Tag: nevin manimala

Epilepsy Res. 2022 Mar 4;182:106895. doi: 10.1016/j.eplepsyres.2022.106895. Online ahead of print.

ABSTRACT

BACKGROUND: Focal seizures are associated with various co-morbidities. Seizure disorders also affect the quality of life of the patients. A huge proportion of patients continue to have uncontrolled seizures despite the availability of numerous antiepileptic drugs. Novel therapeutic targets too, have failed to overcome this problem. Therefore, drugs acting on conventional targets are being explored. Perampanel is one such drug. The present study aimed to assess its efficacy, safety, and effect on quality of life and cognition in patients aged 12 years and above.

METHODS: Database search was conducted using keywords perampanel, partial seizures and randomized controlled trials (RCTs). Single and double blinded RCTs were included in the analysis. The primary outcomes assessed were 50% responder rate and seizure freedom rates. Secondary outcomes assessed were Improvement in Clinical Global Improvement for Change (CGI-C), number of patients who experienced adverse events, number of patients who withdrew from trials, adverse drug reaction (ADR) profile from Vigibase, long term safety, quality of Life (QoL) assessment and cognitive assessment, especially in adolescents. The Risk ratios (RR) were calculated for these parameters.

RESULTS: 24 full text articles were obtained out of a total 421 studies. From these seven double blind randomized controlled trials were included in the meta-analysis. Perampanel treated patients showed higher 50% responder rates than those treated with placebo. The Risk Ratios (RRs) were 1.39 [95% confidence interval (CI) 1.08-1.79], 1.83 [95% CI 1.51 – 2.22] and 1.81 [95% CI 1.45-2.27] for the 4 mg per day, 8 mg once daily and 12 mg once daily subgroups of perampanel respectively. The RRs for the seizure freedom rates were 4.52 [95% CI 1.30-15.73], 3.65 [95% CI 1.40-9.52] and 2.14 [95% CI 1.11-4.11] for 4 mg per day, 8 mg once daily and 12 mg once daily subgroups of perampanel respectively. There was a significantly higher risk of TEAEs with the 8 mg and 12 mg doses of perampanel as compared to that with placebo. Number of patients who withdrew from the trials due to adverse events was statistically significant in only the 12 mg subgroup of perampanel in comparison to that with placebo group.

CONCLUSION: Perampanel was observed to be an effective add on drug for treating pharmacoresistant focal seizures. The patients achieved higher 50% response rates and freedom from seizures with its use. Tolerability of perampanel was more at lower doses.

PMID:35305446 | DOI:10.1016/j.eplepsyres.2022.106895

Ticks Tick Borne Dis. 2022 Mar 8;13(3):101937. doi: 10.1016/j.ttbdis.2022.101937. Online ahead of print.

ABSTRACT

Two multiplex SYBR Green based real-time PCR assays were standardized and evaluated to detect DNA from four canine haemoparasites (Babesia gibsoni, Babesia vogeli, Ehrlichia canis and Hepatozoon canis), along with internal controls from dogs from selected districts of Punjab state, India. Amplicons of 126 bp, 337 bp, 234 bp and 106 bp corresponding to B. gibsoni (18S rRNA gene), B. vogeli (18S rRNA gene), E. canis (virB9 gene), and H. canis (18S rRNA gene) were obtained, without any non-specific amplification. Microscopic evaluation of 200 blood samples from dogs revealed the prevalence of B. gibsoni, E. canis and H. canis as 1.5%, 1.5% and 1.0%, respectively, while with the multiplex real-time PCR assays the values for B. gibsoni, B. vogeli, E. canis, and H. canis were 8.0%, 1.5%, 3.5% and 23.5%, respectively, with concurrent infections of B. gibsoni and H. canis (3.5%); E. canis and H. canis (2.0%) and B. gibsoni, B. vogeli, E. canis, and H. canis (0.5%). The diagnostic sensitivity of the multiplex real-time PCR assays with respect to microscopy in the detection of B. gibsoni, E. canis and H. canis was 100% while the specificity for B. gibsoni, B. vogeli, E. canis, and H. canis was 93%, 100%, 98% and 77%, respectively, revealing the respective strength of agreement as ″fair″, ″slight″, ″moderate″ and ″slight″ by kappa value statistics, and the data were statistically significant, for detection of B. gibsoni and E. canis infections, by Fisher’s exact test. The analytical sensitivity of the multiplex PCR assays in detection of DNAs was 8.59 × 10⁵ and 9.9 × 10⁶ copies for B. vogeli and E. canis, respectively, and 1.15 × 10⁶ and 3.41 × 10⁵ copies for B. gibsoni and H. canis, respectively. Assessment of risk factors viz. age, sex, breed, season and locations showed no significant association with the prevalence of these haemoparasites except for B. vogeli, E. canis and H. canis where significant associations were found for location, age and breed, respectively by multiplex real-time PCR assays.

PMID:35305431 | DOI:10.1016/j.ttbdis.2022.101937

Gen Hosp Psychiatry. 2022 Mar 10;76:3-15. doi: 10.1016/j.genhosppsych.2022.03.003. Online ahead of print.

ABSTRACT

OBJECTIVES: To describe the implementation of a collaborative care (CC) screening and treatment program for major depression in people with cancer, found to be effective in clinical trials, into routine outpatient care of a cancer center.

METHOD: A mixed-methods observational study guided by the RE-AIM implementation framework using quantitative and qualitative data collected over five years.

RESULTS: Program set-up took three years and required more involvement of CC experts than anticipated. Barriers to implementation were uncertainty about whether oncology or psychiatry owned the program and the hospital’s organizational complexity. Selecting and training CC team members was a major task. 90% (14,412/16,074) of patients participated in depression screening and 61% (136/224) of those offered treatment attended at least one session. Depression outcomes were similar to trial benchmarks (61%; 78/127 patients had a treatment response). After two years the program obtained long-term funding. Facilitators of implementation were strong trial evidence, effective integration into cancer care and ongoing clinical and managerial support.

CONCLUSION: A CC program for major depression, designed for the cancer setting, can be successfully implemented into routine care, but requires time, persistence and involvement of CC experts. Once operating it can be an effective and valued component of medical care.

PMID:35305403 | DOI:10.1016/j.genhosppsych.2022.03.003

Vet Parasitol. 2022 Mar 11;304:109696. doi: 10.1016/j.vetpar.2022.109696. Online ahead of print.

ABSTRACT

The filarial parasite Dirofilaria immitis causes dirofilariosis, a potentially fatal pulmonary condition in canids and felines. Dirofilariosis can be prevented by treatment with a prophylactic macrocyclic lactone (ML) regimen. Unfortunately, ML-resistant D. immitis isolates, genetically distinct from the wildtype population, have been confirmed via molecular markers. DNA-based tests for ML-resistance are costly and time-consuming. There lacks a simple and reliable in vitro biological test to differentiate D. immitis infections resulting from inadequate adherence to recommended prophylaxis regimens from those caused by truly resistant D. immitis isolates. The goal of the current study was to develop a minimally invasive rapid diagnostic in vitro biological assay to differentiate ML-susceptible from ML-resistant D. immitis isolates. The in vitro assay was developed based on the concept that MLs act on the microfilariae (mf) by paralyzing the excretory pore muscle, inhibiting the release of molecules, including enzymes, that regulate host immunity. The basis of the in vitro diagnostic assay is to assess the effects of ivermectin (IVM) exposure on the secretion of enzymes by the D. immitis mf at a concentration that distinguishes the ML-susceptible from ML-resistant isolates. The metabolic enzyme, triosephosphate isomerase (TPI), was chosen due to high abundance in the D. immitis secretome. In this study, the in vitro TPI enzymatic assay was optimized and tested in eight laboratory-maintained isolates. The ML-susceptible Missouri, Berkeley, and Georgia II isolate; the putative ML-susceptible Georgia III, and Big Head; and the ML-resistant JYD-34, Metairie, and WildCat. We observed mixed results, Missouri and Berkeley had statistically significant decreases in TPI activity following 24-hour in vitro IVM exposure. The three resistant isolates, JYD-34, Metairie, and WildCat showed no change in TPI activity following IVM exposure. The susceptible, or putative susceptible Georgia II, Georgia III, and Big Head isolates had a phenotypic response consistent with ML-resistance based on the in vitro assay. However, increasing genotypic evidence has presented a mixed genotype for the three isolates, indicating they may be partially selected for ML-resistance. The measurement of changes in enzymatic activity and the in vitro TPI enzymatic activity assay consequently does not appear to be a reliable detection method for ML-resistance but may be useful for identifying fully susceptible isolates.

PMID:35305421 | DOI:10.1016/j.vetpar.2022.109696

Placenta. 2022 Mar 10;121:109-115. doi: 10.1016/j.placenta.2022.03.006. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to quantify uterine artery (UtA) blood flow and its hemodynamic components throughout the first trimester of pregnancy using Doppler ultrasound.

METHODS: Cross-sectional cohort study involving women undergoing a routine ultrasound scan between 5 and 13 weeks’ gestation. UtA blood flow was measured using Pulsed-wave Color Doppler to assess blood flow velocity across the cardiac cycle and M-mode Color Power Angio imaging to assess UtA diameter. A formula was applied to calculate systolic and diastolic blood flow volumes according to Poiseuille’s equation.

RESULTS: A total of 330 women with a single viable first-trimester pregnancy agreed to participate in this study. A stepwise increase in total UtA blood flow was observed during the first trimester, with significant increases at 7, 8, and 11 weeks. No significant differences in blood flow were observed between right and left UtAs. However, there was a statistically significant difference when comparing the UtA based on higher and lower blood flow, with a mean ± SD of 64.4% ± 10.5% through the former (p < 0.001). The increase in the UtA blood flow was secondary to an increase in the blood flow rate between 5 and 10 weeks. A significant increase in UtA diameter was only identified from 11 weeks onwards.

DISCUSSION: UtA blood flow in the first trimester is asymmetrical, at a constant ratio of ≈2:1. An interpretive model of the possible origin of this pattern during early pregnancy is proposed.

PMID:35305397 | DOI:10.1016/j.placenta.2022.03.006

Spectrochim Acta A Mol Biomol Spectrosc. 2022 Mar 12;275:121138. doi: 10.1016/j.saa.2022.121138. Online ahead of print.

ABSTRACT

Multi-source spectroscopy is increasingly applied in water contaminant analysis, and general existing spectral features are based on direct mathematical statistics rather than revealing inherent connection between multisource spectra, which has restricted the accuracy and robustness performance. Here in, a novel method is proposed and it is based on the inherent connection between fluorescence and absorption spectra, which can reflect deeper information than conventional methods. The relevant theory was analyzed based on energy level transition and the symmetry between absorption and fluorescence spectra, and then three features were extracted related to internal molecular properties and dependent on two sources of spectral information simultaneously. The three features include the width of the fluorescence emission peak, Stokes shift and symmetry axis between absorption peak and fluorescent emission peak, that correspond to bandwidth of the ground state, vibrational relaxations and conjugate systems respectively. Their significant change of values in monitoring can reflect richer and deeper information in pollution events for contamination tracing and subsequent processing, such as the category, common properties and functional groups of contaminants. The effectiveness of this feature extraction method was assessed by conducting experiments with sample mixtures of typical chemicals and four real water samples. The results highlight the potential of these features in water pollution early warning and contaminant analysis with richer information and stronger robustness.

PMID:35305359 | DOI:10.1016/j.saa.2022.121138

Lancet Neurol. 2022 Apr;21(4):329-341. doi: 10.1016/S1474-4422(22)00027-8.

ABSTRACT

BACKGROUND: Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression of Alzheimer’s disease. Although studies in animal models suggest that TREM2 is protective against Alzheimer’s pathology, its effect on tau pathology and its potential beneficial role in people with Alzheimer’s disease is still unclear. Our aim was to study associations between the dynamics of soluble TREM2, as a biomarker of TREM2 signalling, and amyloid β (Aβ) deposition, tau-related pathology, neuroimaging markers, and cognitive decline, during the progression of autosomal dominant Alzheimer’s disease.

METHODS: We did a longitudinal analysis of data from the Dominantly Inherited Alzheimer Network (DIAN) observational study, which includes families with a history of autosomal dominant Alzheimer’s disease. Participants aged over 18 years who were enrolled in DIAN between Jan 1, 2009, and July 31, 2019, were categorised as either carriers of pathogenic variants in PSEN1, PSEN2, and APP genes (n=155) or non-carriers (n=93). We measured amounts of cleaved soluble TREM2 using a novel immunoassay in CSF samples obtained every 2 years from participants who were asymptomatic (Clinical Dementia Rating [CDR]=0) and annually for those who were symptomatic (CDR>0). CSF concentrations of Aβ40, Aβ42, total tau (t-tau), and tau phosphorylated on threonine 181 (p-tau) were measured by validated immunoassays. Predefined neuroimaging measurements were total cortical uptake of Pittsburgh compound B PET (PiB-PET), cortical thickness in the precuneus ascertained by MRI, and hippocampal volume determined by MRI. Cognition was measured using a validated cognitive composite (including DIAN word list test, logical memory delayed recall, digit symbol coding test [total score], and minimental status examination). We based our statistical analysis on univariate and bivariate linear mixed effects models.

FINDINGS: In carriers of pathogenic variants, a high amyloid burden at baseline, represented by low CSF Aβ42 (β=-4·28 × 10^-2 [SE 0·013], p=0·0012), but not high cortical uptake in PiB-PET (β=-5·51 × 10^-3 [0·011], p=0·63), was the only predictor of an augmented annual rate of subsequent increase in soluble TREM2. Augmented annual rates of increase in soluble TREM2 were associated with a diminished rate of decrease in amyloid deposition, as measured by Aβ42 in CSF (r=0·56 [0·22], p=0·011), in presymptomatic carriers of pathogenic variants, and with diminished annual rate of increase in PiB-PET (r=-0·67 [0·25], p=0·0060) in symptomatic carriers of pathogenic variants. Presymptomatic carriers of pathogenic variants with annual rates of increase in soluble TREM2 lower than the median showed a correlation between enhanced annual rates of increase in p-tau in CSF and augmented annual rates of increase in PiB-PET signal (r=0·45 [0·21], p=0·035), that was not observed in those with rates of increase in soluble TREM2 higher than the median. Furthermore, presymptomatic carriers of pathogenic variants with rates of increase in soluble TREM2 above or below the median had opposite associations between Aβ42 in CSF and PiB-PET uptake when assessed longitudinally. Augmented annual rates of increase in soluble TREM2 in presymptomatic carriers of pathogenic variants correlated with decreased cortical shrinkage in the precuneus (r=0·46 [0·22]), p=0·040) and diminished cognitive decline (r=0·67 [0·22], p=0·0020).

INTERPRETATION: Our findings in autosomal dominant Alzheimer’s disease position the TREM2 response within the amyloid cascade immediately after the first pathological changes in Aβ aggregation and further support the role of TREM2 on Aβ plaque deposition and compaction. Furthermore, these findings underpin a beneficial effect of TREM2 on Aβ deposition, Aβ-dependent tau pathology, cortical shrinkage, and cognitive decline. Soluble TREM2 could, therefore, be a key marker for clinical trial design and interpretation. Efforts to develop TREM2-boosting therapies are ongoing.

FUNDING: German Research Foundation, US National Institutes of Health.

PMID:35305339 | DOI:10.1016/S1474-4422(22)00027-8

J Environ Manage. 2022 Mar 16;312:114909. doi: 10.1016/j.jenvman.2022.114909. Online ahead of print.

ABSTRACT

Floating treatment wetlands (FTWs), artificial systems constructed from buoyant mats and planted with emergent macrophytes, represent a potential retrofit to enhance the dissolved nutrient removal performance of existing retention ponds. Treatment occurs as water flows through the dense network of roots suspended in the water column, providing opportunities for pollutants to be removed via filtration, sedimentation, plant uptake, and adsorption to biofilms in the root zone. Despite several recent review articles summarizing the growing body of research on FTWs, FTW design guidance and strategies to optimize their contributions to pollutant removal from stormwater are lacking, due in part to a lack of statistical analysis on FTW performance at the field scale. A meta-analysis of eight international FTW studies was performed to investigate the influence of retention pond, catchment, and FTW design characteristics on effluent concentrations of nutrients and total suspended solids (TSS). Random forest regression, a tree-based machine learning approach, was used to model complex interactions between a suite of predictor variables to identify design strategies for both retention ponds and FTWs to enhance treatment of nutrient and sediment. Results indicate that pond design features, especially loading ratio and pond depth (which should be limited to 200:1 and 1.75 m, respectively), are most influential to effluent water quality, while the benefits of FTWs were limited to improving mitigation of phosphorus species and TSS which was primarily influenced by FTW coverage and planting density. Findings from this work inform wet retention pond and FTW design, as well as guidance on scenarios where FTW implementation is most appropriate, to improve dissolved nutrient and sediment removal in urban runoff.

PMID:35305357 | DOI:10.1016/j.jenvman.2022.114909

Addict Behav. 2022 Mar 15;130:107307. doi: 10.1016/j.addbeh.2022.107307. Online ahead of print.

ABSTRACT

INTRODUCTION: Product placement in music videos is a growing promotional strategy. This study examined the impact of e-cigarette product placement and imagery in music videos on susceptibility to use e-cigarettes among young adults.

METHODS: A non-probability sample of young adults (18 to 24) in Southern California were recruited to participate in an experiment over Zoom. Participants were randomized into a treatment or a control group. The treatment group watched seven music videos with e-cigarette product placement and imagery. The control group watched the same seven music videos with all e-cigarette product placement and imagery digitally removed. Participants completed a questionnaire after watching the music videos. The focus of the analysis was on susceptibility to use e-cigarettes in the future among never users (n = 303).

RESULTS: Participants in the treatment group who had never used e-cigarettes were more likely to report intentions to try e-cigarettes in the future (OR = 1.94, 95% CI [1.08, 3.54], compared to participants in the control group. Participants in the treatment group who had never used e-cigarettes were more likely to report peer influence (OR = 1.97, 95% CI [1.19, 3.32], compared to participants in the control group. While these subitems of susceptibility to use e-cigarettes were statistically significant, the relationship between the treatment group and the composite measure of susceptibility was not.

CONCLUSION: Exposure to e-cigarette product placement in music videos may increase young adults’ intentions to try e-cigarettes in the future. Federal, state, and local tobacco control regulatory bodies should consider strategies to reduce e-cigarette product placement in music videos.

PMID:35305325 | DOI:10.1016/j.addbeh.2022.107307

Lancet. 2022 Mar 16:S0140-6736(22)00462-7. doi: 10.1016/S0140-6736(22)00462-7. Online ahead of print.

ABSTRACT

BACKGROUND: The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort.

METHODS: Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases).

FINDINGS: The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54-0·58); for hospital admission and death, HR estimates were 0·41 (0·39-0·43) and 0·31 (0·26-0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85-1·42) in those younger than 10 years, decreasing to 0·25 (0·21-0·30) in 60-69-year-olds, and then increasing to 0·47 (0·40-0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32-0·68]) and unvaccinated (0·18 [0·06-0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88-1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48-0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28-0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8-11 weeks post-booster vs unvaccinated: 0·22 [0·20-0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2.

INTERPRETATION: The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections.

FUNDING: Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council.

PMID:35305296 | DOI:10.1016/S0140-6736(22)00462-7