Category: Statistics

J Toxicol Environ Health A. 2024 Jun 26:1-10. doi: 10.1080/15287394.2024.2369255. Online ahead of print.

ABSTRACT

Sarcoidosis is a chronic granulomatous disease predominantly affecting the lungs and inducing significant morbidity and elevated mortality rate. The etiology of the disease is unknown but may involve exposure to an antigenic agent and subsequent inflammatory response resulting in granuloma formation. Various environmental and occupational risk factors have been suggested by previous observations, such as moldy environments, insecticides, and bird breeding. Our study investigated the association of air pollution with diagnosis of sarcoidosis using a case-control design. Penn State Health electronic medical records from 2005 to 2018 were examined for adult patients with (cases) and without (controls) an International Classification of Disease (ICD)-9 or -10 code for sarcoidosis. Patient addresses were geocoded and 24-hr residential-level air pollution concentrations were estimated using spatio-temporal models of particulate matter <2.5 μm (PM_2.5), ozone, and PM_2.5 elemental carbon (EC) and moving averages calculated. In total, 877 cases and 34,510 controls were identified. Logistic regression analysis did not identify significant associations between sarcoidosis incidence and air pollution exposure estimates. However, the odds ratio (OR) for EC for exposures occurring 7-10 years prior did approach statistical significance, and ORs exhibited an increasing trend for longer averaging periods. Data suggested a latency period of more than 6 years for PM_2.5 and EC for reasons that are unclear. Overall, results for PM_2.5 and EC suggest that long-term exposure to traffic-related air pollution may contribute to the development of sarcoidosis and emphasize the need for additional research and, if the present findings are substantiated, for public health interventions addressing air quality as well as increasing disease surveillance in areas with a large burden of PM_2.5 and EC.

PMID:38922578 | DOI:10.1080/15287394.2024.2369255

Clin Rheumatol. 2024 Jun 26. doi: 10.1007/s10067-024-07043-x. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes.

METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure.

RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure.

CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

PMID:38922553 | DOI:10.1007/s10067-024-07043-x

Clin Rheumatol. 2024 Jun 26. doi: 10.1007/s10067-024-07040-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Omega-3 possesses anti-inflammatory and lipid metabolism modifying effects in rheumatoid arthritis (RA), but inconsistency exists among previous studies. This meta-analysis intended to explore the effects of omega-3 supplementation on fatty acid distribution, blood lipid profiles, inflammation, and disease activity in RA patients.

METHODS: This meta-analysis followed the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) protocol. PubMed, Web of Science, and Embase databases were searched until August 31, 2023.

RESULTS: Eighteen randomized controlled trials with 1018 RA patients were included. Regarding fatty acid distribution, omega-3 supplementation increased eicosapentaenoic acid (EPA) [standardized mean difference (SMD): 0.74; 95% confidence interval (CI): 0.46, 1.01; P < 0.001] and docosahexanoic acid (DHA) (SMD: 0.62; 95% CI: 0.35, 0.89; P < 0.001), but reduced omega-6:omega-3 ratio (SMD: -1.06; 95% CI: -1.39, -0.73; P < 0.001) in RA patients. Regarding blood lipid, omega-3 supplementation decreased triglyceride (TG) in RA patients (SMD: -0.47; 95% CI: -0.78, -0.16; P = 0.003). Regarding clinical symptoms, omega-3 supplementation reduced tender joint count (TJC) in RA patients (SMD: -0.59; 95% CI: -0.79, -0.39; P < 0.001). Notably, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score on 28 joints (DAS28) score were slightly decreased by omega-3 supplementation but without statistical significance (all P > 0.05). Publication bias was low, and stability assessed by sensitivity analysis was good.

CONCLUSION: Omega-3 supplementation increases EPA and DHA, but reduces the omega-6:omega-3 ratio, TG, and TJC in RA patients.

PMID:38922552 | DOI:10.1007/s10067-024-07040-0

Clin Rheumatol. 2024 Jun 26. doi: 10.1007/s10067-024-07035-x. Online ahead of print.

ABSTRACT

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.

PMID:38922551 | DOI:10.1007/s10067-024-07035-x

Int Urol Nephrol. 2024 Jun 26. doi: 10.1007/s11255-024-04121-6. Online ahead of print.

ABSTRACT

PURPOSE: Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients’ short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS’s oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral.

METHODS: We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction.

RESULTS: Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8-5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon.

CONCLUSIONS: MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.

PMID:38922534 | DOI:10.1007/s11255-024-04121-6

Daru. 2024 Jun 26. doi: 10.1007/s40199-024-00523-0. Online ahead of print.

ABSTRACT

BACKGROUND: The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.

OBJECTIVE: This study used ‘pathway/gene-set analysis’ Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.

METHODS: A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.

RESULTS: 9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.

CONCLUSION: This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.

PMID:38922530 | DOI:10.1007/s40199-024-00523-0

Eur J Popul. 2024 Jun 26;40(1):22. doi: 10.1007/s10680-024-09708-4.

ABSTRACT

Recent demographic changes in Western countries have resulted in higher rates of partnership dissolution and serial partnering, and an increase in childbearing across multiple partnerships. This has given rise to more complex family dynamics including multi-partner fertility (MPF), defined as having biological children with two or more partners. Yet estimates of MPF in the UK have not previously been available. This paper describes an ‘indirect approach’ to estimate the prevalence of MPF in the UK, for men and women, given different assumptions. The paper additionally explores differences in MPF according to own and parental educational attainment. Amongst those born in Britain in 1970, 12-14% of men and 15-18% of women experienced MPF by age 42, depending on the assumptions made. For most of the cohort, MPF occurred with two different coresidential partners. We have established that MPF is a common family formation in the UK, but there are large educational disparities in MPF prevalence.

PMID:38922521 | DOI:10.1007/s10680-024-09708-4

Asian Spine J. 2024 Jun 25. doi: 10.31616/asj.2022.0451. Online ahead of print.

ABSTRACT

STUDY DESIGN: Retrospective study.

PURPOSE: To compare and correlate technetium-99m methylene diphosphonate uptake between benign and metastatic bone lesions using semiquantitative analysis of maximum standard uptake value (SUVmax) and mean Hounsfield unit (HU) in single-photon emission computed tomography-computed tomography (SPECT-CT).

OVERVIEW OF LITERATURE: Qualitative interpretation of metastatic bone lesions in breast cancer on bone scintigraphy is often complicated by coexisting benign lesions.

METHODS: In total, 185 lesions were identified on bone and SPECT-CT scans from 32 patients. Lesions were classified as metastatic (109 sclerotic lesions) and benign (76 lesions) morphologically on low-dose CT. Semiquantitative analysis using SUVmax and mean HU was performed on the lesions and compared. To discriminate benign and metastatic lesions, the correlation between SUVmax and mean HU was determined using the intraclass correlation coefficients.

RESULTS: The SUVmax was higher in metastatic lesions (20.66±14.36) but lower in benign lesions (10.18±12.79) (p<0.001). The mean HU was lower in metastatic lesions (166.62±202.02) but higher in benign lesions (517.65±192.8) (p<0.001). A weak negative correlation was found between the SUVmax and the mean HU for benign lesions, and a weak positive correlation was noted between the SUVmax and the mean HU on malignant lesions with no statistical significance (p=0.394 and 0.312, respectively). The cutoff values obtained were 10.8 for SUVmax (82.6% sensitivity and 84.2% specificity) and 240.86 for the mean HU (98.7% sensitivity and 88.1% specificity) in differentiating benign from malignant bone lesions.

CONCLUSIONS: Semiquantitative assessment using SUVmax and HU can complement qualitative analysis. Metastatic lesions had higher SUVmax but lower mean HU than benign lesions, whereas benign lesions demonstrated higher mean HU but lower SUVmax. A weak correlation was found between the SUVmax and the mean HU on malignant and benign lesions. Cutoff values of 10.8 for the SUVmax and 240.86 for the mean HU may differentiate bone metastases from benign lesions.

PMID:38917860 | DOI:10.31616/asj.2022.0451

Asian Spine J. 2024 Jun 25. doi: 10.31616/asj.2023.0447. Online ahead of print.

ABSTRACT

STUDY DESIGN: A retrospective cohort study.

PURPOSE: This study aimed to assess the reliability of quantitative computed tomography (QCT) in measuring bone mineral density (BMD) of instrumented vertebrae and investigate the effect of less paraspinal muscle damage on BMD changes after lumbar interbody fusion.

OVERVIEW OF LITERATURE: Patients always experience a decrease in vertebral BMD after lumbar interbody fusion. However, to the best of our knowledge, no study has analyzed the effect of paraspinal muscles on BMD changes.

METHODS: This retrospective analysis included a total of 155 patients who underwent single-level lumbar fusion, with 81 patients in the traditional group and 74 patients in the Wiltse group (less paraspinal muscle damage). QCT was used to measure the volumetric BMD (vBMD), Hounsfield unit value, and cross-sectional area of the paraspinal muscles at the upper instrumented vertebrae (UIV), vertebrae one segment above the UIV (UIV+1), and the vertebrae one segment above the UIV+1 (UIV+2). Statistical analyses were performed.

RESULTS: No significant differences in general data were observed between the two groups (p>0.05). Strong correlations were noted between the preoperative and 1-week postoperative vBMD of each segment (p<0.01), with no significant difference between the two time points in both groups (p>0.05). Vertebral BMD loss was significantly higher in UIV+1 and UIV+2 in the traditional group than in the Wiltse group (-13.6%±19.1% vs. -4.2%±16.5%, -10.8%±20.3% vs. -0.9%±37.0%; p<0.05). However, no statistically significant difference was observed in the percent vBMD changes in the UIV segment between the two groups (37.7%±70.1% vs. 36.1%±78.7%, p>0.05).

CONCLUSIONS: QCT can reliably determine BMD in the instrumented spine after lumbar interbody fusion. With QCT, we found that reducing paraspinal muscle destruction through the Wiltse approach during surgery can help preserve the adjacent vertebral BMD; however, it does not help increase the BMD in the instrumented vertebrae.

PMID:38917852 | DOI:10.31616/asj.2023.0447

Physiol Meas. 2024 Jun 25. doi: 10.1088/1361-6579/ad5bbb. Online ahead of print.

ABSTRACT

The cerebral vasculature is formed of an intricate network of blood vessels over many different length scales. Changes in their structure and connection are implicated in multiple cerebrovascular and neurological disorders. In this study, we present a novel approach to the quantitative analysis of the cerebral macrovasculature using computational and mathematical tools in a large dataset. &#xD;Approach. We analysed a publicly available vessel dataset from a cohort of 56 (32/24 F/M) healthy subjects. This dataset includes digital reconstructions of human brain macrovasculatures. We then propose a new mathematical model to compute blood flow dynamics and pressure distributions within these 56-representative cerebral macrovasculatures and quantify the results across this cohort.&#xD;Main results. Statistical analysis showed that the steady state level of cerebrovascular resistance (CVR) gradually increases with age in both men and women. These age-related changes in CVR are in good agreement with previously reported values. All subjects were found to have only small phase angles (< 6°) between blood pressure and blood flow at the cardiac frequency.&#xD;Significance. These results showed that the dynamic component of blood flow adds very little phase shift at the cardiac frequency, which implies that the cerebral macrocirculation can be regarded as close to steady state in its behaviour, at least in healthy populations, irrespective of age or sex. This implies that the phase shift observed in measurements of blood flow in cerebral vessels is caused by behaviour further down the vascular bed. This behaviour is important for future statistical models of the dynamic maintenance of oxygen and nutrient supply to the brain.

PMID:38917841 | DOI:10.1088/1361-6579/ad5bbb