSH
- Humans MeSH
- Molecular Structure MeSH
- Cell Line, Tumor MeSH
- Oxidation-Reduction MeSH
- Pentacyclic Triterpenes MeSH
- Cell Proliferation drug effects MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis MeSH
- Drug Screening Assays, Antitumor MeSH
- Selenium * chemistry MeSH
- Density Functional Theory MeSH
- Triterpenes * chemistry pharmacology chemical synthesis MeSH
- Dose-Response Relationship, Drug MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
