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Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images

PLoS Genet. 2021 May 12;17(5):e1009497. doi: 10.1371/journal.pgen.1009497. Online ahead of print.

ABSTRACT

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function.

PMID:33979322 | DOI:10.1371/journal.pgen.1009497

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Serum MicroRNA Transcriptomics and Acute Rejection or Recurrent Hepatitis C Virus in Human Liver Allograft Recipients: A Pilot Study

Transplantation. 2021 May 11. doi: 10.1097/TP.0000000000003815. Online ahead of print.

ABSTRACT

BACKGROUND: Acute rejection (AR) and recurrent HCV (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management.

METHODS: We performed small RNA sequencing and miRNA microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized RT-qPCR assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients. The association between biopsy diagnosis and miRNA abundance was analyzed by logistic regression and calculating the area under the receiver operating characteristic curve.

RESULTS: Nine miRNAs- miR-22, miR-34a, miR-122, miR-148a, miR-192, miR-193b, miR-194, miR-210 and miR-885-5p- were identified by both sRNA-seq and TLDA to be associated with NINV-AR. Logistic regression analysis of absolute levels of miRNAs and goodness-of-fit of predictors identified a linear combination of miR-34a + miR-210 (P<0.0001) as the best statistical model and miR-122 + miR-210 (P<0.0001) as the best model that included miR-122. A different linear combination of miR-34a + miR-210 (P<0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft inflammation, and miR-34a + miR-122 (P<0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft fibrosis.

CONCLUSIONS: Circulating levels of miRNAs, quantified using customized RT-qPCR assays, may offer a rapid and noninvasive means of diagnosing AR in human liver allografts and for discriminating AR from intragraft inflammation or fibrosis due to recurrent HCV.Supplemental Visual Abstract; http://links.lww.com/TP/C231.

PMID:33979314 | DOI:10.1097/TP.0000000000003815

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Patient-reported recovery in upper abdominal cancer surgery care: A prospective study

Sci Prog. 2021 Apr-Jun;104(2):368504211016938. doi: 10.1177/00368504211016938.

ABSTRACT

The study aimed to describe and analyse patient-reported recovery in patients after upper abdominal cancer surgery. This study had a quantitative design and patients were consecutively included in a university hospital in southern Sweden. Twenty-four patients answered the Postoperative Recovery Profile (PRP) questionnaire at three measurement points. All five dimensions were affected. In the physical symptoms dimension, the majority of patients reported a lack of energy upon discharge. High levels of anxiety were reported. Over 50% of patients reported some degree of depressed mood at all three measurement points. In the social dimension, the majority of patients reported some degree of being dependent on help from others in everyday life at 4 weeks after discharge. Few patients are fully recovered at 4 weeks after discharge. Individual patient-reported recovery estimates may be valuable in identifying and planning interventions tailored to each patient’s needs throughout the care process.

PMID:33979255 | DOI:10.1177/00368504211016938

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Validity and reliability of the QLQ-MY20 module for assessing the health-related quality of life in Brazilians with multiple myeloma

Curr Med Res Opin. 2021 May 12:1. doi: 10.1080/03007995.2021.1929136. Online ahead of print.

ABSTRACT

PURPOSE: Multiple myeloma (MM) is a rare but treatable hematological cancer, which makes Health-Related Quality of Life (HRQoL) an important patient-report outcome measure in clinical studies. The Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY20) was developed by the European Organization for Research and Treatment of Cancer (EORTC) to measure HRQoL in people with MM. However, the Brazilian Portuguese version of QLQ-MY20 has not yet been validated for Brazil. This study aimed to evaluate the validity and reliability of the instrument for application in Brazilian patients with MM.

METHODS: This is a cross-sectional methodological study with patients seen in health services in Belo Horizonte, Brazil. The variables were collected through face-to-face interviews with the QLQ-MY20 instrument and complemented with data from medical records. Content validity analyses (content validity coefficient – CVC; correctness ratio), convergent and divergent validity (Spearman’s correlation coefficient – CC), internal consistency, and temporal reproducibility (test-retest; intraclass correlation coefficient – ICC) were performed.

RESULTS: 225 patients were included and 71.1% were older than 60. The analysis of the judging committee showed adequate content validity. We observed mainly a good internal consistency of the items and good discrimination power in the convergent and divergent validity. High ICC values were observed through the test-retest, and there was no difference in the scores between the two moments, which shows good temporal stability of the instrument.

CONCLUSION: The study allowed us to conclude that the Brazilian version of the QLQ-MY20 module is valid and reliable, and thus suitable for application in Brazilians living with MM.

PMID:33979261 | DOI:10.1080/03007995.2021.1929136

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Urinary NGAL as a Diagnostic and Prognostic Marker for Acute Kidney Injury in Cirrhosis: A Prospective Study

Clin Transl Gastroenterol. 2021 May 11;12(5):e00359. doi: 10.14309/ctg.0000000000000359.

ABSTRACT

INTRODUCTION: Urinary neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in differentiating acute tubular necrosis (ATN) from other types of acute kidney injuries (AKIs) in cirrhosis, particularly hepatorenal syndrome (HRS). However, NGAL is not currently available in clinical practice in North America.

METHODS: Urinary NGAL was measured in a prospective cohort of 213 US hospitalized patients with decompensated cirrhosis (161 with AKI and 52 reference patients without AKI). NGAL was assessed for its ability to discriminate ATN from non-ATN AKI and to predict 90-day outcomes.

RESULTS: Among patients with AKI, 57 (35%) had prerenal AKI, 55 (34%) had HRS, and 49 (30%) had ATN, with a median serum creatinine of 2.0 (interquartile range 1.5, 3.0) mg/dL at enrollment. At an optimal cutpoint of 244 μg/g creatinine, NGAL distinguished ATN (344 [132, 1,429] μg/g creatinine) from prerenal AKI (45 [0, 154] μg/g) or HRS (110 [50, 393] μg/g; P < 0.001), with a C statistic of 0.762 (95% confidence interval 0.682, 0.842). By 90 days, 71 of 213 patients (33%) died. Higher median NGAL was associated with death (159 [50, 865] vs 58 [0, 191] μg/g; P < 0.001). In adjusted and unadjusted analysis, NGAL significantly predicted 90-day transplant-free survival (P < 0.05 for all Cox models) and outperformed Model for End-Stage Liver Disease score by C statistic (0.697 vs 0.686; P = 0.04), net reclassification index (37%; P = 0.008), and integrated discrimination increment (2.7%; P = 0.02).

DISCUSSION: NGAL differentiates the type of AKI in cirrhosis and may improve prediction of mortality; therefore, it holds potential to affect management of AKI in cirrhosis.

PMID:33979307 | DOI:10.14309/ctg.0000000000000359

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Child mortality associated with maternal HIV status: a retrospective analysis in Rwanda, 2005-2015

BMJ Glob Health. 2021 May;6(5):e004398. doi: 10.1136/bmjgh-2020-004398.

ABSTRACT

INTRODUCTION: Child mortality remains highest in regions of the world most affected by HIV/AIDS. The aim of this study was to assess child mortality rates in relation to maternal HIV status from 2005 to 2015, the period of rapid HIV treatment scale-up in Rwanda.

METHODS: We used data from the 2005, 2010 and 2015 Rwanda Demographic Health Surveys to derive under-2 mortality rates by survey year and mother’s HIV status and to build a multivariable logistic regression model to establish the association of independent predictors of under-2 mortality stratified by mother’s HIV status.

RESULTS: In total, 12 010 live births were reported by mothers in the study period. Our findings show a higher mortality among children born to mothers with HIV compared with HIV negative mothers in 2005 (216.9 vs 100.7 per 1000 live births) and a significant reduction in mortality for both groups in 2015 (72.0 and 42.4 per 1000 live births, respectively). In the pooled reduced multivariable model, the odds of child mortality was higher among children born to mothers with HIV, (adjusted OR, AOR 2.09; 95% CI 1.57 to 2.78). The odds of child mortality were reduced in 2010 (AOR 0.69; 95% CI 0.59 to 0.81) and 2015 (AOR 0.35; 95% CI 0.28 to 0.44) compared with 2005. Other independent predictors of under-2 mortality included living in smaller families of 1-2 members (AOR 5.25; 95% CI 3.59 to 7.68), being twin (AOR 4.93; 95% CI 3.51 to 6.92) and being offspring from mothers not using contraceptives at the time of the survey (AOR 1.6; 95% CI 1.38 to 1.99). Higher education of mothers (completed primary school: (AOR 0.74; 95% CI 0.64 to 0.87) and secondary or higher education: (AOR 0.53; 95% CI 0.38 to 0.74)) was also associated with reduced child mortality.

CONCLUSIONS: This study shows an important decline in under-2 child mortality among children born to both mothers with and without HIV in Rwanda over a 10-year span.

PMID:33975886 | DOI:10.1136/bmjgh-2020-004398

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Improving Holistic Care Skills for Advanced Practice Registered Nurses: Integration of a Complementary and Alternative Medicine Course into a Doctor of Nursing Practice Curriculum

J Dr Nurs Pract. 2021 May 11:JDNP-D-20-00077. doi: 10.1891/JDNP-D-20-00077. Online ahead of print.

ABSTRACT

BACKGROUND: Complementary alternative medicine (CAM) is an expanding domain of healing practices harmonized with Western medicine to provide comprehensive treatment of individuals as holistic beings. Patients and healthcare providers worldwide are increasingly inviting and employing CAM practices into healthcare delivery routines. Implementation of courses to introduce CAM into Advanced Practice Registered Nurse (APRN) programs exposes future practitioners to current best practices for integrative treatment strategies and encourages consideration when developing a holistic patient-centered care plan.

OBJECTIVE/METHODS: A case presentation of an interprofessional CAM course delivered to military graduate nursing students with a pretest posttest course survey to evaluate student’s confidence and knowledge of CAM theory and practices. The format included online modules, evidence-based literature critique, knowledge checks, and an immersive hands-on immersion experience.

RESULTS: A total of 240 pre-/postcourse surveys were completed by military graduate nursing students (N = 140) participating in a CAM course. Statistically significant increases in CAM knowledge, communication, and skills confidence levels were found. Following participation in the course, nearly all students (97%) agreed CAM is important and benefits future advanced practice.

CONCLUSION/NURSING IMPLICATIONS: CAM is a compendium of holistic healing modalities increasingly being utilized by patients worldwide with similar requests for alternative care techniques from healthcare providers. Military APRN students participating in a CAM course increased knowledge and confidence, and garnered appreciation for an expanded skill set to augment future practice. Case presentation is compelling for standard inclusion of CAM and similar graduate interprofessional courses into all APRN programs.

PMID:33975904 | DOI:10.1891/JDNP-D-20-00077

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Histological background of dedifferentiated solitary fibrous tumour

J Clin Pathol. 2021 May 11:jclinpath-2020-207311. doi: 10.1136/jclinpath-2020-207311. Online ahead of print.

ABSTRACT

AIMS: Dedifferentiation is a histological phenomenon characterised by abrupt transition of histology to a sarcomatous component with high-grade malignant potential in solitary fibrous tumour (SFT). The authors histologically reviewed SFT cases to reveal the histological background of dedifferentiated SFTs.

METHODS: Clinicopathological and histopathological findings of 145 SFT cases were reviewed. Immunohistochemical staining and genetic analysis were also performed.

RESULTS: The non-dedifferentiated components showed a cellular component in 45 of 145 (31%), high mitotic rate (≥4/10 high-powered field) in 12 of 145 (8.2%) tumours, necrosis in 7 of 145 (4.8%) tumours, multinodular growth pattern in 39 of 132 (29.5%) available tumours and intratumoural fibrous septa in 37 of 131 (28.2%). Immunohistochemically, the non-dedifferentiated components were positive for CD34 in 128 of 141 (90.7%), bcl-2 in 101 of 133 (75.9%), nuclear pattern of β-catenin in 64 of 127 (50.3%) and p16 in 22 of 140 (15.7%). Loss of Rb protein expression was detected in 17 of 110 (15.4%) cases. Statistically, cellular component, multinodular structure, p16 overexpression and Rb protein loss were significantly associated with dedifferentiation. Moreover, cellular component and multinodular structure were significantly associated with p16 overexpression and Rb protein loss. All the non-deddifferentiated components showed wild type of p53 expression. The dedifferentiated components of all 10 dedifferentiated tumours presented positivity for p16 in 9 of 10 (90%) and mutational type of p53 in 5 of 10 (50%). Loss of Rb protein expression was detected in 6 of 10 (60%).

CONCLUSIONS: The authors propose that cellular or multinodular transformation may be associated with dedifferentiation. They also suggest that cellular and multinodular transformation may be associated with p16 overexpression and Rb downregulation.

PMID:33975913 | DOI:10.1136/jclinpath-2020-207311

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Distress Thermometer in breast cancer: systematic review and meta-analysis

BMJ Support Palliat Care. 2021 May 11:bmjspcare-2021-002960. doi: 10.1136/bmjspcare-2021-002960. Online ahead of print.

ABSTRACT

OBJECTIVE: This meta-analysis aimed to reach a summarised estimate of distress prevalence screened by Distress Thermometer (DT) among patients with breast cancer and compare different pooled prevalence estimated between different subgroups.

METHODS: Two independent interviewers conducted a systematic search from PubMed, EMBASE, Ovid and Cochrane Library and checked related reviews and meta-analyses for eligible studies. The studies that identified distress of patients with breast cancer with DT were included. After extracting demographic characteristics and distress prevalence, the pooled analysis and the forest plot were completed by using STATA V.12.0 software. We conducted a subgroup analysis based on demographic and methodological characteristics of the studies. The publication bias was estimated by funnel plot.

RESULTS: Seventeen studies describing 3870 patients with breast cancer were included in this meta-analysis. The distress prevalence of patients with breast cancer varied from 25.3% to 71.7% among these studies. The pooled distress prevalence was 50% (95% CI 49% to 52%) for the overall sample. The pooled distress prevalence rates in DT ≥7, DT ≥5 and DT ≥4 subgroups were 37% (95% CI 35% to 40%), 45% (95% CI 40% to 49%) and 62% (95% CI 60% to 65%), respectively. The distress prevalence had statistically significant differences between subgroups, which were differentiated by the initial time of distress identified, papers’ publication time, patients’ average age and country. There was no publication bias among the included studies.

CONCLUSION: The distress prevalence was high among patients with breast cancer. Routine and timely screening of distress for patients with breast cancer is of great significance in oncology management.

PMID:33975827 | DOI:10.1136/bmjspcare-2021-002960

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Impact of three-dimensional chemoradiation on pelvic bone mineral density, low back pain, and disability in cervical cancer: a prospective study

Int J Gynecol Cancer. 2021 May 11:ijgc-2020-002290. doi: 10.1136/ijgc-2020-002290. Online ahead of print.

ABSTRACT

OBJECTIVE: To prospectively analyze the effect of three-dimensional chemoradiation on the bone mineral density of pelvic bones and its association with low back pain and disability in patients with locally advanced cervical cancer.

METHODS: In biopsy proven locally advanced cervical cancer patients, bone mineral density and T scores for lumbar vertebrae 5, dorsal thoracic vertebrae 12, and T scores for the femoral neck were analyzed. Low back pain was scored using the visual analog scale while disability scoring was done using the Oswestry low back pain disability scale. Furthermore, a subgroup analysis for patients (classified according to menopausal status) was performed.

RESULTS: In total, 106 patients were analyzed. A statistically significant decline in mean bone mineral density was observed at all three sites (vertebrae 5 and 12, and the femoral neck) post-chemoradiation therapy compared with pretreatment bone mineral density (0.671 vs 0.828, -2.083 vs -1.531, -2.503 vs -1.626; all p<0.001). Similarly, in subgroup analyses, at all three sites, pre-menopausal patients showed a statistically significant association (0.876 vs 0.697, -1.203 vs -0.2.761, -1.403 vs -2.232; all p<0.001) while a non-significant association was observed for post-menopausal patients at vertebrae 12 (-1.707 vs -1.719; p=0.09) with a statistically significant association at vertebrae 5 and the femoral neck (0.803 vs 0.656, -1.746 vs -2.648; p<0.01). Although statistically significant low back pain and disability scores were observed overall and irrespective of menopausal status, no correlation between bone mineral density and low back pain and disability was observed.

CONCLUSION: Pelvic bone mineral density decreases significantly after chemoradiation, irrespective of menopausal status. However, no correlation with low back pain and disability was observed. Pelvic bone mineral density analysis should be considered before chemoradiation in cervical cancer.

PMID:33975860 | DOI:10.1136/ijgc-2020-002290