Nevin Manimala

J Stat Theory Appl. 2022 Oct 15:1-25. doi: 10.1007/s44199-022-00050-4. Online ahead of print.

ABSTRACT

The distribution of the ratio of two independently distributed Lindley random variables $X$ and $Y$ , with different parameters, is derived. The associated distributional properties are provided. Furthermore, the proposed ratio distribution is fitted to two applications data (COVID-19 and Bladder Cancer Data), and compared it with some well-known right-skewed variations of Lindley distribution, namely; Lindley distribution, new generalized Lindley distribution, new quasi Lindley distribution and a three parameter Lindley distribution. The numerical result of the study reveals that the proposed distribution of two independent Lindley random variables fits better to the above said data sets than the compared distribution.

PMID:36268516 | PMC:PMC9568952 | DOI:10.1007/s44199-022-00050-4

BMC Neurol. 2022 Oct 20;22(1):388. doi: 10.1186/s12883-022-02913-w.

ABSTRACT

BACKGROUND: Multiple sclerosis is an inflammatory and neurodegenerative disease. People with multiple sclerosis (pwMS) experience chronic fatigue which is difficult to deal with therapeutically and greatly affects health-related quality of life (QOL). PwMS are aware of the lack of generalized dietary advice related to their disease, leading to self-experimentation with diet. It is necessary to provide objective information about dietary interventions for pwMS. We aim to provide an objective synthesis of the evidence for efficacy and safety of specific diets in pwMS through a rapid review and meta-analyses of randomized controlled trials (RCTs), examining symptomatic fatigue (MFIS), QOL, Expanded-Disability-Status-Scale (EDSS), and severe adverse events.

METHODS: We have carried out a rapid review (MEDLINE and EMBASE) up to December 2021, with PRISMA methodology, and meta-analyses, of (RCTs). All statistical analyses were performed using the comprehensive meta-analysis (CMA) -RStudio 4.1.3. The analysis used weighted mean differences (WMD) and a 95% confidence interval (CI) using a random-effects model to compare the effects of the dietary intervention with the control.

RESULTS: Eight studies met the inclusion criteria. Of these eight studies, five analyzed EDSS, three MFIS, and three QOL. A total of 515 patients were analyzed. These meta-analyses cumulative evidence support that dietary intervention is associated with a trend of reduction in fatigue (308 patients studied) -the difference between means (SMD) of the control group and intervention group was -2,033, 95%-IC (-3,195, -0,152), a p-value of 0.0341)-, an increase in QOL (77 patients studied), no significant effect on EDSS (337 patients studied), and no severe adverse events.

CONCLUSIONS: It is difficult to reach a high level of evidence in dietary studies. Our findings show that dietary intervention is associated with a trend of reduction in fatigue in MS. Taking into account the potential of dietary interventions and the benefit/risk ratio in their favor, neurologists must be aware of the great importance of making interventions on diet in MS if necessary. There are dietary interventions with some evidence of benefit for patients with MS, which could be chosen based on adherence, patient preferences, and individual outcomes. Large prospective clinical trials are needed to shed further light on this topic.

PMID:36266639 | DOI:10.1186/s12883-022-02913-w

BMC Pediatr. 2022 Oct 20;22(1):609. doi: 10.1186/s12887-022-03666-8.

ABSTRACT

BACKGROUND: Feeding practices during early years may have long-lasting influences on eating behaviors, growth patterns and body mass index (BMI) trajectory. The objectives of this study were to characterize early feeding practices among mothers in Saudi Arabia and examine their associations with child birthweight and BMI z-score (BMIz) at preschool.

METHODS: This is a cross-sectional study including 209 mother-child dyads who were recruited from different preschools around the city of Jeddah, Saudi Arabia. Mothers completed the study questionnaire over the telephone and preschoolers’ anthropometric measurements were objectively measured using standardized procedures. Primary predictors included variables pertaining to breastfeeding initiation, breastfeeding duration, formula milk introduction, complementary feeding, and offering fruit juice, date syrup-milk mixture, and soda drinks in a baby bottle. The study’s primary outcome was BMIz at preschool. Mothers reported child’s birthweight and sociodemographic characteristics. Descriptive statistics were used to characterize early feeding practices. Bivariate analyses and linear regression analysis were used to examine the association of early feeding practices with child birthweight and BMIz at preschool.

RESULTS: About half of the mothers reported that they have offered fruit juice and/or date syrup-milk mixture in a baby bottle (52.2% and 45.9% respectively), with an average duration of 11.5 months (SD = 7.73) and 5.90 months (SD = 6.13), respectively. Children who were offered fruit juice and/or date syrup-milk mixture in a baby bottle had significantly lower birthweights compared to children who were not (M = 2.79, SD = 0.59 vs. M = 3.06, SD = 0.69, P < 0.01 and M = 2.79, SD = 0.67 vs. M = 3.03, SD = 0.62, P < 0.01, respectively). There was a negative association between introducing fruit juice in a baby bottle and child BMIz at preschool (β: -0.18, 95% confidence interval (CI): -0.83, -0.11); This association was not significant after adjusting for child birthweight and other covariates (β: -0.10, 95% CI: -0.64, 0.09).

CONCLUSION: A large proportion of mothers reported offering fruit juice and date syrup-milk mixture in a baby bottle. Additional research is needed to understand associations with child birthweight and BMIz. Longitudinal and interventions studies can help inform counseling guidelines and community campaigns in order to improve early feeding practices in the region.

PMID:36266622 | DOI:10.1186/s12887-022-03666-8

BMC Infect Dis. 2022 Oct 20;22(1):793. doi: 10.1186/s12879-022-07774-9.

ABSTRACT

BACKGROUND: Monoclonal antibodies (mAbs) and antivirals have been approved for early therapy of coronavirus disease (COVID-19), however, in the real-life setting, there are difficulties to prescribe these therapies within few days from symptom onset as recommended, and effectiveness of combined use of these drugs have been hypothesised in most-at-risk patients (such as those immunocompromised) but data supporting this strategy are limited.

METHODS: We describe the real-life experience of SARS-CoV-2 antivirals and/or monoclonal antibodies (mAbs) and focus on the hospitalisation rate due to the progression of COVID-19. Clinical results obtained through our risk-stratification algorithm and benefits achieved through a strategic proximity territorial centre are provided. We also report a case series with an in-depth evaluation of SARS-CoV-2 genome in relationship with treatment strategy and clinical evolution of patients.

RESULTS: Two hundred eighty-eight patients were analysed; 94/288 (32.6%) patients were treated with mAb monotherapy, 171/288 (59.4%) patients were treated with antivirals, and 23/288 (8%) patients received both mAbs and one antiviral drug. Haematological malignancies were more frequent in patients treated with combination therapy than in the other groups (p = 0.0003). There was a substantial increase in the number of treated patients since the opening of the centre dedicated to early therapies for COVID-19. The provided disease-management and treatment appeared to be effective since 98.6% patients recovered without hospital admission. Moreover, combination therapy with mAbs and antivirals seemed successful because all patients admitted to the hospital for COVID-19 did not receive such therapies, while none of the most-at-risk patients treated with combination therapy were hospitalized or reported adverse events.

CONCLUSIONS: A low rate of COVID-19 progression requiring hospital admission was observed in patients included in this study. The dedicated COVID-19 proximity territorial service appeared to strengthen the regional sanitary system, avoiding the overwhelming of other services. Importantly, our results also support early combination therapy: it is possible that this strategy reduces the emergence of escape mutants of SARS-CoV-2, thereby increasing efficacy of early treatment, especially in immunocompromised individuals.

PMID:36266619 | DOI:10.1186/s12879-022-07774-9

Am J Hematol. 2022 Oct 20. doi: 10.1002/ajh.26764. Online ahead of print.

ABSTRACT

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic haematopoietic cell transplantation (allo-HCT) for chronic phase (CP) CML has dramatically decreased. Imatinib was the 1^st TKI introduced to the clinical arena, predominantly utilised in the 1^st line setting. In cases of insufficient response, resistance or intolerance, CML patients can subsequently be treated with either a 2^nd or 3^rd generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2 or 3 TKI prior to allo-HCT for CP CML in 904 patients. A total of 323-, 371- and 210 patients had 1, 2 or 3 TKI prior to transplant respectively; imatinib (n=778), dasatinib (n=508), nilotinib (n=353), bosutinib (n=12) and ponatinib (n=44). The majority had imatinib as first TKI (n=747, 96%). Transplants were performed in CP1, n=549, CP2, n=306, and CP3, n=49. With a median follow-up of 52 months, 5-year OS for the entire population was 64.4% (95% CI 60.9-67.9 %), PFS 50% (95% CI 46.3-53.7%), RI 28.7% (95% CI 25.4-32.0%) and NRM 21.3% (95% CI 18.3-24.2%). No difference in OS, PFS, RI or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p=ns). Significant factors influencing OS and PFS were >CP1 vs CP1 and Karnofsky performance (KPS) score > 80 vs ≤80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection. This article is protected by copyright. All rights reserved.

PMID:36266607 | DOI:10.1002/ajh.26764

Int Ophthalmol. 2022 Oct 20. doi: 10.1007/s10792-022-02558-1. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the efficacy and safety of using Mitomycin-C (MMC) or Ologen implant as an adjunct to combined trabeculotomy-trabeculectomy (CTT) surgery relative to non-augmented CTT surgery in achieving higher success rates in patients with primary congenital glaucoma (PCG).

STUDY DESIGN: A prospective triple-armed randomized controlled clinical trial was conducted in the period between April 2019 and May 2021, targeting 75 eyes of patients with PCG over one year, with patients being followed up for at least one whole year.

PATIENTS AND METHODS: The study included 75 eyes; only 70 fulfilled the inclusion criteria and were randomly assigned to one of the three study groups using a computer program to generate random number list. Eyes were treated by either CTT without augmentation, CTT augmented with MMC, or CTT augmented with Ologen implant. Only 63 eyes completed one year of follow-up and were evenly distributed among the three study groups; with 21 eyes in each group were statistically analyzed.

OUTCOME MEASURES: Our primary outcome measure is to report and compare the percentage of patients who demonstrated complete success with intraocular pressure (IOP) controlled and maintained below 21 mmHg without the use of antiglaucoma medications or additional glaucoma surgery over a one-year follow-up. Secondary outcome measures include reporting failure, intra- and postoperative complications of the three surgical modalities, postoperative corneal diameter, clearance of corneal edema, and postoperative cup/disk (C/D) ratio.

RESULTS: Complete success was achieved in 17 eyes (81.0%) in CTT group, 18 eyes (85.7%) in MMC group, and 17 eyes (81.0%) in Ologen group. Qualified success (IOP < 21 with or without antiglaucoma medications) was achieved in 18 eyes (85.7%) in both the CTT and the Ologen groups, with 19 eyes (90.5%) in the MMC group. Failure was observed in three eyes (14.3%) in both CTT and Ologen groups and two eyes (9.5%) in the MMC group. Based on survival analysis, CTT group had a cumulative success probability of 95.2% at three months, which dropped to 85.7% at six months and remained at that level for the 9th and 12th months of follow-up. With respect to the MMC group, the cumulative success probability at three months was 95.2%, dropped to 90.5% at six months, and remained at that level for the 9th and 12th months of follow-up. While in the Ologen group, the cumulative success probability at three months was 85.7% and remained at the same level during the 6th, 9th, and 12th months of follow-up, with p value = 0.862 using the logrank test.

CONCLUSION: CTT is a safe and effective primary surgical intervention in patients with PCG without the need for augmentation while preserving the augmented procedure’s use for recurrent cases.

PMID:36266601 | DOI:10.1007/s10792-022-02558-1

Mol Imaging Biol. 2022 Oct 20. doi: 10.1007/s11307-022-01781-7. Online ahead of print.

ABSTRACT

PURPOSE: The presence and functional competence of intratumoral CD8⁺ T cells is often a barometer for successful immunotherapeutic responses in cancer. Despite this understanding and the extensive number of clinical-stage immunotherapies focused on potentiation (co-stimulation) or rescue (checkpoint blockade) of CD8⁺ T cell antitumor activity, dynamic biomarker strategies are often lacking. To help fill this gap, immuno-PET nuclear imaging has emerged as a powerful tool for in vivo molecular imaging of antibody targeting. Here, we took advantage of immuno-PET imaging using ⁸⁹Zr-IAB42M1-14, anti-mouse CD8 minibody, to characterize CD8⁺ T-cell tumor infiltration dynamics following ICOS (inducible T-cell co-stimulator) agonist antibody treatment alone and in combination with PD-1 blocking antibody in a model of mammary carcinoma.

PROCEDURES: Female BALB/c mice with established EMT6 tumors received 10 µg, IP of either IgG control antibodies, ICOS agonist monotherapy, or ICOS/PD-1 combination therapy on days 0, 3, 5, 7, 9, 10, or 14. Imaging was performed at 24 and 48 h post IV dose of ⁸⁹Zr IAB42M1-14. In addition to ⁸⁹Zr-IAB42M1-14 uptake in tumor and tumor-draining lymph node (TDLN), 3D radiomic features were extracted from PET/CT images to identify treatment effects. Imaging mass cytometry (IMC) and immunohistochemistry (IHC) was performed at end of study.

RESULTS: ⁸⁹Zr-IAB42M1-14 uptake in the tumor was observed by day 11 and was preceded by an increase in the TDLN as early as day 4. The spatial distribution of ⁸⁹Zr-IAB42M1-14 was more uniform in the drug treated vs. control tumors, which had spatially distinct tracer uptake in the periphery relative to the core of the tumor. IMC analysis showed an increased percentage of cytotoxic T cells in the ICOS monotherapy and ICOS/PD-1 combination group compared to IgG controls. Additionally, temporal radiomics analysis demonstrated early predictiveness of imaging features.

CONCLUSION: To our knowledge, this is the first detailed description of the use of a novel immune-PET imaging technique to assess the kinetics of CD8⁺ T-cell infiltration into tumor and lymphoid tissues following ICOS agonist and PD-1 blocking antibody therapy. By demonstrating the capacity for increased spatial and temporal resolution of CD8⁺ T-cell infiltration across tumors and lymphoid tissues, these observations underscore the widespread potential clinical utility of non-invasive PET imaging for T-cell-based immunotherapy in cancer.

PMID:36266600 | DOI:10.1007/s11307-022-01781-7

Parasitol Res. 2022 Oct 21. doi: 10.1007/s00436-022-07687-1. Online ahead of print.

ABSTRACT

Cystic echinococcosis (CE) is a neglected helminthic zoonosis in many parts of the world. Some CE cysts in the intermediate host are non-fertile. Considering the function of microRNAs in many biological processes such as embryonic development, cell proliferation, and apoptosis, this study investigated the function and comparison of miR-71 and let-7 in fertile and non-fertile CE cysts. Here, we determined the expression level of the miRNAs for 33 animal cysts and 16 human cysts (Echinococcus granulosus sensu stricto (G1). The quantitative real-time PCR method was conducted for the expression evaluation of miR-71 and let-7. The expression of both miRNAs in all samples was determined using the following formula: [ΔCT = CT (target) – CT (internal control)]. A comparison of Δct of miR-71 and let-7 in fertile and non-fertile cysts did not show a significant difference (P = 0.911 and 0.354). In cattle, sheep, and humans, Δct of miR-71, and let-7 were higher, respectively. Therefore, the mean expression of miR-71 and let-7 indicates an increase in humans compared to other intermediate hosts. Also, statistical results show a significant difference in the expression of these miRNAs in sheep, cattle, and human cysts (P = 0.025 and 0.01). The lower expression of these miRNAs in cattle cysts and their common infertility might be associated with the hypothesis and function of miRNAs in the fertility of CE cysts. So we should not ignore the function and role of miRNAs in this subject due to the importance of infertility in E. granulosus epidemiology.

PMID:36266590 | DOI:10.1007/s00436-022-07687-1

Oral Radiol. 2022 Oct 20. doi: 10.1007/s11282-022-00661-8. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the potential of maxillary molar dimensions as predictors of the presence of the second mesiobuccal (MB2) canal.

METHODS: Micro-computed tomography scans were obtained from 47 maxillary molars, out of which 26 had the MB2 canal. The distance between root canals, extension of the canals, and thickness of surrounding dentin were obtained from axial images at the furcation level, 3 mm from the apex, and 5 mm from the apex. The association between the measurements and the presence of the MB2 canal was assessed using multiple logistic regression and odds ratio.

RESULTS: At the furcation level, the bucco-palatal extension of the MB1 canal significantly decreased the chance of the presence of the MB2 canal. Regarding the thickness of surrounding dentin measurements, the mesial and distal aspects of the MB1 canal at 3 mm from the apex were statistically significant to decrease and increase the chance of presence of the MB2 canal, respectively. Regarding the extension of the canals, only buccal-palatal extension seems to decrease the chance of the presence of the MB2 canal.

CONCLUSION: The presence of the MB2 canal in the mesiobuccal root of maxillary molars is associated with the bucco-palatal extension and surrounding dentin thickness of the first mesiobuccal canal, and seems to be unrelated to the dimensions of the distobuccal and palatal roots.

PMID:36266556 | DOI:10.1007/s11282-022-00661-8

J Immigr Minor Health. 2022 Oct 20. doi: 10.1007/s10903-022-01418-5. Online ahead of print.

ABSTRACT

Community outreach and engagement has been a regular activity of the National Cancer Institute at its designated Cancer Centers. However, in 2016, community outreach and engagement became a required activity for all cancer centers. Yet there is a gap in the literature that provides guidelines for developing materials that resonate with communities. We developed the PEARL rubric to fulfill that gap from our work developing culturally sensitive breast cancer education materials for African American and Immigrant African women. We conducted a targeted literature review to understand the approaches that have been used for developing education materials for communities. We reviewed the literature and distilled key elements into our PEARL guide for creating culturally appropriate education materials. PEARL consists of five elements: Plain language and understandability, Explicit data, statistics, and graphs, Affirmative framing, Representative content, and Local connection. PEARL is a modern comprehensive guide that researchers can use for creating culturally sensitive materials. It is designed to guide researchers develop educational materials who have little to no experience in community engagement.

PMID:36266493 | DOI:10.1007/s10903-022-01418-5