Category: Nevin Manimala

Hum Vaccin Immunother. 2024 Dec 31;20(1):2384180. doi: 10.1080/21645515.2024.2384180. Epub 2024 Aug 6.

ABSTRACT

During the coronavirus disease 2019 (COVID-19) pandemic, scheduled vaccinations were postponed, mass vaccination programmes were suspended and opportunities for healthcare workers to administer vaccines ad hoc decreased. The aims of this systematic literature review were to determine the impact of the COVID-19 pandemic on vaccine confidence, intent and uptake in preexisting routine childhood or adult vaccination programmes, and to identify factors associated with changes in acceptance, intent and uptake of preexisting vaccines. Medline and Embase were searched for studies in Australia, Brazil, Canada, China, Japan, the USA, and European countries, published between 1 January 2021 and 4 August 2022. A complementary gray literature search was conducted between 11 and 13 October 2022, and supplemented with additional gray research in October 2023. In total, 54 citations were included in the review. Study design and geography were heterogeneous. The number of adults who received or intended to receive an influenza or pneumococcal vaccine was higher during the pandemic than in previous seasons (n = 28 studies). In addition, increased acceptance of adult vaccinations was observed during 2020-21 compared with 2019-20 (n = 12 studies). The rates of childhood vaccinations decreased during the COVID-19 pandemic across several countries (n = 11 studies). Factors associated with changes in intention to receive a vaccination, or uptake of influenza vaccine, included previous vaccination, older age, higher perceived risk of contracting COVID-19, anxiety regarding the pandemic and fear of contracting COVID-19. Acceptance and uptake of influenza and pneumococcal vaccines generally increased after onset of the COVID-19 pandemic.

PMID:39106971 | DOI:10.1080/21645515.2024.2384180

Can J Ophthalmol. 2024 Aug 3:S0008-4182(24)00187-X. doi: 10.1016/j.jcjo.2024.06.018. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize the impact of multiple waves of COVID-19 on pediatric ophthalmology at a tertiary care hospital.

METHODS: Medical records were reviewed from pediatric patients seen for ophthalmic emergencies at the Montreal Children’s Hospital (Montreal, Canada) from 5 COVID-19 periods: March 13 to May 31, 2020; September 20, 2020, to February 21, 2021; March 21 to May 31, 2021; August 17 to November 5, 2021; and December 19, 2021, to January 25, 2022, as well as 2 pre-COVID time periods: March 13 to May 31, in 2018 and 2019).

RESULTS: There was a significant reduction in ophthalmic consultations when comparing pre-COVID to all 5 COVID waves (p < 0.0001). There was an increase in the average number of daily urgent (p = 0.01) ophthalmic consultations from waves 1 to 4. Mean household income of patients was not significantly pre-COVID compared to during the 5 COVID waves (p = 0.96). The most common referral reason was ocular trauma (38.0% of cases). There was a nonsignificant trend demonstrating more infectious disease presentations during waves 3 to 5 (p = 0.07). There was no difference in symptom duration prior to presentation (p = 0.54); however, there was a difference in the time between emergency room and ophthalmology assessment in waves 3 and 4 compared with wave 5 (p = 0.003).

CONCLUSION: The number of pediatric ophthalmology consultations was less during the 5 COVID waves than pre-COVID. An increase in urgent pediatric ophthalmology consultations occurred as COVID-19 infection rates in Quebec decreased. Access to health care and time to care were preserved across waves compared with prepandemic.

PMID:39106963 | DOI:10.1016/j.jcjo.2024.06.018

J R Soc Interface. 2024 Aug;21(217):20240004. doi: 10.1098/rsif.2024.0004. Epub 2024 Aug 7.

ABSTRACT

Mechanistic mathematical models such as ordinary differential equations (ODEs) have a long history for their use in describing population dynamics and determining estimates of key parameters that summarize the potential growth or decline of a population over time. More recently, geographic information systems (GIS) have become important tools to provide a visual representation of statistically determined parameters and environmental features over space. Here, we combine these tools to form a ‘GIS-ODE’ approach to generate spatiotemporal maps predicting how projected changes in thermal climate may affect population densities and, uniquely, population dynamics of Ixodes ricinus, an important tick vector of several human pathogens. Assuming habitat and host densities are not greatly affected by climate warming, the GIS-ODE model predicted that, even under the lowest projected temperature increase, I. ricinus nymph densities could increase by 26-99% in Scotland, depending on the habitat and climate of the location. Our GIS-ODE model provides the vector-borne disease research community with a framework option to produce predictive, spatially explicit risk maps based on a mechanistic understanding of vector and vector-borne disease transmission dynamics.

PMID:39106949 | DOI:10.1098/rsif.2024.0004

J Reprod Immunol. 2024 Aug 2;165:104310. doi: 10.1016/j.jri.2024.104310. Online ahead of print.

ABSTRACT

RESEARCH QUESTION: Despite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction.

DESIGN: A retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes.

RESULTS: 79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes.

CONCLUSION: The use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

PMID:39106544 | DOI:10.1016/j.jri.2024.104310

J Reprod Immunol. 2024 Aug 3;165:104313. doi: 10.1016/j.jri.2024.104313. Online ahead of print.

ABSTRACT

Provoked, localized, vulvodynia (PVD) is the main subtype of vulvodynia. Although the etiology of PVD is still a topic of debate, inflammation caused by cytokines responding to a dysregulated microbiome is one of the leading proposed theories. Therefore, the purpose of our study is to further explore the cytokine profiles in the study group with PVD using multiplex immunoassays based on electrochemiluminescence. We compared a panel of 26 distinct cytokines levels in the study group with PVD (n = 23) to the control group (n = 18) and cytokine concentrations were measured using MESO QuickPlex SQ 120 instrument with 5 different multiplex assays. Statistical analysis used the Mann-Whitney U test, two-sided p-values, and a significance level of α = 0.05. Differences in cytokine concentrations are described as negligible, small, medium, or large based on Cliff’s δ. Concentrations of three cytokines were significantly lower in the PVD group: a large difference in IP-10 (p = 0.029*) and medium differences in IL-1RA⁴ (p = 0.030*) and IL-12 (p = 0.034*). One cytokine level was significantly higher in the PVD group: a medium difference for IL-6 (p = 0.037*). Due to the lack of consistency in elevation of inflammatory profiles, it is not enough to support persistent inflammation as the etiology behind PVD. However, these findings may indicate there is a possible immune response deficiency in some patients who have PVD. The resemblance of cytokine profile in our study to cytokine profile of people with chronic yeast infection further support this proposed mechanism behind PVD. Future studies involving history and testing for yeast infection are necessary to explore this possibility further.

PMID:39106543 | DOI:10.1016/j.jri.2024.104313

Neuroimage Clin. 2024 Jul 25;43:103646. doi: 10.1016/j.nicl.2024.103646. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: After a concussion diagnosis, the most important issue for patients and loved ones is how long it will take them to recover. The main objective of this study is to develop a prognostic model of concussion recovery. This model would benefit many patients worldwide, allowing for early treatment intervention.

METHODS: The Concussion Assessment, Research and Education (CARE) consortium study enrolled collegiate athletes from 30 sites (NCAA athletic departments and US Department of Defense service academies), 4 of which participated in the Advanced Research Core, which included diffusion-weighted MRI (dMRI) data collection. We analyzed the dMRI data of 51 injuries of concussed athletes scanned within 48 h of injury. All athletes were cleared to return-to-play by the local medical staff following a standardized, graduated protocol. The primary outcome measure is days to clearance of unrestricted return-to-play. Injuries were divided into early (return-to-play < 28 days) and late (return-to-play >= 28 days) recovery based on the return-to-play clinical records. The late recovery group meets the standard definition of Persisting Post-Concussion Symptoms (PPCS). Data were processed using automated, state-of-the-art, rigorous methods for reproducible data processing using brainlife.io. All processed data derivatives are made available at https://brainlife.io/project/63b2ecb0daffe2c2407ee3c5/dataset. The microstructural properties of 47 major white matter tracts, 5 callosal, 15 subcortical, and 148 cortical structures were mapped. Fractional Anisotropy (FA) and Mean Diffusivity (MD) were estimated for each tract and structure. Correlation analysis and Receiver Operator Characteristic (ROC) analysis were then performed to assess the association between the microstructural properties and return-to-play. Finally, a Logistic Regression binary classifier (LR-BC) was used to classify the injuries between the two recovery groups.

RESULTS: The mean FA across all white matter volume was negatively correlated with return-to-play (r = -0.38, p = 0.00001). No significant association between mean MD and return-to-play was found, neither for FA nor MD for any other structure. The mean FA of 47 white matter tracts was negatively correlated with return-to-play (rμ = -0.27; rσ = 0.08; r_min = -0.1; r_max = -0.43). Across all tracts, a large mean ROC Area Under the Curve (AUC_FA) of 0.71 ± 0.09 SD was found. The top classification performance of the LR-BC was AUC = 0.90 obtained using the 16 statistically significant white matter tracts.

DISCUSSION: Utilizing a free, open-source, and automated cloud-based neuroimaging pipeline and app (https://brainlife.io/docs/tutorial/using-clairvoy/), a prognostic model has been developed, which predicts athletes at risk for slow recovery (PPCS) with an AUC=0.90, balanced accuracy = 0.89, sensitivity = 1.0, and specificity = 0.79. The small number of participants in this study (51 injuries) is a significant limitation and supports the need for future large concussion dMRI studies and focused on recovery.

PMID:39106542 | DOI:10.1016/j.nicl.2024.103646

Mult Scler Relat Disord. 2024 Jun 20;89:105740. doi: 10.1016/j.msard.2024.105740. Online ahead of print.

ABSTRACT

BACKGROUND: Spasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies.

METHODS: This was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient’s overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase.

RESULTS: Of 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were -0.23 for nabiximols and -0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS.

CONCLUSION: Despite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. CLINICAL TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): : NCT04657666.

PMID:39106541 | DOI:10.1016/j.msard.2024.105740

Stud Hist Philos Sci. 2024 Aug 5;107:1-10. doi: 10.1016/j.shpsa.2024.07.005. Online ahead of print.

ABSTRACT

We propose that the epistemic functions of replication in science are best understood by relating them to kinds of experimental error/uncertainty. One kind of replication, which we call “direct replications,” principally serves to assess the reliability of an experiment through its precision: the presence and degree of random error/statistical uncertainty. The other kind of replication, which we call “conceptual replications,” principally serves to assess the validity of an experiment through its accuracy: the presence and degree of systematic errors/uncertainties. To illustrate the aptness of this general view, we examine the Hubble constant controversy in astronomy, showing how astronomers have responded to the concordances and discordances in their results by carrying out the different kinds of replication that we identify, with the aim of establishing a precise, accurate value for the Hubble constant. We contrast our view with Machery’s “re-sampling” account of replication, which maintains that replications only assess reliability.

PMID:39106538 | DOI:10.1016/j.shpsa.2024.07.005

Injury. 2024 Aug 2;55(10):111766. doi: 10.1016/j.injury.2024.111766. Online ahead of print.

ABSTRACT

BACKGROUND: The sustentaculum tali is a biomechanically important stabilizer of the hindfoot and contributes to articular congruency of the subtalar joint. Sustentaculum injury associated with a talus fracture has been described infrequently and treatment of this combined injury varies. The purpose of this study was to describe and evaluate the outcomes of the combined talus and sustentaculum fracture.

METHODS: Retrospective chart and radiographic review was performed on all talus fractures (n = 436) requiring operative fixation over a 21-year period at a single Level-1 trauma center. All talus fractures with sustentaculum fractures were included. Statistical analysis was performed using Chi-squared and Fishers exact tests where appropriate.

RESULTS: Sustentaculum fractures occurred in 6.2 % (n = 27) of patients with talus fractures. Average follow-up was 14 months; 18.5 % were open fractures, 88.8 % were from high-energy mechanisms, and 44.4 % were polytraumas. Diagnosis of the sustentaculum fracture was missed on presenting radiographs in 69.2 % (n = 18). The most common associated talus fracture was a talar neck fracture (40.7 %) and the majority (73.7 %) were Hawkins II. Overall, 40.7 % (n = 11) of the sustentaculum fractures were treated with independent fixation and 7.4 % (n = 2) were treated with acute subtalar arthrodesis. Subtalar post-traumatic osteoarthritis (PTOA) at final follow-up was seen in 23.1 % of combined injuries. Independent sustentaculum fixation did not influence the rate of PTOA or re-operation (p = 0.92, p = 0.91, respectively).

CONCLUSION: Talar fractures have an associated sustentaculum fracture in approximately 6 % of cases, especially with Hawkins II fracture-dislocations. Over two-thirds of the associated sustentaculum fractures were missed on presenting radiographs, reiterating the need for heightened awareness and consideration of advanced imaging for all talus fractures. The rate of PTOA following these combined injuries at mean follow-up of 24 months does not exceed established rates after isolated talus fractures. Further research is required to determine the optimal management of the sustentaculum in these combined injuries.

LEVEL OF EVIDENCE: IV.

PMID:39106534 | DOI:10.1016/j.injury.2024.111766

Psychiatry Res Neuroimaging. 2024 Jul 6;343:111858. doi: 10.1016/j.pscychresns.2024.111858. Online ahead of print.

ABSTRACT

Autism is a neurodevelopmental disorder that manifests in individuals during childhood and has enduring consequences for their social interactions and communication. The prediction of Autism Spectrum Disorder (ASD) in individuals based on the differences in brain networks and activities have been studied extensively in the recent past, however, with lower accuracies. Therefore in this research, identification at the early stage through computer-aided algorithms to differentiate between ASD and TD patients is proposed. In order to identify features, a Multi-Layer Perceptron (MLP) model is developed which utilizes logistic regression on characteristics extracted from connectivity matrices of subjects derived from fMRI images. The features that significantly contribute to the classification of individuals as having Autism Spectrum Disorder (ASD) or typically developing (TD) are identified by the logistic regression model. To enhance emphasis on essential attributes, an AND operation is integrated. This involves selecting features demonstrating statistical significance across diverse logistic regression analyses conducted on various random distributions. The iterative approach contributes to a comprehensive understanding of relevant features for accurate classification. By implementing this methodology, the estimation of feature importance became more dependable, and the potential for overfitting is moderated through the evaluation of model performance on various subsets of data. It is observed from the experimentation that the highly correlated Left Lateral Occipital Cortex and Right Lateral Occipital Cortex ROIs are only found in ASD. Also, it is noticed that the highly correlated Left Cerebellum Tonsil and Right Cerebellum Tonsil are only found in TD participants. Among the MLP classifier, a recall of 82.61 % is achieved followed by Logistic Regression with an accuracy of 72.46 %. MLP also stands out with a commendable accuracy of 83.57 % and AUC of 0.978.

PMID:39106532 | DOI:10.1016/j.pscychresns.2024.111858