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Nevin Manimala Statistics

A Bayesian feature allocation model for identifying cell subpopulations using CyTOF data

J R Stat Soc Ser C Appl Stat. 2023 Apr 25;72(3):718-738. doi: 10.1093/jrsssc/qlad029. eCollection 2023 Jun.

ABSTRACT

A Bayesian feature allocation model (FAM) is presented for identifying cell subpopulations based on multiple samples of cell surface or intracellular marker expression level data obtained by cytometry by time of flight (CyTOF). Cell subpopulations are characterized by differences in marker expression patterns, and cells are clustered into subpopulations based on their observed expression levels. A model-based method is used to construct cell clusters within each sample by modeling subpopulations as latent features, using a finite Indian buffet process. Non-ignorable missing data due to technical artifacts in mass cytometry instruments are accounted for by defining a static missingship mechanism. In contrast with conventional cell clustering methods, which cluster observed marker expression levels separately for each sample, the FAM-based method can be applied simultaneously to multiple samples, and also identify important cell subpopulations likely to be otherwise missed. The proposed FAM-based method is applied to jointly analyse three CyTOF datasets to study natural killer (NK) cells. Because the subpopulations identified by the FAM may define novel NK cell subsets, this statistical analysis may provide useful information about the biology of NK cells and their potential role in cancer immunotherapy which may lead, in turn, to development of improved NK cell therapies.

PMID:37325776 | PMC:PMC10264057 | DOI:10.1093/jrsssc/qlad029

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Nevin Manimala Statistics

Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome

J Med Genet. 2023 Jun 15:jmg-2023-109344. doi: 10.1136/jmg-2023-109344. Online ahead of print.

ABSTRACT

BACKGROUND: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS.

METHODS: 1465 individuals with LS (557 MLH1, 517 MSH2/EPCAM, 299 MSH6 and 92 PMS2) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with ‘family’ as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted.

RESULTS: Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years.

CONCLUSION: The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS.

PMID:37321833 | DOI:10.1136/jmg-2023-109344

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ASAS consensus definition of early axial spondyloarthritis

Ann Rheum Dis. 2023 Jun 15:ard-2023-224232. doi: 10.1136/ard-2023-224232. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a consensual definition for the term ‘early axial spondyloarthritis-axSpA’-and ‘early peripheral spondyloarthritis-pSpA’.

METHODS: The ASAS (Assessment of SpondyloArthritis international Society-Spondyloarthritis EARly definition) steering committee convened an international working group (WG). Five consecutive steps were followed: (1) systematic literature review (SLR); (2) discussion of SLR results within the WG and ASAS community; (3) a three-round Delphi survey inviting all ASAS members to select the items that should be considered for the definition; (4) presentation of Delphi results to the WG and ASAS community and (5) ASAS voting and endorsement (2023 annual meeting).

RESULTS: Following the SLR, consensus was to proceed with an expert-based definition for early axSpA (81% in favour) but not for pSpA (54% against). Importantly, early axSpA should be based on symptom duration taking solely axial symptoms into account. 151-164 ASAS members participated in the Delphi surveys. Consensus was achieved for considering the following items within early axSpA definition: duration of symptoms ≤2 years; axial symptoms defined as cervical/thoracic/back/buttock pain or morning stiffness; regardless of the presence/absence of radiographic damage. The WG agreed that in patients with a diagnosis of axSpA ‘early axSpA’ should be defined as a duration of ≤2 years of axial symptoms. Axial symptoms should include spinal/buttock pain or morning stiffness and should be considered by a rheumatologist as related to axSpA. The ASAS community endorsed this proposal (88% in favour).

CONCLUSIONS: Early axSpA has newly been defined, based on expert consensus. This ASAS definition should be adopted in research studies addressing early axSpA.

PMID:37321799 | DOI:10.1136/ard-2023-224232

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Acaricidal efficacy evaluation of amitraz and diazinon against Amblyomma variegatum tick species in Waghimra zone, northern Ethiopia

Vet Parasitol Reg Stud Reports. 2023 Jul;42:100885. doi: 10.1016/j.vprsr.2023.100885. Epub 2023 May 4.

ABSTRACT

Ticks pose a substantial economic burden associated with production loss and treatment costs globally. Ethiopia has tremendous livestock resources, but its productivity is hindered by various animal health challenges in which ticks are the top priority, with a limited response to acaricidal treatments. Hence, we designed an acaricidal efficacy trial for the top commercially available Chemicals (amitraz and diazinon) to examine their efficacy against the widely distributed tick species (Amblyoma variegatum). Ticks were collected from animals admitted to veterinary clinics with no history of treatment with acaricides. Adult Immersion Technique (AIT) was employed to detect acaricidal resistance, and the mean percent control and antiparasitic efficacy were used to estimate tick susceptibility with a completely randomized laboratory-based trial (CRT). The mean weights of eggs laid by ticks subjected to amitraz and diazinon indicated that amitraz had a better egg-laying-inhibition effect than diazinon. The mean control percentages of amitraz and diazinon were 92.8 ± 5.6% and 69.7 ± 3.1%, respectively, with a highly significant difference (P-value = 0.00). The antiparasitic efficacy of the two drugs was 57.5 ± 0.96 and 37.5% ± 0.96 for amitraz and diazinon, respectively, which revealed that amitraz was statistically better than diazinon in killing adult ticks (P-value =0.026). In general, ticks treated with diazinon showed evidence of resistance development, and amitraz is relatively the most effective acaricide; we recommend its use in the study area and other locations with similar settings.

PMID:37321790 | DOI:10.1016/j.vprsr.2023.100885

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Identification and estimation of the prevalence of ectoparasites of backyard chicken in Boloso Sore District, Wolaita zone, southern Ethiopia

Vet Parasitol Reg Stud Reports. 2023 Jul;42:100884. doi: 10.1016/j.vprsr.2023.100884. Epub 2023 May 4.

ABSTRACT

BACKGROUND: Poultry ectoparasites are the basic cause of retarded growth, low liveliness and poor condition of birds directly by inducing irritation, discomfort, tissue damage, blood loss, toxicosis, allergies and dermatitis which in turn reduce the quality and quantities of meat and egg production and indirectly by being mechanical or biological vectors of pathogens.

METHOD: A cross-sectional study was conducted from November 2020 to April 2021 to identify and estimate the prevalence of ectoparasites of chicken managed under a backyard system in the selected area of Boloso Sore district of Wolaita zone, southern Ethiopia. A total of 322 chickens of different age groups, breeds and both sexes were selected by simple random technique and examined for ectoparasite.

RESULTS: From the total, 56.52%(182/322) of chickens were infested with one or more species of ectoparasites that mainly grouped into fleas 30.34%(98/322), lice 21.7%(70/322) and fowl tick 4.34%(14/322), there by six species of ectoparasites were identified. Among them, Echidnophaga gallinacean (stick tight flea) 30.34%(98/322) was the most prevalent ectoparasite species followed by lice species (Menopon gallinae 11.80% (38/322), Menacanthus stramineous 6.21%(20/322), Goniocotes gigas 2.48% (8/70) and Goniocotes gallinae 1.24%(4/322) while the least identified was fowl tick (Argas persicus) 4.34%(14/322). Age of the chicken was shown statistically significant (p < 0.05) association with the infestation of ectoparasites in which young chicken was found more (72.5%) infested than adults (27.5%). Also, there was a statistically significant (P < 0.05) difference in the prevalence rate of ectoparasites between both sexes of the chicken, in which females (71.4%) was higher than that of male chicken (28.6%). The local breed was found more highly infested (57.1%) than exotic breeds (42.9%) but the difference was not statistically significant (P > 0.05). There was statistically nonsignificant (P > 0.05) flea infestation in adults 34.14% (43/126) than in young 28.06% (55/196), females 31.34% (63/201) than males 20.66% (25/121), and local breed 31.76% (54/170) than exotic breed 28.95% (44/152). Lice prevalence was statistically nonsignificant (p-value >0.05) higher in adults 38.89% (49/126) than young 10.71% (21/196), female 25.87% (52/201) than males 14.88% (18/121) and local breed 24.12% (41/170) than exotic breed 19.08% (29/152).

CONCLUSION: Generally, the study indicated that the external parasites were highly prevalent in backyard chickens in the study area, which was associated with a lack of attention to the hygienic management system, treatment and control practices which necessitate the application of integrated prevention and control measures like awareness creation to the community on the overall effect of ectoparasites on the productivity of poultry and prevention methods.

PMID:37321789 | DOI:10.1016/j.vprsr.2023.100884

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Analysis of serum proteomics data identifies a quantitative association between beta-defensin 2 at baseline and clinical response to IL-17 blockade in psoriatic arthritis

RMD Open. 2023 Jun;9(2):e003042. doi: 10.1136/rmdopen-2023-003042.

ABSTRACT

OBJECTIVES: Despite several effective targeted therapies, biomarkers that predict whether a patient with psoriatic arthritis (PsA) will respond to a particular treatment are currently lacking.

METHODS: We analysed proteomics data from serum samples of nearly 2000 patients with PsA in placebo-controlled phase-III clinical trials of the interleukin-17 inhibitor secukinumab. To discover predictive biomarkers of clinical response, we used statistical learning with controlled feature selection. The top candidate was validated using an ELISA and was separately assessed in a trial of almost 800 patients with PsA treated with secukinumab or the tumour necrosis factor inhibitor adalimumab.

RESULTS: Serum levels of beta-defensin 2 (BD-2) at baseline were found to be robustly associated with subsequent clinical response (eg, American College of Rheumatology definition of 20%, 50% and 70% improvement) to secukinumab, but not to placebo. This finding was validated in two independent clinical studies not used for discovery. Although BD-2 is known to be associated with psoriasis severity, the predictivity of BD-2 was independent of baseline Psoriasis Area and Severity Index. The association between BD-2 and response to secukinumab was observed as early as 4 weeks and maintained up to 52 weeks. BD-2 was also found to predict response to treatment with adalimumab. Unlike in PsA, BD-2 was not predictive of response to secukinumab in rheumatoid arthritis.

CONCLUSIONS: In PsA, BD-2 at baseline is quantitatively associated with clinical response to secukinumab. Patients with high levels of BD-2 at baseline reach and sustain higher rates of clinical response after treatment with secukinumab.

PMID:37321668 | DOI:10.1136/rmdopen-2023-003042

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Lung Cancer Screening Among Mammography Patients: Knowledge, Eligibility, Participation, and Interest

J Am Board Fam Med. 2023 Jun 15:jabfm.2022.220423R1. doi: 10.3122/jabfm.2022.220423R1. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine lung cancer screening eligibility, knowledge, and interest and to quantify the effect of the expanded 2021 lung cancer screening eligibility criteria among women presenting for screening mammography, a group with demonstrable interest in cancer screening.

METHODS: A single-page survey was distributed to patients presenting for screening mammography, from January-March 2020 and June 2020-January 2021, at 2 academic medical centers on the East and West Coasts. The population served by the East Coast institution has greater poverty, greater ethnic/racial diversity, and lower education levels. Survey questions included age, smoking history, lung cancer screening knowledge, participation, and interest. Lung cancer screening eligibility was determined for both 2013 and 2021 USPSTF guidelines. Descriptive statistics were calculated, and data were compared between groups using the Chi-square test, Mann-Whitney nonparametric test, and the 2-sample t test.

RESULTS: 5512 surveys were completed; 33% (1824) of women reported a history of smoking-30% (1656) former smokers and 3% (156) current smokers. Among women with a smoking history, 7% (127/1824) were eligible for lung cancer screening using 2013% and 11% (207/1824) using the 2021 USPSTF criteria. Interest in lung cancer screening was high (73%; 151/207) among eligible women using 2021 USPSTF criteria, but only 42% (87/207) had heard of lung cancer screening and only 28% (57/207) had received prior LDCT screening.

CONCLUSION: Eligible screening mammography patients reported high levels of interest in lung cancer screening but low levels of knowledge and participation. Linking mammography and LDCT appointments may improve lung cancer screening participation.

PMID:37321658 | DOI:10.3122/jabfm.2022.220423R1

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Addressing Healthcare Utilization and Costs for Older Adults with Limited Mobility through a Multidisciplinary Home-Based Primary Care Program

J Am Board Fam Med. 2023 Jun 15:jabfm.2022.220222R3. doi: 10.3122/jabfm.2022.220222R3. Online ahead of print.

ABSTRACT

INTRODUCTION: Home-based primary care (HBPC) has shown promise in the management of multiple chronic conditions for patients who are homebound or who have limited mobility. The objective of this study was to implement and evaluate an HBPC program that integrates the services of clinical pharmacists and community aging services providers in a community-based setting.

METHODS: Mountain Area Health Education Center’s (MAHEC) HBPC program brought together an interdisciplinary team including medical providers, pharmacists, and community aging services providers to conduct home visits with older adults (age 50+). A single-arm, prepost analysis was conducted to determine differences from the year before program enrollment to the year postenrollment. We examined the frequency of health care visits, high-cost health care utilization (emergency department [ED] utilization and hospitalizations), and health care costs. Descriptive statistics characterized the study population and outcomes. Fisher’s Exact Tests were used to determine if there was a significant difference between years.

RESULTS: There were 130 home visits with 62 patients enrolled in the program. The Medicare Annual Wellness Visit (AWV) was completed for 32 (51.6%) patients. There were 13 (21.0%) and 12 (19.4%) individuals who had at least 1 ED visit and hospitalization, respectively, pre-enrollment as compared with 8 (12.9%) and 9 (14.5%) individuals postenrollment (p-value = 0.05, p-value = 0.06). During the postenrollment year, patient enrollees had an average per-member-per-month (PMPM) cost of $1567.96 as compared with $3053.21 in the year prior.

CONCLUSIONS: Pharmacist and community agency services-integrated HBPC was implemented in the community setting. There was a decrease in high-cost health care utilization and total health care expenditures for patients as compared with the previous year.

PMID:37321655 | DOI:10.3122/jabfm.2022.220222R3

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Virtual reality for pain reduction during Intravenous injection among pediatrics: a systematic review and meta-analysis of controlled clinical trials

Clin Exp Pediatr. 2023 Jun 14. doi: 10.3345/cep.2022.01193. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous (IV) injection often causes pain, fear, and anxiety in pediatrics. Virtual reality (VR) is a relatively new intervention that can be used to provide distraction during or to prepare patients for IV injections, however, so far no meta-analysis has been conducted to examine the evidence regarding the effectiveness of VR in reducing pain in pediatric IV injection.

METHODS: The search in electronic databases of PubMed, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials was established on 7 August 2022. The methodological quality of the studies was measured by the Delphi checklist. Chi-squared (Chi2) test and measure its quantity by the I2 statistic were applied for measuring the heterogeneity across studies. A summary measure of the mean difference in pain scores between virtual reality and control groups was obtained using a random-effects model. All statistical analyses were set at a significance level of 0.05 using Stata software, version 14.

RESULTS: In total, nine studies were included. Findings reported interventions of virtual reality during intravenous placement among pediatrics. The meta-analysis of the difference in means of the pain score between the intervention and control groups showed significant reductions in the virtual reality group (MD 0.47; 95% CI: 0.3, 0.65; I 2 = 9.1%). There was no heterogeneity among the included studies.

CONCLUSION: Our results suggested that the use of VR is effective in reducing the pain of IV injection in pediatrics. There was no heterogeneity among studies that reported the effectiveness of using VR in reducing IV injection pain in pediatrics. The Delphi checklist was used to measure study quality.

PMID:37321586 | DOI:10.3345/cep.2022.01193

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Clinical Practice Guidelines for Attention-deficit/Hyperactivity Disorder: Recent Updates

Clin Exp Pediatr. 2023 Jun 14. doi: 10.3345/cep.2021.01466. Online ahead of print.

ABSTRACT

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders found in children and adolescents. The American Academy of Pediatrics (AAP) first published a clinical practice guideline on ADHD in 2000, which was revised in 2011 and re-published together with an accompanying process-of-care algorithm. More recently, the 2019 clinical practice guideline revision was published. Since the 2011 guideline, the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), was released. In addition, the Society of Developmental and Behavioral Pediatrics (SDBP) recently released another clinical practice guideline for complex ADHD. Although there are nonessential changes reflected in these updates, a number of changes have still been made; for example, the DSM-5 criteria lowered the diagnostic threshold for ADHD in older teens and adults. Additionally, the criteria were revised to facilitate application to older teens and adults, and a comorbid diagnosis with autism spectrum disorder is now allowed. Meanwhile, the 2019 AAP guideline added the recommendation related to comorbid conditions with ADHD. Lastly, SDBP developed a complex ADHD guideline, covering areas such as comorbid conditions, moderate-to-severe impairment, treatment failure, and diagnostic uncertainty. In addition, other national ADHD guidelines have been published, as have European guidelines for managing ADHD during the Covid-19 pandemic. To facilitate ADHD management in a primary care, it is important to provide and review clinical guidelines and recent updates. In this article, we will review and summarize the recent clinical guidelines and their updates.

PMID:37321571 | DOI:10.3345/cep.2021.01466