OBJECTIVES: Olfactory dysfunction (OD) is common and carries significant personal and societal burden. Accurate assessment is necessary for good clinical and research practice but is highly dependent on the assessment technique used. Current practice with regards to UK/international clinical assessment is unknown. We aimed to capture current clinical practice, with reference to contemporaneously available guidelines. We further aimed to compare UK to international practice. DESIGN: Anonymous online questionnaire with cross-sectional non-probability sampling. Subgroup analysis according to subspeciality training in rhinology ('rhinologists' and 'non-rhinologists') was performed, with geographical comparisons only made according to subgroup. PARTICIPANTS: ENT surgeons who assess olfaction. RESULTS: Responses were received from 465 clinicians (217 from UK and 17 countries total). Country-specific response rate varied, with the lowest rate being obtained from Japan (1.4%) and highest from Greece (72.5%). Most UK clinicians do not perform psychophysical smell testing during any of the presented clinical scenarios-though rhinologists did so more often than non-rhinologists. The most frequent barriers to testing related to service provision (e.g., time/funding limitations). Whilst there was variability in practice, in general, international respondents performed psychophysical testing more frequently than those from the UK. Approximately 3/4 of all respondents said they would like to receive training in psychophysical smell testing. Patient reported outcome measures were infrequently used in the UK/internationally. More UK respondents performed diagnostic MRI scanning than international respondents. CONCLUSIONS: To our knowledge, this is the most comprehensive UK-based, and only international survey of clinical practice in the assessment of OD. We present recommendations to improve practice, including increased education and funding for psychophysical smell testing. We hope this will promote accurate and reliable olfactory assessment, as is the accepted standard in other sensory systems.
- MeSH
- čich * fyziologie MeSH
- hodnocení výsledků péče pacientem MeSH
- lidé MeSH
- poruchy čichu * diagnóza MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- stupeň vzdělání MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Impaired physical performance and muscle strength are recognized risk factors for fragility fractures, frequently associated with osteoporosis and sarcopenia. However, the integration of muscle strength and physical performance in the comprehensive assessment of fracture risk is still debated. Therefore, this cross-sectional study aimed to assess the potential role of hand grip strength (HGS) and short physical performance battery (SPPB) for predicting fragility fractures and their correlation with Fracture Risk Assessment Tool (FRAX) with a machine learning approach. METHODS: In this cross-sectional study, a group of postmenopausal women underwent assessment of their strength, with the outcome measured using the HSG, their physical performance evaluated using the SPPB, and the predictive algorithm for fragility fractures known as FRAX. The statistical analysis included correlation analysis using Pearson's r and a decision tree model to compare different variables and their relationship with the FRAX Index. This machine learning approach allowed to create a visual decision boundaries plot, providing a dynamic representation of variables interactions in predicting fracture risk. RESULTS: Thirty-four patients (mean age 63.8±10.7 years) were included. Both HGS and SPPB negatively correlate with FRAX major (r=-0.381, P=0.034; and r=-0.407, P=0.023 respectively), whereas only SPPB significantly correlated with an inverse proportionality to FRAX hip (r=-0.492, P=0.001). According to a machine learning approach, FRAX major ≥20 and/or hip ≥3 might be reported for an SPPB<6. Concurrently, HGS<17.5 kg correlated with FRAX major ≥20 and/or hip ≥3. CONCLUSIONS: In light of the major findings, this cross-sectional study using a machine learning model related SPPB and HGS to FRAX. Therefore, a precise assessment including muscle strength and physical performance might be considered in the multidisciplinary assessment of fracture risk in post-menopausal women.
- MeSH
- hodnocení rizik MeSH
- kostní denzita * fyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteoporotické fraktury * epidemiologie etiologie MeSH
- postmenopauza MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- síla ruky MeSH
- tělesná a funkční výkonnost MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Membrane transporters are important determinants of drug bioavailability. Their expression and activity affect the intracellular drug concentration in leukemic cells impacting response to therapy. Pharmacogenomics represents genetic markers that reflect allele arrangement of genes encoding drug transporters associated with treatment response. In previous work, we identified SNP rs460089 located in the promotor of SLC22A4 gene encoding imatinib transporter OCTN1 as influential on response of patients with chronic myeloid leukemia treated with imatinib. Patients with rs460089-GC pharmacogenotype had significantly superior response to first-line imatinib treatment compared to patients with rs460089-GG. This study investigated whether pharmacogenotypes of rs460089 are associated with sustainability of treatment-free remission (TFR) in patients from the EUROpean Stop Kinase Inhibitor (EURO-SKI) trial. In the learning sample, 176 patients showed a significantly higher 6-month probability of molecular relapse free survival (MRFS) in patients with GC genotype (73%, 95% CI: 60-82%) compared to patients with GG (51%, 95% CI: 41-61%). Also over time, patients with GC genotype had significantly higher MRFS probabilities compared with patients with GG (HR: 0.474, 95% CI: 0.280-0.802, p = 0.0054). Both results were validated with data on 93 patients from the Polish STOP imatinib study. In multiple regression models, in addition to the investigated genotype, duration of TKI therapy (EURO-SKI trial) and duration of deep molecular response (Polish study) were identified as independent prognostic factors. The SNP rs460089 was found as an independent predictor of TFR.
- MeSH
- antitumorózní látky * škodlivé účinky MeSH
- chronická myeloidní leukemie * farmakoterapie genetika MeSH
- imatinib mesylát terapeutické užití MeSH
- inhibitory proteinkinas terapeutické užití MeSH
- lidé MeSH
- membránové transportní proteiny terapeutické užití MeSH
- prognóza MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.
- MeSH
- akutní promyelocytární leukemie * diagnóza farmakoterapie epidemiologie MeSH
- dospělí MeSH
- incidence MeSH
- lidé MeSH
- patologická kompletní odpověď MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- sekundární malignity * farmakoterapie MeSH
- tretinoin MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT). RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.
PURPOSE: The AIEOP-BFM ALL 2009 protocol included, at the end of the induction phase, a randomized study of patients with high-risk (HR) ALL to investigate if an intensive exposure to pegylated L-asparaginase (PEG-ASNASE, 2,500 IU/sqm once a week × 4) on top of BFM consolidation phase IB allowed us to decrease minimal residual disease (MRD) and improve outcome. PATIENTS AND METHODS: A total of 1,097 patients presented, from June 2010 to February 2017, with one or more of the following HR criteria: KMT2A::AFF1 rearrangement, hypodiploidy, prednisone poor response, poor bone marrow response at day 15 (Flow MRD ≥10%), or no complete remission (CR) at the end of induction. Of them, 809 (85.1%) were randomly assigned to receive (404) or not receive (405) four weekly doses of PEG-ASNASE. RESULTS: By intention to treat (ITT) analysis, there was no significant difference in the proportion of patients with polimerase chain reaction MRD ≥5 × 10-4 at the end of phase IB in the experimental versus control arm (13.9% v 17.0%, P = .25). The 5-year event-free survival (median follow-up 6.3 years) by ITT in the experimental and control arms was 70.4% (2.3) versus 75.0% (2.2; P = .18), and the 5-year overall survival was 81.5% (2.0) versus 84.0% (1.9; P = .25), respectively. The corresponding 5-year cumulative incidence of death in CR was 9.5% (1.5) versus 5.7% (1.2; P = .08), and that of relapse was 17.7% (1.9) versus 17.2% (1.9), respectively (P = .94). Adverse reactions in phase IB occurred in 22.2% and 8.9% of patients in the experimental and control arm, respectively (P < .001). CONCLUSION: Additional PEG-ASNASE in phase IB did not translate into a benefit for decreasing relapse incidence but was associated with higher toxicity. Further improvements with conventional chemotherapy might be difficult in the context of intensive treatment protocols.
- MeSH
- akutní lymfatická leukemie * MeSH
- asparaginasa * MeSH
- kojenec MeSH
- lidé MeSH
- lokální recidiva nádoru farmakoterapie MeSH
- polyethylenglykoly MeSH
- prednison škodlivé účinky MeSH
- přežití po terapii bez příznaků nemoci MeSH
- protokoly antitumorózní kombinované chemoterapie škodlivé účinky MeSH
- randomizované kontrolované studie jako téma MeSH
- recidiva MeSH
- výsledek terapie MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
BACKGROUND: Faecal microbiota transplantation (FMT) is the standard treatment for patients with multiple recurrent Clostridioides difficile infection (rCDI). Recently, new commercially developed human microbiota-derived medicinal products have been evaluated and Food and Drug Administration-approved with considerable differences in terms of composition, administration, and targeted populations. OBJECTIVES: To review available data on the different microbiota-derived treatments at the stage of advanced clinical evaluation and research in rCDI in comparison with FMT. SOURCES: Phase II or III trials evaluating a microbiota-derived medicinal product to prevent rCDI. CONTENT: Two commercial microbiota-derived medicinal products are approved by the Food and Drug Administration: Rebyota (RBX2660 Ferring Pharmaceuticals, marketed in the United States) and VOWST (SER-109 -Seres Therapeutics, marketed in the United States), whereas VE303 (Vedanta Biosciences Inc) will be studied in phase III trial. RBX2660 and SER-109 are based on the processing of stools from healthy donors, whereas VE303 consists of a defined bacterial consortium originating from human stools and produced from clonal cell banks. All have proven efficacy to prevent rCDI compared with placebo in patients considered at high risk of recurrence. However, the heterogeneity of the inclusion criteria, and the time between each episode and CDI diagnostics makes direct comparison between trials difficult. The differences regarding the risk of recurrence between the treatment and placebo arms were lower than previously described for FMT (FMT: Δ = 50.5%; RBX2660-phase III: Δ = 13.1%; SER-109-phase III: Δ = 28%; high-dose VE303-phase-II: Δ = 31.7%). All treatments presented a good overall safety profile with mainly mild gastrointestinal symptoms. IMPLICATIONS: Stool-derived products and bacterial consortia need to be clearly distinguished in terms of product characterization and their associated risks with specific long-term post-marketing evaluation similar to registries used for FMT. Their place in the therapeutic strategy for patients with rCDI requires further studies to determine the most appropriate patient population and administration route to prevent rCDI.
- MeSH
- Clostridioides difficile * MeSH
- fekální transplantace MeSH
- klostridiové infekce * mikrobiologie MeSH
- lidé MeSH
- mikrobiota * MeSH
- recidiva MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Scientific evidence regularly guides policy decisions1, with behavioural science increasingly part of this process2. In April 2020, an influential paper3 proposed 19 policy recommendations ('claims') detailing how evidence from behavioural science could contribute to efforts to reduce impacts and end the COVID-19 pandemic. Here we assess 747 pandemic-related research articles that empirically investigated those claims. We report the scale of evidence and whether evidence supports them to indicate applicability for policymaking. Two independent teams, involving 72 reviewers, found evidence for 18 of 19 claims, with both teams finding evidence supporting 16 (89%) of those 18 claims. The strongest evidence supported claims that anticipated culture, polarization and misinformation would be associated with policy effectiveness. Claims suggesting trusted leaders and positive social norms increased adherence to behavioural interventions also had strong empirical support, as did appealing to social consensus or bipartisan agreement. Targeted language in messaging yielded mixed effects and there were no effects for highlighting individual benefits or protecting others. No available evidence existed to assess any distinct differences in effects between using the terms 'physical distancing' and 'social distancing'. Analysis of 463 papers containing data showed generally large samples; 418 involved human participants with a mean of 16,848 (median of 1,699). That statistical power underscored improved suitability of behavioural science research for informing policy decisions. Furthermore, by implementing a standardized approach to evidence selection and synthesis, we amplify broader implications for advancing scientific evidence in policy formulation and prioritization.
- MeSH
- behaviorální vědy * metody trendy MeSH
- COVID-19 * epidemiologie etnologie prevence a kontrola MeSH
- komunikace MeSH
- kultura MeSH
- lékařská praxe založená na důkazech * metody MeSH
- lidé MeSH
- pandemie * prevence a kontrola MeSH
- sociální normy MeSH
- veřejné zdravotnictví metody trendy MeSH
- vůdcovství MeSH
- vytváření politiky * MeSH
- zdravotní politika * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND OBJECTIVES: Trigeminal neuralgia affects approximately 2% of patients with multiple sclerosis (MS) and often shows higher rates of pain recurrence after treatment. Previous studies on the effectiveness of stereotactic radiosurgery (SRS) for trigeminal neuralgia did not consider the different MS subtypes, including remitting relapsing (RRMS), primary progressive (PPMS), and secondary progressive (SPMS). Our objective was to investigate how MS subtypes are related to pain control (PC) rates after SRS. METHODS: We conducted a retrospective multicenter analysis of prospectively collected databases. Pain status was assessed using the Barrow National Institute Pain Intensity Scales. Time to recurrence was estimated through the Kaplan-Meier method and compared groups using log-rank tests. Logistic regression was used to calculate the odds ratio (OR). RESULTS: Two hundred and fifty-eight patients, 135 (52.4%) RRMS, 30 (11.6%) PPMS, and 93 (36%) SPMS, were included from 14 institutions. In total, 84.6% of patients achieved initial pain relief, with a median time of 1 month; 78.7% had some degree of pain recurrence with a median time of 10.2 months for RRMS, 8 months for PPMS, 8.1 months for SPMS ( P = .424). Achieving Barrow National Institute-I after SRS was a predictor for longer periods without recurrence ( P = .028). Analyzing PC at the last available follow-up and comparing with RRMS, PPMS was less likely to have PC (OR = 0.389; 95% CI 0.153-0.986; P = .047) and SPMS was more likely (OR = 2.0; 95% CI 0.967-4.136; P = .062). A subgroup of 149 patients did not have other procedures apart from SRS. The median times to recurrence in this group were 11.1, 9.8, and 19.6 months for RRMS, PPMS, and SPMS, respectively (log-rank, P = .045). CONCLUSION: This study is the first to investigate the relationship between MS subtypes and PC after SRS, and our results provide preliminary evidence that subtypes may influence pain outcomes, with PPMS posing the greatest challenge to pain management.
- MeSH
- bolest etiologie chirurgie MeSH
- lidé MeSH
- lokální recidiva nádoru chirurgie MeSH
- management bolesti metody MeSH
- neuralgie trigeminu * radioterapie chirurgie MeSH
- radiochirurgie * metody MeSH
- retrospektivní studie MeSH
- roztroušená skleróza * chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.
- MeSH
- COVID-19 * MeSH
- lidé MeSH
- mnohočetný myelom * terapie MeSH
- pandemie MeSH
- registrace MeSH
- SARS-CoV-2 MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
