Nevin Manimala

Int J Gynecol Cancer. 2023 Aug 17:ijgc-2023-004563. doi: 10.1136/ijgc-2023-004563. Online ahead of print.

ABSTRACT

OBJECTIVE: Although global disparities in survival rates for patients with ovarian cancer have been described, variation in care has not been assessed globally. This study aimed to evaluate global ovarian cancer care and barriers to care.

METHODS: A survey was developed by international ovarian cancer specialists and was distributed through networks and organizational partners of the International Gynecologic Cancer Society, the Society of Gynecologic Oncology, and the European Society of Gynecological Oncology. Respondents received questions about care organization. Outcomes were stratified by World Bank Income category and analyzed using descriptive statistics and logistic regressions.

RESULTS: A total of 1059 responses were received from 115 countries. Respondents were gynecological cancer surgeons (83%, n=887), obstetricians/gynecologists (8%, n=80), and other specialists (9%, n=92). Income category breakdown was as follows: high-income countries (46%), upper-middle-income countries (29%), and lower-middle/low-income countries (25%). Variation in care organization was observed across income categories. Respondents from lower-middle/low-income countries reported significantly less frequently that extensive resections were routinely performed during cytoreductive surgery. Furthermore, these countries had significantly fewer regional networks, cancer registries, quality registries, and patient advocacy groups. However, there is also scope for improvement in these components in upper-middle/high-income countries. The main barriers to optimal care for the entire group were patient co-morbidities, advanced presentation, and social factors (travel distance, support systems). High-income respondents stated that the main barriers were lack of surgical time/staff and patient preferences. Middle/low-income respondents additionally experienced treatment costs and lack of access to radiology/pathology/genetic services as main barriers. Lack of access to systemic agents was reported by one-third of lower-middle/low-income respondents.

CONCLUSIONS: The current survey report highlights global disparities in the organization of ovarian cancer care. The main barriers to optimal care are experienced across all income categories, while additional barriers are specific to income levels. Taking action is crucial to improve global care and strive towards diminishing survival disparities and closing the care gap.

PMID:37591611 | DOI:10.1136/ijgc-2023-004563

J Nucl Med. 2023 Aug 17:jnumed.123.265723. doi: 10.2967/jnumed.123.265723. Online ahead of print.

ABSTRACT

Conventional whole-body static ¹⁸F-FDG PET imaging provides a semiquantitative evaluation of overall glucose metabolism without insight into the specific transport and metabolic steps. Here we demonstrate the ability of total-body multiparametric ¹⁸F-FDG PET to quantitatively evaluate glucose metabolism using macroparametric quantification and assess specific glucose delivery and phosphorylation processes using microparametric quantification for studying recovery from coronavirus disease 2019 (COVID-19). Methods: The study included 13 healthy subjects and 12 recovering COVID-19 subjects within 8 wk of confirmed diagnosis. Each subject had a 1-h dynamic ¹⁸F-FDG scan on the uEXPLORER total-body PET/CT system. Semiquantitative SUV and the SUV ratio relative to blood (SUVR) were calculated for different organs to measure glucose utilization. Tracer kinetic modeling was performed to quantify the microparametric blood-to-tissue ¹⁸F-FDG delivery rate [Formula: see text] and the phosphorylation rate k ₃, as well as the macroparametric ¹⁸F-FDG net influx rate ([Formula: see text]). Statistical tests were performed to examine differences between healthy subjects and recovering COVID-19 subjects. The effect of COVID-19 vaccination was also investigated. Results: We detected no significant difference in lung SUV but significantly higher lung SUVR and [Formula: see text] in COVID-19 recovery, indicating improved sensitivity of kinetic quantification for detecting the difference in glucose metabolism. A significant difference was also observed in the lungs with the phosphorylation rate k ₃ but not with [Formula: see text], which suggests that glucose phosphorylation, rather than glucose delivery, drives the observed difference of glucose metabolism. Meanwhile, there was no or little difference in bone marrow ¹⁸F-FDG metabolism measured with SUV, SUVR, and [Formula: see text] but a significantly higher bone marrow [Formula: see text] in the COVID-19 group, suggesting a difference in glucose delivery. Vaccinated COVID-19 subjects had a lower lung [Formula: see text] and a higher spleen [Formula: see text] than unvaccinated COVID-19 subjects. Conclusion: Higher lung glucose metabolism and bone marrow glucose delivery were observed with total-body multiparametric ¹⁸F-FDG PET in recovering COVID-19 subjects than in healthy subjects, implying continued inflammation during recovery. Vaccination demonstrated potential protection effects. Total-body multiparametric PET of ¹⁸F-FDG can provide a more sensitive tool and more insights than conventional whole-body static ¹⁸F-FDG imaging to evaluate metabolic changes in systemic diseases such as COVID-19.

PMID:37591539 | DOI:10.2967/jnumed.123.265723

J Sport Rehabil. 2023 Aug 16:1-8. doi: 10.1123/jsr.2022-0359. Online ahead of print.

ABSTRACT

CONTEXT: An easy-to-administer, function-based questionnaire to assess patients with various foot problems was required for a Greek-speaking population. This study aimed to translate and cross-culturally adapt the Quick Foot and Ankle Ability Measure (Quick-FAAM) into Greek and evaluate its reliability and validity.

DESIGN: Cross-sectional study.

METHODS: Established international guidelines for the cross-cultural adaptation of questionnaires were followed. The face and content validity of the Greek version of the Quick-FAAM (Quick-FAAM-GR), as well as the internal consistency and test-retest reliability upon repeated administration after 5 days, were examined. In addition, the construct validity of the scale was examined via exploratory factor analysis as well as by testing for associations with the Manchester Foot Pain and Disability Index, the 12-item Short-Form Survey (version 2), and a functional balance assessment test-the Y-Balance Test.

RESULTS: Sixty participants (18 women) with self-reported chronic ankle instability symptoms, with a median (interquartile range) age of 27 (7.7) years, participated in the study. Half of the participants were included in the test-retest reliability study. The Quick-FAAM-GR demonstrated face and content validity. Excellent internal consistency (Cronbach α = .961) and intrarater test-retest reliability (intraclass correlation coefficient ICC[2,1] = .93) were demonstrated, with a comparable error margin to the original version (standard error of the measurement = 2.1, 95% minimum detectable change = 5.9). Associations of the Quick-FAAM-GR scores to other questionnaires ranged from weak to strong (Spearman rho), all being statistically significant (Manchester Foot Pain and Disability Index from -.26, P = .04, to -.67, P < .001, and 12-item Short-Form Survey, version 2, between .41 and .72, P < .001), and to the Y-Balance Test between lower-limb differences (-.35 to -.58, P < .001). The exploratory factor analysis confirmed the single-factor structure of this scale. No floor/ceiling effects were observed.

CONCLUSIONS: The Greek Quick-FAAM has proven to be a valid and reliable tool for evaluating chronic ankle instability and can be used for clinical and research purposes in Greek-speaking individuals.

PMID:37591505 | DOI:10.1123/jsr.2022-0359

J Pediatr (Rio J). 2023 Aug 14:S0021-7557(23)00089-X. doi: 10.1016/j.jped.2023.07.006. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the lifestyle and quality of life in Brazilian children and adolescents during the COVID-19 social distancing period in 2020.

METHODS: This cross-sectional study evaluated children and adolescents (2-18 years of age) and their parents, who voluntarily participated in an online survey. Snowball sampling was used to recruit participants during the first 6 months of the pandemic. A questionnaire was used to characterize the study population. The PedsQL 4.0 and the EUROHIS-QOL 8-item index were used to assess the quality of life (QoL) in children/adolescents and parents, respectively. Data were analyzed using SPSS 18.0 statistical program through the ANOVA with post hoc Bonferroni analysis, student’s t test, and the generalized estimating equation.

RESULTS: Mean screen time increased from 2h pre-pandemic to 5h during the pandemic (p < 0.001), which was associated with a decline in PedSQL4.0 scores (from 75.7 ± 2.6 to 71.3 ± 13.7, p < 0.001). Unhealthy eating habits increased from 11% to 34% and were associated with worse QoL scores compared with improved or unchanged eating habits during the pandemic (69.7 ± 13.3 vs 72.80 ± 13.4 vs 76.4 ± 12.6; p < 0.001). Poor sleep quality increased from 9% to 31.7% and was associated with worse QoL scores compared to improved or unchanged sleep quality during the pandemic (67.3 ± 13.1 vs 74.5 ± 13.1 vs 76.8 ± 12.2; p < 0.05). Physical exercise was associated with better PedSQL4.0 scores (77.5 ± 12.3 vs 72.5 ± 14.4; p < 0.001). Children aged 2-4y old had the best QoLscores.

CONCLUSIONS: Pandemic-related social distancing promoted significant lifestyle changes in children and adolescents, increasing screen time, reducing physical activity, and worsening food and sleep quality, which resulted in worse QoL scores.

PMID:37591484 | DOI:10.1016/j.jped.2023.07.006

Eur J Pharm Sci. 2023 Aug 15:106566. doi: 10.1016/j.ejps.2023.106566. Online ahead of print.

ABSTRACT

The series of conferences of the Global Bioequivalence Harmonisation Initiative (GBHI) was started in 2015 by the European Federation for Pharmaceutical Sciences (EUFEPS). All GBHI meetings so far were co-organised together with the American Association of Pharmaceutical Scientists (AAPS). Beginning with the 3^rd workshop US-FDA joined as co-sponsor – to support global harmonisation of regulatory recommendations for bioequivalence (BE) assessment. At the 5^th GBHI conference the following BE topics were intensively discussed and the following main conclusions were drawn: 1) Statistical considerations for BE assessment in specific situations covering scaling approaches for highly variable drug (HVD) products, two-stage adaptive design and opportunities of modelling and simulation to support BE: Even though special BE study concepts like adaptive designs are not often used in practise so far, a majority of the workshop participants were in favour of a more frequent application of such approaches. The regulatory conditions relevant in this context need further concretisation and harmonisation between the regions. Moreover, modelling and simulation were considered as a promising and evolving approach, also for BE development programmes. 2) Fed versus fasting conditions in BE trials: Findings that BE between generic products could be confirmed only after fasted administration but failed under fed conditions seem more an exception than the rule. Obviously, BCS class IV compounds are most problematic in this context. Differences in critical excipients such as surfactants or pH-modifiers may be relevant reasons for different sensitivity for interactions in fasted versus fed conditions. Consequently, such deviations in composition of generic preparations should be avoided. Moreover, confirmation of BE may be generally difficult comparing different dosage forms, such like capsules versus tablets, especially in fed state. 3) BE assessment of locally acting drug products applied topically to the skin: Appropriateness and potential benefit of in-vitro tests as alternatives to clinical efficacy studies have been comprehensively discussed. In addition to the already well-established in-vitro release and permeation tests, other techniques were suggested, e.g., Raman spectroscopy or dermal open flow microperfusion. Validation of those methods is challenging and, despite significant progress already achieved during previous years, more research is needed before they may be fully accepted for regulatory purposes. 4) BE evaluation of narrow therapeutic index (NTI) drugs: The discrepancies among regulatory agencies in necessity of tighter BE acceptance ranges, the recommendations for inclusion of peak and total drug exposure into BE assessment with more restrictive criteria and the importance of comparison of the product-related within-subject variability for NTI drugs were debated. Arguments in favour and against the different approaches were presented and discussed but need further consideration before harmonisation can be achieved. The highly interactive meeting and extensive exchange between regulators and scientists from industry and academia resulted in useful progress in open BE issues and supported the goal of science-driven harmonisation.

PMID:37591469 | DOI:10.1016/j.ejps.2023.106566

Resuscitation. 2023 Aug 15:109937. doi: 10.1016/j.resuscitation.2023.109937. Online ahead of print.

ABSTRACT

AIM: Assessment of neurologic injury within the immediate hours following out-of-hospital cardiac arrest (OHCA) resuscitation remains a major clinical challenge. Extracellular vesicles (EVs), small bodies derived from cytosolic contents during injury, may provide the opportunity for “liquid biopsy” within hours following resuscitation, as they contain proteins and RNA linked to cell type of origin. We evaluated whether micro-RNA (miRNA) from serologic EVs were associated with post-arrest neurologic outcome.

METHODS: We obtained serial blood samples in an OHCA cohort. Using novel microfluidic techniques to isolate EVs based on EV surface marker GluR2 (present on excitatory neuronal dendrites enriched in hippocampal tissue), we employed reverse transcription quantitative polymerase chain reaction (RT-qPCR) methods to measure a panel of miRNAs and tested association with dichotomized modified Rankin Score (mRS) at discharge.

RESULTS: EVs were assessed in 27 post-arrest patients between 7/3/2019-7/21/2022; 9 patients experienced good outcomes. Several miRNA species including miR-124 were statistically associated with mRS at discharge when measured within 6 hours of resuscitation (AUC=0.84 for miR-124, p<0.05). In a Kendall ranked correlation analysis, miRNA associations with outcome were not strongly correlated with standard serologic marker measurements, or amongst themselves, suggesting that miRNA provide distinct information from common protein biomarkers.

CONCLUSIONS: This study explores the associations between miRNAs from neuron-derived EVs (NDEs) and circulating protein biomarkers within 6 hours with neurologic outcome, suggesting a panel of very early biomarker may be useful during clinical care. Future work will be required to test larger cohorts with a broader panel of miRNA species.

PMID:37591443 | DOI:10.1016/j.resuscitation.2023.109937

Sci Total Environ. 2023 Aug 15:166316. doi: 10.1016/j.scitotenv.2023.166316. Online ahead of print.

ABSTRACT

Hydrated electrons (e_aq^–) exhibit rapid degradation of diverse persistent organic contaminants (OCs) and hold great promise as a formidable reducing agent in water treatment. However, the diverse structures of compounds exert different influences on the second-order rate constant of hydrated electron reactions (k_eaq^–), while the same OCs demonstrate notable discrepancies in k_eaq^– values across different pH levels. This study aims to develop machine learning (ML) models that can effectively simulate the intricate reaction kinetics between e_aq^– and OCs. Furthermore, the introduction of the pH variable enables a comprehensive investigation into the impact of ambient conditions on this process, thereby improving the practicality of the model. A dataset encompassing 701 k_eaq^– values derived from 351 peer-reviewed publications was compiled. To comprehensively investigate compound properties, this study introduced molecular descriptor (MD), molecular fingerprint (MF), and the integration of both (MD + MF) as model variables. Furthermore, 60 sets of predictive models were established utilizing two variable screening methodologies (MLR and RF) and ten prominent algorithms. Through statistical parameter analysis, it was determined that descriptors combined with MD and MF, the RF screening method, and the symbolism algorithm exhibited the best predictive efficacy. Importantly, the combination of descriptor models exhibited significantly superior performance compared to individual MF and MD models. Notably, the optimal model, denoted as RF – (MF + MD) – LGB, exhibited highly satisfactory predictive results (R²_tra = 0.967, Q²_tra = 0.840, R²_ext = 0.761). The mechanistic explanation study based on Shapley Additive Explanations (SHAP) values further elucidated the crucial influences of polarity, pH, molecular weight, electronegativity, carbon-carbon double bonds, and molecular topology on the degradation of OCs by e_aq^–. The proposed modeling approach, particularly the integration of MF and MD, alongside the introduction of pH, may furnish innovative ideas for advanced reduction or oxidation processes (ARPs/AOPs) and machine learning applications in other domains.

PMID:37591396 | DOI:10.1016/j.scitotenv.2023.166316

Sci Total Environ. 2023 Aug 15:166347. doi: 10.1016/j.scitotenv.2023.166347. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Recent cross-sectional studies found that exposure to ambient air pollution (AP) was associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). The alternation of blood lipids may explain the association, but epidemiological evidence is lacking. We aimed to examine whether and to what extent the association between long-term exposure to AP and incident MAFLD is mediated by blood lipids and dyslipidemia in a prospective cohort.

METHODS: We included 6350 participants from the China Multi-Ethnic Cohort (CMEC, baseline 2018-2019, follow-up 2020-2021). Three-year average (2016-2018) of AP (PM₁, PM_2.5, PM₁₀, NO₂), blood lipids (TC, LDL-C, HDL-C, TG with their combinations) and incident MAFLD for each individual were assessed chronologically. Linear and logistic regression was used to assess the associations among AP, blood lipids, and MAFLD, and the potential mediation effects of blood lipids were evaluated using causal mediation analysis.

RESULTS: A total of 744 participants were newly diagnosed with MAFLD at follow-up. The odds ratios of MAFLD associated with a 10 μm increase in PM₁, PM_2.5, and PM₁₀ were 1.35 (95 % CI: 1.14, 1.58), 1.34 (1.10, 1.65) and 1.28 (1.14, 1.44), respectively. Blood lipids are important mediators between AP and incident MAFLD. LDL-C (Proportion Mediated: 6.9 %), non-HDL (13.4 %), HDL-C (20.7 %), LDL/HDL (30.1 %), and dyslipidemia (6.5 %) significantly mediated the association between PM_2.5 and MAFLD. For PM₁, the indirect effects were similar to those for PM_2.5, with a larger value for the direct effect, and the mediation proportion by blood lipids was less for NO₂.

CONCLUSION: Blood lipids are important mediators between AP and MAFLD, and can explain 5 %-30 % of the association between AP and incident MAFLD, particularly cholesterol-related variables, indicating that AP could lead to MAFLD through the alternation of blood lipids. These findings provided mechanical evidence of AP leading to MAFLD in epidemiological studies.

PMID:37591384 | DOI:10.1016/j.scitotenv.2023.166347

J Affect Disord. 2023 Aug 15:S0165-0327(23)01055-8. doi: 10.1016/j.jad.2023.08.083. Online ahead of print.

ABSTRACT

OBJECTIVE: The external behavioural manifestations and internal neural mechanisms of anhedonia are sexually dimorphic. This study aimed to explore the sex differences in the regional brain neuroimaging features of anhedonia in the context of major depressive disorder (MDD).

METHOD: The resting-fMRI by applying amplitude of low-frequency fluctuation (ALFF) method was estimated in 414 patients with MDD (281 high anhedonia [HA], 133 low anhedonia [LA]) and 213 healthy controls (HC). The effects of two factors in patients with MDD were analysed using a 2 (sex: male, female) × 2 (group: HA, LA) ANOVA concerning the brain regions in which statistical differences were identified between patients with MDD and HC. We followed up with patients with HA at baseline, and 43 patients completed a second fMRI scan in remission. Paired t-test was performed to compare the ALFF values of anhedonia-related brain regions between the baseline and remission periods.

RESULTS: For the sex-by-group interaction, the bilateral insula, right hippocampus, right post cingulum cortex, and left putamen showed significant differences. Furthermore, the abnormally elevated ALFF values in anhedonia-related brain regions at baseline decreased in remission.

CONCLUSION: Our findings point to the fact that the females showed unique patterns of anhedonia-related brain activity compared to males, which may have clinical implications for interfering with the anhedonia symptoms in MDD. Using task fMRI, we can further examine the distinct characteristics between consumption anhedonia and anticipation anhedonia in MDD.

PMID:37591350 | DOI:10.1016/j.jad.2023.08.083

Diabetes Res Clin Pract. 2023 Aug 15:110880. doi: 10.1016/j.diabres.2023.110880. Online ahead of print.

ABSTRACT

Addition of an active surveillance virtual glucose management (VGM) system to usual consultation-based diabetes inpatient care at our hospital was associated with a decrease in hospital-acquired infection from 8.7% (17/196) to 3.5% (6/172) with an adjusted odds ratio of 0.17 (95%CI: 0.05 – 0.61), and a reduction in hypoglycemic and hyperglycemic patient-stay days.

PMID:37591345 | DOI:10.1016/j.diabres.2023.110880