Tag: pubmed

Ann Clin Transl Neurol. 2022 Nov 17. doi: 10.1002/acn3.51702. Online ahead of print.

ABSTRACT

OBJECTIVE: We conducted a Mendelian randomization (MR) study to disentangle causal associations between women’s reproductive behaviors and ischemic stroke (IS) and investigate the roles of two modifiable risk factors (body mass index (BMI) and educational attainment (EA)) in these associations.

METHODS: Using summary-level data from large-scale genome-wide association studies, we performed univariable MR to examine whether there is genetic evidence that women’s reproductive traits are causally associated with IS and its subtypes. Multivariable MR and MR mediation analysis were used to investigate whether BMI and EA are common mechanisms or mediators for these associations. A set of sensitivity analyses were conducted to test valid MR assumptions.

RESULTS: We observed consistent and statistically significant associations across female and sex-combined analyses for earlier age at first birth (AFB) and age at first sexual intercourse (AFS) with a higher risk of IS and large-artery atherosclerotic stroke (LAS) risk in the primary analysis. The odds ratios of IS per 1 SD increase in genetically predicted early AFB and AFS were 0.93 (95% CI, 0.86-0.99; p = 0.046) and 0.83 (95% CI, 0.70-0.97, p = 0.020), respectively. Further analyses indicated that BMI played a shared role in AFS and IS/LAS while EA played a shared role in AFS/AFB and IS/LAS as well as a mediator in the path from AFS to IS/LAS.

INTERPRETATION: These findings may inform prevention strategies and interventions directed toward relative women’s reproductive behaviors and IS. Future studies are warranted to explore other factors related to EA which are responsible for these causalities.

PMID:36398399 | DOI:10.1002/acn3.51702

J Sex Marital Ther. 2022 Nov 17:1-12. doi: 10.1080/0092623X.2022.2146026. Online ahead of print.

ABSTRACT

Gender affirming surgery (GAS) helps individuals to achieve a physical presence consistent with their gender identity. In this study, we explored the decision, expectation, experience, satisfaction, and quality of life (QOL) of transgender women (TGWs) who have undergone GAS and compared their QOL with transfeminine individuals (TFs) who have not and are seeking to do so in Thailand. The median overall QOL score of the TGWs who have undergone GAS was slightly higher than that of the TFs who have not (95 (92-103) vs. 92 (86-98); p = 0.003), which was also reflected in the specific domains of psychological health, social relationships, and environmental health, the exception being physical health. Not being financially prepared was the most relevant reason for delaying undergoing GAS among the TFs who have not undergone it and want to do so. In addition, more than half of the TGWs who have undergone GAS regretted not being socially accepted after surgery. Although the difference between the QOLs of the two groups is statistically significant, the clinical significance should be further investigated to provide more insight. In addition, the higher QOL of TGWs might not solely be due to having undergone GAS.

PMID:36398380 | DOI:10.1080/0092623X.2022.2146026

J Anim Ecol. 2022 Nov 17. doi: 10.1111/1365-2656.13838. Online ahead of print.

ABSTRACT

Dispersal is a key life-history trait for most species and is essential to ensure connectivity and gene flow between populations and facilitate population viability in variable environments. Despite the increasing importance of range shifts due to global change, dispersal has proved difficult to quantify, limiting empirical understanding of this phenotypic trait and wider synthesis. Here we introduce a statistical framework to estimate standardised dispersal kernels from biased data. Based on this, we compare empirical dispersal kernels for European breeding birds considering age (average dispersal; natal, before first breeding; and breeding dispersal, between subsequent breeding attempts) and sex (females and males) and test whether different dispersal properties are phylogenetically conserved. We standardised and analysed data from an extensive volunteer-based bird ring-recoveries database in Europe (EURING) by accounting for biases related to different censoring thresholds in reporting between countries and to migratory movements. Then, we fitted four widely used probability density functions in a Bayesian framework to compare and provide the best statistical descriptions of the different age and sex-specific dispersal kernels for each bird species. The dispersal movements of the 234 European bird species analysed were statistically best explained by heavy-tailed kernels, meaning that while most individuals disperse over short distances, long-distance dispersal is a prevalent phenomenon in almost all bird species. The phylogenetic signal in both median and long dispersal distances estimated from the best-fitted kernel was low (Pagel’s λ < 0.25), while it reached high values (Pagel’s λ >0.7) when comparing dispersal distance estimates for fat-tailed dispersal kernels. As expected in birds, natal dispersal was on average 5 km greater than breeding dispersal, but sex-biased dispersal was not detected. Our robust analytical framework allows sound use of widely available mark-recapture data in standardised dispersal estimates. We found strong evidence that long-distance dispersal is common among European breeding bird species and across life stages. The dispersal estimates offer a first guide to selecting appropriate dispersal kernels in range expansion studies and provide new avenues to improve our understanding of the mechanisms and rules underlying dispersal events.

PMID:36398379 | DOI:10.1111/1365-2656.13838

Artif Organs. 2022 Nov 17. doi: 10.1111/aor.14457. Online ahead of print.

ABSTRACT

BACKGROUND: ECMO support is associated with the development of a systemic hyper-inflammatory response, which may become quite significant and extreme in some cases. We hypothesise that Cytosorb or Jafron therapy may benefit patients on V-A ECMO in terms of levels of inflammatory markers such as IL-6, complications and overall outcomes.

METHODS: We conducted a retrospective study of prospectively collected data in a single tertiary care center between January 2021 and April 2022. At the time of the analysis of this article, 20 patients on V-A ECMO had cytokine adsorption while on ECMO support: Cytosorb group (n=10), Jafron group (n=10). In 10 ECMO supported patients cytokine adsorption was not used, this group served as a control group, which may be quite significant in some cases. Evaluation of the level of inflammatory markers (IL-1, 6, 8; CRP, Leukocyte, Lactate, PCT, NT-proBNP, TNF-α) were performed.

RESULTS: There were statistically significant longer CPB time, aortic cross clamp time and ICU stay in cytokine adsorption groups than in control group, but there were no differences between subgroups with different types of haemoadsorption used. Moreover, in control group mortality rate was higher than the cytokine adsorption groups (60 % vs 20%, p 0.02). All patients had elevation of inflammatory markers in perioperative and immediate postoperative period. After 72 hours of intensive care, blood inflammation markers had tendency to decline.

CONCLUSION: At the time of writing, hemadsorption in patients requiring V-A ECMO support represents good therapeutic effect. This effect is permanent for the whole period of extracorporeal cytokine hemadsorption application for both CytoSorb and Jafron HA330 devices.

PMID:36398369 | DOI:10.1111/aor.14457

World J Nucl Med. 2022 Sep 9;21(4):302-313. doi: 10.1055/s-0042-1750400. eCollection 2022 Dec.

ABSTRACT

Background Conventional imaging is useful to assess interbody fusion by showing complete trabecular bony bridging, but has a low positive predictive value for pseudarthrosis. Because alterations of bone metabolism may precede structural anatomical changes on computed tomography (CT), we aimed to investigate the ability of fluorine 18 sodium fluoride positron emission tomography/computed tomography ( ¹⁸ F-NaF PET/CT) to identify pseudarthrosis after spinal fusion using surgical revision as the reference standard. Methods We retrospectively reviewed ¹⁸ F-NaF PET/CT scans performed between February 2019 and September 2020 in patients experiencing pain after spinal fusion. We included the 18 patients who underwent revision surgery for suspicion of pseudarthrosis. Five consecutive patients who were clearly fused on CT served as the control group. Results In the revision surgery group ( n =18), visual assessment by ¹⁸ F-NaF PET/CT revealed that all 22 cages with an increased ¹⁸ F-NaF uptake around intercorporal fusion material had mobility at revision surgery, whereas none of the fused patients ( n =5) showed uptake around cage/intervertebral disk space. Among the 18 patients with presumed aseptic pseudarthrosis, intraoperative cultures revealed surgical site infection (SSI) caused by Cutibacterium acnes ( C. acnes ) in seven patients (38.9%). There was a statistically significant difference in standardized uptake values and uptake ratios between the revision surgery and control groups ( p =5.3× 10 ^-6 and p =0.0002, respectively). Conclusions ¹⁸ F-NaF PET/CT imaging appeared as a useful tool to identify pseudarthrosis following spinal fusion. The unexpectedly high prevalence (38.9%) of SSI caused by C. acnes found in presumed aseptic patients supports the utility of intraoperative cultures in revision cases for pseudarthrosis, even without preoperative clinical suspicion of SSI.

PMID:36398308 | PMC:PMC9666003 | DOI:10.1055/s-0042-1750400

World J Nucl Med. 2022 Sep 2;21(4):283-289. doi: 10.1055/s-0042-1750015. eCollection 2022 Dec.

ABSTRACT

Aim Radium-223 has been the first-approved targeted Alpha therapy agent. We retrospectively assessed different factors influencing the overall survival (OS) and patient management. Setting and Design Thirty-two metastatic castration-resistant prostate cancer (mCRPC) patients’ hematological parameters, number of cycles, performance status, and toxicities were evaluated for OS. Radium 223 dichloride (Radium-223) was administered every 4 weeks for a maximum of six cycles. Primary and secondary end points were OS, progression free survival (PFS), therapy toxicities, change in performance status, biochemical response, and skeletal-related events (SREs). Materials and Methods Patients’ median age was 77 years (range: 57-90 years) and median follow-up was 399 days (range: 5-1,761 days). A total of 163 cycles were administered in 32 patients, with 4 or less cycles in 8 patients (25%) and 5 or more cycles in 24 patients (75%). Among eight patients with 4 or less cycles, three patients died, of which two patients died due to neutropenic sepsis. Statistical Analysis Mann-Whitney test was used to compare the cycle groups; Spearman’s correlation coefficient was used to see the relation of different variables with OS. Log rank test was used for group comparison while Kaplan-Meier survivorship was used for OS. Results Statistical correlation was seen between the number of cycles ( p =0.037) and hemoglobin ( p =0.028). Kaplan-Meier OS ( p =0.038) was correlated with the number of cycles (≤ 4 cycles and ≥ 5 cycles). OS was 173 days in patients with one to four cycles, 226 days in five cycles, and 493 days in six cycles. Myelosuppression leading to stopping of full six cycles was seen in 7 of 32 patients (22%) and significantly correlated to inferior OS ( p =0.048). Conclusion Higher number of Radium-223 cycles was seen to be associated with better OS. Prior myelosuppression was associated with poor OS. Patients with better hematological profile were more likely to complete the maximum number of the cycles with a better OS.

PMID:36398304 | PMC:PMC9665971 | DOI:10.1055/s-0042-1750015

Drug Saf. 2022 Nov 17. doi: 10.1007/s40264-022-01254-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Electronic health record (EHR) or medical claims-based algorithms (i.e., operational definitions) can be used to define safety outcomes using real-world data. However, existing tools do not allow researchers and decision-makers to adequately appraise whether a particular algorithm is fit for purpose (FFP) to support regulatory decisions on drug safety surveillance. Our objective was to develop a tool to enable regulatory decision-makers and other stakeholders to appraise whether a given algorithm is FFP for a specific decision context.

METHODS: We drafted a set of 77 generic items informed by regulatory guidance documents, existing instruments, and publications. The outcome of ischemic stroke served as an exemplar to inform the development of draft items. The items were designed to be outcome independent. We conducted a three-round online Delphi panel to develop and refine the tool and achieve consensus on items (> 70% agreement) among panel participants composed of regulators, researchers from pharmaceutical organizations, academic clinicians, methodologists, pharmacoepidemiologists, and cardiologists. We conducted a qualitative analysis of panel responses. Five pairs of reviewers independently evaluated two ischemic stroke algorithm validation studies to test its application. We developed a user guide, with explanation and elaboration for each item, guidance on essential and additional elements for user responses, and an illustrative example of a complete assessment. Furthermore, we conducted a 2-h online stakeholder panel of 16 participants from regulatory agencies, academic institutions, and industry. We solicited input on key factors for an FFP assessment, their general reaction to the Algorithm CErtaInty Tool (ACE-IT), limitations of the tool, and its potential use.

RESULTS: The expert panel reviewed and made changes to the initial list of 77 items. The panel achieved consensus on 38 items, and the final version of the ACE-IT includes 34 items after removal of duplicate items. Applying the tool to two ischemic stroke algorithms demonstrated challenges in its application and identified shared concepts addressed by more than one item. The ACE-IT was viewed positively by the majority of stakeholders. They identified that the tool could serve as an educational resource as well as an information-sharing platform. The time required to complete the assessment was identified as an important limitation. We consolidated items with shared concepts and added a preliminary screen section and a summary assessment box based on their input. The final version of the ACE-IT is a 34-item tool for assessing whether algorithm validation studies on safety outcomes are FFP. It comprises the domains of internal validity (24 items), external validity (seven items), and ethical conduct and reporting of the validation study (three items). The internal validity domain includes sections on objectives, data sources, population, outcomes, design and setting, statistical methods, reference standard, accuracy, and strengths and limitations. The external validity domain includes items that assess the generalizability to a proposed target study. The domain on ethics and transparency includes items on ethical conduct and reporting of the validation study.

CONCLUSION: The ACE-IT supports a structured, transparent, and flexible approach for decision-makers to appraise whether electronic health record or medical claims-based algorithms for safety outcomes are FFP for a specific decision context. Reliability and validity testing using a larger sample of participants in other therapeutic areas and further modifications to reduce the time needed to complete the assessment are needed to fully evaluate its utility for regulatory decision-making.

PMID:36396894 | DOI:10.1007/s40264-022-01254-4

Brain Imaging Behav. 2022 Nov 17. doi: 10.1007/s11682-022-00737-3. Online ahead of print.

ABSTRACT

Motor disability is a dominant and restricting symptom in multiple sclerosis, yet its neuroimaging correlates are not fully understood. We apply statistical and machine learning techniques on multimodal neuroimaging data to discriminate between multiple sclerosis patients and healthy controls and to predict motor disability scores in the patients. We examine the data of sixty-four multiple sclerosis patients and sixty-five controls, who underwent the MRI examination and the evaluation of motor disability scales. The modalities used comprised regional fractional anisotropy, regional grey matter volumes, and functional connectivity. For analysis, we employ two approaches: high-dimensional support vector machines run on features selected by Fisher Score (aiming for maximal classification accuracy), and low-dimensional logistic regression on the principal components of data (aiming for increased interpretability). We apply analogous regression methods to predict symptom severity. While fractional anisotropy provides the classification accuracy of 96.1% and 89.9% with both approaches respectively, including other modalities did not bring further improvement. Concerning the prediction of motor impairment, the low-dimensional approach performed more reliably. The first grey matter volume component was significantly correlated (R = 0.28-0.46, p < 0.05) with most clinical scales. In summary, we identified the relationship between both white and grey matter changes and motor impairment in multiple sclerosis. Furthermore, we were able to achieve the highest classification accuracy based on quantitative MRI measures of tissue integrity between patients and controls yet reported, while also providing a low-dimensional classification approach with comparable results, paving the way to interpretable machine learning models of brain changes in multiple sclerosis.

PMID:36396890 | DOI:10.1007/s11682-022-00737-3

Int J Obes (Lond). 2022 Nov 17. doi: 10.1038/s41366-022-01239-4. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the relationship between body composition and leukocyte telomere length (LTL) in healthy Chinese children aged 6-11 years.

METHODS: This cross-sectional study enrolled 406 healthy children (175 girls and 231 boys). The relative telomere length in their peripheral blood leukocytes was determined via quantitative polymerase chain reaction. Dual-energy X-ray absorptiometry was used to determine body fat content and regional fat distribution, appendicular skeletal muscle mass (ASM), bone mineral density (BMD) and bone mineral content (BMC) at the total body (TB) and total body less head (TBLH) levels, and total body lean mass (TBLM) was then determined. ASM/height² (ASMI) was also calculated.

RESULTS: After adjusting for potential covariates, multiple linear regression analyses revealed that neither body fat content nor regional body fat distribution were significantly associated with LTL (β = -8.48 × 10^-6-1.44 × 10^-1, p = 0.227-0.959). However, ASM, ASMI, TB BMC/TB BMD, TBLH BMC/TBLH BMD and TBLM were positively associated with LTL (β = 8.95 × 10^-6-4.95 × 10^-1, p = 0.005-0.035). Moreover, analysis of covariance revealed there was a statistically significant dose-dependent positive association between LTL and ASM, TB BMC/BMD, TBLH BMC/BMD, and TBLM (p-trend = 0.002-0.025).

CONCLUSIONS: Skeletal muscle mass and bone mass but not body fat content or distribution were significantly associated with LTL in this pediatric population.

PMID:36396857 | DOI:10.1038/s41366-022-01239-4

J Nephrol. 2022 Nov 18. doi: 10.1007/s40620-022-01478-8. Online ahead of print.

ABSTRACT

BACKGROUND: Tubulointerstitial nephritis and uveitis syndrome (TINU) is a rare condition characterised by bilateral uveitis and interstitial nephritis. There is no nationally, or internationally agreed upon treatment regimen. A systematic review was undertaken to report the renal outcomes in TINU, and treatments used.

METHODS: Medline (1969-2021) and EMBASE (1988-2021) databases were searched for primary studies, clinical practice guidelines and case reports of adult and paediatric TINU cases, as defined by Mandeville criteria. Two reviewers identified articles meeting inclusion criteria (registered with PROSPERO). Data were extracted into a synthesis table and meta-analysis performed. Quality of case series was also assessed.

RESULTS: One hundred twenty-two articles were identified, totalling 257 cases included in the meta-analysis. Females were more commonly affected than males (2:1), and median age was 19 years. GFR at follow-up correlated with nadir GFR, and the proportion with GFR <90 ml/min/1.73 m² was statistically different between adult and paediatric groups. Of the entire cohort, 40% had GFR <90 ml/min/1.73 m² at follow-up. Glucocorticoid monotherapy was the most common treatment (70%); other strategies included no treatment (9%) and immunosuppressant drugs (e.g. azathioprine), mostly in steroid-resistant cases, or as ‘steroid-sparing’ alternatives.

CONCLUSIONS: The majority of literature regarding TINU is limited to case reports and case series. There are no prospective trials assessing the effects of different treatments on renal outcomes, and currently employed treatment strategies are physician-specific without a reliable evidence-base. Prospective data collection as part of multicentre trials should be a research focus to improve the evidence-base.

PMID:36396848 | DOI:10.1007/s40620-022-01478-8