Tag: pubmed

JAMA Oncol. 2022 Oct 13. doi: 10.1001/jamaoncol.2022.4649. Online ahead of print.

ABSTRACT

IMPORTANCE: Breast cancer is the most common invasive subsequent malignant disease in childhood cancer survivors, though limited data exist on changes in breast cancer rates as primary cancer treatments have evolved.

OBJECTIVE: To quantify the association between temporal changes in cancer treatment over 3 decades and subsequent breast cancer risk.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 5-year cancer survivors diagnosed when younger than 21 years between 1970 and 1999, with follow-up through December 5, 2020.

EXPOSURES: Radiation and chemotherapy dose changes over time.

MAIN OUTCOMES AND MEASURES: Breast cancer cumulative incidence rates and age-specific standardized incidence ratios (SIRs) compared across treatment decades (1970-1999). Piecewise exponential models estimated invasive breast cancer and ductal carcinoma in situ (DCIS) risk and associations with treatment exposures, adjusted for age at childhood cancer diagnosis and attained age.

RESULTS: Among 11 550 female survivors (median age, 34.2 years; range 5.6-66.8 years), 489 developed 583 breast cancers: 427 invasive, 156 DCIS. Cumulative incidence was 8.1% (95% CI, 7.3%-9.0%) by age 45 years. An increased breast cancer risk (SIR, 6.6; 95% CI, 6.1-7.2) was observed for survivors compared with the age-sex-calendar-year-matched general population. Changes in therapy by decade included reduced rates of chest (34% in the 1970s, 22% in the 1980s, and 17% in the 1990s) and pelvic radiotherapy (26%, 17%, and 13% respectively) and increased rates of anthracycline chemotherapy exposures (30%, 51%, and 64%, respectively). Adjusting for age and age at diagnosis, the invasive breast cancer rate decreased 18% every 5 years of primary cancer diagnosis era (rate ratio [RR], 0.82; 95% CI, 0.74-0.90). When accounting for chest radiotherapy exposure, the decline attenuated to an 11% decrease every 5 years (RR, 0.89; 95% CI, 0.81-0.99). When additionally adjusted for anthracycline dose and pelvic radiotherapy, the decline every 5 years increased to 14% (RR, 0.86; 95% CI, 0.77-0.96). Although SIRs of DCIS generally increased over time, there were no statistically significant changes in incidence.

CONCLUSIONS AND RELEVANCE: Invasive breast cancer rates in childhood cancer survivors have declined with time, especially in those younger than 40 years. This appears largely associated with the reduced use of chest radiation therapy, but was tempered by concurrent changes in other therapies.

PMID:36227603 | DOI:10.1001/jamaoncol.2022.4649

JAMA Netw Open. 2022 Oct 3;5(10):e2231633. doi: 10.1001/jamanetworkopen.2022.31633.

ABSTRACT

IMPORTANCE: Older Syrian refugees have a high burden of noncommunicable diseases (NCDs) and economic vulnerability.

OBJECTIVES: To develop and internally validate a predictive model to estimate inability to manage NCDs in older Syrian refugees, and to describe barriers to NCD medication adherence.

DESIGN, SETTING, AND PARTICIPANTS: This nested prognostic cross-sectional study was conducted through telephone surveys between September 2020 and January 2021. All households in Lebanon with Syrian refugees aged 50 years or older and who received humanitarian assistance from a nongovernmental organization were invited to participate. Refugees who self-reported having chronic respiratory disease (CRD), diabetes, history of cardiovascular disease (CVD), or hypertension were included in the analysis. Data were analyzed from November 2021 to March 2022.

MAIN OUTCOMES AND MEASURES: The main outcome was self-reported inability to manage any NCD (including CRD, CVD, diabetes, or hypertension). Predictors of inability to manage any NCD were assessed using logistic regression models. The model was internally validated using bootstrapping techniques, which gave an estimate of optimism. The optimism-adjusted discrimination is presented using the C statistic, and calibration of the model is presented using calibration slope (C slope).

RESULTS: Of 3322 older Syrian refugees, 1893 individuals (median [IQR] age, 59 [54-65] years; 1089 [57.5%] women) reported having at least 1 NCD, among whom 351 (10.6% overall; 18.6% of those with ≥1 NCD) had CRD, 781 (23.7% overall; 41.4% of those with ≥1 NCD) had diabetes, 794 (24.1% overall; 42.2% of those with ≥1 NCD) had history of CVD, and 1388 (42.3% overall; 73.6% of those with ≥1 NCD) had hypertension. Among individuals with NCDs, 387 participants (20.4%) were unable to manage at least 1 of their NCDs. Predictors for inability to manage NCDs were age, nonreceipt of cash assistance, household water insecurity, household food insecurity, and having multiple chronic diseases, with an adjusted C statistic of 0.650 (95% CI, 0.620-0.676) and C slope of 0.871 (95% CI, 0.729-1.023). The prevalence of nonadherence to medication was 9.2%, and the main reasons for nonadherence were unaffordability of medication (40.8%; 95% CI, 33.4%-48.5%) and the belief that they no longer required the medication after feeling better (22.4%; 95% CI, 16.4%-29.3%).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the predictors of inability to manage NCDs among older Syrian refugees in Lebanon were mainly related to financial barriers. Context-appropriate assistance is required to overcome financial barriers and enable equitable access to medication and health care.

PMID:36227600 | DOI:10.1001/jamanetworkopen.2022.31633

JAMA Netw Open. 2022 Oct 3;5(10):e2236621. doi: 10.1001/jamanetworkopen.2022.36621.

ABSTRACT

IMPORTANCE: Patient experience and patient safety are 2 major domains of health care quality; however empirical data on the association of physician vs nonphysician chief executive officers (CEOs) with public and private quality measures are rare but critical to evaluate as hospitals increasingly seek out physician CEOs.

OBJECTIVES: To evaluate whether there is an association of CEO background with hospital quality and to investigate differences in hospital characteristics between hospitals with a physician CEO vs those with a nonphysician CEO.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used 2019 data from 3 sources (ie, the American Hospital Association [AHA] Annual Survey, the Hospital Consumer Assessment of Healthcare Providers and Systems [HCAHPS], and the Leapfrog Hospital Safety Grades) to identify statistical differences in hospital characteristics and outcomes. Data were analyzed from April to December 2021 .

MAIN OUTCOMES AND MEASURES: Multivariable ordinal logistic regression was used to examine the association of physician CEOs with hospital quality assessment outcomes while controlling for other confounding factors. Characteristics from the AHA Annual Survey database were assessed as potential confounders, including hospital control, bed size, region, teaching status, and patient volume.

RESULTS: The AHA database contained 6162 hospitals; 1759 (29%) had HCAHPS ratings, 1824 (30%) had Leapfrog grades, and 383 (6%) had physician CEOs. A positive Spearman correlation coefficient was found between physician CEOs and HCAHPS patient willingness to recommend the hospital (ρ = 0.0756; P = .002), but the association between CEO medical background and Leapfrog safety grades or HCAHPS ratings did not reach a level of significance in the multivariable ordinal logistic regression models.

CONCLUSIONS AND RELEVANCE: In this study, a positive correlation was found between physician CEOs and HCAHPS patient willingness to recommend the hospital, but the multivariable analysis did not find an association between hospital physician CEOs and the examined quality and safety outcomes.

PMID:36227592 | DOI:10.1001/jamanetworkopen.2022.36621

Logoped Phoniatr Vocol. 2022 Oct 13:1-8. doi: 10.1080/14015439.2022.2130422. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to see if the effects of the sub-domains of the Voice Handicap Index-10 (VHI-10) and Voice Related Quality of Life (VRQoL) differ in organic (OD) and functional dysphonia (FD).

METHOD: A total of 162 patients completed the validated Turkish versions of the Voice Handicap Index-10 (VHI-10) and Voice-Related Quality of Life (VRQoL). Physical (pVHI-10), emotional (eVHI-10) and functional (fVHI-10) sub-domains of VHI-10 and physical-functional (PF-VRQoL), socio-emotional (SE-VRQoL) dimensions of VRQoL were assessed. Confirmatory factor analysis (CFA) was used to compare the sub-domains of these questionnaires between diagnostic categories.

RESULTS: The total and sub-domain scores of both VHI-10 and VRQoL were not statistically different between the two etiologic categories of dysphonia (MANOVA, p > .05). The total VHI-10 and total VRQoL scores were significantly and moderately correlated in both the OD and FD groups. During CFA, 4 models were constructed for the OD and FD groups for VHI-10 and VRQoL factors. There was no significant difference between OD and FD groups in terms of path coefficients of sub-domains (z test, p > .05).

CONCLUSION: In terms of VHI-10 and VRQoL, the sub-domains of each questionnaire are equally important in both organic and functional dysphonia. Functional disorders do not depend only on “emotional” factors, and neither do organic problems. Factor analysis should be included when performing a study on patient-reported outcome measures.

PMID:36227585 | DOI:10.1080/14015439.2022.2130422

Arthritis Rheumatol. 2022 Oct 13. doi: 10.1002/art.42375. Online ahead of print.

ABSTRACT

OBJECTIVES: There is paucity of population-based studies investigating the epidemiology of lupus nephritis (LN) in the US and long-term secular trends of the disease and its outcomes. We aimed to examine the epidemiology of LN in a well-defined eight-county region in the US.

METHODS: Patients with incident LN between 1976 and 2018 (1976-2009 Olmsted County, 2010-2018 eight-county region) in Minnesota were identified. Age- and sex-specific incidence rates and point prevalence for four decades, adjusted to the projected 2000 US population, were reported. Standardized mortality ratios (SMR), survival rates, and time to end-stage renal disease (ESRD) were estimated.

RESULTS: There were 72 patients with incident LN between 1976-2018. Mean age at diagnosis was 38.4 years (SD 16.24), 76% were female, and 69% non-Hispanic White. Average annual LN incidence between 1976 and 2018 was 1 per 100,000 population (95%CI 0.8-1.3) and highest in the 30-39 age group. Between 1976-1989 and 2000-2018 periods, overall incidence of LN increased from 0.7 to 1.3 per 100,000, but this was not statistically significant. Estimated LN prevalence increased from 16.8 in 1985 to 21.2 per 100,000 in 2015. LN had an SMR of 6.33 (95% CI 3.81-9.89) with no improvement in mortality gap in the last four decades. At 10 years, survival was 70%, and 13% had ESRD.

CONCLUSION: The incidence and prevalence of LN in this area increased in the last four decades. LN patients have poor outcomes with high rates of ESRD and mortality rates six times that of the general population. This article is protected by copyright. All rights reserved.

PMID:36227575 | DOI:10.1002/art.42375

Pulm Ther. 2022 Oct 13. doi: 10.1007/s41030-022-00200-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Aspiration pneumonia is the predominant form of pneumonia in the elderly. Low oral intake levels and malnutrition have been reported to be associated with increased mortality and loss of function in aspiration pneumonia. However, the relationship between start of feeding and readmission, which is associated with malnutrition and low oral intake levels, has not been reported. The purpose of this study was to clarify the relationship between start of feeding and functional prognosis in aspiration pneumonia.

METHODS: Patients’ basic information, comorbidities, severity of pneumonia, swallowing function, time from admission to the start of feeding, geriatric nutritional risk index (GNRI), readmission, and Barthel index (BI) were evaluated in 160 patients. The patients were divided into two groups-a readmission group and a non-readmission group-and statistical verification was performed.

RESULTS: The readmission group was 62 cases (38.8%). Univariate analysis showed that the time from admission to the start of feeding was significantly longer in the readmission group (p < 0.001). Age was significantly higher and nutrition parameters were lower in the readmission group (p = 0.001, 0.006). Furthermore, according to logistic regression analysis, readmission was associated with age (odds ratio, 1.063; p = 0.007; 95% confidence interval (CI) 1.017-1.111) and time from admission to the start of feeding (odds ratio 1.080; p < 0.001; 95% CI 1.025-1.137).

CONCLUSION: The time from admission to the start of feeding was significantly longer in the readmitted patients. A comprehensive intervention with multidisciplinary collaboration should be performed from the early stage of hospitalization.

TRIAL REGISTRATION: This study is registered in the UMIN-Clinical Trials Registry (UMIN-CTR). UMIN-CTR meets the criteria of the International Committee of Medical Journal Editors (ICMJE). (Registration number: 000047141).

PMID:36227574 | DOI:10.1007/s41030-022-00200-0

Methods Mol Biol. 2023;2553:325-393. doi: 10.1007/978-1-0716-2617-7_16.

ABSTRACT

Breast cancer is one of the most common cancers in women worldwide, which causes an enormous number of deaths annually. However, early diagnosis of breast cancer can improve survival outcomes enabling simpler and more cost-effective treatments. The recent increase in data availability provides unprecedented opportunities to apply data-driven and machine learning methods to identify early-detection prognostic factors capable of predicting the expected survival and potential sensitivity to treatment of patients, with the final aim of enhancing clinical outcomes. This tutorial presents a protocol for applying machine learning models in survival analysis for both clinical and transcriptomic data. We show that integrating clinical and mRNA expression data is essential to explain the multiple biological processes driving cancer progression. Our results reveal that machine-learning-based models such as random survival forests, gradient boosted survival model, and survival support vector machine can outperform the traditional statistical methods, i.e., Cox proportional hazard model. The highest C-index among the machine learning models was recorded when using survival support vector machine, with a value 0.688, whereas the C-index recorded using the Cox model was 0.677. Shapley Additive Explanation (SHAP) values were also applied to identify the feature importance of the models and their impact on the prediction outcomes.

PMID:36227551 | DOI:10.1007/978-1-0716-2617-7_16

Methods Mol Biol. 2023;2553:221-263. doi: 10.1007/978-1-0716-2617-7_12.

ABSTRACT

Research in synthetic biology and metabolic engineering require a deep understanding on the function and regulation of complex pathway genes. This can be achieved through gene expression profiling which quantifies the transcriptome-wide expression under any condition, such as a cell development stage, mutant, disease, or treatment with a drug. The expression profiling is usually done using high-throughput techniques such as RNA sequencing (RNA-Seq) or microarray. Although both methods are based on different technical approaches, they provide quantitative measures of the expression levels of thousands of genes. The expression levels of the genes are compared under different conditions to identify the differentially expressed genes (DEGs), the genes with different expression levels under different conditions. DEGs, usually involving thousands in number, are then investigated using bioinformatics and data analytic tools to infer and compare their functional roles between conditions. Dealing with such large datasets, therefore, requires intensive data processing and analyses to ensure its quality and produce results that are statistically sound. Thus, there is a need for deep statistical and bioinformatics knowledge to deal with high-throughput gene expression data. This represents a barrier for wet biologists with limited computational, programming, and data analytic skills that prevent them from getting the full potential of the data. In this chapter, we present a step-by-step protocol to perform transcriptome analysis using GeneCloudOmics, a cloud-based web server that provides an end-to-end platform for high-throughput gene expression analysis.

PMID:36227547 | DOI:10.1007/978-1-0716-2617-7_12

Methods Mol Biol. 2023;2553:41-56. doi: 10.1007/978-1-0716-2617-7_3.

ABSTRACT

Machine learning is revolutionizing molecular biology and bioengineering by providing powerful insights and predictions. Massively parallel reporter assays (MPRAs) have emerged as a particularly valuable class of high-throughput technique to support such algorithms. MPRAs enable the simultaneous characterization of thousands or even millions of genetic constructs and provide the large amounts of data needed to train models. However, while the scale of this approach is impressive, the design of effective MPRA experiments is challenging due to the many factors that can be varied and the difficulty in predicting how these will impact the quality and quantity of data obtained. Here, we present a computational tool called FORECAST, which can simulate MPRA experiments based on fluorescence-activated cell sorting and subsequent sequencing (commonly referred to as Flow-seq or Sort-seq experiments), as well as carry out rigorous statistical estimation of construct performance from this type of experimental data. FORECAST can be used to develop workflows to aid the design of MPRA experiments and reanalyze existing MPRA data sets.

PMID:36227538 | DOI:10.1007/978-1-0716-2617-7_3

Lasers Med Sci. 2022 Oct 13. doi: 10.1007/s10103-022-03652-7. Online ahead of print.

ABSTRACT

The effect of near infrared (NIR) laser irradiation on proliferation and osteogenic differentiation of buccal fat pad-derived stem cells and the role of transient receptor potential (TRP) channels was investigated in the current research. After stem cell isolation, a 940 nm laser with 0.1 W, 3 J/cm² was used in pulsed and continuous mode for irradiation in 3 sessions once every 48 h. The cells were cultured in the following groups: non-osteogenic differentiation medium/primary medium (PM) and osteogenic medium (OM) groups with laser-irradiated (L +), without irradiation (L -), laser treated + Capsazepine inhibitor (L + Cap), and laser treated + Skf96365 inhibitor (L + Skf). Alizarin Red staining and RT-PCR were used to assess osteogenic differentiation and evaluate RUNX2, Osterix, and ALP gene expression levels. The pulsed setting showed the best viability results (P < 0.05) and was used for osteogenic differentiation evaluations. The results of Alizarin red staining were not statistically different between the four groups. Osterix and ALP expression increased in the (L +) group. This upregulation abrogated in the presence of Capsazepine, TRPV1 inhibitor (L + Cap); however, no significant effect was observed with Skf96365 (L + Skf).

PMID:36227520 | DOI:10.1007/s10103-022-03652-7