Nevin Manimala

JMIR Res Protoc. 2023 Oct 24;12:e51861. doi: 10.2196/51861.

ABSTRACT

BACKGROUND: Hepatitis A outbreaks in the United Kingdom are uncommon. Most people develop mild to moderate symptoms that resolve, without sequelae, within months. However, in high-risk groups, including those with underlying chronic liver disease (CLD), hepatitis A infection can be severe, with a higher risk of mortality and morbidity. The Health Security Agency and the National Institute of Health and Care Excellence recommend preexposure hepatitis A vaccination given in 2 doses to people with CLD, regardless of its cause. There are currently no published reports of vaccination coverage for people with CLD in England or internationally.

OBJECTIVE: This study aims to describe hepatitis A vaccination coverage in adults with CLD in a UK primary care setting and compare liver disease etiology, sociodemographic characteristics, and comorbidities in people who are and are not exposed to the hepatitis A vaccine.

METHODS: We will conduct a retrospective cohort study with data from the Primary Care Sentinel Cohort of the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub database, which is nationally representative of the English population. We will include people aged 18 years and older who have been registered in general practices in the Research and Surveillance Centre network and have a record of CLD between January 1, 2012, and December 31, 2022, including those with alcohol-related liver disease, chronic hepatitis B, chronic hepatitis C, nonalcohol fatty liver disease, Wilson disease, hemochromatosis, and autoimmune hepatitis. We will carefully curate variables using the Systematized Nomenclature of Medicine Clinical Terms. We will report the sociodemographic characteristics of those who are vaccinated. These include age, gender, ethnicity, population density, region, socioeconomic status (measured using the index of multiple deprivation), obesity, alcohol consumption, and smoking. Hepatitis A vaccination coverage for 1 and 2 doses will be calculated using an estimate of the CLD population as the denominator. We will analyze the baseline characteristics using descriptive statistics, including measures of dispersion. Pairwise comparisons of case-mix characteristics, comorbidities, and complications will be reported according to vaccination status. A multistate survival model will be fitted to estimate the transition probabilities among four states: (1) diagnosed with CLD, (2) first dose of hepatitis A vaccination, (3) second dose of hepatitis A vaccination, and (4) death. This will identify any potential disparities in how people with CLD get vaccinated.

RESULTS: The Research and Surveillance Centre population comprises over 8 million people. The reported incidence of CLD is 20.7 cases per 100,000. International estimates of hepatitis A vaccine coverage vary between 10% and 50% in this group.

CONCLUSIONS: This study will describe the uptake of the hepatitis A vaccine in people with CLD and report any disparities or differences in the characteristics of the vaccinated population.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51861.

PMID:37874614 | DOI:10.2196/51861

Lab Chip. 2023 Oct 24. doi: 10.1039/d3lc00499f. Online ahead of print.

ABSTRACT

Single-nanoparticle detection has received tremendous interest due to its significance in fundamental physics and biological applications. Here, we demonstrate an optical nanofibre-enabled microfluidic sensor for the detection and sizing of nanoparticles. Benefitting from the strong evanescent field outside the nanofibre, a nanoparticle close to the nanofibre can scatter a portion of the field energy to the environment, resulting in a decrease in the transmitted intensity of the nanofibre. On the other hand, the narrow and shallow microfluidic channel provides a femtoliter-scale detection region, making nanoparticles flow through the detection region one by one. By real-time monitoring of the transmitted intensity of the nanofibre, the detection of a single polystyrene (PS) nanoparticle as small as 100 nm in diameter and exosomes in solution is realised. Based on a statistical analysis, the mean scattering signal is related to the size of the nanoparticle. Experimentally, a mixture of nanoparticles of different diameters (200, 500, and 1000 nm) in solution is identified. To demonstrate its potential in biological applications, high-throughput counting of yeasts using a pair of microchannels and dual-wavelength detection of fluorescently labelled nanoparticles are realised. We believe that the developed nanoparticle sensor holds great potential for the multiplexed and rapid sensing of diverse viruses.

PMID:37874569 | DOI:10.1039/d3lc00499f

Neuro Endocrinol Lett. 2023 Oct 23;44(7). Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the effect of postnatal primary repair surgery time on short-term (first 30 days) prognosis in newborns with Meningomyelocele (MMC).

METHODS: The study was conducted in the neonatal intensive care unit at a tertiary training and research hospital. The records of 41 MMC neonates were retrospectively reviewed. Demographic and clinical characteristics, surgical time, hospitalization and antibiotic duration, complications and associated anomalies were recorded.

RESULTS: There were 18 newborns in the early surgery (≤3 days) group and 23 newborns in the late surgery (>3 days up to 30 days) group.. There was no difference between groups in terms of birth weight, gestational week, head circumference, sex and type of delivery (p > 0.05). The length of hospitalization (17.2 ± 8.2 days vs 24.8 ± 16.1 days, p > 0.05) and antibiotic duration (11.8 ± 7.6 days vs 13.8 ± 10.1 days, p > 0.05) did not have significant difference. The number of neonates reoperated in the first 30 days was similar in early surgery group and in late surgery group (5 (27.7%) vs 6 (26.1%), p > 0.05). The number of patients requiring ventriculoperitoneal shunt was 9 (50%) in the early surgery group and 13 (56.5%) in the late surgery group. Surgical complications such as minor-major wound dehiscence, cerebrospinal fluid leakage, local infection, meningitis and ventriculitis were not statistically different between the groups (9 (50%) vs 8 (34.8%), (p > 0.05).

CONCLUSION: Surgical complications were not statistically different between the early and late surgery group, although the presence of surgical complications may be effective in the short-term prognosis of MMC.

PMID:37874554

Neuro Endocrinol Lett. 2023 Oct 23;44(7). Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the magnetic resonance imaging (MRI) and computed tomography (CT) findings along with other surgical and pathologic features as prognosis predictors in pancreatic neuroendocrine tumors (PNETs).

METHODS: In this study, we retrospectively analyzed a clinical data pool of patients with pathologically confirmed PNETs. CT and MRI findings were evaluated as potential prediction parameters of tumor-nodes-metastases (TNM) stage and grade, using Fisher’s exact test. Univariate and multivariate logistic regression models were used to estimate the risk factors associated with tumor recurrence after surgery. The Kaplan-Meier method and Cox proportional hazards model were used for recurrence-free survival analysis.

RESULTS: The predictors of higher TNM stages were tumor diameter, tumor boundary, distant metastases, and lymphadenopathy on CT scan. From MRI images, tumor diameter, T2-weighted image, tumor enhancement, and pancreatic duct dilatation showed statistically significant differences among TNM stages. Univariate analysis showed that American Joint Committee on Cancer (AJCC) TNM stage, World Health Organization (WHO) tumor grade, sex, smoking, and drinking were associated with tumor recurrence and disease-free survival (DFS); while tumor and metastasis also affected DFS. Multivariate survival analysis confirmed that AJCC TNM was an independent predictor after adjusting other covariates. Peripancreatic invasion and lymph node metastases as well as blurred boundary detected by CT or MRI may be independent risk factors for TNM stage and clinical outcome of PNETs.

CONCLUSION: TNM stage is a valuable predictor of prognosis in PNETs. Information from CT and MRI imaging can be used to determine the TNM stage, and to estimate the tumor prognosis, guide the follow-up, and avoid ineffective treatments.

PMID:37874552

Eur J Clin Invest. 2023 Oct 24:e14114. doi: 10.1111/eci.14114. Online ahead of print.

ABSTRACT

BACKGROUND: Rheumatic heart disease remains the most common cardiovascular disease in children and young adults. The outcome of interventional versus medical therapy on the long term is not fully elucidated yet. This study provides contemporary data on the clinical profile, treatment and follow up of patients with rheumatic mitral stenosis (MS) in Tanzania.

METHODS: Patients’ medical information, investigations and treatment data were recorded in this prospective cohort study. They were followed up for 6-24 months to determine the long-term outcome. Interventional therapy was defined as a combination of surgery and percutaneous balloon mitral valvuloplasty. Kaplan-Meier curves and Cox proportional hazards model were used in analyses. p-Value < 0.05 was considered statistically significant.

RESULTS: We enrolled 290 consecutive patients. Interventions were done in half of the patients. Median follow up was 23.5 months. Mortality was higher in the medical than interventional treatment (10.4% vs. 4%, log-rank p = 0.001). Median age was 36 years, females (68.3%) and low income (55.5%). Multivalvular disease was found in 116 (40%) patients, atrial fibrillation (31.4%), stroke/transient ischaemic attack (18.9%) and heart failure class III-IV (44.1%). Median (IQR) duration of disease was 3 (4) years, secondary prophylaxis (27.7%) and oral anticoagulants use (62.3%). In multivariable analysis, the risk of death among patients on medical was 3.07 times higher than those on interventional treatment (crude HR 3.07, 95% CI 1.43-6.56, p = 0.004), 2.44 times higher among patients with arrhythmias versus without arrhythmias (crude HR 2.44, 95% CI 1.19-4.49, p = 0.015) and 2.13 times higher among patients with multivalvular than single valve disease (crude HR 2.13, 95% CI 1.09-4.16, p = 0.026).

CONCLUSIONS: Intervention is carrying low mortality compared to medical treatment. Arrhythmias and multivalvular disease are associated with a high mortality. Rheumatic MS is more prevalent in young people, females and individuals with low income. There is a late hospital presentation and a low use of both secondary prophylactic antibiotics and anticoagulants.

PMID:37874538 | DOI:10.1111/eci.14114

Odontology. 2023 Oct 24. doi: 10.1007/s10266-023-00851-8. Online ahead of print.

ABSTRACT

To evaluate the osteogenic potential of platelet-rich fibrin (PRF) and low-level laser therapy (LLLT) on human stem cells from the apical papilla (SCAP) we isolated, characterized, and then cultured in an osteogenic medium cells with PRF and/or LLLT (660 nm, 6 J/m2-irradiation). Osteogenic differentiation was assessed by bone nodule formation and expression of bone morphogenetic proteins (BMP-2 and BMP-4), whereas the molecular mechanisms were achieved by qRT-PCR and RNA-seq analysis. Statistical analysis was performed by ANOVA and Tukey’s post hoc tests (p < 0.05* and p < 0.01**). Although PRF and LLLT increased bone nodule formation after 7 days and peaked at 21 days, the combination of PRF + LLLT led to the uppermost nodule formation. This was supported by increased levels of BMP-2 and -4 osteogenic proteins (p < 0.005). Furthermore, the PRF + LLLT relative expression of specific genes involved in osteogenesis, such as osteocalcin, was 2.4- (p = 0.03) and 28.3- (p = 0.001) fold higher compared to the PRF and LLLT groups, and osteopontin was 22.9- and 1.23-fold higher, respectively (p < 0.05), after 7 days of interaction. The transcriptomic profile revealed that the combination of PRF + LLLT induces MSX1, TGFB1, and SMAD1 expression, after 21 days of osteogenic differentiation conditions exposition. More studies are required to understand the complete cellular and molecular mechanisms of PRF plus LLLT on stem cells. Overall, we demonstrated for the first time that the combination of PRF and LLLT would be an excellent therapeutic tool that can be employed for dental, oral, and craniofacial repair and other tissue engineering applications.

PMID:37874511 | DOI:10.1007/s10266-023-00851-8

Psychometrika. 2023 Oct 24. doi: 10.1007/s11336-023-09937-2. Online ahead of print.

ABSTRACT

Optimal treatment regimes (OTRs) have been widely employed in computer science and personalized medicine to provide data-driven, optimal recommendations to individuals. However, previous research on OTRs has primarily focused on settings that are independent and identically distributed, with little attention given to the unique characteristics of educational settings, where students are nested within schools and there are hierarchical dependencies. The goal of this study is to propose a framework for designing OTRs from multisite randomized trials, a commonly used experimental design in education and psychology to evaluate educational programs. We investigate modifications to popular OTR methods, specifically Q-learning and weighting methods, in order to improve their performance in multisite randomized trials. A total of 12 modifications, 6 for Q-learning and 6 for weighting, are proposed by utilizing different multilevel models, moderators, and augmentations. Simulation studies reveal that all Q-learning modifications improve performance in multisite randomized trials and the modifications that incorporate random treatment effects show the most promise in handling cluster-level moderators. Among weighting methods, the modification that incorporates cluster dummies into moderator variables and augmentation terms performs best across simulation conditions. The proposed modifications are demonstrated through an application to estimate an OTR of conditional cash transfer programs using a multisite randomized trial in Colombia to maximize educational attainment.

PMID:37874510 | DOI:10.1007/s11336-023-09937-2

Mol Neurobiol. 2023 Oct 24. doi: 10.1007/s12035-023-03692-2. Online ahead of print.

ABSTRACT

Structural epilepsies display complex immune activation signatures. However, it is unclear which neuroinflammatory pathways drive pathobiology. Transcriptome studies of brain resections from mesial temporal lobe epilepsy (mTLE) patients revealed a dysregulation of transforming growth factor β, interferon α/β, and nuclear factor erythroid 2-related factor 2 pathways. Since these pathways are regulated by ubiquitin-specific proteases (USP), in particular USP15, we hypothesized that USP15 blockade may provide therapeutic relief in treatment-resistant epilepsies. For validation, transgenic mice which either constitutively or inducibly lack Usp15 gene expression underwent intrahippocampal kainate injections to induce mTLE. We show that the severity of status epilepticus is unaltered in mice constitutively lacking Usp15 compared to wild types. Cell death, reactive gliosis, and changes in the inflammatory transcriptome were pronounced at 4 days after kainate injection. However, these brain inflammation signatures did not differ between genotypes. Likewise, induced deletion of Usp15 in chronic epilepsy did not affect seizure generation, cell death, gliosis, or the transcriptome. Concordantly, siRNA-mediated knockdown of Usp15 in a microglial cell line did not impact inflammatory responses in the form of cytokine release. Our data show that a lack of USP15 is insufficient to modulate the expression of relevant neuroinflammatory pathways in an mTLE mouse model and do not support targeting USP15 as a therapeutic approach for pharmacoresistant epilepsy.

PMID:37874479 | DOI:10.1007/s12035-023-03692-2

Patient. 2023 Oct 24. doi: 10.1007/s40271-023-00649-4. Online ahead of print.

ABSTRACT

Health preference research (HPR) is being increasingly conducted to better understand patient preferences for medical decisions. However, patients vary in their desire to play an active role in medical decisions. Until now, few studies have considered patients’ preferred roles in decision making. In this opinion paper, we advocate for HPR researchers to assess and account for role preferences in their studies, to increase the relevance of their work for medical and shared decision making. We provide recommendations on how role preferences can be elicited and integrated with health preferences: (1) in formative research prior to a health preference study that aims to inform medical decisions or decision makers, (2a) in the development of health preference instruments, for instance by incorporating a role preference instrument and (2b) by clarifying the respondent’s role in the decision prior to the preference elicitation task or by including role preferences as an attribute in the task itself, and (3) in statistical analysis by including random parameters or latent classes to raise awareness of heterogeneity in role preferences and how it relates to health preferences. Finally, we suggest redefining the decision process as a model that integrates the role and health preferences of the different parties that are involved. We believe that the field of HPR would benefit from learning more about the extent to which role preferences relate to health preferences, within the context of medical and shared decision making.

PMID:37874464 | DOI:10.1007/s40271-023-00649-4

Int Ophthalmol. 2023 Oct 24. doi: 10.1007/s10792-023-02892-y. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the accuracy of a point-of-view cataract surgery simulation video in representing different subjective experiences of patients undergoing the procedure.

METHODS: One hundred consecutive post-cataract-surgery patients were shown a short simulation video of the surgery obtained through a porcine eye model during the first postoperative week. Patients then answered a multiple-choice questionnaire regarding their visual and tactile intraoperative experiences and how those experiences matched the simulation.

RESULTS: Of the patients surveyed (n = 100), 78% (n = 78) recalled visual experiences during surgery, 11% recalled pain (n = 11), and 6.4% (n = 5) recalled frightening experiences. Thirty-six percent of patients (n = 36) were interviewed after their second cataract surgery; there was no statistically significant difference between anxiety scores reported before the first eye surgery and second eye surgery (p = 0.147). Among all patients who recalled visual experiences (n = 78), nearly half (47.4%) reported that the video was the same/similar to their experience. Forty-eight percent of the patients recommended future patients to watch the video before their procedures, and more than a third (36%) agreed that watching the video before surgery would have helped them to relax.

CONCLUSIONS: Our model reflects the wide range of subjective patient experiences during and after surgery. The high percentage of patients who found the video accurate in different ways suggests that, with more development, point-of-view cataract simulation videos could prove useful for educational or clinical use. Further research may be done to confirm the simulation’s utility, by screening the video for subjects before operations.

PMID:37874440 | DOI:10.1007/s10792-023-02892-y