Author: Nevin Manimala

Proc Natl Acad Sci U S A. 2021 Sep 7;118(36):e2105328118. doi: 10.1073/pnas.2105328118.

ABSTRACT

Brain microstructure plays a key role in driving the transport of drug molecules directly administered to the brain tissue, as in Convection-Enhanced Delivery procedures. The proposed research analyzes the hydraulic permeability of two white matter (WM) areas (corpus callosum and fornix) whose three-dimensional microstructure was reconstructed starting from the acquisition of electron microscopy images. We cut the two volumes with 20 equally spaced planes distributed along two perpendicular directions, and, on each plane, we computed the corresponding permeability vector. Then, we considered that the WM structure is mainly composed of elongated and parallel axons, and, using a principal component analysis, we defined two principal directions, parallel and perpendicular, with respect to the axons’ main direction. The latter were used to define a reference frame onto which the permeability vectors were projected to finally obtain the permeability along the parallel and perpendicular directions. The results show a statistically significant difference between parallel and perpendicular permeability, with a ratio of about two in both the WM structures analyzed, thus demonstrating their anisotropic behavior. Moreover, we find a significant difference between permeability in corpus callosum and fornix, which suggests that the WM heterogeneity should also be considered when modeling drug transport in the brain. Our findings, which demonstrate and quantify the anisotropic and heterogeneous character of the WM, represent a fundamental contribution not only for drug-delivery modeling, but also for shedding light on the interstitial transport mechanisms in the extracellular space.

PMID:34480003 | DOI:10.1073/pnas.2105328118

Tob Control. 2021 Sep 3:tobaccocontrol-2021-056717. doi: 10.1136/tobaccocontrol-2021-056717. Online ahead of print.

ABSTRACT

OBJECTIVE: We sought to conduct a systematic review and meta-analysis of evidence to inform policies that reduce density and proximity of tobacco retailers.

DATA SOURCES: Ten databases were searched on 16 October 2020: MEDLINE via PubMed, PsycINFO, Global Health, LILACS, Embase, ABI/Inform, CINAHL, Business Source Complete, Web of Science and Scopus, plus grey literature searches using Google and the RAND Publication Database.

STUDY SELECTION: Included studies used inferential statistics about adult participants to examine associations between tobacco retailer density/proximity and tobacco use behaviours and health outcomes. Of 7373 studies reviewed by independent coders, 37 (0.5%) met inclusion criteria.

DATA EXTRACTION: Effect sizes were converted to a relative risk reduction (RRR) metric, indicating the presumed reduction in tobacco use outcomes based on reducing tobacco retailer density and decreasing proximity.

DATA SYNTHESIS: We conducted a random effects meta-analysis and examined heterogeneity across 27 studies through subgroup analyses and meta-regression. Tobacco retailer density (RRR=2.55, 95% CI 1.91 to 3.19, k=155) and proximity (RRR=2.38, 95% CI 1.39 to 3.37, k=100) were associated with tobacco use behaviours. Pooled results including both density and proximity found an estimated 2.48% reduction in risk of tobacco use from reductions in tobacco retailer density and proximity (RRR=2.48, 95% CI 1.95 to 3.02, k=255). Results for health outcomes came from just two studies and were not significant. Considerable heterogeneity existed.

CONCLUSIONS: Across studies, lower levels of tobacco retailer density and decreased proximity are associated with lower tobacco use. Reducing tobacco supply by limiting retailer density and proximity may lead to reductions in tobacco use. Policy evaluations are needed.

PMID:34479990 | DOI:10.1136/tobaccocontrol-2021-056717

Postgrad Med J. 2021 Sep 3:postgradmedj-2020-139382. doi: 10.1136/postgradmedj-2020-139382. Online ahead of print.

ABSTRACT

BACKGROUND: Postpartum haemorrhage is one of the direct and the leading causes of maternal morbidity and mortality. There are many risk factors of postpartum haemorrhage, which vary in different settings. Therefore, the purpose of this study was to assess postpartum haemorrhage and associated factors among mothers who gave birth in public health facilities.

METHODS: A cross-sectional study was employed from 17 November 2019 to 15 February 2020. The study participants were selected using a systematic sampling technique. The data were entered and cleaned using EpiData V.3.1 then exported to SPSS V.20 for analysis. Factors associated with postpartum haemorrhage were selected for multiple logistic regression at the probability value (p value) of less than 0.2 in the χ² analysis. Statistically significant associated factors were identified at probability value (p value) less than 0.05 and adjusted OR (AOR) with a 95% CI.

RESULTS: The mean age of participants was 31.3 (SD ±5.7) years. This study found that the prevalence of postpartum haemorrhage was 13.6% (67). Age of participants (AOR 12.5, 95% CI 4.0 to 38.6), disrespectful maternity care (AOR 8.4, 95% CI 3.2 to 22.0), labour induction and augmentation (AOR 6.97, 95% CI 2.34 to 20.8), the prolonged second stage of labour (AOR 9.9, 95% CI 2.6 to 37.1) and no antenatal care visit (AOR 10.1, 95% CI 3.4 to 29.7) were statistically significant associated factors of postpartum haemorrhage.

CONCLUSIONS: The prevalence of postpartum haemorrhage is high. The age of the participants, disrespectful maternity care, labour induction and augmentation, the prolonged second stage of labour and no antenatal care visit were independent predictors of postpartum haemorrhage.

PMID:34479977 | DOI:10.1136/postgradmedj-2020-139382

Postgrad Med J. 2021 Sep 3:postgradmedj-2021-141014. doi: 10.1136/postgradmedj-2021-141014. Online ahead of print.

ABSTRACT

Surveys are quick and easy to produce. This paper outlines some of the many problems that should be anticipated.

PMID:34479976 | DOI:10.1136/postgradmedj-2021-141014

Cancer Epidemiol Biomarkers Prev. 2021 Sep 3:cebp.0476.2021. doi: 10.1158/1055-9965.EPI-21-0476. Online ahead of print.

ABSTRACT

BACKGROUND: Experimental studies suggest that iron overload might increase pancreatic cancer (PC) risk. We evaluated whether prediagnostic hemochromatosis and iron-overload diseases, including sideroblastic and congenital dyserythropoietic anemias and non-alcoholic related chronic liver disease (NACLD), were associated with PC risk in older adults.

METHODS: We conducted a population-based, case-control study within the United States’ Surveillance, Epidemiology, and End Results Program (SEER)-Medicare linked data. Incident primary PC cases were adults > 66 years. Controls were alive at the time cases were diagnosed and matched to cases (4:1 ratio) by age, sex, and calendar-year. Hemochromatosis, iron-overload anemias, and NACLD were reported 12 or more months before PC diagnosis or control selection using Medicare claims data. Adjusted unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) between hemochromatosis, sideroblastic and congenital dyserythropoietic anemias NACLD, and PC.

RESULTS: Between 1992-2015, 80,074 PC cases and 320,296 controls were identified. Overall, we did not observe statistically significant associations between hemochromatosis, sideroblastic anemia, or congenital dyserythropoietic anemia and PC; however, sideroblastic anemia was associated with later primary PC (OR: 1.30, 95% CI: 1.03-1.64). NACLD was associated with first (OR: 1.10, 95% CI: 1.01-1.19), later (OR: 1.17, 95% CI: 1.02-1.35), and all (OR: 1.12, 95% CI: 1.04-1.20) PC.

CONCLUSION: Overall hemochromatosis and iron-overload anemias were not associated with PC, whereas NACLD was associated with increased risk in this large study of older adults.

IMPACT: These results partly support the hypothesis that iron-overload diseases increases PC risk.

PMID:34479949 | DOI:10.1158/1055-9965.EPI-21-0476

BMJ Open. 2021 Sep 3;11(9):e051904. doi: 10.1136/bmjopen-2021-051904.

ABSTRACT

INTRODUCTION: Person-centred outcome measures improve quality of care and patient outcomes but are used inconsistently in palliative care practice. To address this implementation gap, we developed the ‘RESOLVE Implementation Strategy’. This protocol describes a process evaluation to explore mechanisms through which this strategy does, or does not, support the implementation of outcome measures in routine palliative care practice.

METHODS AND ANALYSIS: Multistrand, mixed-methods process evaluation. Strand one will collect routine outcomes data (palliative Phase of Illness, Integrated Palliative care Outcomes Scale, Australia-modified Karnofsky Performance Status) to map the changes in use of outcome measures over 12 months (July 2021-July 2022). Strand two will collect survey data over the same 12-month period to explore how professionals’ understandings of, skills in using and ability to build organisational practices around, outcome measures change over time. Strand three will collect interview data to understand the mechanisms underpinning/affecting our implementation strategy. Thematic framework analysis and descriptive statistics will be used to analyse qualitative and quantitative data, respectively.

ETHICS AND DISSEMINATION: For strand one, ethical approval has been obtained (Cambridge REC, REF: 20/EE/0188). For strands two and three, ethical approval has been obtained from Hull York Medical School ethics committee (2105). Tailored feedback of study findings will be provided to participating sites. Abstracts and papers will be submitted to national/international conferences and peer-reviewed journals. Lay and policy briefings and newsletters will be shared through patient and public involvement and project networks, plus via the project website.

PMID:34479939 | DOI:10.1136/bmjopen-2021-051904

BMJ Open. 2021 Sep 3;11(9):e051003. doi: 10.1136/bmjopen-2021-051003.

ABSTRACT

INTRODUCTION: Acute traumatic coagulopathy (ATC) in bleeding trauma patients increase in-hospital mortality. Fibrinogen concentrate (FC) and prothrombin complex concentrate (PCC) are two purified concentrates of clotting factors that have been used to treat ATC. However, there is a knowledge gap on their use compared with the standard of care, the transfusion of plasma.

METHODS AND ANALYSIS: The factors in the initial resuscitation of severe trauma 2 trial is a multicentre, randomised, parallel-control, single-blinded, phase IV superiority trial. The study aims to address efficacy and safety of the early use of FC and PCC compared with a plasma-based resuscitation. Adult trauma patients requiring massive haemorrhage protocol activation on hospital arrival will receive FC 4 g and PCC 2000 IU or plasma 4 U, based on random allocation. The primary outcome is a composite of the cumulative number of all units of red cells, plasma and platelets transfused within 24 hours following admission. Secondary outcomes include measures of efficacy and safety of the intervention. Enrolment of 350 patients will provide an initial power >80% to demonstrate superiority for the primary outcome. After enrolment of 120 patients, a preplanned adaptive interim analysis will be conducted to reassess assumptions, check for early superiority demonstration or reassess the sample size for remainder of the study.

ETHICS AND DISSEMINATION: The study has been approved by local and provincial research ethics boards and will be conducted according to the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. As per the Tri-Council Policy Statement, patient consent will be deferred due to the emergency nature of the interventions. If superiority is established, results will have a major impact on clinical practice by reducing exposure to non-virally inactivated blood products, shortening the time for administration of clotting factors, correct coagulopathy more efficaciously and reduce the reliance on AB plasma.

TRIAL REGISTRATION NUMBER: NCT04534751, pre results.

PMID:34479938 | DOI:10.1136/bmjopen-2021-051003

Trop Med Int Health. 2021 Sep 3. doi: 10.1111/tmi.13676. Online ahead of print.

ABSTRACT

Arterial stiffness is a known indicator for cardiovascular disease. However, the factors that lead to arterial stiffening have primarily been studied in participants from high-income countries. We performed pulse wave velocity (PWV), the gold standard measure of arterial stiffness, on 808 Tanzanian adults (ages 18 to 65) enrolled in a longitudinal cohort studying trends in blood pressure. As expected, PWV was strongly associated with age, blood pressure and sex. We controlled for these factors in our statistical analysis. Lifestyle metrics were compared across multiple PWV quantiles. We found that determinants of PWV varied by sex: in female participants, PWV was associated with common obesity metrics and menopause, while in male participants, PWV was associated with HIV status and duration of anti-retroviral therapy (ART). Further clinical and lifestyle factors such as marriage status and type of occupation were also significantly associated with PWV and moderated by sex. Together our data demonstrate the importance of studying sex-specific causal pathways for arterial stiffness and of including under-represented populations in these studies.

PMID:34478605 | DOI:10.1111/tmi.13676

Mol Ecol. 2021 Sep 3. doi: 10.1111/mec.16162. Online ahead of print.

ABSTRACT

Evidence that telomere length (TL) and dynamics can be interpreted as proxy for ‘life stress’ experienced by individuals stems largely from correlational studies. We tested for effects of an experimental increase of workload on telomere dynamics by equipping male great tits (Parus major) with a 0.9 gram backpack for a full year. In addition, we analysed associations between natural life-history variation, TL and TL dynamics. Carrying 5% extra weight for a year did not significantly accelerate telomere attrition. This agrees with our earlier finding that this experiment did not affect survival or future reproduction. Apparently, great tit males were able to compensate behaviourally or physiologically for the increase in locomotion costs we imposed. We found no cross-sectional association between reproductive success and TL, but individuals with higher reproductive success (number of recruits) lost fewer telomere base pairs in the subsequent year. We used the TRF method to measure TL, which method yields a TL distribution for each sample, and the association between reproductive success and telomere loss was more pronounced in the higher percentiles of the telomere distribution, in agreement with the higher impact of ageing on longer telomeres within individuals. Individuals with longer telomeres and less telomere shortening were more likely to survive to the next breeding season, but these patterns did not reach statistical significance. Whether successful individuals are characterized by losing fewer or more base pairs from their telomeres varies between species, and we discuss aspects of ecology and social organisation that may explain this variation.

PMID:34478576 | DOI:10.1111/mec.16162

J Magn Reson Imaging. 2021 Sep 3. doi: 10.1002/jmri.27909. Online ahead of print.

ABSTRACT

BACKGROUND: Autoimmune encephalitis (AE) is a noninfectious emergency with severe clinical attacks. It is difficult for the earlier diagnosis of acute AE due to the lack of antibody detection resources.

PURPOSE: To construct a deep learning (DL) algorithm using multi-sequence magnetic resonance imaging (MRI) for the identification of acute AE.

STUDY TYPE: Retrospective.

POPULATION: One hundred and sixty AE patients (90 women; median age 36), 177 herpes simplex virus encephalitis (HSVE) (89 women; median age 39), and 184 healthy controls (HC) (95 women; median age 39) were included. Fifty-two patients from another site were enrolled for external validation.

FIELD STRENGTH/SEQUENCE: 3.0 T; fast spin-echo (T₁ WI, T₂ WI, fluid attenuated inversion recovery imaging) and spin-echo echo-planar diffusion weighted imaging.

ASSESSMENT: Five DL models based on individual or combined four MRI sequences to classify the datasets as AE, HSVE, or HC. Reader experiment was further carried out by radiologists.

STATISTICAL TESTS: The discriminative performance of different models was assessed using the area under the receiver operating characteristic curve (AUC). The optimal threshold cut-off was identified when sensitivity and specificity were maximized (sensitivity + specificity – 1) in the validation set. Classification performance using confusion matrices was reported to evaluate the diagnostic value of the models and the radiologists’ assessments before being assessed by the paired t-test (P < 0.05 was considered significant).

RESULTS: In the internal test set, the fusion model achieved the significantly greatest diagnostic performance than single-sequence DL models with AUCs of 0.828, 0.884, and 0.899 for AE, HSVE, and HC, respectively. The model demonstrated a consistently high performance in the external validation set with AUCs of 0.831 (AE), 0.882 (HSVE), and 0.892 (HC). The fusion model also demonstrated significantly higher performance than all radiologists in identifying AE (accuracy between the fuse model vs. average radiologist: 83% vs. 72%).

DATA CONCLUSION: The proposed DL algorithm derived from multi-sequence MRI provided desirable identification and classification of acute AE.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

PMID:34478565 | DOI:10.1002/jmri.27909