Categories
Nevin Manimala Statistics

Do Lymph Node Ratio and Histopathologic Parameters Have Any Prognostic Value in Primary Parotid Gland Carcinomas?

Turk Arch Otorhinolaryngol. 2023 Jun;61(2):58-65. doi: 10.4274/tao.2023.2023-3-5. Epub 2023 Sep 18.

ABSTRACT

OBJECTIVE: To analyze the demographic characteristics and the pathological results of neck dissection in primary parotid gland (PG) cancer patients, and to investigate the effects of histopathological parameters (perineural invasion, lymphovascular invasion, and extracapsular spread), neck metastasis, stage and lymph node ratio (LNR) on survival.

METHODS: Patients who underwent parotidectomy for malignant PG tumors between 2000 and 2019 years were retrospectively reviewed from the medical records. Thirty patients who were treated with parotidectomy and neck dissection were included in the study. Lymph node ratio was calculated as the ratio of the number of metastatic lymph nodes (LN) to the total number of excised LNs. Tumor stage, regional LN metastasis, LNR, perineural invasion, lymphovascular invasion, and extracapsular spread were reviewed for the effects on survival with the Kaplan-Meier analysis.

RESULTS: The study included 17 (57%) male and 13 (43%) female patients. Their mean age was 67.93±16.90 years (range, 50-85 years). The average number of the excised LN was 26.03±11.79 (range, 3-50). Mean LNR was 0.16±0.26. The Kaplan-Meier analysis showed that neck metastasis (p=0.001) and LNR (p<0.001) were associated with shorter survival times compared to perineural invasion (p=0.818), lymphovascular invasion (p=0.154), extracapsular spread (p=0.410) and stage (p=0.294). In multivariate COX regression analysis, only LNR had a statistically significant difference (p=0.027) compared to the other parameters.

CONCLUSION: The present study suggests that LNR and neck metastasis are associated with shorter survival times in PG cancers. Lymph node ratio can be used as a prognostic marker in these patients.

PMID:37727816 | PMC:PMC10506524 | DOI:10.4274/tao.2023.2023-3-5

Categories
Nevin Manimala Statistics

High-dimensional supervised classification in a context of non-independence of observations to identify the determining SNPs in a phenotype

Infect Dis Model. 2023 Sep 9;8(4):1079-1087. doi: 10.1016/j.idm.2023.09.002. eCollection 2023 Dec.

ABSTRACT

This work addresses the problem of supervised classification for highly correlated high-dimensional data describing non-independent observations to identify SNPs related to a phenotype. We use a general penalized linear mixed model with a single random effect that performs simultaneous SNP selection and population structure adjustment in high-dimensional prediction models. Specifically, the model simultaneously selects variables and estimates their effects, taking into account correlations between individuals. Single nucleotide polymorphisms (SNPs) are a type of genetic variation and each SNP represents a difference in a single DNA building block, namely a nucleotide. Previous research has shown that SNPs can be used to identify the correct source population of an individual and can act in isolation or simultaneously to impact a phenotype. In this regard, the study of the contribution of genetics in infectious disease phenotypes is of great importance. In this study, we used uncorrelated variables from the construction of blocks of correlated variables done in a previous work to describe the most related observations of the dataset. The model was trained with 90% of the observations and tested with the remaining 10%. The best model obtained with the generalized information criterion (GIC) identified the SNP named rs2493311 located on the first chromosome of the gene called PRDM16 ((PR/SET domain 16)) as the most decisive factor in malaria attacks.

PMID:37727806 | PMC:PMC10505671 | DOI:10.1016/j.idm.2023.09.002

Categories
Nevin Manimala Statistics

Persistence of immunological memory as a potential correlate of long-term, vaccine-induced protection against Ebola virus disease in humans

Front Immunol. 2023 Sep 1;14:1215302. doi: 10.3389/fimmu.2023.1215302. eCollection 2023.

ABSTRACT

INTRODUCTION: In the absence of clinical efficacy data, vaccine protective effect can be extrapolated from animals to humans, using an immunological biomarker in humans that correlates with protection in animals, in a statistical approach called immunobridging. Such an immunobridging approach was previously used to infer the likely protective effect of the heterologous two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen. However, this immunobridging model does not provide information on how the persistence of the vaccine-induced immune response relates to durability of protection in humans.

METHODS AND RESULTS: In both humans and non-human primates, vaccine-induced circulating antibody levels appear to be very stable after an initial phase of contraction and are maintained for at least 3.8 years in humans (and at least 1.3 years in non-human primates). Immunological memory was also maintained over this period, as shown by the kinetics and magnitude of the anamnestic response following re-exposure to the Ebola virus glycoprotein antigen via booster vaccination with Ad26.ZEBOV in humans. In non-human primates, immunological memory was also formed as shown by an anamnestic response after high-dose, intramuscular injection with Ebola virus, but was not sufficient for protection against Ebola virus disease at later timepoints due to a decline in circulating antibodies and the fast kinetics of disease in the non-human primates model. Booster vaccination within three days of subsequent Ebola virus challenge in non-human primates resulted in protection from Ebola virus disease, i.e. before the anamnestic response was fully developed.

DISCUSSION: Humans infected with Ebola virus may benefit from the anamnestic response to prevent disease progression, as the incubation time is longer and progression of Ebola virus disease is slower as compared to non-human primates. Therefore, the persistence of vaccine-induced immune memory could be considered as a potential correlate of long-term protection against Ebola virus disease in humans, without the need for a booster.

PMID:37727795 | PMC:PMC10505757 | DOI:10.3389/fimmu.2023.1215302

Categories
Nevin Manimala Statistics

Association of serum vitamin D concentration with the final course of hospitalization in patients with COVID-19

Front Immunol. 2023 Sep 1;14:1231813. doi: 10.3389/fimmu.2023.1231813. eCollection 2023.

ABSTRACT

BACKGROUND: Vitamin D deficiency is a substantial public health problem. The present study evaluated the association between vitamin D concentration and hospitalization and mortality risk in patients with coronavirus disease 19 (COVID-19).

METHODS: This study used the COronavirus in LOwer Silesia (COLOS) dataset collected between February 2020 and June 2021. The medical records of 474 patients with confirmed severe acute respiratory syndrome 2 (SARS-CoV-2) infection, and whose vitamin D concentration was measured, were analyzed.

RESULTS: We determined a significant difference in vitamin D concentration between discharged patients and those who died during hospitalization (p = 0.0096). We also found an effect of vitamin D concentration on the risk of death in patients hospitalized due to COVID-19. As vitamin D concentration increased, the odds ratio (OR) for death slightly decreased (OR = 0.978; 95% confidence interval [CI] = 0.540-0.669). The vitamin D concentration cutoff point was 15.40 ng/ml. In addition, patients with COVID-19 and serum 25-hydroxyvitamin D (25(OH)D) concentrations < 30 ng/ml had a lower survival rate than those with serum 25(OH)D ≥ 30 ng/ml (log-rank test p = 0.0018). Moreover, a Cox regression model showed that patients with an estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2 and higher vitamin D concentrations had a 2.8% reduced risk of mortality (hazard ratio HR = 0.972; CI = 0.95-0,99; p = 0.0097).

CONCLUSIONS: The results indicate an association between 25(OH)D levels in patients with COVID-19 and the final course of hospitalization and risk of death.

PMID:37727794 | PMC:PMC10505823 | DOI:10.3389/fimmu.2023.1231813

Categories
Nevin Manimala Statistics

Knowledge, attitude and perceptions of pharmacists regarding renal dose adjustment among chronic kidney disease patients in Pakistan

J Pharm Policy Pract. 2023 Sep 19;16(1):102. doi: 10.1186/s40545-023-00606-4.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) poses a significant public health challenge. CKD patients have compromised renal function, which not only alters the pharmacokinetics of drugs but also their pharmacodynamics. Adjusting drug doses for these patients is essential to achieve the intended clinical outcomes, prevent adverse drug events, and halt further progression of the disease. Pharmacists play a pivotal role in ensuring safe and appropriate therapy for CKD patients. However, there is a noticeable absence of national dosing guidelines for CKD in Pakistan, coupled with a scarcity of studies exploring the knowledge, attitude, and perception of renal dose adjustments in the country. This study aimed to evaluate the knowledge, attitudes, and perceptions of pharmacists in the Khyber Pakhtunkhwa province and Islamabad regarding renal dose adjustments.

METHODOLOGY: A cross-sectional study was conducted to gauge the knowledge, attitude, and perception of pharmacists working in various cities of Khyber Pakhtunkhwa and the capital city, Islamabad, from February to May 2023. The Renal Dosing Questionnaire-13 (RDQ-13) scale was employed for this purpose. The survey link was disseminated through emails, and the RDQ-13 scale was also completed in person by pharmacists from hospitals, clinics, community, and retail settings who interact with CKD patients. Univariate linear regression was employed, and factors with a p value < 0.25 were subjected to multivariate linear regression. For comparing knowledge, attitude, and perception scores of pharmacists, the independent t test and one-way ANOVA were utilized as appropriate. A p value < 0.05 was deemed statistically significant.

RESULTS: Of the 384 pharmacists approached, 270 completed the RDQ-13 scale, resulting in a response rate of 70.3%. The overall knowledge score regarding renal dose adjustment was 21.24 ± 2.18 (mean ± SD). Attitude scores averaged at 10.04 ± 1.81, and perception scores at 7.19 ± 2.15. Multivariate analysis indicated a positive correlation between the pharmacists’ perception scores and gender, with male pharmacists scoring higher than their female counterparts.

CONCLUSIONS: The study underscores the importance of instituting targeted training programs for pharmacists, ensuring access to dependable resources, and promoting research and results dissemination in the realm of renal pharmacotherapy to enhance public health outcomes.

PMID:37726861 | DOI:10.1186/s40545-023-00606-4

Categories
Nevin Manimala Statistics

Exploring the ability of machine learning-based virtual screening models to identify the functional groups responsible for binding

J Cheminform. 2023 Sep 19;15(1):84. doi: 10.1186/s13321-023-00755-3.

ABSTRACT

Many recently proposed structure-based virtual screening models appear to be able to accurately distinguish high affinity binders from non-binders. However, several recent studies have shown that they often do so by exploiting ligand-specific biases in the dataset, rather than identifying favourable intermolecular interactions in the input protein-ligand complex. In this work we propose a novel approach for assessing the extent to which machine learning-based virtual screening models are able to identify the functional groups responsible for binding. To sidestep the difficulty in establishing the ground truth importance of each atom of a large scale set of protein-ligand complexes, we propose a protocol for generating synthetic data. Each ligand in the dataset is surrounded by a randomly sampled point cloud of pharmacophores, and the label assigned to the synthetic protein-ligand complex is determined by a 3-dimensional deterministic binding rule. This allows us to precisely quantify the ground truth importance of each atom and compare it to the model generated attributions. Using our generated datasets, we demonstrate that a recently proposed deep learning-based virtual screening model, PointVS, identified the most important functional groups with 39% more efficiency than a fingerprint-based random forest, suggesting that it would generalise more effectively to new examples. In addition, we found that ligand-specific biases, such as those present in widely used virtual screening datasets, substantially impaired the ability of all ML models to identify the most important functional groups. We have made our synthetic data generation framework available to facilitate the benchmarking of new virtual screening models. Code is available at https://github.com/tomhadfield95/synthVS .

PMID:37726844 | DOI:10.1186/s13321-023-00755-3

Categories
Nevin Manimala Statistics

A descriptive analysis of the contents of Care Response, an international data set of patient-reported outcomes for chiropractic patients

Chiropr Man Therap. 2023 Sep 19;31(1):37. doi: 10.1186/s12998-023-00509-w.

ABSTRACT

BACKGROUND: Databases have become an important tool in understanding trends and correlations in health care by collecting demographic and clinical information. Analysis of data collected from large cohorts of patients can have the potential to generate insights into factors identifying treatments and the characteristics of subgroups of patients who respond to certain types of care. The Care Response (CR) database was designed to capture patient-reported outcome measures (PROMs) for chiropractic patients internationally. Although several papers have been published analysing some of the data, its contents have not yet been comprehensively documented. The primary aim of this study was to describe the information in the CR database. The secondary aim was to determine whether there was suitable information available to better understand subgroups of chiropractic patients and responsiveness to care. This would be achieved by enabling correlations among patient demographics, diagnoses, and therapeutic interventions with machine learning approaches.

METHODS: Data in all available fields were requested with no date restriction. Data were collected on 12 April 2022. The output was manually scanned for scope and completeness. Tables were created with categories of information. Descriptive statistics were applied.

RESULTS: The CR database collects information from patients at the first clinical visit, 14, 30, and 90 days subsequently. There were 32,468 patient responses; 3210 patients completed all fields through the 90 day follow up period. 45% of respondents were male; 54% were female; the average age was 49. There was little demographic information, and no information on diagnoses or therapeutic interventions. We received StartBack, numerical pain scale, patient global impression of change, and Bournemouth questionnaire data, but no other PROMs.

CONCLUSIONS: The CR database is a large set of PROMs for chiropractic patients internationally. We found it unsuitable for machine learning analysis for our purposes; its utility is limited by a lack of demographic information, diagnoses, and therapeutic interventions. However, it can offer information about chiropractic care in general and patient satisfaction. It could form the basis for a useful clinical tool in the future, if reformed to be more accessible to researchers and expanded with more information collected.

PMID:37726831 | DOI:10.1186/s12998-023-00509-w

Categories
Nevin Manimala Statistics

Promoting alcohol treatment engagement post-hospitalization with brief intervention, medications and CBT4CBT: protocol for a randomized clinical trial in a diverse patient population

Addict Sci Clin Pract. 2023 Sep 19;18(1):55. doi: 10.1186/s13722-023-00407-9.

ABSTRACT

BACKGROUND: Alcohol use disorder (AUD) commonly causes hospitalization, particularly for individuals disproportionately impacted by structural racism and other forms of marginalization. The optimal approach for engaging hospitalized patients with AUD in treatment post-hospital discharge is unknown. We describe the rationale, aims, and protocol for Project ENHANCE (ENhancing Hospital-initiated Alcohol TreatmeNt to InCrease Engagement), a clinical trial testing increasingly intensive approaches using a hybrid type 1 effectiveness-implementation approach.

METHODS: We are randomizing English and/or Spanish-speaking individuals with untreated AUD (n = 450) from a large, urban, academic hospital in New Haven, CT to: (1) Brief Negotiation Interview (with referral and telephone booster) alone (BNI), (2) BNI plus facilitated initiation of medications for alcohol use disorder (BNI + MAUD), or (3) BNI + MAUD + initiation of computer-based training for cognitive behavioral therapy (CBT4CBT, BNI + MAUD + CBT4CBT). Interventions are delivered by Health Promotion Advocates. The primary outcome is AUD treatment engagement 34 days post-hospital discharge. Secondary outcomes include AUD treatment engagement 90 days post-discharge and changes in self-reported alcohol use and phosphatidylethanol. Exploratory outcomes include health care utilization. We will explore whether the effectiveness of the interventions on AUD treatment engagement and alcohol use outcomes differ across and within racialized and ethnic groups, consistent with disproportionate impacts of AUD. Lastly, we will conduct an implementation-focused process evaluation, including individual-level collection and statistical comparisons between the three conditions of costs to providers and to patients, cost-effectiveness indices (effectiveness/cost ratios), and cost-benefit indices (benefit/cost ratios, net benefit [benefits minus costs). Graphs of individual- and group-level effectiveness x cost, and benefits x costs, will portray relationships between costs and effectiveness and between costs and benefits for the three conditions, in a manner that community representatives also should be able to understand and use.

CONCLUSIONS: Project ENHANCE is expected to generate novel findings to inform future hospital-based efforts to promote AUD treatment engagement among diverse patient populations, including those most impacted by AUD.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05338151.

PMID:37726823 | DOI:10.1186/s13722-023-00407-9

Categories
Nevin Manimala Statistics

HIV viral load suppression among people with mental disorders at two urban HIV clinics in Uganda: a parallel convergent mixed methods study using the social ecological model

AIDS Res Ther. 2023 Sep 19;20(1):68. doi: 10.1186/s12981-023-00567-3.

ABSTRACT

BACKGROUND: Uganda adopted and implemented the Universal Test and Treat (UTT) guidelines in 2017, which require HIV-infected persons to be initiated on antiretroviral therapy (ART) at any CD4 + cell count, and to be routinely monitored for viral load to assess response to ART. However, there is paucity of data on viral load suppression (VLS) among people living with HIV (PLHIV) with mental disorders. We conducted a parallel convergent mixed methods study to determine HIV VLS among people with a mental disorder and explored the socio-cultural determinants of VLS at Butabika hospital and Mulago (ISS) HIV Clinics in Uganda.

METHODS: We conducted a retrospective medical records review; seven key informant interviews (KII) among purposively selected healthcare providers and 12 in-depth interviews (IDI) among clinically stable PLHIV with a mental disorder. Data was collected on demographics, mental disorder, ART, viral load status, social support, stigma, and disclosure of HIV status. Quantitative data was analysed using descriptive statistics and modified Poisson regression, while Inductive thematic analysis was used for the qualitative data.

RESULTS: Of the 240 PLHIV with a mental disorder who were enrolled, 161 (67.1%) were female with mean age 38.9 (± 11.2) years. Overall, 88.8% (95% Cl: 84.0 – 92.2%) achieved VLS. Age (aPR = 1.00, 95%Cl = 1.00-1.00), male gender (aPR = 0.90, 95%Cl = 0.82-0.98), divorced (aPR = 0.88, 95%Cl = 0.82-0.94), widowed (aPR = 0.84, 95%Cl = 0.83-0.86), baseline CD4 count < 200 (aPR = 0.89, 95%Cl = 0.85-0.94), psychotic mental disorders (aPR = 1.11; 95%CI = 1.08-1.13) and fair (85-94%) ART adherence level (aPR = 0.69, 95%Cl = 0.55-0.87) and TDF/3TC/DTG (aPR = 0.92; 95%CI = 0.91-0.94) were associated with HIV VLS. Social support from family members, knowledge of impact of negative thoughts on VLS, fear of breaking up with partners and compassionate healthcare providers positively influenced VLS. Stigma and discrimination from the community, self-perceived stigma hindering social relations, socio-economic challenges and psychiatric drug stock-outs negatively affected VLS.

CONCLUSION AND RECOMMENDATIONS: HIV VLS among PLHIV with mental disorders at institutions that provide integrated HIV and mental health care is still below the UNAIDS 95% target. Health promotion messaging focusing on benefits of VLS and countering stigma to create a safe environment; and active involvement of family members in care could improve HIV treatment outcomes for PLHIV with mental disorders.

PMID:37726822 | DOI:10.1186/s12981-023-00567-3

Categories
Nevin Manimala Statistics

How to assess hypercoagulability in heparin-induced thrombocytopenia? Biomarkers of potential value to support therapeutic intensity of non-heparin anticoagulation

Thromb J. 2023 Sep 19;21(1):100. doi: 10.1186/s12959-023-00546-8.

ABSTRACT

BACKGROUND: In case of heparin-induced thrombocytopenia (HIT), the switch to a non-heparin anticoagulant is mandatory, at a therapeutic dose. Such a treatment has limitations though, especially for patients with renal and/or hepatic failure. Candidate laboratory tests could detect the more coagulable HIT patients, for whom therapeutic anticoagulation would be the more justified.

PATIENTS AND METHODS: This was a monocentre observational prospective study in which 111 patients with suspected HIT were included. Nineteen were diagnosed with HIT (ELISA and platelet activation assay), among whom 10 were classified as HITT + when a thrombotic event was present at diagnosis or during the first following week. Two plasma prethrombotic biomarkers of in vivo activation of the haemostasis system, procoagulant phospholipids (ProcoagPPL) associated with extracellular vesicles and fibrin monomers (FM test), as well as in vitro thrombin potential (ST Genesia; low picomolar tissue factor) after heparin neutralization (heparinase), were studied. The results were primarily compared between HITT + and HITT- patients.

RESULTS: Those HIT + patients with thrombotic events in acute phase or shortly after (referred as HITT+) had a more coagulable phenotype than HIT + patients without thrombotic events since: (i) clotting times related to plasma procoagulant phospholipids tended to be shorter; (ii) fibrin monomers levels were statistically significantly higher (p = 0.0483); (iii) thrombin potential values were statistically significantly higher (p = 0.0404). Of note, among all patients suspected of suffering from HIT, we did not evidence a hypercoagulable phenotype in patients diagnosed with HIT compared to patients for whom the diagnosis of HIT was ruled out.

CONCLUSION: The three tests could help identify those HIT patients the most prone to thrombosis.

PMID:37726772 | DOI:10.1186/s12959-023-00546-8