There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability samples. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is a multi-country/multi-language survey conducting multivariable/LASSO-regularized regression models and network analyses to identify modifiable/non-modifiable factors associated with wellbeing (WHO-5)/composite psychopathology (P-score) change. It enrolled general population-representative/weighted-non-probability samples (26/04/2020-19/06/2022). Participants included 121,066 adults (age=42±15.9 years, females=64 %, representative sample=29 %) WHO-5/P-score worsened (SMD=0.53/SMD=0.74), especially initially during the pandemic. We identified 15 modifiable/nine non-modifiable risk and 13 modifiable/three non-modifiable protective factors for WHO-5, 16 modifiable/11 non-modifiable risk and 10 modifiable/six non-modifiable protective factors for P-score. The 12 shared risk/protective factors with highest centrality (network-analysis) were, for non-modifiable factors, country income, ethnicity, age, gender, education, mental disorder history, COVID-19-related restrictions, urbanicity, physical disorder history, household room numbers and green space, and socioeconomic status. For modifiable factors, we identified medications, learning, internet, pet-ownership, working and religion as coping strategies, plus pre-pandemic levels of stress, fear, TV, social media or reading time, and COVID-19 information. In multivariable models, for WHO-5, additional non-modifiable factors with |B|>1 were income loss, COVID-19 deaths. For modifiable factors we identified pre-pandemic levels of social functioning, hobbies, frustration and loneliness, and social interactions as coping strategy. For P-scores, additional non-modifiable/modifiable factors were income loss, pre-pandemic infection fear, and social interactions as coping strategy. COH-FIT identified vulnerable sub-populations and actionable individual/environmental factors to protect well-being/mental health during crisis times. Results inform public health policies, and clinical practice.
- MeSH
- COVID-19 * epidemiologie psychologie prevence a kontrola MeSH
- dospělí MeSH
- duševní zdraví * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- multivariační analýza MeSH
- ochranné faktory * MeSH
- pandemie MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Patients with bipolar disorder (BD) and major depressive disorder (MDD) exhibit depressive episodes with similar symptoms despite having different and poorly understood underlying neurobiology, often leading to misdiagnosis and improper treatment. This exploratory study examined whole-brain functional connectivity (FC) using FC multivariate pattern analysis (fc-MVPA) to identify the FC patterns with the greatest ability to distinguish between currently depressed patients with BD type I (BD I) and those with MDD. METHODOLOGY: In a cross-sectional design, 41 BD I, 40 MDD patients and 63 control participants completed resting state functional magnetic resonance imaging scans. Data-driven fc-MVPA, as implemented in the CONN toolbox, was used to identify clusters with differential FC patterns between BD patients and MDD patients. The identified cluster was used as a seed in a post hoc seed-based analysis (SBA) to reveal associated connectivity patterns, followed by a secondary ROI-to-ROI analysis to characterize differences in connectivity between these patterns among BD I patients, MDD patients and controls. RESULTS: FC-MVPA identified one cluster located in the right frontal pole (RFP). The subsequent SBA revealed greater FC between the RFP and posterior cingulate cortex (PCC) and between the RFP and the left inferior/middle temporal gyrus (LI/MTG) and lower FC between the RFP and the left precentral gyrus (LPCG), left lingual gyrus/occipital cortex (LLG/OCC) and right occipital cortex (ROCC) in MDD patients than in BD patients. Compared with the controls, ROI-to-ROI analysis revealed lower FC between the RFP and the PCC and greater FC between the RFP and the LPCG, LLG/OCC and ROCC in BD patients; in MDD patients, the analysis revealed lower FC between the RFP and the LLG/OCC and ROCC and greater FC between the RFP and the LI/MTG. CONCLUSIONS: Differences in the RFP FC patterns between currently depressed patients with BD and those with MDD suggest potential neuroimaging markers that should be further examined. Specifically, BD patients exhibit increased FC between the RFP and the motor and visual networks, which is associated with psychomotor symptoms and heightened compensatory frontoparietal FC to counter distractibility. In contrast, MDD patients exhibit increased FC between the RFP and the default mode network, corresponding to sustained self-focus and rumination.
- MeSH
- bipolární porucha * patofyziologie diagnostické zobrazování MeSH
- depresivní porucha unipolární * patofyziologie diagnostické zobrazování MeSH
- dospělí MeSH
- konektom metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mapování mozku metody MeSH
- mozek patofyziologie diagnostické zobrazování MeSH
- multivariační analýza MeSH
- nervová síť diagnostické zobrazování patofyziologie MeSH
- nervové dráhy patofyziologie diagnostické zobrazování MeSH
- průřezové studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Data on the clinical significance of iron deficiency (ID) in patients with myocardial infarction (MI) are conflicting. This may be related to the use of various ID criteria. We aimed to compare the association of different ID criteria with all-cause mortality after MI. METHODS: Consecutive patients hospitalized for their first MI at a large tertiary heart center were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality. RESULTS: From the 1,156 patients included (aged 64±12 years, 25 % women), 194 (16.8 %) patients died during the median follow-up of 3.4 years. After multivariate adjustment, iron level ≤13 μmol/L (HR 1.67, 95 % CI 1.19-2.34) and the combination of iron level ≤12.8 μmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L (HR 2.56, 95 % CI 1.64-3.99) termed as PragueID criteria were associated with increased mortality risk and had additional predictive value to the GRACE score. Compared to the model including iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95 % CI 0.52-0.69) by reclassifying patients into a higher-risk group. No association between ferritin level and mortality was found. 51 % of patients had low iron levels, and 58 % fulfilled the PragueID criteria. CONCLUSION: Iron deficiency is common among patients with the first MI. The PragueID criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality and should be evaluated in future interventional studies for the identification of patients potentially benefiting from intravenous iron therapy.
- MeSH
- anemie z nedostatku železa * mortalita MeSH
- deficit železa MeSH
- ferritin krev MeSH
- hospitalizace MeSH
- infarkt myokardu * mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- multivariační analýza MeSH
- příčina smrti MeSH
- proporcionální rizikové modely MeSH
- receptory transferinu krev MeSH
- rizikové faktory MeSH
- senioři MeSH
- železo * krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Negative symptoms (NS) represent a detrimental symptomatic domain in schizophrenia affecting social and occupational outcomes. AIMS: We aimed to identify factors from the baseline visit (V1) - with a mean illness duration of 0.47 years (SD = 0.45) - that predict the magnitude of NS at the follow-up visit (V3), occurring 4.4 years later (mean +/- 0.45). METHOD: Using longitudinal data from 77 first-episode schizophrenia spectrum patients, we analysed eight predictors of NS severity at V3: (1) the age at disease onset, (2) age at V1, (3) sex, (4) diagnosis, (5) NS severity at V1, (6) the dose of antipsychotic medication at V3, (7) hospitalisation days before V1 and; (8) the duration of untreated psychosis /DUP/). Secondly, using a multiple linear regression model, we studied the longitudinal relationship between such identified predictors and NS severity at V3 using a multiple linear regression model. RESULTS: DUP (Pearson's r = 0.37, p = 0.001) and NS severity at V1 (Pearson's r = 0.49, p < 0.001) survived correction for multiple comparisons. The logarithmic-like relationship between DUP and NS was responsible for the initial stunning incremental contribution of DUP to the severity of NS. For DUP < 6 months, with the sharpest DUP/NS correlation, prolonging DUP by five days resulted in a measurable one-point increase in the 6-item negative symptoms PANSS domain assessed 4.9 (+/- 0.6) years after the illness onset. Prolongation of DUP to 14.7 days doubled this NS gain, whereas 39 days longer DUP tripled NS increase. CONCLUSION: The results suggest the petrification of NS during the early stages of the schizophrenia spectrum and a crucial dependence of this symptom domain on DUP. These findings are clinically significant and highlight the need for primary preventive actions.
Introduction: It is often questioned whether to perform replantation or revision amputation for amputation injuries in elderly patients and smokers. According to the current indication criteria, neither old age nor smoking in the absence of other risk factors are considered to be risk factors for replantation failure. However, many microsurgeons still may make the decision not to perform digital replantation based solely on these factors. Material and methods: In order to evaluate the influence of both factors, we provided univariate and multivariate analyses of patients who underwent replantation at our centre during a 10-year period. We divided patients in two groups according to age (< and ≥ 60 years) and smoking status. Results: In the univariate analysis, there were no differences in immediate results between the two age groups. In the multivariate analysis, no statistical difference was found in neither long-term nor short-term results between the two age groups and between smokers and non-smokers. Conclusion: Smoking and age should not be considered the only risk factors when deciding whether to perform digital replantation.
Effects of processing and extraction solvents on antioxidant properties and other characteristics were evaluated for ten medicinal plant species originating from two different localities and two production years. A combination of spectroscopic and liquid chromatography techniques possessed data for multivariate statistics. Water, 50% (v/v) ethanol, and dimethyl sulfoxide (DMSO) were compared to select the most suitable solvent for the isolation of functional components from the frozen/dried medicinal plants. DMSO and 50% (v/v) ethanol were evaluated as more efficient for phenolic compounds and colorants extraction, while water was more useful for element extraction. Drying and extraction of herbs with 50% (v/v) ethanol was the most appropriate treatment to ensure a high yield of most compounds. The satisfactory differentiation of herbs (61.8-100%) confirmed the significant effect of the processing, geographical, and seasonal factors on target functional component concentrations. Total phenolic and total flavonoid compounds content, total antioxidant activity expressed as TAA, yellowness, chroma, and browning index were identified as the most important markers for medicinal plant differentiation.
- MeSH
- antioxidancia chemie MeSH
- chromatografie kapalinová MeSH
- dimethylsulfoxid MeSH
- ethanol chemie MeSH
- fenoly chemie MeSH
- léčivé rostliny * chemie MeSH
- multivariační analýza MeSH
- roční období MeSH
- rostlinné extrakty chemie MeSH
- rozpouštědla chemie MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. METHODS: Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. RESULTS: The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%-44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675-0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. CONCLUSIONS: We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients.
- MeSH
- adenokarcinom mortalita patologie patofyziologie terapie MeSH
- adenoskvamózní karcinom mortalita patologie patofyziologie terapie MeSH
- adjuvantní chemoterapie MeSH
- adjuvantní radioterapie MeSH
- asymptomatické nemoci MeSH
- dospělí MeSH
- hysterektomie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru mortalita patologie patofyziologie terapie MeSH
- lymfatické uzliny patologie MeSH
- míra přežití MeSH
- multivariační analýza MeSH
- nádory děložního čípku mortalita patologie patofyziologie terapie MeSH
- neuroendokrinní karcinom mortalita patologie patofyziologie terapie MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- spinocelulární karcinom mortalita patologie patofyziologie terapie MeSH
- staging nádorů MeSH
- trachelektomie MeSH
- tumor burden MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing. PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA). RESULTS: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA. INTERPRETATION: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.
- MeSH
- biologické markery metabolismus MeSH
- cystektomie metody MeSH
- interleukin-6 krev MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- multivariační analýza MeSH
- nádory močového měchýře krev chirurgie MeSH
- pooperační období MeSH
- předoperační období MeSH
- proporcionální rizikové modely MeSH
- prospektivní studie MeSH
- receptory interleukinu-6 krev MeSH
- regresní analýza MeSH
- rozhodování MeSH
- senioři MeSH
- systémy pro podporu klinického rozhodování MeSH
- urotel patologie chirurgie MeSH
- výsledek terapie MeSH
- zánět MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.
- MeSH
- antigen CA-19-9 krev MeSH
- ceramidy krev MeSH
- lidé MeSH
- lipidomika metody MeSH
- lysofosfatidylcholiny krev MeSH
- metabolismus lipidů genetika MeSH
- multivariační analýza MeSH
- nádorové biomarkery krev genetika MeSH
- nádory slinivky břišní krev diagnóza mortalita patologie MeSH
- proporcionální rizikové modely MeSH
- senzitivita a specificita MeSH
- sfingomyeliny krev MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The pharmaceutical industry has to tackle the explosion of high amounts of poorly soluble APIs. This phenomenon leads to numerous sophisticated solutions. These include the use of multifactorial data analysis identifying correlations between the components and dosage form properties, laboratory and production process parameters with respect to the API liberation Example of such API is bicalutamide. Improved liberation is achieved by particle size reduction. Laboratory batches, with different PSD of API, were filled into gelatinous capsules and consequently granulated for tablet compression. Comparative dissolution profiles with Casodex 150 mg (Astra Zeneca) were performed. The component analysis was used for the statistical evaluation of f1 and f2 factors and D(v,0.9) and D[4,3] parameters of PSD to identify optimal PSD values. Suitable PSD limits for API were statistically confirmed in laboratory and in commercial scale with respect to optimized tablet properties. The tablets were bioequivalent with originator (n = 20; 90% CI for ln AUC0-120: 99.8-111.9%; 90% CI for ln cmax: 101.1-112.9%). In conclusion, the micronisation of the API is still an efficient and inexpensive method improving the bioavailability, although there are more complicated and expensive methods available. Statistical multifactorial methods improved the safety and reproducibility of production.
- MeSH
- anilidy chemická syntéza metabolismus MeSH
- biologická dostupnost MeSH
- chemie farmaceutická metody MeSH
- multivariační analýza MeSH
- nitrily chemická syntéza metabolismus MeSH
- tablety MeSH
- terapeutická ekvivalence MeSH
- tosylové sloučeniny chemická syntéza metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
