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Nevin Manimala Statistics

DNA methylation profile of inflammatory breast cancer and its impact on prognosis and outcome

Clin Epigenetics. 2024 Jul 6;16(1):89. doi: 10.1186/s13148-024-01695-x.

ABSTRACT

BACKGROUND: Inflammatory breast cancer (IBC) is a rare disease characterized by rapid progression, early metastasis, and a high mortality rate.

METHODS: Genome-wide DNA methylation analysis (EPIC BeadChip platform, Illumina) and somatic gene variants (105 cancer-related genes) were performed in 24 IBCs selected from a cohort of 140 cases.

RESULTS: We identified 46,908 DMPs (differentially methylated positions) (66% hypomethylated); CpG islands were predominantly hypermethylated (39.9%). Unsupervised clustering analysis revealed three clusters of DMPs characterized by an enrichment of specific gene mutations and hormone receptor status. The comparison among DNA methylation findings and external datasets (TCGA-BRCA stages III-IV) resulted in 385 shared DMPs mapped in 333 genes (264 hypermethylated). 151 DMPs were associated with 110 genes previously detected as differentially expressed in IBC (GSE45581), and 68 DMPs were negatively correlated with gene expression. We also identified 4369 DMRs (differentially methylated regions) mapped on known genes (2392 hypomethylated). BCAT1, CXCL12, and TBX15 loci were selected and evaluated by bisulfite pyrosequencing in 31 IBC samples. BCAT1 and TBX15 had higher methylation levels in triple-negative compared to non-triple-negative, while CXCL12 had lower methylation levels in triple-negative than non-triple-negative IBC cases. TBX15 methylation level was associated with obesity.

CONCLUSIONS: Our findings revealed a heterogeneous DNA methylation profile with potentially functional DMPs and DMRs. The DNA methylation data provided valuable insights for prognostic stratification and therapy selection to improve patient outcomes.

PMID:38971778 | DOI:10.1186/s13148-024-01695-x

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Cost-effectiveness of single-pill and separate-pill administration of antihypertensive triple combination therapy: a population-based microsimulation study

BMC Public Health. 2024 Jul 6;24(1):1808. doi: 10.1186/s12889-024-19346-4.

ABSTRACT

BACKGROUND: Single-pill combination (SPC) of three antihypertensive drugs has been shown to improve adherence to therapy compared with free combinations, but little is known about its long-term costs and health consequences. This study aimed to evaluate the lifetime cost-effectiveness profile of a three-drug SPC of an angiotensin-converting enzyme inhibitor, a calcium-channel blocker, and a diuretic vs the corresponding two-pill administration (a two-drug SPC plus a third drug separately) from the Italian payer perspective.

METHODS: A cost-effectiveness analysis was conducted using multi-state semi-Markov modeling and microsimulation. Using the healthcare utilization database of the Lombardy Region (Italy), 30,172 and 65,817 patients aged ≥ 40 years who initiated SPC and two-pill combination, respectively, between 2015 and 2018 were identified. The observation period extended from the date of the first drug dispensation until death, emigration, or December 31, 2019. Disease and cost models were parametrized using the study cohort, and a lifetime microsimulation was applied to project costs and life expectancy for the compared strategies, assigning each of them to each cohort member. Costs and life-years gained were discounted by 3%. Probabilistic sensitivity analysis with 1,000 samples was performed to address parameter uncertainty.

RESULTS: Compared with the two-pill combination, the SPC increased life expectancy by 0.86 years (95% confidence interval [CI] 0.61-1.14), with a mean cost differential of -€12 (95% CI -9,719-8,131), making it the dominant strategy (ICER = -14, 95% CI -€15,871-€7,113). The cost reduction associated with the SPC was primarily driven by savings in hospitalization costs, amounting to €1,850 (95% CI 17-7,813) and €2,027 (95% CI 19-8,603) for patients treated with the SPC and two-pill combination, respectively. Conversely, drug costs were higher for the SPC (€3,848, 95% CI 574-10,640 vs. €3,710, 95% CI 263-11,955). The cost-effectiveness profile did not significantly change according to age, sex, and clinical status.

CONCLUSIONS: The SPC was projected to be cost-effective compared with the two-pill combination at almost all reasonable willingness-to-pay thresholds. As it is currently prescribed to only a few patients, the widespread use of this strategy could result in benefits for both patients and the healthcare system.

PMID:38971775 | DOI:10.1186/s12889-024-19346-4

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Optimisation of indole acetic acid production by Neopestalotiopsis aotearoa endophyte isolated from Thymus vulgaris and its impact on seed germination of Ocimum basilicum

BMC Biotechnol. 2024 Jul 6;24(1):46. doi: 10.1186/s12896-024-00872-3.

ABSTRACT

BACKGROUND: Microbial growth during plant tissue culture is a common problem that causes significant losses in the plant micro-propagation system. Most of these endophytic microbes have the ability to propagate through horizontal and vertical transmission. On the one hand, these microbes provide a rich source of several beneficial metabolites.

RESULTS: The present study reports on the isolation of fungal species from different in vitro medicinal plants (i.e., Breynia disticha major, Breynia disticha, Duranta plumieri, Thymus vulgaris, Salvia officinalis, Rosmarinus officinalis, and Ocimum basilicum l) cultures. These species were tested for their indole acetic acid (IAA) production capability. The most effective species for IAA production was that isolated from Thymus vulgaris plant (11.16 µg/mL) followed by that isolated from sweet basil plant (8.78 µg/mL). On screening for maximum IAA productivity, medium, “MOS + tryptophan” was chosen that gave 18.02 μg/mL. The macroscopic, microscopic examination and the 18S rRNA sequence analysis indicated that the isolate that given code T4 was identified as Neopestalotiopsis aotearoa (T4). The production of IAA by N. aotearoa was statistically modeled using the Box-Behnken design and optimized for maximum level, reaching 63.13 µg/mL. Also, IAA extract was administered to sweet basil seeds in vitro to determine its effect on plant growth traits. All concentrations of IAA extract boosted germination parameters as compared to controls, and 100 ppm of IAA extract exhibited a significant growth promotion effect for all seed germination measurements.

CONCLUSIONS: The IAA produced from N. aotearoa (T4) demonstrated an essential role in the enhancement of sweet basil (Ocimum basilicum) growth, suggesting that it can be employed to promote the plant development while lowering the deleterious effect of using synthetic compounds in the environment.

PMID:38971771 | DOI:10.1186/s12896-024-00872-3

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The effectiveness and safety of acupoint herbal patching for allergic rhinitis: protocol for a systematic review and meta-analysis

Syst Rev. 2024 Jul 6;13(1):172. doi: 10.1186/s13643-024-02598-x.

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) is a common inflammatory disease of the nasal mucosa that is characterized by symptoms such as sneezing, nasal congestion, nasal itching, and rhinorrhoea. In recent years, acupoint herbal patching (AHP) therapy has gained a growing interest as a potential management option for AR. This systematic review and meta-analysis will evaluate the clinical research evidence on the effectiveness and safety of AHP as a treatment option for AR outside of the Sanfu or Sanjiu days (summer or winter solstice). The results of this review will provide up-to-date evidence-based guidance for healthcare providers and individuals seeking alternative treatments for AR.

METHODS: A comprehensive search of electronic databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, China National Knowledge Infrastructure (CNKI), CQVIP, Sino-Med, and Wanfang Databases) will be conducted from their inception to June 2023. The inclusion criteria will be limited to randomized controlled trials that evaluate the effectiveness or efficacy of non-Sanfu or non-Sanjiu AHP for AR. The primary outcome measure will be the total nasal symptom score. The methodological quality of included studies will be assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2), and meta-analyses will be performed using RevMan (V.5.3) statistical software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to determine the certainty of evidence.

DISCUSSION: This systematic review and meta-analysis will provide valuable insights into the effectiveness and safety of non-Sanfu or non-Sanjiu AHP as a treatment option for AR. The study aims to produce a high-quality review by adhering to PRISMA-P guidelines and using clinical guideline recommended outcome measures. The results of this review may offer additional treatment options for AR patients who seek complementary and alternative therapies, and hold significant implications for future research in this field. Overall, this study has the potential to inform clinical practice and improve patient outcomes.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022181322.

PMID:38971762 | DOI:10.1186/s13643-024-02598-x

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Beyond the diagnosis of drug-resistant Tuberculosis in Norway: patients’ experiences before, during and after treatment

BMC Public Health. 2024 Jul 6;24(1):1801. doi: 10.1186/s12889-024-19342-8.

ABSTRACT

BACKGROUND: This study aims to explore the varied experiences of patients with drug-resistant tuberculosis in Norway. The study emphasizes challenges and implications of being diagnosed with drug-resistant tuberculosis, including the impact on psychosocial health during the diagnosis, disease, treatment, isolation and recovery phases. Norway is a low endemic country of tuberculosis. Most patients are immigrants, and some of them have recently arrived in the country. Patients undergoing treatment for drug-resistant tuberculosis endure prolonged and demanding treatment that could affect their psychosocial health.

METHODS: This qualitative study conducted 16 in-depth interviews with individuals aged 18 years and above who were diagnosed with drug-resistant tuberculosis. All participants completed the treatment between 2008 and 2020. Fourteen participants were immigrants, and eight of them had resided in Norway for less than four years before diagnosis. Data analysis followed the six-phase reflexive thematic analysis framework, focusing on identifying patterns in participants’ experiences, thoughts, expectations and attitudes.

RESULTS: The narratives of the participants highlighted the complexities of navigating the diagnosis of drug-resistant tuberculosis, treatment, side effects and life after treatment. Immigrants encountered additional challenges, including language barriers and adapting to new social environments. All participants reported experiencing physical health issues that additionally affected their mental health and social activity. Several participants had a delayed or prolonged diagnosis that complicated their disease trajectory. Participants with suspected or confirmed contagious pulmonary tuberculosis underwent hospital isolation for periods ranging from weeks to six months. The participants reported mental health issues, social isolation and stigma, however few were offered follow-up by a psychologist. Many participants had persistent problems at the time of the interviews. Three main themes emerged from the analysis: Delayed and prolonged diagnosis; Psychosocial impact of isolation during treatment; The life after tuberculosis.

CONCLUSION: This study highlights the enduring impact of drug-resistant tuberculosis on patients and the significance of timely diagnosis, psychosocial support and post-treatment follow-up. The participants universally faced serious implications of the disease, including stigma and isolation. Participants who experienced delayed diagnosis, reflected on missed early intervention opportunities. We recommend further research in low endemic countries to evaluate the international and local recommendations on psychosocial support.

PMID:38971760 | DOI:10.1186/s12889-024-19342-8

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The use of diagnostic ultrasound by primary care physicians in Switzerland – a cross-sectional study

BMC Prim Care. 2024 Jul 6;25(1):246. doi: 10.1186/s12875-024-02491-5.

ABSTRACT

BACKGROUND: Diagnostic ultrasound has become a bedside tool widely available to many primary care physicians (PCPs) in Europe. It is often used as point-of-care ultrasonography (POCUS) in this setting. In Switzerland, certain POCUS examinations are listed as learning objectives in existing ultrasound training programs (we defined these examinations as swissPOCUS = sPOCUS). Ultrasound performed by PCPs can lead to faster diagnostic workup and reduce referral to secondary care units. However, adequate training is crucial to guarantee high quality. To guide the development of ultrasound training programs for PCPs, this study explores the use of ultrasound in primary care in Switzerland.

METHODS: This was a cross-sectional study. We invited PCPs from the Swiss practice-based research network “Sentinella” to collect data on the first 5 daily ultrasounds they ordered or performed themselves. Participating PCPs collected data for 3 months – divided into 4 groups to account for seasonal differences.

RESULTS: Out of 188 PCPs invited, 81.9% provided data through an initial questionnaire. 46.8% provided data on 1616 ultrasounds. 56.5% of PCPs had access to ultrasound machines, while 29.8% had completed formal training. 77% of the reported ultrasounds were self-performed; 27% of the reported scans (35% of all self-performed scans) were performed by PCPs with incomplete or no formal training. The main areas of interest were the abdominal (57.9%) and the musculoskeletal (22%) region. 36.9% of reported examinations were sPOCUS exams. Among PCPs with access to US machines, the percentages of referred examinations were similar for sPOCUS (11.9%) and non-sPOCUS (11.3%) indications. However, some sPOCUS musculoskeletal ultrasounds were often referred (e.g. tendon/ligament/muscle injuries or cutaneous/subcutaneous tumour).

CONCLUSION: Most Swiss PCPs had access to ultrasound equipment and performed a majority of both sPOCUS and non-sPOCUS scans themselves, often without or with incomplete training. This reflects the fact that POCUS was only recently introduced in Switzerland. There is a need for easily accessible POCUS training programs aimed at PCPs in Switzerland. Training courses for PCPs should focus on abdominal and musculoskeletal ultrasound, because these were the most common sites for scans, and because some sPOCUS musculoskeletal examinations showed a particularly high percentage of referral.

PMID:38971759 | DOI:10.1186/s12875-024-02491-5

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Intersectional socioeconomic disparities in continuous smoking through pregnancy among pre-pregnant smokers in Sweden between 2006 and 2016

BMC Pregnancy Childbirth. 2024 Jul 6;24(1):465. doi: 10.1186/s12884-024-06647-0.

ABSTRACT

BACKGROUND: While well-established associations exist between socioeconomic conditions and smoking during pregnancy (SDP), less is known about social disparities in the risk of continuous SDP. Intersectional analyses that consider multiple social factors simultaneously can offer valuable insight for planning smoking cessation interventions.

METHODS: We include all 146,222 pregnancies in Sweden between 2006 and 2016 where the mother smoked at three months before pregnancy. The outcome was continuous SDP defined as self-reported smoking in the third trimester. Exposures were age, education, migration status and civil status. We examined all exposures in a mutually adjusted unidimensional analysis and in an intersectional model including 36 possible combinations. We present ORs with 95% Confidence Intervals, and the Area Under the Curve (AUC) as a measure of discriminatory accuracy (DA).

RESULTS: In our study, education status was the factor most strongly associated to continuous SDP among women who smoked at three months before pregnancy. In the unidimensional analysis women with low and middle education had ORs for continuous SDP of 6.92 (95%CI 6.63-7.22) and 3.06 (95%CI 2.94-3.18) respectively compared to women with high education. In the intersectional analysis, odds of continuous SDP were 17.50 (95%CI 14.56-21.03) for married women born in Sweden aged ≥ 35 years with low education, compared to the reference group of married women born in Sweden aged 25-34 with high education. AUC-values were 0.658 and 0.660 for the unidimensional and intersectional models, respectively.

CONCLUSION: The unidimensional and intersectional analyses showed that low education status increases odds of continuous SDP but that in isolation education status is insufficient to identify the women at highest odds of continuous SDP. Interventions targeted to social groups should be preceded by intersectional analyses but further research is needed before recommending intensified smoking cessation to specific social groups.

PMID:38971755 | DOI:10.1186/s12884-024-06647-0

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Insights on associations between the frequency of use of diverse social media products and social networks use disorder tendencies from a German speaking sample

BMC Res Notes. 2024 Jul 5;17(1):189. doi: 10.1186/s13104-024-06833-5.

ABSTRACT

OBJECTIVE: In the present work we investigate how individual differences in at least occasionally using distinct social media platforms is linked to social networks use disorder (SNUD) tendencies. A final sample of n = 2200 participants filled in the AICA-C-9 measure to get insights into individual differences in overuse of social media and participants also indicated which platforms they used at least once a month.

RESULTS: The analysis revealed a robust positive association between number of at least occasionally used social media apps and SNUD tendencies (r = .44, p < .001). Further, platforms differed in terms of their “addictive potential”, if one takes associations between frequency of distinct platforms use and SNUD tendencies as a proxy for this (and of course the actual descriptive statistics of the SNUD scale for the (non-)frequent user groups of the different platforms). In this regard, at least occasionally using some platforms (here Tumblr, Twitter and TikTok) was associated with highest SNUD tendencies. Moreover, largest differences in terms of effect sizes between the occasional and non-occasional user groups regarding SNUD scores could be observed for Instagram, WhatsApp, and TikTok. The present work bases on data from a larger project investigating associations between SNUD and tobacco use disorder.

PMID:38970143 | DOI:10.1186/s13104-024-06833-5

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Discrepancies between self-reported medication in adherence and indirect measurement adherence among patients undergoing antiretroviral therapy: a systematic review

Infect Dis Poverty. 2024 Jul 5;13(1):51. doi: 10.1186/s40249-024-01221-4.

ABSTRACT

BACKGROUND: Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools.

METHODS: We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles.

RESULTS: The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P < 0.05), with Pearson correlation coefficients of 0.843 for individual adherence and 0.684 for group adherence. During meta-epidemiological one-step analysis, SR-measured adherence was determined to be 3.94% (95% CI: -4.48-13.44%) higher for individual adherence and 16.14% (95% CI: 0.81-18.84%) higher for group adherence compared to indirectly measured results. Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements. Furthermore, network meta-analysis revealed that for both individual and group adherence, the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices, with some demonstrating statistical significance (P < 0.05).

CONCLUSIONS: The findings underscored the complexity of accurately measuring medication adherence among ART patients. Significant variability was observed across studies, with self-report methods showing a significant tendency towards overestimation. Year of reporting, geographic region, and adherence measurement tools appeared to influence the differences between SR and indirect measurements. Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors.

PMID:38970140 | DOI:10.1186/s40249-024-01221-4

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The serum level of vitamin D and prevalence of vitamin D deficiency among children with asthma in Asia and Africa: a systematic review and meta-analysis

Arch Public Health. 2024 Jul 5;82(1):103. doi: 10.1186/s13690-024-01321-5.

ABSTRACT

BACKGROUND: Several studies on the serum level of vitamin D and the percentage of vitamin D deficiency in children with asthma have been conducted in Asia and Africa, but the results have been inconsistent and inconclusive, requiring a systematic review and meta-analysis to assess the strength of the evidence.

OBJECTIVE: The objective of this review is to synthesize evidence on serum levels of vitamin D and the percentage of vitamin D deficiency among children with asthma in Asia and Africa.

METHODS: To identify relevant articles, a comprehensive search was conducted across various databases and repositories such as PubMed, Google Scholar, Hinary, Web of Science, ResearchGate, as well as gray literature sources. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed during the retrieval process. Data extraction was performed following a standardized format based on the JBI (Joanna Briggs Institute) data extraction guidelines. Microsoft Excel was utilized for data extraction, and subsequently, the data was exported to STATA 17 for further analysis. To assess the heterogeneity among the included studies, Cochrane Q-statistics and the I2 tests were employed. Publication bias was assessed using the Egger test and funnel plot.

RESULT: This meta-analysis investigated 33 articles encompassing a total of 3432 children diagnosed with asthma. The findings demonstrated that in low- or middle-income countries across Africa and Asia, children with asthma had an average serum vitamin D level of 21.9 ng/ml (95% confidence interval [CI]: 18.0-25.9 ng/ml), with 53.7% (95% CI: 40.5-66.9) experiencing vitamin D deficiency. Additionally, when considering the continent, children with asthma in Asia had an average serum vitamin D level of 18.5 ng/ml (95% CI: 13.8-23.3), while those in Africa had a level of 28.7 ng/ml (95% CI: 22.7-34.8). The analysis further explored different sub-group analyses. Depending on the study design, case-control studies yielded an average serum vitamin D level of 20.3 ng/ml (95% CI: 18.2-22.4), whereas cross-sectional studies resulted in 23.8 ng/ml (95% CI: 17.5-30.1). Based on publication year, studies published on or before 2015 had an average serum level of 21.0 ng/ml (95% CI: 18.0-24.0), while those published after 2015 had a level of 22.4 ng/ml (95% CI: 17.2-27.7). Moreover, when considering sample size, studies with 100 participants or less had an average serum level of 21.7 ng/ml (95% CI: 17.3-26.1), while studies with more than 100 participants had a level of 22.1 ng/ml (95% CI: 18.6-25.6).

CONCLUSION: Children with asthma in Asia and Africa were found to have low serum levels of vitamin D and a high percentage of vitamin D deficiency. This highlights the importance of early detection and monitoring of vitamin D levels in these children to prevent potential complications associated with vitamin D deficiency. Taking proactive measures to address and manage vitamin D deficiency is crucial for the well-being of children with asthma in these regions.

PMID:38970116 | DOI:10.1186/s13690-024-01321-5