Tag: statistics

ACS Infect Dis. 2022 Mar 30. doi: 10.1021/acsinfecdis.1c00513. Online ahead of print.

ABSTRACT

Leishmaniasis is one of the neglected tropical diseases with a worldwide distribution, affecting humans and animals. In the absence of an effective vaccine, current treatment is through the use of chemotherapy; however, existing treatments have frequent appearance of drug resistance and therapeutic failure (TF). The identification of factors that contribute to TF in leishmaniasis will provide the basis for a future therapeutic strategy more efficient for the control of this disease. In this article, we have evaluated the transcriptomic changes in the host cells THP-1 after infection with clinical Leishmania infantum isolates from leishmaniasis patients with TF. Our results show that distinct L. infantum isolates differentially modulate host cell response, inducing phenotypic changes that probably may account for parasite survival and TF of patients. Analysis of differential expression genes (DEGs), with a statistical significance threshold of a fold change ≥ 2 and a false discovery rate value ≤ 0.05, revealed a different number of DEGs according to the Leishmanialine. Globally, there was a similar number of genes up- and downregulated in all the infected host THP-1 cells, with exception of Hi-L2221, which showed a higher number of downregulated DEGs. We observed a total of 58 DEGs commonly modulated in all infected host cells, including upregulated (log₂FC ≥ 1) and downregulated (log₂FC ≤ -1) genes. Based on the results obtained from the analysis of RNA-seq, volcano plot, and GO enrichment analysis, we identified the most significant transcripts of relevance for their possible contribution to the TF observed in patients with leishmaniasis.

PMID:35352952 | DOI:10.1021/acsinfecdis.1c00513

J Manag Care Spec Pharm. 2022 Mar 30:1-12. doi: 10.18553/jmcp.2022.21436. Online ahead of print.

ABSTRACT

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers’ bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

PMID:35352995 | DOI:10.18553/jmcp.2022.21436

Ann Agric Environ Med. 2022 Mar 21;29(1):143-148. doi: 10.26444/aaem/145769. Epub 2022 Feb 11.

ABSTRACT

INTRODUCTION: Clinical manifestation of organophosphates toxicity may be differentiate and include cholinergic toxidrome, intermediate syndrome, OP-induced delayed polyneuropathy to chronic OP-induced neuropsychiatric disorder (OPIDN). Patients symptoms, along with decrease in cholinesterase serum level, determines the possible diagnosis of organophosphate poisoning.

OBJECTIVE: The aim of the study was to present the clinical manifestation and cholinesterase level changes in intoxication with organophosphorus compounds in patients.

MATERIAL AND METHODS: A data base was created by analysis of the hospital documents of 34 patients hospitalized due to organophosphate intoxication. Statistical analysis involved frequency tables with percentage values, the application of non-parametric Chi-square test and parametric t-Student test (with homogeneity of variance Levine test). The level of static significance was set to p=0.05.

RESULTS: In fatal hospitalizations (20.6%), cholinesterase level was significantly lower (265.87 U/l) than in other patients (4254.78 U/l; p<0.05). Similarly, levels of cholinesterase were decreased in group of patients with acute respiratory failure (999.79 U/l vs 4943.86 U/l in other patients; p<0.05), patients with multi-organ dysfunction syndrome (244.13 U/l vs 4914.89 U/l in other patients; p<0.05) and those with cardiac arrest (547 U/l vs 4636.25 U/l in other patients). A statistically significant difference was also observed in cholinesterase level of patients who required mechanical ventilation (548.17 U/l vs 5219.71 U/l in other group). The study revealed that 29.4% of poisonings were suicidal.

CONCLUSIONS: The management of a patient with organophosphate poisoning remains challenging and requires continuous control. A significant step in the diagnostic process is the assessment changes in both the clinical picture and cholinesterase level.

PMID:35352918 | DOI:10.26444/aaem/145769

Ann Agric Environ Med. 2022 Mar 21;29(1):115-119. doi: 10.26444/aaem/144842. Epub 2021 Dec 28.

ABSTRACT

INTRODUCTION AND OBJECTIVE: CT examination is an important diagnostic tool in assessment of the severity of the infection and course of the disease. The aim of the study was to evaluate the degree and frequency of involvement of individual lung lobes and the population Lobe Involvement Coefficient (pLIC) value in the investigated population.

MATERIAL AND METHODS: The analyzed material comprised 124 patients aged 18-92 years. CT examinations were performed using a 16- and 32-row CT LightSpeed apparatus. The spatial distribution of typical Covid -19 pathological changes was analyzed, divided into five lung lobes. The degree of the severity of lobe involvement was assessed using counters and percentages, as well as the population Lobe Involvement Coefficient (pLIC). Statistical analysis of data was performed with the use of Statistica 10.0 software. Values were measured on an oridinal scale. Anova Friedman’s test was used to compare lobes.

RESULTS: Statistically significant differences in the involvement between most of the individual lobes were shown. There was no statistically significant difference in the degree of lobe involvement between the left and right upper lobes, nor in the left and right lower lobes. The highest pILC was demonstrated for the lower lobe and the lowest value was obtained for the middle lobe.

CONCLUSIONS: The lower lobes were affected most frequently and most severely, with no statistical difference between the right and left sides. The middle lobe was affected relatively least frequently and lightly. The introduced pLIC index allows quantitative assessment of individual lobes involvement in relation to the entire studied population.

PMID:35352914 | DOI:10.26444/aaem/144842

Ann Agric Environ Med. 2022 Mar 21;29(1):80-85. doi: 10.26444/aaem/133369. Epub 2021 Mar 5.

ABSTRACT

INTRODUCTION: The favourable or unfavourable process of a patient’s adaptation to a challenging medical condition may indicate that certain adjustment reactions, which can be either constructive or undesirable, tend to prevail.

OBJECTIVE: The aim of the study was to examine the adjustment reactions of patients, and to define the correlation between the reactions and socio-demographic factors, health self-assessment, satisfaction with medical care, duration of treatment, and limitations in women treated for rheumatoid arthritis.

MATERIAL AND METHODS: The study was conducted at the Department of Rheumatology and Connective Tissue Diseases and the Specialist Outpatient Clinic of the Independent Public Teaching Hospital No. 4 in Lublin, Poland. The Polish adaptation of the Reactions to Impairment and Disability Inventory RIDI (H. Livneh, R. Antonak, 1990) was used in the study, together with an Original Questionnaire. A p-value of <0.05 was set to define statistical differences. Analysis was performed using commercial SPSS Statistics software (IBM Corp., Armonk, NY).

RESULTS: Adjustment reactions, adaptive reactions, i.e. adjustment (3±0.5) and acknowledgement (2.6±0.4) were found to markedly prevail, while the lowest mean value was observed for denial (1.9±0.4), which was considered a negative reaction. Longer duration of the disease was associated with a lower level of external hostility. Low health self-assessment and significant limitations impairing everyday activities, caused by pain, deformity and impaired joint mobility, were mostly related to unfavourable early and intermediate non-adaptive reactions.

CONCLUSIONS: Knowledge of the adjustment reactions and their moderating factors appears to be crucial in the planning of measures aimed at the rehabilitation of RA patients.

PMID:35352909 | DOI:10.26444/aaem/133369

Ann Agric Environ Med. 2022 Mar 21;29(1):86-93. doi: 10.26444/aaem/133760. Epub 2021 Mar 23.

ABSTRACT

INTRODUCTION: Physical activity has a positive effect on health. The level of physical activity changes with age. Elderly people often reduce their physical activity, among other things, due to deteriorating health or the belief that it is inappropriate to indulge in sports or be physically active at old agge. On the other hand, the lack of systematic physical activity in the elderly can lead to a reduction in the body’s efficiency in many health aspects. Although there are many methods of measuring human physical activity, there is no ideal tool for measuring that activity.

OBJECTIVE: The main aim of the study was to assess the effectiveness of the use of selected methods of measuring physical activity in the elderly, as well as to evaluate the influence of the measured activity on the nutritional status of women over 60 years of age.

MATERIAL AND METHODS: The study was carried out in the area of western Poland in a group of 110 generally healthy women above the age of 60, who were divided into 3 groups of intensity of undertaken physical activity (low active 30.00%, moderately active 41.82% and active 28.18%). A pedometer and a physical activity diary were used to measure physical activity. Body composition was assessed by the bioelectrical impedance method which uses a body composition analyzer. Body height and weight, lean mass of limbs and body, adipose tissue content, total water content, waist circumference to hip circumference (WHR), and BMI (Body Mass Index) were assessed.

RESULTS: The correlation coefficient between the methods of assessing physical activity, i.e. the number of minutes/day and the number of steps/day, was 0.92 and was statistically significant at the level of p<0.001. This was assumed to be a strict correlation. Based on the physical activity diary, it was estimated that women spent an average of 92.85 minutes a day on physical activity, while the data obtained from the pedometer showed that they performed an average of 4,462 steps a day. The average age of the respondents was 67.25 years, and average BMI – 28.07 kg/m².

CONCLUSIONS: A close correlation was demonstrated between the applied methods for assessing physical activity shows about the appropriate selection of methods, as well as, due to their ease of use, their use to assess physical activity in the elderly.

PMID:35352910 | DOI:10.26444/aaem/133760

Ann Agric Environ Med. 2022 Mar 21;29(1):63-71. doi: 10.26444/aaem/147277. Epub 2022 Mar 16.

ABSTRACT

INTRODUCTION AND OBJECTIVE: Serological assays for Lyme disease (LD) routinely performed in laboratories often give inconclusive results, thereby making correct diagnosis difficult and delaying treatment. The aim of the study was to assess the usefulness of a commercial Optiplex Borrelia (OB) assay in the serological diagnostics of LD. Based on the results obtained in a previous study on the seroreactivity of the sera of patients with LD to Borrelia spp. antigens using enzyme immunoassays (ELISA) and immunoblotting (IB), the same sera were re-analyzed using the OB assay.

RESULTS: The assays carried out with the use of OB method showed a statistically significant lower number of positive/borderline results for the presence of IgM antibodies, compared to the ELISA assay. Moreover, statistically lower positive/borderline results were obtained for antibodies in the IgG class with use of the OB method, compared to the IB assay and a two-stage diagnostic protocol (ELISA with IB). The specificity analysis showed that in both the IB and OB assays, anti-OspC IgM and anti-p41 antibodies were detected. Additionally, high positive/borderline values were found in the OB assay for native antigens derived from B. afzelii lysate. The IB assay most frequently detected antibodies against OspC, p39 (BmpA) and VlsE proteins in the IgG class. There were fewer positives/borderlines for anti-p41-I B. afzelii antibodies in the OB assay and a higher number for antigens: VlsE-C6, p18 B. afzelii (DbpA), and p39 B. afzelii (BmpA).

CONCLUSIONS: Answering the question whether the OB assay could replace the traditional, two-step method of LD diagnostics, it can be concluded that it could not. It can be used to diagnose LD only as a complementary assay and not as an optimal and dedicated method of Borrelia spp. infection detection.

PMID:35352907 | DOI:10.26444/aaem/147277

J Chem Inf Model. 2022 Mar 30. doi: 10.1021/acs.jcim.1c01438. Online ahead of print.

ABSTRACT

Conformational sampling of protein structures is essential for understanding biochemical functions and for predicting thermodynamic properties such as free energies. Where previous approaches rely on sequential sampling procedures, recent developments in generative deep neural networks rendered possible the parallel, statistically independent sampling of molecular configurations. To be able to accurately generate samples of large molecular systems from a high-dimensional multimodal equilibrium distribution function, we developed a hierarchical approach based on expressive normalizing flows with rational quadratic neural splines and coarse-grained representation. Furthermore, system specific priors and adaptive and property-based controlled learning was designed to diminish the likelihood for the generation of high-energy structures during sampling. Finally, backmapping from a coarse-grained to fully atomistic representation is performed through an equivariant transformer model. We demonstrate the applicability of the method on the one-shot configurational sampling of a protein system with more than a hundred amino acids. The results show enhanced expressivity that diminish the invertibility constraints inherent in the normalizing flow framework. Moreover, the capacity of the hierarchical normalizing flow model was tested on a challenging case study of the folding/unfolding dynamics of the peptide chignolin.

PMID:35352898 | DOI:10.1021/acs.jcim.1c01438

Stat Med. 2022 Mar 30. doi: 10.1002/sim.9390. Online ahead of print.

ABSTRACT

Mediation models are a set of statistical techniques that investigate the mechanisms that produce an observed relationship between an exposure variable and an outcome variable in order to deduce the extent to which the relationship is influenced by intermediate mediator variables. For a case-control study, the most common mediation analysis strategy employs a counterfactual framework that permits estimation of indirect and direct effects on the odds ratio scale for dichotomous outcomes, assuming either binary or continuous mediators. While this framework has become an important tool for mediation analysis, we demonstrate that we can embed this approach in a unified likelihood framework for mediation analysis in case-control studies that leverages more features of the data (in particular, the relationship between exposure and mediator) to improve efficiency of indirect effect estimates. One important feature of our likelihood approach is that it naturally incorporates cases within the exposure-mediator model to improve efficiency. Our approach does not require knowledge of disease prevalence and can model confounders and exposure-mediator interactions, and is straightforward to implement in standard statistical software. We illustrate our approach using both simulated data and real data from a case-control genetic study of lung cancer.

PMID:35352841 | DOI:10.1002/sim.9390

Yonsei Med J. 2022 Apr;63(4):305-316. doi: 10.3349/ymj.2022.63.4.305.

ABSTRACT

This present systematic review examines spine surgery literature supporting augmented reality (AR) technology and summarizes its current status in spinal surgery technology. Database search strategies were retrieved from PubMed, Web of Science, Cochrane Library, Embase, from the earliest records to April 1, 2021. Our review briefly examines the history of AR, and enumerates different device application workflows in a variety of spinal surgeries. We also sort out the pros and cons of current mainstream AR devices and the latest updates. A total of 45 articles are included in our review. The most prevalent surgical applications included are the augmented reality surgical navigation system and head-mounted display. The most popular application of AR is pedicle screw instrumentation in spine surgery, and the primary responsible surgical levels are thoracic and lumbar. AR guidance systems show high potential value in practical clinical applications for the spine. The overall number of cases in AR-related studies is still rare compared to traditional surgical-assisted techniques. These lack long-term clinical efficacy and robust surgical-related statistical data. Changing healthcare laws as well as the increasing prevalence of spinal surgery are generating critical data that determines the value of AR technology.

PMID:35352881 | DOI:10.3349/ymj.2022.63.4.305