Nevin Manimala

Trials. 2023 Oct 5;24(1):639. doi: 10.1186/s13063-023-07647-9.

ABSTRACT

BACKGROUND: Many infants in low-resourced settings at high risk of infectious disease morbidity and death are deprived of the immunological and nutritional benefits of breast milk, through an attenuated duration of breast milk exposure. South Africa has one of the lowest exclusive breastfeeding rates in Africa, with 8% of infants under 6 months of age. We assume that breastfeeding is sustained among women living with HIV receiving weekly text messages and motivational interviewing and that this contributes to improved infant health outcomes.

OBJECTIVES: (1) To evaluate the effectiveness of a combined intervention of mobile phone text messaging and motivational interviewing in promoting (a) exclusive breastfeeding and (b) any form of breastfeeding, until 6 months of child age, compared to usual care, among mothers living with HIV. (2) To evaluate the effectiveness of a combined intervention on (a) reduction in all-cause hospitalization and mortality rates and (b) improvements in infant linear growth, compared to usual care, among HIV-exposed infants aged 0-6 months.

METHODS: We are conducting a clinical trial to determine whether text messaging plus motivational interviewing prolongs breastfeeding and improves infant health outcomes. We are recruiting 275 women living with HIV and their HIV-exposed infants at birth and randomly assign study interventions for 6 months.

STATISTICAL METHODS: Breastfeeding rates are compared between the study groups using a standard proportion test and binomial regression. Survival endpoints are presented using Kaplan-Meier survival curves and compared between the study groups using the Cox proportional-hazards regression model. The count endpoint is analysed using the Poisson random-effects model and mean cumulative function. We use mixed linear regression models to assess the evolution of infant growth over time. The maximum likelihood method will be used to handle missing data.

DISCUSSION: The study findings may facilitate decision-making on (1) whether implementation of the breastfeeding policy achieved the desired outcomes, (2) interventions needed to sustain breastfeeding, and (3) whether the interventions do have an impact on child health.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05063240. Pan African Clinical Trial Registry PACTR202110870407786. Oct. 1, 2021.

PMID:37794523 | DOI:10.1186/s13063-023-07647-9

Syst Rev. 2023 Oct 4;12(1):186. doi: 10.1186/s13643-023-02346-7.

ABSTRACT

BACKGROUND: Emotional support is key to improve older adults’ subjective health, and psychological, social and emotional well-being. However, many older adults living in the community lack emotional support, increasing the risk for loneliness, depression, anxiety, potentially avoidable healthcare use and costs, and premature death. Multiple intersecting factors may influence emotional support of older adults in the community, but these are poorly understood. Studies have focused on specific populations (e.g., older adults with depression, cancer). Although relevant, these studies may not capture modifiable factors for the wider and more diverse population of older adults living in the community. Our scoping review will address these important gaps. We will identify and synthesize the evidence on factors that influence emotional support of older adults in the community.

METHODS: We will use the Johanna Briggs Institute updated methodological guidance for the conduct of scoping reviews to guide our review process. We will search MEDLINE, EMBASE, APA Psycinfo, CINAHL, Dissertations and Theses Global, and Scopus from inception. We will include studies published in English, examining factors influencing emotional support of older adults residing in community, without restrictions on the study design or year of publication. We will also include gray literature (dissertations and reports). Two independent reviewers will conduct title, abstract, and full-text screening, as well as risk of bias assessment, using validated quality appraisal tools based on study designs. Discrepancies will be resolved by consensus. The primary reviewer will extract the data from all studies, and the second reviewer will check the extractions of all the studies. We will use descriptive statistics and narrative synthesis for analysis. Family/friend caregivers and older adults involved as an advisory group will help with explaining the findings in terms of whether associations observed reflect their experiences and reality. We will analyze the discussion and generate themes, and summarize in a narrative form.

DISCUSSION: This scoping review may identify factors that could be modified or mitigated to improve emotional support provision for older adults residing in community. The knowledge will inform the development of tailored interventions directed to older adults and their caregivers.

SYSTEMATIC REVIEW REGISTRATION: https://doi.org/10.17605/OSF.IO/4TAEB (associated project link: osf.io/6y48t).

PMID:37794514 | DOI:10.1186/s13643-023-02346-7

Arthroplasty. 2023 Oct 5;5(1):51. doi: 10.1186/s42836-023-00207-1.

ABSTRACT

BACKGROUND: Few studies have investigated the kinematics after reverse total shoulder arthroplasty (RTSA). This study aimed to compare the shoulder kinematics in RTSA patients during shoulder abduction on the scapular plane with and without a load and yield information regarding the function of stabilizing the joints against gravity for the functional assessment of the shoulder after RTSA, which could lead to changes in postoperative rehabilitation treatment.

METHODS: Twenty RTSA patients (7 men, 13 women; mean age: 78.1 [64-90] years) were examined. First, active shoulder abduction in the scapular plane was captured using single-plane fluoroscopic X-ray images. Imaging was performed by stipulating that one shoulder abduction cycle should be completed in 6 s. Two trials were conducted: one under a load equivalent to 2% of body weight and one without a load. Next, a three-dimensional (3D) model of each humeral and scapular component was matched to the silhouette of the fluoroscopic image to estimate the 3D dynamics. By using the 3D dynamic model obtained, the kinematics of the glenosphere and humeral implant were calculated relative to the shoulder abduction angle on the scapular plane and were compared between groups with and without a load. A one-way analysis of variance and a post hoc paired t-test with a statistical significance level of 0.05 were performed.

RESULTS: The humeral internal rotation decreased with a load at shoulder abduction between 40° and 90° on the scapular plane (P < 0.01, effect size: 0.15). No significant differences in scapular upward rotation (P = 0.57, effect size: 0.022), external rotation (P = 0.83, effect size: 0.0083) and posterior tilting (P = 0.74, effect size: 0.013) were observed between groups with and without a load. The main effect was not observed with and without a load (P = 0.86, effect size: 0.0072). However, the scapulohumeral rhythm was significantly greater without a load during shoulder joint abduction between 40° and 60° on the scapular plane.

CONCLUSION: In RTSA patients, the glenohumeral joint was less internally rotated, and the scapulohumeral rhythm decreased under loaded conditions. It was stabilized against the load through the mechanical advantage of the deltoid muscle and other muscles.

PMID:37794512 | DOI:10.1186/s42836-023-00207-1

Clin Epigenetics. 2023 Oct 4;15(1):157. doi: 10.1186/s13148-023-01570-1.

ABSTRACT

BACKGROUND: Early detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC.

RESULTS: First, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test.

CONCLUSIONS: Overall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.

PMID:37794510 | DOI:10.1186/s13148-023-01570-1

Breast Cancer Res. 2023 Oct 4;25(1):115. doi: 10.1186/s13058-023-01721-5.

ABSTRACT

BACKGROUND: B7 homology 4 (B7-H4), a potential target for cancer therapy, has been demonstrated to inhibit T cell cytotoxicity in the early stages of breast cancer. However, B7-H4 manipulating breast tumor immune microenvironment (TIME) in the tumor progression remains unknown.

METHODS: We engineered T cells with B7-H4-specific chimeric antigen receptors (CARs) and performed a T cell co-culture assay to characterize B7-H4 expression level in breast cancer cells escaping from T cell cytotoxicity. We generated B7-H4 knockout (KO) and overexpression (OE) breast cancer cells to determine the epithelial-to-mesenchymal transition (EMT) and stemness characteristics in vitro and in vivo, including tumor proliferation, migration, metastasis and chemoresistance. The Cancer Genome Atlas breast cancer database was accessed to investigate the correlation between B7-H4 expression levels and EMT characteristics in patients with breast cancer.

RESULTS: Our result found that B7-H4 expression level was significantly reduced in a subset of breast cancer cells that escaped from the cytotoxicity of B7-H4 CAR-T cells. Compared with wild type cells, B7-H4 KO cells prompt EMT and stemness characteristics, including migration, invasion and metastasis, and OE cells vice versa. The increase in H3K27me3 in KO cells confirmed the epigenetic reprogramming of cancer stem cells. The IC50 of doxorubicin or oxaliplatin significantly increased in KO cells, which was in agreement with a decrease in OE cells. Moreover, a trend of downregulated B7-H4 from stage I to stage II breast cancer patients indicates that the low-expressing B7-H4 breast cancer cells escaping from TIME have spread to nearby breast lymph nodes in the cancer progression.

CONCLUSIONS: Our study illuminates the novel role of renouncing B7-H4 in breast cancer cells through immune escape, which contributes to EMT processes and provides new insights for breast cancer treatments.

PMID:37794509 | DOI:10.1186/s13058-023-01721-5

BMC Res Notes. 2023 Oct 4;16(1):251. doi: 10.1186/s13104-023-06536-3.

ABSTRACT

OBJECTIVE: HIV remains a global burden, with the Sub-Saharan Africa (SSA) region reporting the largest number of people living with HIV/AIDS (PLHIV). An exponential improvement in the accessibility and uptake of antiretroviral treatment across SSA has significantly improved outcomes for PLHIV. Hence, HIV care goals have shifted from reducing mortality and morbidity to improving health-related quality of life (HRQoL). This study uses generic and condition-specific HRQoL outcomes to holistically determine the HRQoL of Zimbabwean adult PLHIV and associated factors. HRQoL is a dynamic subject construct that warrants continuous evaluation to provide meaningful feedback to various stakeholders. We enrolled 536 adult PLHIV in Zimbabwe. Collected data were analyzed through descriptive statistics and multivariate binary logistic regression.

RESULTS: Our study shows a high HRQoL perception by Zimbabwean PLHIV. Anxiety, depression, and poor environmental health were widely reported domains influencing HRQoL. Also, being aware of HIV status for over a year, not experiencing an adverse event, being married, having adequate finances and food security and having higher educational status were associated with higher HRQoL. It is essential to integrate mental health care into routine HIV care to improve treatment outcomes and HRQoL. Last, implementing bespoke multisectoral HRQoL-enhancement interventions is paramount.

PMID:37794503 | DOI:10.1186/s13104-023-06536-3

J Cardiothorac Surg. 2023 Oct 4;18(1):268. doi: 10.1186/s13019-023-02370-7.

ABSTRACT

BACKGROUND: This study aims to investigate the outcomes of patients who received early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy due to esophageal cancer.

METHODS: A prospective randomized clinical trial was performed between March 2020 and June 2022. Patients who were scheduled for thoracoscopic and laparoscopic esophagectomy due to esophageal cancer were enrolled. Then, these patients were assigned to the control group (traditional postoperative care) and study group (traditional postoperative care with early bronchoscopic sputum aspiration and lavage). The outcomes, which included the length of hospital stay and medical expenses, and postoperative complications, which included pulmonary infection, atelectasis, respiratory dysfunction and anastomotic leakage, were compared between these two groups.

RESULTS: A total of 106 patients were enrolled for the present study, and 53 patients were assigned for the control and study groups. There were no statistically significant differences in gender, age, and location of the esophageal cancer between the two groups. Furthermore, the length of hospital stay was statistically significantly shorter and the medical expenses were lower during hospitalization in the study group, when compared to the control group (12.3 ± 1.2 vs. 18.8 ± 1.3 days, 5.5 ± 0.9 vs. 7.2 ± 1.2 Chinese Yuan, respectively; all, P < 0.05). Moreover, there were statistically significantly fewer incidences of overall complications in study group, when compared to the control group (20.7% vs.45.2%, P < 0.05).

CONCLUSIONS: For patients with esophageal cancer, early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy can shorten the length of hospital stay, and lower the medical expense and incidence of postoperative complications.

PMID:37794501 | DOI:10.1186/s13019-023-02370-7

J Orthop Surg Res. 2023 Oct 4;18(1):750. doi: 10.1186/s13018-023-04235-0.

ABSTRACT

BACKGROUND: Osteonecrosis of the femoral head is a degenerative condition linked to corticosteroids, alcoholism, or trauma. With its rising prevalence due to increased hormone drug use and its debilitating effects on young to middle-aged individuals, understanding its association with specific laboratory indicators can aid early diagnosis and prevention.

METHODS: Upon retrospective analysis of the clinical data pertaining to individuals diagnosed with femoral head necrosis, spanning from January 2016 to January 2022, a comprehensive evaluation was conducted within the same time frame. The study aimed to ascertain the presence of femoral head necrosis in a total of 1176 individuals. A total of 1036 healthy patients were recruited randomly, ensuring that their ages matched. The risk variables associated with the utilization of logistic regression analysis and analysis techniques are employed. The patient examines the age distribution within a specific age group.

RESULTS: The levels of high-density lipoprotein, low-density lipoprotein A1, lipoprotein B1, total protein, albumin, globulin, and other lipophilic metabolism and coagulation markers exhibited a statistically significant increase compared to the control group. A multifactor logistic regression analysis was conducted to identify potential risk factors associated with femoral head necrosis in patients.

CONCLUSION: Femoral head necrosis is associated with a range of variables including coagulation malfunction, lipid metabolic abnormalities, and inflammation.

PMID:37794495 | DOI:10.1186/s13018-023-04235-0

Genome Med. 2023 Oct 4;15(1):79. doi: 10.1186/s13073-023-01233-z.

ABSTRACT

BACKGROUND: Genome-wide association studies (GWAS) of Alzheimer’s disease (AD) have identified several risk loci, but many remain unknown. Cerebrospinal fluid (CSF) biomarkers may aid in gene discovery and we previously demonstrated that six CSF biomarkers (β-amyloid, total/phosphorylated tau, NfL, YKL-40, and neurogranin) cluster into five principal components (PC), each representing statistically independent biological processes. Here, we aimed to (1) identify common genetic variants associated with these CSF profiles, (2) assess the role of associated variants in AD pathophysiology, and (3) explore potential sex differences.

METHODS: We performed GWAS for each of the five biomarker PCs in two multi-center studies (EMIF-AD and ADNI). In total, 973 participants (n = 205 controls, n = 546 mild cognitive impairment, n = 222 AD) were analyzed for 7,433,949 common SNPs and 19,511 protein-coding genes. Structural equation models tested whether biomarker PCs mediate genetic risk effects on AD, and stratified and interaction models probed for sex-specific effects.

RESULTS: Five loci showed genome-wide significant association with CSF profiles, two were novel (rs145791381 [inflammation] and GRIN2D [synaptic functioning]) and three were previously described (APOE, TMEM106B, and CHI3L1). Follow-up analyses of the two novel signals in independent datasets only supported the GRIN2D locus, which contains several functionally interesting candidate genes. Mediation tests indicated that variants in APOE are associated with AD status via processes related to amyloid and tau pathology, while markers in TMEM106B and CHI3L1 are associated with AD only via neuronal injury/inflammation. Additionally, seven loci showed sex-specific associations with AD biomarkers.

CONCLUSIONS: These results suggest that pathway and sex-specific analyses can improve our understanding of AD genetics and may contribute to precision medicine.

PMID:37794492 | DOI:10.1186/s13073-023-01233-z

EBioMedicine. 2023 Oct 2;97:104823. doi: 10.1016/j.ebiom.2023.104823. Online ahead of print.

ABSTRACT

BACKGROUND: Excessive use of blood cultures (BCs) in Emergency Departments (EDs) results in low yields and high contamination rates, associated with increased antibiotic use and unnecessary diagnostics. Our team previously developed and validated a machine learning model to predict BC outcomes and enhance diagnostic stewardship. While the model showed promising initial results, concerns over performance drift due to evolving patient demographics, clinical practices, and outcome rates warrant continual monitoring and evaluation of such models.

METHODS: A real-time evaluation of the model’s performance was conducted between October 2021 and September 2022. The model was integrated into Amsterdam UMC’s Electronic Health Record system, predicting BC outcomes for all adult patients with BC draws in real time. The model’s performance was assessed monthly using metrics including the Area Under the Curve (AUC), Area Under the Precision-Recall Curve (AUPRC), and Brier scores. Statistical Process Control (SPC) charts were used to monitor variation over time.

FINDINGS: Across 3.035 unique adult patient visits, the model achieved an average AUC of 0.78, AUPRC of 0.41, and a Brier score of 0.10 for predicting the outcome of BCs drawn in the ED. While specific population characteristics changed over time, no statistical points outside the statistical control range were detected in the AUC, AUPRC, and Brier scores, indicating stable model performance. The average BC positivity rate during the study period was 13.4%.

INTERPRETATION: Despite significant changes in clinical practice, our BC stewardship tool exhibited stable performance, suggesting its robustness to changing environments. Using SPC charts for various metrics enables simple and effective monitoring of potential performance drift. The assessment of the variation of outcome rates and population changes may guide the specific interventions, such as intercept correction or recalibration, that may be needed to maintain a stable model performance over time. This study suggested no need to recalibrate or correct our BC stewardship tool.

FUNDING: No funding to disclose.

PMID:37793210 | DOI:10.1016/j.ebiom.2023.104823