Tag: statistics

Ann Surg Oncol. 2023 Feb 3. doi: 10.1245/s10434-023-13148-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Receipt of chemotherapy is associated with decreased satisfaction after breast surgery, but whether timing as adjuvant versus neoadjuvant (NAC) affects patient-reported outcomes (PROs) is unclear. We examined associations between chemotherapy timing and PROs after breast-conserving surgery (BCS) and mastectomy with immediate reconstruction (M-IR).

METHODS: In this retrospective cohort study of patients with stage I-III breast cancer undergoing chemotherapy between January 2017 and December 2019, we compared satisfaction with breasts (SABTR) and chest physical well-being (PWB-CHEST) between chemotherapy groups in BCS and M-IR cohorts. Median SABTR and PWB-CHEST scores (scale 0-100) were compared between chemotherapy groups at baseline and for 3 years postoperatively. Factors associated with SABTR and PWB-CHEST at 1 and 2 years were assessed with multivariable linear regression.

RESULTS: Overall, 640 patients had BCS and 602 had M-IR; 210 (33%) BCS patients and 294 (49%) M-IR patients had NAC. Following BCS, SABTR was higher than baseline at all postoperative timepoints, whereas 3-year SABTR remained similar to baseline following M-IR, independent of chemotherapy timing. In both surgical cohorts, PWB-CHEST was lowest after NAC at 6 months compared with baseline but was similar to adjuvant counterparts by 3 years. NAC was not a statistically significant predictor of SABTR or PWB-CHEST in either surgical cohort on multivariable analysis.

CONCLUSIONS: For patients with breast cancer who require chemotherapy, neoadjuvant versus adjuvant timing does not impact long-term PROs in this study. These findings may inform shared decision making regarding the sequence of treatment in patients with operable disease.

PMID:36737530 | DOI:10.1245/s10434-023-13148-5

Commun Biol. 2023 Feb 3;6(1):143. doi: 10.1038/s42003-023-04491-0.

ABSTRACT

Human lifespan is reported to be heritable. Although previous genome-wide association studies (GWASs) have identified several loci, a limited number of studies have assessed the genetic associations with the real survival information on the participants. We conducted a GWAS to identify loci associated with survival time in the Japanese individuals participated in the BioBank Japan Project by carrying out sex-stratified GWASs involving 78,029 males and 59,664 females. Of them, 31,324 (22.7%) died during the mean follow-up period of 7.44 years. We found a novel locus associated with survival (BET1L; P = 5.89 × 10^-9). By integrating with eQTL data, we detected a significant overlap with eQTL of BET1L in skeletal muscle. A gene-set enrichment analysis showed that genes related to the BCAR1 protein-protein interaction subnetwork influence survival time (P = 1.54 × 10^-7). These findings offer the candidate genes and biological mechanisms associated with human lifespan.

PMID:36737517 | DOI:10.1038/s42003-023-04491-0

Pharmacoecon Open. 2023 Feb 3. doi: 10.1007/s41669-023-00392-4. Online ahead of print.

ABSTRACT

OBJECTIVES: The treatments for high-grade non-muscle invasive bladder cancer (NMIBC) vary between bladder preserving intravesical approaches and radical cystectomy. The impact of these treatments on health-related quality of life may vary widely. The purpose of this study was to elicit the general public’s perspective on quality of life, measured as utility scores associated with treatment for Bacillus Calmette-Guerin (BCG)-unresponsive NMIBC and disease progression, for supporting economic evaluation of newly developed treatments for NMIBC.

MATERIALS AND METHODS: Part I involved the development and testing of health states describing NMIBC, which was informed by a rapid review, expert input and a patient advisor. Part II involved elicitation of societal utility values for the different health states. Time trade-off (TTO) interviews were conducted with members of the UK general public. Five health states described different NMIBC scenarios including disease recurrence and progression. Participants ranked each health state, followed by the TTO valuation exercise. Descriptors included NMIBC symptom severity, impact and treatment characteristics.

RESULTS: In total, 202 members of the general public participated. The mean age was 46 (standard deviation [SD] 14.6) years. Sample mean (SD) EQ-5D-5L visual analogue scale (VAS) and index scores were 83.2 (12.3) and 0.89 (0.18), respectively. Mean utilities were 0.781 for No High-Grade Recurrence, 0.586 for High-Grade Recurrence, 0.572 for > 1-Year Post-cystectomy and 0.283 for metastatic disease. The First Year Post-cystectomy path health state had a mean utility of 0.288. Pairwise comparisons found statistically significant differences between utilities (p < 0.001), except between High-Grade Recurrence and > 1-Year Post-cystectomy (p = 0.524). There were significant differences in utility scores by age and employment status.

CONCLUSION: This study provides utility scores for health states describing living with NMIBC, which is associated with a significant health-related quality-of-life burden. These values address an existing gap in available data and have the potential to be used in models evaluating the cost-effectiveness of both current and newly developed treatments for bladder cancer.

PMID:36737511 | DOI:10.1007/s41669-023-00392-4

Hepatol Int. 2023 Feb 3. doi: 10.1007/s12072-022-10469-7. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.

APPROACH AND RESULTS: We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at age 17. Next, we performed pyrosequencing validation of loci within the most 100 strongly associated differentially methylated CpG sites (dmCpGs) for which ≥ 2 probes per gene remained significant across four statistical models with a nominal p value < 0.007. EWAS identified dmCpGs related to three genes (ANK1, MIR10a, PTPRN2) that met our criteria for pyrosequencing. Of the dmCpGs and surrounding loci that were pyrosequenced (ANK1 n = 6, MIR10a n = 7, PTPRN2 n = 3), three dmCpGs in ANK1 and two in MIR10a were significantly associated with NAFLD in adolescence. After adjustment for waist circumference only dmCpGs in ANK1 remained significant. These ANK1 CpGs were also associated with γ-glutamyl transferase and alanine aminotransferase concentrations. Three of twenty-two differentially methylated dmCpGs previously associated with adult NAFLD were associated with NAFLD in adolescence (all adjusted p < 2.3 × 10^-3).

CONCLUSIONS: We identified novel DNA methylation loci associated with NAFLD and serum liver biochemistry markers during adolescence, implicating putative dmCpG/gene regulatory pathways and providing insights for future mechanistic studies.

PMID:36737504 | DOI:10.1007/s12072-022-10469-7

Sci Rep. 2023 Feb 3;13(1):1989. doi: 10.1038/s41598-023-28966-6.

ABSTRACT

The objective of this study was to investigate the impact of lactation stage and parity number on fatty acid and non-volatile polar metabolite profiles in sow colostrum and milk using a metabolomics approach. A total number of 63 colostrum, transient and mature milk were collected from primiparous and multiparous Landrace × Yorkshire crossbred sows. Macrochemical, fatty acid and non-volatile polar metabolite compositions of samples were analyzed using infrared spectrometry, gas chromatography coupled with mass-spectrometry and proton nuclear magnetic resonance spectroscopy, respectively. Univariate and multivariate statistical analysis demonstrated significant impacts of lactation stage and parity number on colostrum and milk compositions. Chemometric analysis revealed significant influences of sow parity on the distinction in fatty acid profiles of mature milk while the distinction in non-volatile polar metabolite profiles was more evident in colostrum. Alterations in the concentration of linoleic (C18:2n6), lignoceric (C24:0), behenic (C22:0), caprylic (C8:0) and myristoleic (C14:1) acid together with those of creatine, creatinine phosphate, glutamate and glycolate were statistically suggested to be mainly affected by sow parity number. Variations in the concentration of these compounds reflected the physiological function of sow mammary gland influenced. This information could be applied for feed and feeding strategies in lactating sows and improving lactating performances.

PMID:36737492 | DOI:10.1038/s41598-023-28966-6

Sci Rep. 2023 Feb 3;13(1):2017. doi: 10.1038/s41598-023-28944-y.

ABSTRACT

Genome-wide association studies (GWAS) have dissected numerous genetic factors underlying refractive errors (RE) such as myopia. Despite significant insights into understanding the genetic architecture of RE, few studies have validated and explored the functional role of candidate genes within these loci. To functionally follow-up on GWAS and characterize the potential role of candidate genes on the development of RE, we prioritized nine genes (TJP2, PDE11A, SHISA6, LAMA2, LRRC4C, KCNQ5, GNB3, RBFOX1, and GRIA4) based on biological and statistical evidence; and used CRISPR/cas9 to generate knock-out zebrafish mutants. These mutant fish were screened for abnormalities in axial length by spectral-domain optical coherence tomography and refractive status by eccentric photorefraction at the juvenile (2 months) and adult (4 months) developmental stage. We found a significantly increased axial length and myopic shift in refractive status in three of our studied mutants, indicating a potential involvement of the human orthologs (LAMA2, LRRC4C, and KCNQ5) in myopia development. Further, in-situ hybridization studies showed that all three genes are expressed throughout the zebrafish retina. Our zebrafish models provide evidence of a functional role of these three genes in refractive error development and offer opportunities to elucidate pathways driving the retina-to-sclera signaling cascade that leads to myopia.

PMID:36737489 | DOI:10.1038/s41598-023-28944-y

Br Dent J. 2023 Feb 3. doi: 10.1038/s41415-023-5507-4. Online ahead of print.

ABSTRACT

Aim(s) We tested the following hypotheses: would better oral hygiene self-care (OHS) influence cardiovascular (CVD) mortality? Will using mouthwash in addition to OHS affect CVD mortality? How does mouthwash usage impact the oral microbes?Design and methods Among 354 dentate subjects from the Kuopio Oral Health and Heart study, the association of OHS with CVD mortality was assessed using Cox regression analyses, adjusting for age, sex, smoking, dyslipidemia, diabetes, hypertension and education. Additionally, whether using mouthwash would affect this relationship was evaluated.Results In the multivariable-adjusted models, OHS was associated with a 51% reduction in the risk of CVD mortality (hazard ratio [HR] 0.49 [0.28-0.85]; p = 0.01). Even those who had coronary artery disease at baseline showed a marginally significant benefit (0.50 [0.24-1.06]; p = 0.07). However, mouthwash usage did not change OHS effects (HR = 0.49 [0.27-0.87]; p = 0.01), indicating no additional benefits nor detriments. All tested microbes trended to decrease with mouthwash usage in the short term, but none were statistically significant.Conclusion Good OHS significantly lowered the risk of CVD mortality relative to poor OHS. Mouthwash usage did not show any long-term harm or benefit on CVD mortality beyond the benefits rendered by brushing and flossing.

PMID:36737459 | DOI:10.1038/s41415-023-5507-4

Br Dent J. 2023 Feb 3. doi: 10.1038/s41415-023-5506-5. Online ahead of print.

ABSTRACT

Introduction Rental electronic scooters (e-scooters) were legalised in July 2020 in the UK for use on public roads. This has led to higher numbers of emergency department (ED) attendances for head and neck injuries managed by the oral and maxillofacial surgical (OMFS) department.Aim The aim of this research is to assess the increase in e-scooter injuries requiring OMFS input and analyse factors and management associated.Method Data were collected over a 24-month period. A total of 212 e-scooter-related ED presentations were recorded, with 34 patients requiring input from the OMFS department. For the patients referred to OMFS, numerical and categorical factors used independent T-tests and one-way Analysis of Variance tests, respectively, to determine statistical significance at the 5% confidence level (p <0.05).Results The mean age was 32.8 years (SD = 15.9) in a predominately male cohort (79.4%). Alcohol intoxication was observed in 55.8% of accidents. Injuries were most common on Saturdays (41.2%). Soft tissue injuries were present in 64.7% of patients, bony injuries in 38.2% of patients and dental injuries in 11.8% of patients. Imaging was required for 76.5% of patients. In total, 44% of patients required surgical treatment, 5.9% required major surgery and 38.2% required minor surgery.Conclusion This research supports the literature suggesting significant growth in e-scooter-related injuries and their associated burden of conditions managed by the OMFS department.

PMID:36737457 | DOI:10.1038/s41415-023-5506-5

J Sleep Res. 2023 Feb 3:e13829. doi: 10.1111/jsr.13829. Online ahead of print.

ABSTRACT

The purpose of this study was to investigate how the blood pressure increase observed during menopausal transition is affected by sleep-disordered breathing and the menopause itself. Further, we aimed to find new sleep-disordered breathing related markers that would predict the development of hypertension. Sixty-four community-dwelling premenopausal women aged 45-47 years were studied. Polysomnography, serum follicle stimulating hormone, forced expiratory volume in 1 s, and a physical examination were performed at baseline and again after 10 years of follow-up. Indices for sleep apnea/hypopnea and inspiratory flow-limitation were determined. Regression models were used to study the relationships between variables. Changes in the apnea-hypopnea index or serum follicle stimulating hormone were not significant for blood pressure change. An increase in morning blood pressure during the follow-up period was associated with a body mass-index increase. An increase in evening blood pressure was associated with an increase in inspiratory flow-limitation during non-rapid eye movement sleep. Incident hypertension during the follow-up was associated with hypopnea (median hypopnea index 7.6/h, p = 0.048) during rapid eye movement sleep at baseline. Users of menopausal hormone therapy had a lower rapid eye movement sleep apnea-hypopnea index (1.6/h vs. 6.9/h, p = 0.026) at baseline whereas at follow-up users and non-users did not differ in any way. The progression of menopause or the use of menopausal hormone therapy had a minimal effect on blood pressure in our population. The effects of inspiratory flow-limitation on blood pressure profile should be studied further.

PMID:36737407 | DOI:10.1111/jsr.13829

Am J Orthod Dentofacial Orthop. 2023 Feb 1:S0889-5406(22)00711-9. doi: 10.1016/j.ajodo.2022.10.021. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to assess and compare the duration and outcomes of orthodontic treatment with conventional and self-ligating lingual fixed appliances with the American Board of Orthodontics (ABO) Objective Grading System.

METHODS: Thirty consecutive patients with a complete dentition and Angle Class I malocclusion treated with a conventional lingual bracket system (STb; Ormco, Glendora, Calif) or self-ligating lingual bracket system (GC Experience-L; GC Orthodontics, Breckerfeld, Germany) were included. The occlusal outcome was assessed with the ABO instrument. The treatment duration and ABO scores of the 2 groups were recorded. Statistical analyses were evaluated using independent-sample t tests.

RESULTS: The conventional group had a mean treatment time of 2.10 ± 0.69 years, and the self-ligating group had a treatment duration of 1.68 ± 0.48 years (P >0.05). The mean posttreatment ABO scores in the conventional group were 20.23 ± 5.13, and the mean posttreatment ABO scores in the self-ligating group were 21.00 ± 5.66. No difference was found between the groups regarding the criteria of ABO (P >0.05). The highest scores were given in the assessment of buccolingual inclinations in both conventional and self-ligating lingual bracket groups.

CONCLUSIONS: The design of the lingual appliances used in this study did not influence the treatment duration and the total ABO scores in treating patients with a Class I relationship in this sample. Both types of lingual brackets were especially deficient in correcting buccolingual inclinations. The strengths were their ability to close spaces and correct anterior rotations and overjet regardless of the bracket types.

PMID:36737396 | DOI:10.1016/j.ajodo.2022.10.021