Tag: nevin manimala

Psychiatry Res. 2021 Apr 30;301:113974. doi: 10.1016/j.psychres.2021.113974. Online ahead of print.

ABSTRACT

Effective posttraumatic stress disorder (PTSD) pharmacotherapy is needed. This 12-week randomized multicenter trial evaluated efficacy and safety of TNX-102 SL, a bedtime sublingual formulation of cyclobenzaprine, in patients with military-related PTSD randomized to TNX-102 SL 2.8 mg or 5.6 mg, or placebo. Primary analysis comparing change from baseline in Clinician-Administered PTSD Scale-5 score between 2.8 mg (n=90) and placebo (n=92) was not significant. Secondary analysis of 5.6 mg (n=49) vs placebo demonstrated a mean difference of -4.5 units, p=.05, or, accounting for missing data by multiple imputation, -5.0 units, p=.03. Clinician Global Impression – Improvement responder rate was greater in 5.6 mg than placebo (p=0.04), as was mean functional improvement in Sheehan Disability Scale social domain (p=.03) and trended in work domain (p=.05). Post-hoc analyses showed early sleep improvement predicted improvement in PTSD after 12 weeks for TNX-102 SL (p<.01), not for placebo. Most common administration site reaction in TNX-102 SL groups was oral hypoaesthesia (5.6 mg, 36%; 2.8 mg, 39%; placebo, 2%), while most common systemic adverse event was somnolence (5.6 mg, 16%; 2.8 mg, 12%; placebo, 6%). This provides preliminary evidence that TNX-102 SL 5.6 mg reduces PTSD symptoms, improves sleep and psychosocial function, and is well tolerated. Clinicaltrials.gov Identifier: NCT02277704.

PMID:33979763 | DOI:10.1016/j.psychres.2021.113974

Mult Scler Relat Disord. 2021 Apr 25;52:102972. doi: 10.1016/j.msard.2021.102972. Online ahead of print.

ABSTRACT

BACKGROUND: A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS.

METHODS: A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.

RESULTS: After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI.

CONCLUSION: In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

PMID:33979770 | DOI:10.1016/j.msard.2021.102972

Kidney Blood Press Res. 2021 May 12:1-6. doi: 10.1159/000516206. Online ahead of print.

ABSTRACT

INTRODUCTION: Hyponatraemia is associated with increased mortality in patients undergoing maintenance haemodialysis. In anuric patients, hyponatraemia development depends on the water-sodium ratio in retained fluid within the interdialysis interval (IDI).

OBJECTIVE: This study aimed to calculate the retained sodium-retained water ratio in patients on maintenance haemodialysis and make a differential diagnosis of hyponatraemia according to these data.

METHODS: The amount of retained water was determined as body weight gain (ΔBW) within the IDI. Sodium retention was calculated using our formula: eRNa+ = ΔBW × (SNa+)t2 – total body water (TBW)t1 × ([SNa+]t1 – [SNa+]t2), where TBW represents the calculated volume of the total body water and (SNa+)t1 and (SNa+)t2 represent the sodium concentration at the beginning and at the end of the IDI, respectively. We performed 89 measurements in 32 anuric patients on maintenance haemodialysis.

RESULTS: Hyponatraemia was detected in 13 measurements at the end of the IDI. The ΔBW had no statistically significant difference between normonatraemic and hyponatraemic patients. Hyponatraemic patients had significantly lower levels of retained sodium. The retained water–retained sodium ratio facilitated in differentiating dilution hyponatraemia, nutritional hyponatraemia, depletion hyponatraemia, and dilution hyponatraemia associated with sodium wasting or malnutrition.

CONCLUSION: The composition of retained fluid during the IDI may be hypotonic, hypertonic, or isotonic in relation to the extracellular fluid. Most of the hyponatraemic patients had hypotonic fluid retained during the IDI because of dilution as well as gastrointestinal sodium loss and/or malnutrition.

PMID:33979795 | DOI:10.1159/000516206

Acta Trop. 2021 May 9:105951. doi: 10.1016/j.actatropica.2021.105951. Online ahead of print.

ABSTRACT

OBJECTIVE: This study pursues three main objectives: 1) exploring the spatial distribution patterns of human brucellosis (HB); 2) identifying parameters affecting the disease spread; and 3) modeling and predicting the spatial distribution of HB cases in 2012-2016 and 2017-2018, respectively, in rural districts of Mazandaran province, Iran.

METHODS: We collected data on the disease incidence, demography, ecology, climate, topography, and vegetation. Using the Global Moran’s I statistic, we measured spatial autocorrelation between log (number of HB cases). We applied the Getis-Ord G_i^* statistic to identify areas with high and low risk of the disease. To investigate the relationships between the factors affecting the incidence of HB as input variables together and the factors with the log (number of HB cases) as an output variable, we used the statistical linear regression model and the Pearson correlation coefficient. Then, we implemented a GIS-based adaptive neuro-fuzzy inference system (ANFIS) with two subtractive clustering and fuzzy c-means (FCM) clustering methods to model and predict the spatial distribution of HB.

RESULTS: Global Moran’s I spatial autocorrelation analysis indicated that the type of HB distribution is clustered in all years except 2014 and 2017, which are random. According to the Getis-Ord G_i^* analysis, the location of the hot spots varied during 2012-2018. In 2012 and 2013, most of the hot spots were seen in the west of the province. While in 2018, they were mostly concentrated in the eastern regions of the province. The linear regression model indicated that the parameters affecting the incidence of HB are independent of each other and can explain only 25.3% of the total changes in the log (number of HB cases). The results of the Pearson correlation coefficient showed that there were positive relationships between vegetation, log (population), and the number of sheep and cattle (P-value < 0.05). The above-mentioned factors had the strongest positive correlation with the log (number of HB cases) (P-value < 0.01). These results may be due to the fact that vegetation regions are suitable for livestock grazing, attracting large crowds of people. Therefore, this will increase HB cases. We compared the results of subtractive clustering and FCM clustering methods by evaluation criteria (e.g., linear correlation coefficient (LCC) and mean absolute error (MAE)) in two phases of development and assessment of the ANFIS model. In the evaluation phase, we predicted the spatial distribution of log (number of HB cases) in 2017 and 2018 for subtractive clustering (R² = 0.699, LCC or R = 0.692, MAE = 0.509, MSE = 0.455) and for FCM clustering (R² = 0.704, LCC or R = 0.697, MAE = 0.512, MSE = 0.448) that showed FCM clustering outperformed the subtractive clustering.

CONCLUSION: The findings may have important implications for public health. The emergence of the hot spots in the east of the province can be a warning to the health system. Health authorities can use the findings of this study to predict the spread of HB and perform HB prevention programs. They can also investigate the factors affecting the prevalence of the disease, identify high-risk areas, and ultimately allocate resources to high-risk regions.

PMID:33979640 | DOI:10.1016/j.actatropica.2021.105951

J Clin Epidemiol. 2021 May 9:S0895-4356(21)00140-2. doi: 10.1016/j.jclinepi.2021.04.017. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the impact of guidance and training on the inter-rater reliability (IRR), inter-consensus reliability (ICR) and evaluator burden of the Risk of Bias (RoB) in Non-randomized Studies (NRS) of Interventions (ROBINS-I) tool, and the RoB instrument for NRS of Exposures (ROB-NRSE).

STUDY DESIGN AND SETTING: In a before-and-after study, seven reviewers appraised the RoB using ROBINS-I (n=44) and ROB-NRSE (n=44), before and after guidance and training. We used Gwet’s AC₁ statistic to calculate IRR and ICR.

RESULTS: After guidance and training, the IRR and ICR of the overall bias domain of ROBINS-I and ROB-NRSE improved significantly; with many individual domains showing either a significant (IRR and ICR of ROB-NRSE; ICR of ROBINS-I), or nonsignificant improvement (IRR of ROBINS-I). Evaluator burden significantly decreased after guidance and training for ROBINS-I, whereas for ROB-NRSE there was a slight nonsignificant increase.

CONCLUSION: Overall, there was benefit for guidance and training for both tools. We highly recommend guidance and training to reviewers prior to RoB assessments and that future research investigate aspects of guidance and training that are most effective.

PMID:33979663 | DOI:10.1016/j.jclinepi.2021.04.017

Knee. 2021 May 9;30:267-274. doi: 10.1016/j.knee.2021.04.007. Online ahead of print.

ABSTRACT

BACKGROUND: Delays to diagnosis of anterior cruciate ligament (ACL) injury and specialist consultation continue to place patients at risk of early onset osteoarthritis. Incorporating acute knee clinics within a streamlined accident and emergency (A&E) pathway have shown potential in reducing delay but specific evaluative research is lacking. The aim of this service evaluation was to investigate the effectiveness of an acute knee clinic at one NHS Trust in the United Kingdom (UK), on reducing the delay to diagnosis of ACL injury and specialist consultation compared to a standard A&E pathway.

METHODS: An uncontrolled before and after design was utilised for this service evaluation. Data were collected from historical electronic patient records over a 1-year period with analysed results compared against previously collected data from the same NHS Trust.

RESULTS: 81 records met the criteria for the streamlined A&E pathway and were compared against 50 from the standard A&E pathway. For the streamlined A&E pathway median delay to diagnosis reduced from 97 to 14 days and delay to specialist consultation reduced from 158.5 to 45 days and were of statistical significance. The incorporation of an acute knee clinic was identified as the most influential factor on delay in addition to the location of presentation and mechanism of injury.

CONCLUSIONS: Introducing an acute knee clinic within a streamlined A&E pathway has a clinically relevant effect on reducing delay to diagnosis and specialist consultation and allows findings to be extrapolated and implemented to all UK based NHS Trust A&E departments.

PMID:33979729 | DOI:10.1016/j.knee.2021.04.007

Compr Psychiatry. 2021 Apr 30;108:152242. doi: 10.1016/j.comppsych.2021.152242. Online ahead of print.

ABSTRACT

BACKGROUND: Several studies have shown that interpersonal dependency is a risk factor for prolonged grief disorder (PGD), a disorder that has been recently approved by the American Psychiatric Association Assembly for inclusion in the Diagnostic and Statistical Manual of Mental Disorders-5-Text Revision (DSM-5-TR). Nevertheless, it remains unclear whether this relationship is independent of depression, which may also be related to both loss and interpersonal dependency. Furthermore, anaclitic dependency (maladaptive and immature) compared to relatedness (more adaptive and mature) dependency, and the relationships between these types of dependency and PGD, have not been examined. The aim of the present study was to determine how anaclitic and relatedness dependency are associated with PGD symptom severity, controlling for depressive symptom severity, over and above potential sociodemographic and loss-related confounder variables.

METHODS: Participants (N = 241) bereaved after the death of a family member from 0.5 to 8 years before the survey (M = 3.36, SD = 2.02) completed the Depressive Experiences Questionnaire, the Patient Health Questionnaire-9, and the Prolonged Grief Disorder-13 scale (PG-13).

RESULTS: A hierarchical regression analysis confirmed that anaclitic dependency is positively associated with PGD symptom severity, even when controlling for depression severity and other potential confounder variables. There was no significant association between relatedness dependency and PGD.

CONCLUSIONS: To assess the risk of PGD in individuals bereaved after the death of a family member, it is important to assess anaclitic dependency.

PMID:33979631 | DOI:10.1016/j.comppsych.2021.152242

Cell Rep. 2021 May 11;35(6):109110. doi: 10.1016/j.celrep.2021.109110.

ABSTRACT

Antibody repertoire sequencing enables researchers to acquire millions of B cell receptors and investigate these molecules at the single-nucleotide level. This power and resolution in studying humoral responses have led to its wide applications. However, most of these studies were conducted with a limited number of samples. Given the extraordinary diversity, assessment of these key features with a large sample set is demanded. Thus, we collect and systematically analyze 2,152 high-quality heavy-chain antibody repertoires. Our study reveals that 52 core variable genes universally contribute to more than 99% of each individual’s repertoire; a distal interspersed preferences characterize V gene recombination; the number of public clones between two repertoires follows a linear model, and the positive selection dominates at RGYW motif in somatic hypermutations. Thus, this population-level analysis resolves some critical features of the antibody repertoire and may have significant value to the large cadre of scientists.

PMID:33979623 | DOI:10.1016/j.celrep.2021.109110

Cell Rep. 2021 May 11;35(6):109114. doi: 10.1016/j.celrep.2021.109114.

ABSTRACT

How genes interact with the environment to shape phenotypic variation and evolution is a fundamental question intriguing to biologists from various fields. Existing linear models built on single genes are inadequate to reveal the complexity of genotype-environment (G-E) interactions. Here, we develop a conceptual model for mechanistically dissecting G-E interplay by integrating previously disconnected theories and methods. Under this integration, evolutionary game theory, developmental modularity theory, and a variable selection method allow us to reconstruct environment-induced, maximally informative, sparse, and casual multilayer genetic networks. We design and conduct two mapping experiments by using a desert-adapted tree species to validate the biological application of the model proposed. The model identifies previously uncharacterized molecular mechanisms that mediate trees’ response to saline stress. Our model provides a tool to comprehend the genetic architecture of trait variation and evolution and trace the information flow of each gene toward phenotypes within omnigenic networks.

PMID:33979624 | DOI:10.1016/j.celrep.2021.109114

Hypertens Pregnancy. 2021 May 12:1-9. doi: 10.1080/10641955.2021.1921791. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to assess the accuracy of The Fetal Medicine Foundation (FMF) screening algorithm for the prediction of preeclampsia.METHODS: Out of 138 women with high-risk pregnancies prospectively followed, 30 developed preeclampsia. The clinical examination and biochemical measurements were performed at first, second, early and late third trimester.RESULTS: A lower PAPP-A levels were found in the first trimester, while sFlt/PlGF was increased in the second and early third trimester in preeclampsia (p>0.05). FMF algorithm presented higher specificity (>70%), but had a drawback of lower sensitivity (35-77%).CONCLUSION: FMF algorithm had modest performance in the prediction of preeclampsia for high-risk pregnancies.

PMID:33979553 | DOI:10.1080/10641955.2021.1921791