Tag: statistics

PLoS Comput Biol. 2022 Jun 13;18(6):e1009598. doi: 10.1371/journal.pcbi.1009598. Online ahead of print.

ABSTRACT

Differential sensitivity analysis is indispensable in fitting parameters, understanding uncertainty, and forecasting the results of both thought and lab experiments. Although there are many methods currently available for performing differential sensitivity analysis of biological models, it can be difficult to determine which method is best suited for a particular model. In this paper, we explain a variety of differential sensitivity methods and assess their value in some typical biological models. First, we explain the mathematical basis for three numerical methods: adjoint sensitivity analysis, complex perturbation sensitivity analysis, and forward mode sensitivity analysis. We then carry out four instructive case studies. (a) The CARRGO model for tumor-immune interaction highlights the additional information that differential sensitivity analysis provides beyond traditional naive sensitivity methods, (b) the deterministic SIR model demonstrates the value of using second-order sensitivity in refining model predictions, (c) the stochastic SIR model shows how differential sensitivity can be attacked in stochastic modeling, and (d) a discrete birth-death-migration model illustrates how the complex perturbation method of differential sensitivity can be generalized to a broader range of biological models. Finally, we compare the speed, accuracy, and ease of use of these methods. We find that forward mode automatic differentiation has the quickest computational time, while the complex perturbation method is the simplest to implement and the most generalizable.

PMID:35696417 | DOI:10.1371/journal.pcbi.1009598

PLoS One. 2022 Jun 13;17(6):e0269706. doi: 10.1371/journal.pone.0269706. eCollection 2022.

ABSTRACT

BACKGROUND: The incidence of childhood ALL in Indonesia is still largely unknown. The widely mentioned statistics from other countries turn out to be only estimated figures. Other data do not specify the types of leukemia and are not specifically focused on children. Therefore, this study aims to pool incidence and mortality statistics from available studies in Indonesia.

METHODS: We searched five different academic databases, including Pubmed, MEDLINE, Cochrane Library, Science Direct, and Google Scholar. Three Indonesian databases, such as the Indonesian Scientific Journal Database (ISJD), Neliti, and Indonesia One Search, were also utilized. Incidence was expressed as per 100,000 children. We used the Newcastle-Ottawa scale (NOS) to assess the quality of cohort studies. The inclusion criteria are cohort studies published in the languages of English or Indonesian. For this analysis, we define children as 0-18 years old.

FINDINGS: The incidence rate for childhood ALL was found to be 4.32 per 100,000 children (95% CI 2.65-5.99) with a prediction interval of 1.98 to 9.42 per 100,000 children. The incidence rate is higher in males, with 2.45 per 100,000 children (95% CI 1.98-2.91) and a prediction interval of 1.90 to 3.16 per 100,000 children. As for females, the incidence rate is 2.05 per 100,000 children (95% CI 1.52-2.77) with a prediction interval of 1.52 to 2.77 per 100,000 children. The mortality of childhood ALL ranges from 0.44 to 5.3 deaths per 100,000 children, while the CFR is 3.58% with varying true effect sizes of 2.84% to 4.52%.

INTERPRETATION: With 79.5 million children living in Indonesia in 2018, this means that there were roughly 3,434 new cases of childhood ALL. An organized effort between multiple sectors is needed to improve the registries of childhood ALL in Indonesia.

PMID:35696384 | DOI:10.1371/journal.pone.0269706

Helicobacter. 2022 Jun 13:e12910. doi: 10.1111/hel.12910. Online ahead of print.

ABSTRACT

Helicobacter pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Gradually, H. pylori gastritis will result in gastric atrophy and intestinal metaplasia. Identifying the relationship between intensity of colonization and activity of gastritis helps the clinician in more effective treatment and post-treatment follow-ups. The aim of our work was to analyze the relationship between the density of H. pylori colonization of the gastric mucosa and the severity of histological parameters of gastritis (inflammation activity, gastric atrophy, and intestinal metaplasia). This was a prospective monocentric study conducted from January 2020 to December 2020, collecting patients naive to any anti-H. pylori treatment and having a chronic H. pylori infection documented by histological examination. Epidemiological, endoscopic, and anathomopathological data were collected. Ninety-seven patients with a mean age of 42.6 years [18-65 years] and a sex ratio of M/F = 0.64 were included. The density of H. pylori colonization was mild (+) in 43.3% of patients, moderate (++) in 47.4% of patients, and significant (+++) in 9.3% of patients. Nearly, ten per cent of patients had no gastritis, 33% had mild gastritis, 50.5% had moderate gastritis, and 6.2% had severe gastritis. Gastric atrophy and intestinal metaplasia were found in 44.3% and 10.3% of our population, respectively. Patients with mild H. pylori colonization rates had the highest level of mild activity (59.5%). There was a statistically significant association between the severity of H. pylori infection and gastritis activity (p < .001). Gastric atrophy was significantly associated with the intensity of H. pylori colonization (p = .049). No significant relationship was found between the intensity of colonization and metaplasia (p = .08). Our study shows that there is a statistically significant association between the density of H. pylori and histopathological findings including gastritis activity and intestinal atrophy.

PMID:35696278 | DOI:10.1111/hel.12910

Int J Gynaecol Obstet. 2022 Jun 13. doi: 10.1002/ijgo.14305. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to examine the diagnostic value of ophthalmic arteries Doppler indices in prediction of preeclampsia along with other markers in the third trimester of pregnancy.

METHODS: Normotensive subjects were included during 28-32 weeks’ gestation to undergo uterine and ophthalmic artery Doppler ultrasound. Maternal and fetal characteristics were documented at the visit between the 28-32 weeks of gestation, and the pregnancy associated plasma protein-A (PAPP-A) values in the first trimester were collected to be integrated in a multiparametric prediction model.

RESULTS: Out of 795 included participants, 48 cases progressed to preeclampsia. All assessed ophthalmic Doppler parameters including first and second peak systolic velocities (1^st and 2^nd PSV), second to first PSV Ratio (PR) and pulsatility index (PI)) were statistically different in those developing preeclampsia later on. Average PR (sensitivity: 100%, (95%CI): 0.81-1.00, specificity: 90%, 0.86-0.93) and PI between the eyes, PAPP-A MoM and uterine arteries PI were determined to be the most important predictors of PE which were subsequently integrated in a multiple regression model (sensitivity: 94%, 0.70-1.00, specificity: 93%, 0.89-0.96).

CONCLUSION: This study provided a screening method for individuals at higher risk of progressing towards preeclampsia in the third trimester of pregnancy.

PMID:35696254 | DOI:10.1002/ijgo.14305

Diabetes Care. 2022 Jun 13:dc211789. doi: 10.2337/dc21-1789. Online ahead of print.

ABSTRACT

OBJECTIVE: To identify novel biomarkers of cardiovascular disease (CVD) risk in type 2 diabetes (T2D) via a hypothesis-free global metabolomics study, while taking into account renal function, an important confounder often overlooked in previous metabolomics studies of CVD.

RESEARCH DESIGN AND METHODS: We conducted a global serum metabolomics analysis using the Metabolon platform in a discovery set from the Joslin Kidney Study having a nested case-control design comprising 409 individuals with T2D. Logistic regression was applied to evaluate the association between incident CVD events and each of the 671 metabolites detected by the Metabolon platform, before and after adjustment for renal function and other CVD risk factors. Significant metabolites were followed up with absolute quantification assays in a validation set from the Joslin Heart Study including 599 individuals with T2D with and without clinical evidence of significant coronary heart disease (CHD).

RESULTS: In the discovery set, serum orotidine and 2-piperidinone were significantly associated with increased odds of incident CVD after adjustment for glomerular filtration rate (GFR) (odds ratio [OR] per SD increment 1.94 [95% CI 1.39-2.72], P = 0.0001, and 1.62 [1.26-2.08], P = 0.0001, respectively). Orotidine was also associated with increased odds of CHD in the validation set (OR 1.39 [1.11-1.75]), while 2-piperidinone did not replicate. Furthermore, orotidine, being inversely associated with GFR, mediated 60% of the effects of declining renal function on CVD risk. Addition of orotidine to established clinical predictors improved (P < 0.05) C statistics and discrimination indices for CVD risk (ΔAUC 0.053, rIDI 0.48, NRI 0.42) compared with the clinical predictors alone.

CONCLUSIONS: Through a robust metabolomics approach, with independent validation, we have discovered serum orotidine as a novel biomarker of increased odds of CVD in T2D, independent of renal function. Additionally, orotidine may be a biological mediator of the increased CVD risk associated with poor kidney function and may help improve CVD risk prediction in T2D.

PMID:35696261 | DOI:10.2337/dc21-1789

Int J Prosthodont. 2022 Jun 6. doi: 10.11607/ijp.7942. Online ahead of print.

ABSTRACT

PURPOSE: To compare the changes in quality of life in edentulous patients with single implants supporting mandibular overdentures with two different attachment types before implant placement and after 6 and 24 months.

MATERIALS AND METHODS: Eighty edentulous patients were recruited, and all patients completed the validated Oral Health Impact Profile (OHIP)-EDENT-19 questionnaire before implant surgery. A single implant was placed in the midline of the edentulous mandibles. All implants were allowed to heal for 3 months. After the healing period, randomization into one of two groups was accomplished using sealed envelopes: group A (ball attachment) and group B (locator attachment). The same questionnaire was completed 6 and 24 months postplacement. Mann-Whitney U test for independent samples was used to compare the two groups, while Freidman test was used for comparison within each group. Two-sided P values less than .05 were considered statistically significant.

RESULTS: There was an improvement in all domains of the OHIP-EDENT-19 scores at the 6- and 24-month follow-ups for both groups. The social disability domain showed a statistically significant improvement for group A at 6 and 24 months postplacement (P = .004, .005). Within group A, there was a statistically significant improvement within all seven domains (P = .001); while in group B, four domains (functional limitation, physical pain, psychosocial discomfort, and physical disability) and the total score (P = .001) showed a statistically significant improvement.

CONCLUSION: Both attachments improved the patients’ quality of life at 24 months postplacement. The ball attachment demonstrated a significant improvement regarding the social effects of the prostheses.

PMID:35696234 | DOI:10.11607/ijp.7942

Am J Hematol. 2022 Jun 13. doi: 10.1002/ajh.26627. Online ahead of print.

ABSTRACT

The best stem cell source for T-cell replete HLA-haploidentical transplantation with post-transplant cyclophosphamide (PTCy) remains to be determined. In this EBMT retrospective study we analyzed the impact of stem cell source on leukemia-free survival (LFS) in adult patients with primary refractory or relapsed acute myeloid leukemia (AML) given grafts from HLA-haploidentical donors with PTCy as graft-versus-host disease (GVHD) prophylaxis. A total of 668 patients (249 bone marrow (BM) and 419 peripheral blood stem cells (PBSC) recipients) met the inclusion criteria. The use of PBSC was associated with a higher incidence of grade II-IV (HR = 1.59, P = 0.029) and grade III-IV (HR = 2.08, P = 0.013) acute GVHD. There was a statistical interaction between patient age and the impact of stem cell source for LFS (P < 0.01). In multivariate Cox models, among patients <55 years, the use of PBSC versus BM resulted in comparable LFS (HR = 0.82, P = 0.2). In contrast, in patients ≥55 years of age, the use of PBSC versus BM was associated with higher non-relapse mortality (NRM) (HR = 1.7, P = 0.01), lower LFS (HR = 1.37, P = 0.026) and lower overall survival (OS) (HR = 1.33, P = 0.044). In conclusions, our data suggest that in patients ≥55 years of age with active AML at HLA-haploidentical transplantation, the use of BM instead of PBSC as stem cell source results in lower NRM and better LFS. In contrast among younger patients, the use of PBSC results in at least a comparable LFS. This article is protected by copyright. All rights reserved.

PMID:35696192 | DOI:10.1002/ajh.26627

J Exp Psychol Gen. 2022 Jun 13. doi: 10.1037/xge0001245. Online ahead of print.

ABSTRACT

Human language is unique among animal communication systems, in part because of its dual patterning in which meaningless phonological units combine to form meaningful words (phonological structure) and words combine to form sentences (lexicosyntactic structure). Although dual patterning is well recognized, its emergence in language development has been scarcely investigated. Chief among questions still unanswered is the extent to which development of these separate structures is independent or interdependent, and what supports acquisition of each level of structure. We explored these questions by examining growth of lexicosyntactic and phonological structure in children with normal hearing (n = 49) and children with hearing loss who use cochlear implants (n = 56). Multiple measures of each kind of structure were collected at 2-year intervals (kindergarten through eighth grade), and used to construct latent scores for each type of structure. Growth curve analysis assessed (a) the relative independence of development for each level of structure; (b) interactions between these two levels of structure in real-time language processing; and (c) contributions to growth of each level of structure made by auditory input, socioeconomic status (as proxy for linguistic experience), and speech motor control. Findings suggested that phonological and lexicosyntactic structure develop largely independently. Auditory input, socioeconomic status, and speech motor control help shape these language structures, with the last two factors exerting stronger effects for children with cochlear implants. Only for children with cochlear implants were interdependencies in real-time processing observed, reflecting compensatory mechanisms likely present to help them handle the disproportionately large phonological deficit they exhibit. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35696175 | DOI:10.1037/xge0001245

JAMA Netw Open. 2022 Jun 1;5(6):e2216778. doi: 10.1001/jamanetworkopen.2022.16778.

ABSTRACT

IMPORTANCE: Assessment of the quality of initial care is necessary to target priority actions that can reduce the still high morbidity and mortality due to community-onset severe bacterial infections (COSBIs) among children.

OBJECTIVE: To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, population-based, cohort study and confidential enquiry was conducted between August 2009 and January 2014 in western France, a region accounting for 15% of the French pediatric population (1 968 474 children aged 1 month to 16 years) and including 6 pediatric intensive care units (PICUs) and 35 emergency departments. Participants included all children aged 1 month to 16 years who died before PICU admission or were admitted to a PICU with a COSBI (ie, bacterial sepsis, including meningitis, purpura fulminans, and pulmonary, osteoarticular, intra-abdominal, cardiac, and soft-tissue severe infections). Data were analyzed from March to June 2020.

EXPOSURES: Suboptimal care determined according to evaluation of 8 types of care: (1) the delay in seeking care by family, (2) the physician’s evaluation of severity, (3) the patient’s referral at the first consultation with signs of severity, (4) the timing and (5) dosage of antibiotic treatment, (6) the timing and (7) volume of fluid bolus administration, and (8) the clinical reassessment after fluid bolus.

MAIN OUTCOMES AND MEASURES: Two experts assessed the quality of care before death or PICU admission as optimal, possibly suboptimal, or certainly suboptimal. The consequences and determinants of certainly suboptimal care were identified with multinomial logistic regression and generalized linear mixed models.

RESULTS: Of the 259 children included (median [IQR] age, 24 [6-66] months; 143 boys [55.2%]), 27 (10.4%) died, and 25 (9.6%) had severe sequelae at PICU discharge. The quality of care was certainly suboptimal in 89 cases (34.4%). Suboptimal care was more frequent in children with sequelae (adjusted odds ratio [aOR], 5.61; 95% CI, 1.19-26.36) and less frequent in children who died (aOR, 0.16; 95% CI, 0.04-0.65) vs those surviving without sequelae. Factors independently associated with suboptimal care were age younger than 5 years (aOR, 3.15; 95% CI, 1.25-7.90), diagnosis of sepsis with no source (aOR, 5.77; 95% CI, 1.64-20.30) or meningitis (aOR, 3.39; 95% CI, 1.15-9.96) vs other severe infections, and care by a primary care physician (aOR, 3.22; 95% CI, 1.17-8.88) vs a pediatric hospital service.

CONCLUSIONS AND RELEVANCE: This study found that suboptimal care is frequent in the initial management of COSBI and is associated with severe sequelae. The paradoxical association with reduced risk of death may be explained by an insufficient adjustment on bacterial or host intrinsic factors. Management could be optimized by improving the quality of primary care, especially for young children.

PMID:35696162 | DOI:10.1001/jamanetworkopen.2022.16778

JAMA Intern Med. 2022 Jun 13. doi: 10.1001/jamainternmed.2022.2115. Online ahead of print.

ABSTRACT

IMPORTANCE: Prior evidence suggests that plasma and platelet transfusions from female and parous donors are associated with adverse clinical outcomes, which has led to the predominant use of male donors for plasma and platelets in many countries. However, studies on red blood cell transfusions have been conflicting.

OBJECTIVE: To determine whether blood donor sex and parity affect mortality of patients undergoing transfusion with red blood cells.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used nationwide blood bank and health register data in Sweden and involved a natural experiment created by donor sex and parity being concealed and randomly allocated. Patients were included if they were 18 to 90 years old, did not have a history of blood transfusion, and received a transfusion between January 1, 2010, and December 31, 2017. Patients were followed up from their first red blood cell transfusion until death, emigration, or end of study (June 30, 2018). Data analysis was performed between June 15 and December 15, 2021.

EXPOSURES: (1) Female vs male donors and (2) parous or nonparous female vs male donors.

MAIN OUTCOMES AND MEASURES: Overall survival up to 2 years estimated using inverse probability-weighted Kaplan-Meier estimates and relative risk for additional transfusions within 24 hours.

RESULTS: Among the 368 778 included patients (mean [SD] age, 66.3 [17.7] years; 57.3% female), 2-year survival differences comparing red blood cell transfusions from female and parous donors to male donors were -0.1% (95% CI, -1.3% to 1.1%) and 0.3% (95% CI, -0.6% to 1.2%), respectively. No statistically significant survival differences were observed regardless of patient sex or age. Median (IQR) hemoglobin counts for female donors (13.5 [13.0-14.0] g/dL) were lower than for male donors (14.9 [14.4-15.5] g/dL). Red blood cell transfusions from female donors were associated with a relative risk of 1.12 (95% CI, 1.08-1.17) for additional transfusions within 24 hours but not after adjusting for donor hemoglobin counts (relative risk, 1.03; 95% CI, 0.98-1.08). Pretransfusion patient characteristics were naturally distributed as-if randomized.

CONCLUSIONS AND RELEVANCE: In this nationwide cohort study involving a natural experiment, after accounting for the lower hemoglobin values in blood from female donors, patients undergoing transfusion with blood from female or parous donors did not have higher 2-year mortality compared with recipients of blood from male donors.

PMID:35696128 | DOI:10.1001/jamainternmed.2022.2115