Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.24311823
Mohammadreza Mohebbi, Mojtaba Lotfaliany, Martin O’Hely, Jessica Batti, M. Kotowicz, Lucy Saunders, Richard Page, Sally Beatti, Wolfgang Marx, F. Jacka, Postdoctoral Mojtaba Lotfaliany, Research, Postdoctoral Martin O’Hely, Research Fellow c. Mark, Professor d. Michael Kotowicz, Berk, Research Sally Beattie, Affiliate, Dr Amelia J McGuinness
Objective: To compare the effects of consuming food-based versus supplement-based very low-energy diet (VLED) programs on gut microbiome composition in women with a high body mass index (BMI). Design: An investigator-initiated, single-blind, two-arm, parallel-group randomised controlled-feeding trial with computer-generated 1:1 randomisation. From May 2021 to February 2022, women aged 30-65 years with BMI 30-45 kg/m2 were recruited from southwest Victoria, Australia, and randomised to a three-week food-based or supplement-based VLED program. The primary outcome was between-group differential change in faecal microbiome alpha diversity (Shannon index) from baseline to week three, assessed using shotgun metagenomics. Outcome assessors, study investigators, and analysing statisticians were blinded to group allocation until analysis completion. Allocation concealment was managed by an independent researcher using a computer software system. Modified intention-to-treat (mITT) analyses using linear mixed-effects regression models estimated mean between-group differential changes, reported as beta-coefficient point estimates ({beta}) and 95% confidence intervals (95%CI), adjusted for multiple comparisons. Results: Forty-seven participants were randomised (food-based: n=23, supplement-based: n=24). Of the 45 participants analysed, there was a between-group differential change in the Shannon index (mITT {beta}: 0.37, 95%CI: 0.15 to 0.60) from baseline to week three, with a greater increase in the food-based group (mean change: 0.26, 95%CI: 0.09 to 0.44; n=23) versus supplement-based group (mean change: -0.10, 95%CI: -0.25 to 0.05; n=22). There were 27 non-serious adverse events (food-based: 8, supplement-based: 19), all non-serious. Conclusion: A food-based VLED, with more whole food components and fewer highly processed industrial ingredients, increases gut microbiome diversity more than a supplement-based VLED.
{"title":"The effects of food-based versus supplement-based very low-energy diets on gut microbiome composition and health outcomes in women with high body mass index (The MicroFit Study): a randomised controlled trial","authors":"Mohammadreza Mohebbi, Mojtaba Lotfaliany, Martin O’Hely, Jessica Batti, M. Kotowicz, Lucy Saunders, Richard Page, Sally Beatti, Wolfgang Marx, F. Jacka, Postdoctoral Mojtaba Lotfaliany, Research, Postdoctoral Martin O’Hely, Research Fellow c. Mark, Professor d. Michael Kotowicz, Berk, Research Sally Beattie, Affiliate, Dr Amelia J McGuinness","doi":"10.1101/2024.08.11.24311823","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311823","url":null,"abstract":"Objective: To compare the effects of consuming food-based versus supplement-based very low-energy diet (VLED) programs on gut microbiome composition in women with a high body mass index (BMI). Design: An investigator-initiated, single-blind, two-arm, parallel-group randomised controlled-feeding trial with computer-generated 1:1 randomisation. From May 2021 to February 2022, women aged 30-65 years with BMI 30-45 kg/m2 were recruited from southwest Victoria, Australia, and randomised to a three-week food-based or supplement-based VLED program. The primary outcome was between-group differential change in faecal microbiome alpha diversity (Shannon index) from baseline to week three, assessed using shotgun metagenomics. Outcome assessors, study investigators, and analysing statisticians were blinded to group allocation until analysis completion. Allocation concealment was managed by an independent researcher using a computer software system. Modified intention-to-treat (mITT) analyses using linear mixed-effects regression models estimated mean between-group differential changes, reported as beta-coefficient point estimates ({beta}) and 95% confidence intervals (95%CI), adjusted for multiple comparisons. Results: Forty-seven participants were randomised (food-based: n=23, supplement-based: n=24). Of the 45 participants analysed, there was a between-group differential change in the Shannon index (mITT {beta}: 0.37, 95%CI: 0.15 to 0.60) from baseline to week three, with a greater increase in the food-based group (mean change: 0.26, 95%CI: 0.09 to 0.44; n=23) versus supplement-based group (mean change: -0.10, 95%CI: -0.25 to 0.05; n=22). There were 27 non-serious adverse events (food-based: 8, supplement-based: 19), all non-serious. Conclusion: A food-based VLED, with more whole food components and fewer highly processed industrial ingredients, increases gut microbiome diversity more than a supplement-based VLED.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.12.24311852
M. O'Driscoll, N. Hoze, N. Lefrancq, G. Ribeiro Dos Santos, D. Hoinard, M. Z. Rahman, K. K. Paul, A. M. Naser Titu, M. S. Alam, M. E. Hossain, J. Vanhomwegen, S. Cauchemez, E. S. Gurley, H. Salje
Multiplex immunoassays are facilitating the parallel measurement of antibody responses against multiple antigenically-related pathogens, generating a wealth of high-dimensional data which depict complex antibody-antigen relationships. In this study we develop a generalizable analytical framework to maximize inferences from multi-pathogen serological studies. We fit the model to measurements of IgG antibody binding to 10 arboviral pathogens from a cross-sectional study in northwest Bangladesh with 1,453 participants. We used our framework to jointly infer the prevalence of each pathogen by location and age, as well as the levels of between-pathogen antibody cross-reactivity. We find evidence of endemic transmission of Japanese encephalitis virus as well as recent outbreaks of dengue and chikungunya viruses in this district. Our estimates of antibody cross-reactivity were highly consistent with phylogenetic distances inferred from genetic data. Further, we demonstrated how our framework can be used to identify the presence of circulating cross-reactive pathogens that were not directly tested for, representing a potential opportunity for the detection of novel emerging pathogens. The presented analytical framework will be applicable to the growing number of multi-pathogen studies and will help support the integration of serological testing into disease surveillance platforms.
{"title":"Epidemiological inferences from serological responses to cross-reacting pathogens","authors":"M. O'Driscoll, N. Hoze, N. Lefrancq, G. Ribeiro Dos Santos, D. Hoinard, M. Z. Rahman, K. K. Paul, A. M. Naser Titu, M. S. Alam, M. E. Hossain, J. Vanhomwegen, S. Cauchemez, E. S. Gurley, H. Salje","doi":"10.1101/2024.08.12.24311852","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311852","url":null,"abstract":"Multiplex immunoassays are facilitating the parallel measurement of antibody responses against multiple antigenically-related pathogens, generating a wealth of high-dimensional data which depict complex antibody-antigen relationships. In this study we develop a generalizable analytical framework to maximize inferences from multi-pathogen serological studies. We fit the model to measurements of IgG antibody binding to 10 arboviral pathogens from a cross-sectional study in northwest Bangladesh with 1,453 participants. We used our framework to jointly infer the prevalence of each pathogen by location and age, as well as the levels of between-pathogen antibody cross-reactivity. We find evidence of endemic transmission of Japanese encephalitis virus as well as recent outbreaks of dengue and chikungunya viruses in this district. Our estimates of antibody cross-reactivity were highly consistent with phylogenetic distances inferred from genetic data. Further, we demonstrated how our framework can be used to identify the presence of circulating cross-reactive pathogens that were not directly tested for, representing a potential opportunity for the detection of novel emerging pathogens. The presented analytical framework will be applicable to the growing number of multi-pathogen studies and will help support the integration of serological testing into disease surveillance platforms.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"10 34","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.24311826
Adenike Oluwakemi, PhD. Ogah. PhD, Dr Chrispin Mwando, Dr Kenneth Chanda, Dr Selia Nganjo
Background Limited data is available regarding the prevalence of neonatal anemia and its associated risk factors in areas with constrained resources. Subject and methods In a cross-sectional study, data pertaining to socio-demographic and clinical characteristics of 489 mother-singleton, term newborn pairs were consecutively collected from the admission wards of six public hospitals in Lusaka. The information was then analyzed to determine the prevalence of newborn anemia and its associated risk factors. Newborn and maternal anemia were defined as hemoglobin levels below 15g/dl and 11g/dl, respectively. The relationship between the variables was explored using Chi-square tests and a binary logistic regression model. The findings were reported in terms of p-values, odds ratios, and 95% confidence intervals. Results The prevalence of anemia and severe anemia in newborns was 72.4% and 2.5% respectively, while in mothers it was 30.5% and 14.7% respectively. Delayed cord clamping was performed in 71.4% of the deliveries, and 86.5% of newborns had their hemoglobin levels estimated between 4-6 hours after birth. Maternal pre-delivery hemoglobin data were obtained from the hospital records of 246 (49.7%) out of the 489 mothers in the study. The majority (63.4%) of maternal hemoglobin levels were determined more than 4 weeks before delivery, and this infrequent hemoglobin assessment was significantly associated with newborn anemia (p<0.001; OR 3.60; 95% CI 1.81, 7.14). Additionally, 11% of the 489 mothers had underlying medical conditions, which were also significantly associated with newborn anemia (p=0.019; OR=2.96; [95%CI 1.20, 7.32]). The top three maternal medical conditions were HIV (35.2%), hypertension (25.9%), and Hepatitis B virus infection (13%). Maternal age was significantly associated with newborn anemia, with teenage pregnancy posing the highest risk (93.8%; p<0.001; OR 5.68; [95%CI 1.94, 16.60]). Furthermore, primiparous (p<0.001; OR 5.46 [95% CI 2.02, 14.93]), para 2 (p=0.014; OR=2.11 [95% CI 1.16, 3.83]), and multiparous (p=0.009; OR=4.77; [95% CI 1.48, 15.35]) mothers were more likely to produce anemic newborns compared to other parity. Newborns born before 40 weeks gestation were 3.11 times (95% CI 1.75, 5.52) more likely to have anemia, p<0.001, compared to full-term babies. Normal birthweight babies were less likely to become anemic compared to low birthweight babies (p=0.003; OR=0.31 [95% CI 0.14, 0.68]). Conclusion Enhanced antenatal care for pregnant mothers in resource-limited settings is essential, with particular focus on maternal hemoglobin, nutrition, and medical conditions. Attention should also be given to teenage pregnancy, primiparous and multiparous mothers, as well as preterm and low birthweight babies, to prevent newborn anemia and consequently reduce infant morbidity and mortality.
背景 在资源有限的地区，有关新生儿贫血患病率及其相关风险因素的数据十分有限。研究对象和方法 在一项横断面研究中，研究人员从卢萨卡六家公立医院的入院病房中连续收集了 489 对母亲-胎儿、足月新生儿的社会人口学和临床特征数据。然后对这些信息进行分析，以确定新生儿贫血症的发病率及其相关风险因素。新生儿和产妇贫血分别定义为血红蛋白水平低于 15g/dl 和 11g/dl。利用卡方检验和二元逻辑回归模型探讨了变量之间的关系。研究结果以 p 值、几率比和 95% 置信区间表示。结果 新生儿贫血和严重贫血的发生率分别为 72.4% 和 2.5%，而母亲贫血和严重贫血的发生率分别为 30.5% 和 14.7%。71.4%的分娩延迟了脐带夹闭，86.5%的新生儿在出生后 4-6 小时内进行了血红蛋白水平评估。在 489 名产妇中，有 246 名（49.7%）产妇的产前血红蛋白数据来自医院记录。大多数（63.4%）产妇的血红蛋白水平是在分娩前 4 周以上测定的，而这种不频繁的血红蛋白评估与新生儿贫血有显著关联（P<0.001；OR 3.60；95% CI 1.81，7.14）。此外，489 位母亲中有 11% 的人患有基础疾病，这也与新生儿贫血显著相关（p=0.019；OR=2.96；[95%CI 1.20，7.32]）。产妇的前三种疾病分别是艾滋病（35.2%）、高血压（25.9%）和乙型肝炎病毒感染（13%）。产妇年龄与新生儿贫血密切相关，其中少女怀孕的风险最高（93.8%；P<0.001；OR 5.68；[95%CI 1.94，16.60]）。此外，初产妇（p<0.001；OR 5.46 [95% CI 2.02，14.93]）、二产妇（p=0.014；OR=2.11 [95% CI 1.16，3.83]）和多产妇（p=0.009；OR=4.77；[95% CI 1.48，15.35]）与其他产次的母亲相比，更容易生出贫血的新生儿。与足月儿相比，妊娠 40 周前出生的新生儿患贫血症的几率是足月儿的 3.11 倍（95% CI 1.75，5.52），P<0.001。与低出生体重儿相比，正常出生体重儿贫血的几率较低（P=0.003；OR=0.31 [95% CI 0.14, 0.68]）。结论 在资源有限的环境中，加强对孕妇的产前保健至关重要，尤其要关注孕妇的血红蛋白、营养和医疗状况。还应关注少女怀孕、初产妇和多产妇以及早产儿和低出生体重儿，以预防新生儿贫血，从而降低婴儿发病率和死亡率。
{"title":"Factors determining hemoglobin levels in vaginally delivered term newborns at public hospitals in Lusaka, Zambia","authors":"Adenike Oluwakemi, PhD. Ogah. PhD, Dr Chrispin Mwando, Dr Kenneth Chanda, Dr Selia Nganjo","doi":"10.1101/2024.08.11.24311826","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311826","url":null,"abstract":"Background Limited data is available regarding the prevalence of neonatal anemia and its associated risk factors in areas with constrained resources. Subject and methods In a cross-sectional study, data pertaining to socio-demographic and clinical characteristics of 489 mother-singleton, term newborn pairs were consecutively collected from the admission wards of six public hospitals in Lusaka. The information was then analyzed to determine the prevalence of newborn anemia and its associated risk factors. Newborn and maternal anemia were defined as hemoglobin levels below 15g/dl and 11g/dl, respectively. The relationship between the variables was explored using Chi-square tests and a binary logistic regression model. The findings were reported in terms of p-values, odds ratios, and 95% confidence intervals. Results The prevalence of anemia and severe anemia in newborns was 72.4% and 2.5% respectively, while in mothers it was 30.5% and 14.7% respectively. Delayed cord clamping was performed in 71.4% of the deliveries, and 86.5% of newborns had their hemoglobin levels estimated between 4-6 hours after birth. Maternal pre-delivery hemoglobin data were obtained from the hospital records of 246 (49.7%) out of the 489 mothers in the study. The majority (63.4%) of maternal hemoglobin levels were determined more than 4 weeks before delivery, and this infrequent hemoglobin assessment was significantly associated with newborn anemia (p<0.001; OR 3.60; 95% CI 1.81, 7.14). Additionally, 11% of the 489 mothers had underlying medical conditions, which were also significantly associated with newborn anemia (p=0.019; OR=2.96; [95%CI 1.20, 7.32]). The top three maternal medical conditions were HIV (35.2%), hypertension (25.9%), and Hepatitis B virus infection (13%). Maternal age was significantly associated with newborn anemia, with teenage pregnancy posing the highest risk (93.8%; p<0.001; OR 5.68; [95%CI 1.94, 16.60]). Furthermore, primiparous (p<0.001; OR 5.46 [95% CI 2.02, 14.93]), para 2 (p=0.014; OR=2.11 [95% CI 1.16, 3.83]), and multiparous (p=0.009; OR=4.77; [95% CI 1.48, 15.35]) mothers were more likely to produce anemic newborns compared to other parity. Newborns born before 40 weeks gestation were 3.11 times (95% CI 1.75, 5.52) more likely to have anemia, p<0.001, compared to full-term babies. Normal birthweight babies were less likely to become anemic compared to low birthweight babies (p=0.003; OR=0.31 [95% CI 0.14, 0.68]). Conclusion Enhanced antenatal care for pregnant mothers in resource-limited settings is essential, with particular focus on maternal hemoglobin, nutrition, and medical conditions. Attention should also be given to teenage pregnancy, primiparous and multiparous mothers, as well as preterm and low birthweight babies, to prevent newborn anemia and consequently reduce infant morbidity and mortality.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"30 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.12.24311345
Joakim B. Stenbäck, Daniel Schmidt, Ulrika Noborg, Joel Gustafsson, Peter Norberg, Maria E Andersson, Michael X Fu, Heli Harvala, Johan Ringlander
Deep sequencing of the whole hepatitis B virus genome increases the analytical resolution and has the potential to improve molecular epidemiology investigations. The aim of this work was to develop and evaluate the performance of such deep sequencing using the Nanopore technology. The method includes an initial PCR step to generate two overlapping amplicons that cover the whole HBV genome, followed by sequencing using the Nanopore rapid barcoding kit that allows parallel analysis of several samples in one reaction. The libraries can be sequenced with the standard Nanopore flow cell on MiniIon or GridIon devices, as well as the Flongle. The performance of the method was evaluated by comparing Nanopore and Sanger sequences or qPCR results from 64 clinical samples. The Nanopore-derived consensus sequences were, on average, 99.9% similar to those from Sanger sequencing and the full HBV genome was determined in samples with HBV DNA levels of approximately 3 log10 IU/mL with MagNA pure 96 extraction and < 2 log10 IU/mL using a high-volume manual extraction protocol on a subset of samples from patients with very low viral load (1.62-3.74 IU/mL). A perfect agreement with Sanger/qPCR-derived genotype was seen. The cost of sequencing per genome using the Nanopore method is low, ranging of 6-37 euros. We conclude that whole-genome sequencing of HBV with Nanopore is well suited for genomic characterization, antiviral resistance mutation analysis and genotyping of HBV in a routine laboratory setting
{"title":"Accurate and cost-efficient whole genome sequencing of hepatitis B virus using Nanopore","authors":"Joakim B. Stenbäck, Daniel Schmidt, Ulrika Noborg, Joel Gustafsson, Peter Norberg, Maria E Andersson, Michael X Fu, Heli Harvala, Johan Ringlander","doi":"10.1101/2024.08.12.24311345","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311345","url":null,"abstract":"Deep sequencing of the whole hepatitis B virus genome increases the analytical resolution and has the potential to improve molecular epidemiology investigations. The aim of this work was to develop and evaluate the performance of such deep sequencing using the Nanopore technology. The method includes an initial PCR step to generate two overlapping amplicons that cover the whole HBV genome, followed by sequencing using the Nanopore rapid barcoding kit that allows parallel analysis of several samples in one reaction. The libraries can be sequenced with the standard Nanopore flow cell on MiniIon or GridIon devices, as well as the Flongle. The performance of the method was evaluated by comparing Nanopore and Sanger sequences or qPCR results from 64 clinical samples. The Nanopore-derived consensus sequences were, on average, 99.9% similar to those from Sanger sequencing and the full HBV genome was determined in samples with HBV DNA levels of approximately 3 log10 IU/mL with MagNA pure 96 extraction and < 2 log10 IU/mL using a high-volume manual extraction protocol on a subset of samples from patients with very low viral load (1.62-3.74 IU/mL). A perfect agreement with Sanger/qPCR-derived genotype was seen. The cost of sequencing per genome using the Nanopore method is low, ranging of 6-37 euros. We conclude that whole-genome sequencing of HBV with Nanopore is well suited for genomic characterization, antiviral resistance mutation analysis and genotyping of HBV in a routine laboratory setting","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"29 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.24311847
D. Eratne, M. Kang, C. Lewis, C. Dang, C. Malpas, M. Keem, J. Grewal, Vladimir Marinov, A. Coe, Cath Kaylor-Hughes, Thomas Borchard, Chhoa Keng-Hong, Alexandra Waxmann, Burcu Saglam, Tomáš Kalinčík, Richard Kanaan, W. Kelso, Andrew Evans, S. Farrand, S. Loi, M. Walterfang, C. Stehmann, Qiao-Xin Li, Steven Collins, C. L. Masters, A. Santillo, Henrik Zetterberg, K. Blennow, S. Berkovic, Dennis Velakoulis, Terence J. O’Brien, Patrick Kwan, O. Hansson, Christopher Fowler, Jane Gunn
INTRODUCTION: Many patients with neurodegenerative disorders (ND) face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (ND), a common challenge in clinical settings. METHODS: Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, weight. RESULTS: 337 participants included: 136 ND, 77 PPD, 124 Controls. Plasma NfL was 2.5 fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, AUC 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2 fold elevated, AUC 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40-<60years). Additional findings were cut-offs optimised for sensitivity and specificity, and issues important for future clinical translation CONCLUSIONS: This study adds important evidence for a simple blood-based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings.
{"title":"Plasma and CSF neurofilament light chain distinguish neurodegenerative from primary psychiatric conditions in a clinical setting","authors":"D. Eratne, M. Kang, C. Lewis, C. Dang, C. Malpas, M. Keem, J. Grewal, Vladimir Marinov, A. Coe, Cath Kaylor-Hughes, Thomas Borchard, Chhoa Keng-Hong, Alexandra Waxmann, Burcu Saglam, Tomáš Kalinčík, Richard Kanaan, W. Kelso, Andrew Evans, S. Farrand, S. Loi, M. Walterfang, C. Stehmann, Qiao-Xin Li, Steven Collins, C. L. Masters, A. Santillo, Henrik Zetterberg, K. Blennow, S. Berkovic, Dennis Velakoulis, Terence J. O’Brien, Patrick Kwan, O. Hansson, Christopher Fowler, Jane Gunn","doi":"10.1101/2024.08.11.24311847","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311847","url":null,"abstract":"INTRODUCTION: Many patients with neurodegenerative disorders (ND) face diagnostic delay and misdiagnosis. We investigated blood and cerebrospinal fluid (CSF) neurofilament light chain (NfL) to distinguish ND from primary psychiatric disorders (ND), a common challenge in clinical settings. METHODS: Plasma and CSF NfL levels were measured and compared between groups, adjusting for age, sex, weight. RESULTS: 337 participants included: 136 ND, 77 PPD, 124 Controls. Plasma NfL was 2.5 fold elevated in ND compared to PPD and had strong diagnostic performance (area under the curve, AUC 0.86, 81%/85% specificity/sensitivity) that was comparable to CSF NfL (2 fold elevated, AUC 0.89, 95%/71% specificity/sensitivity). Diagnostic performance was especially strong in younger people (40-<60years). Additional findings were cut-offs optimised for sensitivity and specificity, and issues important for future clinical translation CONCLUSIONS: This study adds important evidence for a simple blood-based biomarker to assist as a screening test for neurodegeneration and distinction from PPD, in clinical settings.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"42 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.24311824
Mahdi Haq, Nabhan Rashad, NeuroCareAI
Introduction: Post traumatic stress disorder (PTSD) is a psychiatric disorder that may develop after exposure to a traumatic event. Patients of traumatic spinal cord injuries are at risk of developing PTSD, and diagnosing this disorder and recognizing risk factors is important for effective treatment. Objective: To determine the prevalence of PTSD in post traumatic spinal cord injury patients and correlate the presence of PTSD to factors such as age, cause of injury, and level of injury. Methods: A descriptive cross sectional study was conducted at Paraplegic Center in Peshawar, Pakistan. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) was used to assess the presence of post traumatic stress disorder in patients at the Paraplegic Center. The study was carried out from 20 December 2014 to 20 February 2015 on a convenience sample of 51 patients. The criterion for inclusion in the study was to have a traumatic spinal cord injury, while the exclusion criterion was to have a spinal cord injury that was non traumatic in nature. Results: Out of 51 patients, 31% met the diagnostic criteria for PTSD. The age group of 15-24 years had a 27% prevalence of PTSD, while the age groups of 25 to 34 years and 35 to 44 years had a PTSD prevalence of 42% and 40% respectively. Patients who had fallen from a height had the highest prevalence of PTSD of 41%, as compared to patients who had other causes of traumatic spinal cord injury. Patients with a lumbar spinal lesion had a PTSD prevalence of 44%, whereas patients with a cervical and thoracic spinal lesion had a PTSD prevalence of 33% and 25% respectively. Conclusion: The study shows that the middle age groups had a higher prevalence of PTSD, and patients who had fallen from a height had the highest prevalence of PTSD. Lumbar spinal lesion patients had a higher prevalence of PTSD than patients who had spinal lesions at the cervical or thoracic level.
{"title":"Post Traumatic Stress Disorder in Patients with Traumatic Spinal Cord Injury","authors":"Mahdi Haq, Nabhan Rashad, NeuroCareAI","doi":"10.1101/2024.08.11.24311824","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311824","url":null,"abstract":"Introduction: Post traumatic stress disorder (PTSD) is a psychiatric disorder that may develop after exposure to a traumatic event. Patients of traumatic spinal cord injuries are at risk of developing PTSD, and diagnosing this disorder and recognizing risk factors is important for effective treatment. Objective: To determine the prevalence of PTSD in post traumatic spinal cord injury patients and correlate the presence of PTSD to factors such as age, cause of injury, and level of injury. Methods: A descriptive cross sectional study was conducted at Paraplegic Center in Peshawar, Pakistan. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) was used to assess the presence of post traumatic stress disorder in patients at the Paraplegic Center. The study was carried out from 20 December 2014 to 20 February 2015 on a convenience sample of 51 patients. The criterion for inclusion in the study was to have a traumatic spinal cord injury, while the exclusion criterion was to have a spinal cord injury that was non traumatic in nature. Results: Out of 51 patients, 31% met the diagnostic criteria for PTSD. The age group of 15-24 years had a 27% prevalence of PTSD, while the age groups of 25 to 34 years and 35 to 44 years had a PTSD prevalence of 42% and 40% respectively. Patients who had fallen from a height had the highest prevalence of PTSD of 41%, as compared to patients who had other causes of traumatic spinal cord injury. Patients with a lumbar spinal lesion had a PTSD prevalence of 44%, whereas patients with a cervical and thoracic spinal lesion had a PTSD prevalence of 33% and 25% respectively. Conclusion: The study shows that the middle age groups had a higher prevalence of PTSD, and patients who had fallen from a height had the highest prevalence of PTSD. Lumbar spinal lesion patients had a higher prevalence of PTSD than patients who had spinal lesions at the cervical or thoracic level.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"28 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.24311824
Mahdi Haq, Nabhan Rashad, NeuroCareAI
Introduction: Post traumatic stress disorder (PTSD) is a psychiatric disorder that may develop after exposure to a traumatic event. Patients of traumatic spinal cord injuries are at risk of developing PTSD, and diagnosing this disorder and recognizing risk factors is important for effective treatment. Objective: To determine the prevalence of PTSD in post traumatic spinal cord injury patients and correlate the presence of PTSD to factors such as age, cause of injury, and level of injury. Methods: A descriptive cross sectional study was conducted at Paraplegic Center in Peshawar, Pakistan. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) was used to assess the presence of post traumatic stress disorder in patients at the Paraplegic Center. The study was carried out from 20 December 2014 to 20 February 2015 on a convenience sample of 51 patients. The criterion for inclusion in the study was to have a traumatic spinal cord injury, while the exclusion criterion was to have a spinal cord injury that was non traumatic in nature. Results: Out of 51 patients, 31% met the diagnostic criteria for PTSD. The age group of 15-24 years had a 27% prevalence of PTSD, while the age groups of 25 to 34 years and 35 to 44 years had a PTSD prevalence of 42% and 40% respectively. Patients who had fallen from a height had the highest prevalence of PTSD of 41%, as compared to patients who had other causes of traumatic spinal cord injury. Patients with a lumbar spinal lesion had a PTSD prevalence of 44%, whereas patients with a cervical and thoracic spinal lesion had a PTSD prevalence of 33% and 25% respectively. Conclusion: The study shows that the middle age groups had a higher prevalence of PTSD, and patients who had fallen from a height had the highest prevalence of PTSD. Lumbar spinal lesion patients had a higher prevalence of PTSD than patients who had spinal lesions at the cervical or thoracic level.
{"title":"Post Traumatic Stress Disorder in Patients with Traumatic Spinal Cord Injury","authors":"Mahdi Haq, Nabhan Rashad, NeuroCareAI","doi":"10.1101/2024.08.11.24311824","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311824","url":null,"abstract":"Introduction: Post traumatic stress disorder (PTSD) is a psychiatric disorder that may develop after exposure to a traumatic event. Patients of traumatic spinal cord injuries are at risk of developing PTSD, and diagnosing this disorder and recognizing risk factors is important for effective treatment. Objective: To determine the prevalence of PTSD in post traumatic spinal cord injury patients and correlate the presence of PTSD to factors such as age, cause of injury, and level of injury. Methods: A descriptive cross sectional study was conducted at Paraplegic Center in Peshawar, Pakistan. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM 5) was used to assess the presence of post traumatic stress disorder in patients at the Paraplegic Center. The study was carried out from 20 December 2014 to 20 February 2015 on a convenience sample of 51 patients. The criterion for inclusion in the study was to have a traumatic spinal cord injury, while the exclusion criterion was to have a spinal cord injury that was non traumatic in nature. Results: Out of 51 patients, 31% met the diagnostic criteria for PTSD. The age group of 15-24 years had a 27% prevalence of PTSD, while the age groups of 25 to 34 years and 35 to 44 years had a PTSD prevalence of 42% and 40% respectively. Patients who had fallen from a height had the highest prevalence of PTSD of 41%, as compared to patients who had other causes of traumatic spinal cord injury. Patients with a lumbar spinal lesion had a PTSD prevalence of 44%, whereas patients with a cervical and thoracic spinal lesion had a PTSD prevalence of 33% and 25% respectively. Conclusion: The study shows that the middle age groups had a higher prevalence of PTSD, and patients who had fallen from a height had the highest prevalence of PTSD. Lumbar spinal lesion patients had a higher prevalence of PTSD than patients who had spinal lesions at the cervical or thoracic level.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"8 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.12.24311864
M. Franchini, A. Casadevall, Q. Dragotakes, D. Focosi
Italy was the first western country to be hit by the COVID-19 pandemic and suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite this initial effort, the proportion of COVID-19 patients treated with CCP during the first two years of the pandemic (2020-2021) was very low (approximately 2% of individuals hospitalized for COVID-19). In this study, we estimated the number of actual inpatient lives saved by CCP treatment in Italy using national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimated the potential number of lives saved if CCP had been deployed to 100% of hospitalized patients or used in 15% to 75% of outpatients. According to these models, CCP usage in 2020-2021 saved between 385-1304 lives , but this number would have increased to 17,751-60,079 if 100% of inpatients had been transfused with CCP. Similarly, broader (15-75%) usage in outpatients could have prevented 21,187-190,689 hospitalizations (desaturating hospitals) and 6,144-81,926 deaths. These data have important implications for convalescent plasma use in future infectious disease emergencies.
{"title":"Avoided and avoidable deaths with the use of COVID-19 convalescent plasma in Italy during the first two years of pandemic","authors":"M. Franchini, A. Casadevall, Q. Dragotakes, D. Focosi","doi":"10.1101/2024.08.12.24311864","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311864","url":null,"abstract":"Italy was the first western country to be hit by the COVID-19 pandemic and suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite this initial effort, the proportion of COVID-19 patients treated with CCP during the first two years of the pandemic (2020-2021) was very low (approximately 2% of individuals hospitalized for COVID-19). In this study, we estimated the number of actual inpatient lives saved by CCP treatment in Italy using national mortality data, and CCP mortality reduction data from meta-analyses of randomized controlled trials and real-world data. We also estimated the potential number of lives saved if CCP had been deployed to 100% of hospitalized patients or used in 15% to 75% of outpatients. According to these models, CCP usage in 2020-2021 saved between 385-1304 lives , but this number would have increased to 17,751-60,079 if 100% of inpatients had been transfused with CCP. Similarly, broader (15-75%) usage in outpatients could have prevented 21,187-190,689 hospitalizations (desaturating hospitals) and 6,144-81,926 deaths. These data have important implications for convalescent plasma use in future infectious disease emergencies.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"10 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.12.24311852
M. O'Driscoll, N. Hoze, N. Lefrancq, G. Ribeiro Dos Santos, D. Hoinard, M. Z. Rahman, K. K. Paul, A. M. Naser Titu, M. S. Alam, M. E. Hossain, J. Vanhomwegen, S. Cauchemez, E. S. Gurley, H. Salje
Multiplex immunoassays are facilitating the parallel measurement of antibody responses against multiple antigenically-related pathogens, generating a wealth of high-dimensional data which depict complex antibody-antigen relationships. In this study we develop a generalizable analytical framework to maximize inferences from multi-pathogen serological studies. We fit the model to measurements of IgG antibody binding to 10 arboviral pathogens from a cross-sectional study in northwest Bangladesh with 1,453 participants. We used our framework to jointly infer the prevalence of each pathogen by location and age, as well as the levels of between-pathogen antibody cross-reactivity. We find evidence of endemic transmission of Japanese encephalitis virus as well as recent outbreaks of dengue and chikungunya viruses in this district. Our estimates of antibody cross-reactivity were highly consistent with phylogenetic distances inferred from genetic data. Further, we demonstrated how our framework can be used to identify the presence of circulating cross-reactive pathogens that were not directly tested for, representing a potential opportunity for the detection of novel emerging pathogens. The presented analytical framework will be applicable to the growing number of multi-pathogen studies and will help support the integration of serological testing into disease surveillance platforms.
{"title":"Epidemiological inferences from serological responses to cross-reacting pathogens","authors":"M. O'Driscoll, N. Hoze, N. Lefrancq, G. Ribeiro Dos Santos, D. Hoinard, M. Z. Rahman, K. K. Paul, A. M. Naser Titu, M. S. Alam, M. E. Hossain, J. Vanhomwegen, S. Cauchemez, E. S. Gurley, H. Salje","doi":"10.1101/2024.08.12.24311852","DOIUrl":"https://doi.org/10.1101/2024.08.12.24311852","url":null,"abstract":"Multiplex immunoassays are facilitating the parallel measurement of antibody responses against multiple antigenically-related pathogens, generating a wealth of high-dimensional data which depict complex antibody-antigen relationships. In this study we develop a generalizable analytical framework to maximize inferences from multi-pathogen serological studies. We fit the model to measurements of IgG antibody binding to 10 arboviral pathogens from a cross-sectional study in northwest Bangladesh with 1,453 participants. We used our framework to jointly infer the prevalence of each pathogen by location and age, as well as the levels of between-pathogen antibody cross-reactivity. We find evidence of endemic transmission of Japanese encephalitis virus as well as recent outbreaks of dengue and chikungunya viruses in this district. Our estimates of antibody cross-reactivity were highly consistent with phylogenetic distances inferred from genetic data. Further, we demonstrated how our framework can be used to identify the presence of circulating cross-reactive pathogens that were not directly tested for, representing a potential opportunity for the detection of novel emerging pathogens. The presented analytical framework will be applicable to the growing number of multi-pathogen studies and will help support the integration of serological testing into disease surveillance platforms.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"37 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12DOI: 10.1101/2024.08.11.24311839
H. Thakkar, C. Reddy, V. R. Passi, A. Miyajiwala, S. Kale, A. Raj, S. Zadey
Background: While studies have investigated the availability of Medical College Hospitals (MCHs) in India, data on geographical accessibility is limited. Our study looks at the current geographical accessibility to these MCHs across 36 states and union territories (UTs) and 735 districts. Methods and Findings: We provided and validated the MCH data acquired from the National Health Profile Report 2022. We took motorized and walking travel-time friction surface rasters from the Malaria Atlas Project 2019 and high-resolution population estimates from WorldPop 2020. Using these, we examined the density of MCHs per million population and the median travel time to the nearest MCH. We assessed the Access Population Coverage (APC), defined as the proportion of the population within 30, 60, 90, and 120 minutes by motorized transport and within 30 and 60 minutes from the nearest MCH by walking. In 2022, India had an average density of 0.47 MCHs per million. The median travel time to the nearest MCH was 67.94 minutes by motorized transport and 589.82 minutes by walking. 71.76% of the population could access the nearest MCH by motorized transport within 60 minutes (range across districts: 0-100%). 4.22% of the population could access the nearest MCH by walking within 30 minutes (range across districts: 0-71.86%). The APC was 62.20% within 60 minutes by motorized transport in rural vs. 92.34% in urban areas. The APC within 60 minutes by motorized transport for public MCHs was 63.62%, while that for private was 45.95%. These estimates do not account for resource availability at the hospitals or vehicular ownership in the population. Conclusions: Median travel time and APC are useful for assessing geographical accessibility. Our study found a wide disparity in MCH access across Indian states and rural vs. urban areas. These analyses can guide the optimal placement of new MCHs.
{"title":"Assessing Population-level Accessibility to Medical College Hospitals in India: A Geospatial Modeling Study","authors":"H. Thakkar, C. Reddy, V. R. Passi, A. Miyajiwala, S. Kale, A. Raj, S. Zadey","doi":"10.1101/2024.08.11.24311839","DOIUrl":"https://doi.org/10.1101/2024.08.11.24311839","url":null,"abstract":"Background: While studies have investigated the availability of Medical College Hospitals (MCHs) in India, data on geographical accessibility is limited. Our study looks at the current geographical accessibility to these MCHs across 36 states and union territories (UTs) and 735 districts. Methods and Findings: We provided and validated the MCH data acquired from the National Health Profile Report 2022. We took motorized and walking travel-time friction surface rasters from the Malaria Atlas Project 2019 and high-resolution population estimates from WorldPop 2020. Using these, we examined the density of MCHs per million population and the median travel time to the nearest MCH. We assessed the Access Population Coverage (APC), defined as the proportion of the population within 30, 60, 90, and 120 minutes by motorized transport and within 30 and 60 minutes from the nearest MCH by walking. In 2022, India had an average density of 0.47 MCHs per million. The median travel time to the nearest MCH was 67.94 minutes by motorized transport and 589.82 minutes by walking. 71.76% of the population could access the nearest MCH by motorized transport within 60 minutes (range across districts: 0-100%). 4.22% of the population could access the nearest MCH by walking within 30 minutes (range across districts: 0-71.86%). The APC was 62.20% within 60 minutes by motorized transport in rural vs. 92.34% in urban areas. The APC within 60 minutes by motorized transport for public MCHs was 63.62%, while that for private was 45.95%. These estimates do not account for resource availability at the hospitals or vehicular ownership in the population. Conclusions: Median travel time and APC are useful for assessing geographical accessibility. Our study found a wide disparity in MCH access across Indian states and rural vs. urban areas. These analyses can guide the optimal placement of new MCHs.","PeriodicalId":18505,"journal":{"name":"medRxiv","volume":"11 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141919459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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