Tag: statistics

Nat Commun. 2021 Mar 12;12(1):1639. doi: 10.1038/s41467-021-21975-x.

ABSTRACT

Conventional human leukocyte antigen (HLA) imputation methods drop their performance for infrequent alleles, which is one of the factors that reduce the reliability of trans-ethnic major histocompatibility complex (MHC) fine-mapping due to inter-ethnic heterogeneity in allele frequency spectra. We develop DEEP*HLA, a deep learning method for imputing HLA genotypes. Through validation using the Japanese and European HLA reference panels (n = 1,118 and 5,122), DEEP*HLA achieves the highest accuracies with significant superiority for low-frequency and rare alleles. DEEP*HLA is less dependent on distance-dependent linkage disequilibrium decay of the target alleles and might capture the complicated region-wide information. We apply DEEP*HLA to type 1 diabetes GWAS data from BioBank Japan (n = 62,387) and UK Biobank (n = 354,459), and successfully disentangle independently associated class I and II HLA variants with shared risk among diverse populations (the top signal at amino acid position 71 of HLA-DRβ1; P = 7.5 × 10^-120). Our study illustrates the value of deep learning in genotype imputation and trans-ethnic MHC fine-mapping.

PMID:33712626 | DOI:10.1038/s41467-021-21975-x

Spinal Cord Ser Cases. 2021 Mar 12;7(1):20. doi: 10.1038/s41394-021-00384-8.

ABSTRACT

STUDY DESIGN: Pre-post intervention.

OBJECTIVE: To explore the potential effect of exoskeletal-assisted walking (EAW) on seated balance for persons with chronic motor complete spinal cord injury (SCI).

SETTING: A SCI research center.

METHODS: Eight participants who were over 18 years of age with chronic SCI and used a wheelchair for mobility were enrolled. Seven able-bodied participants were used for normal seated balance comparative values. Participants with chronic SCI received supervised EAW training using a powered exoskeleton (ReWalk^TM) for a median 30 sessions (range from 7 to 90 sessions). Before and after EAW training, seated balance testing outcomes were collected using computerized dynamic posturography, providing measurements of endpoint excursion (EPE), maximal excursion (MXE), and directional control (DCL). Modified functional reach test (MFRT) and the sub-scales of physical functioning and role limitations due to physical health from the Short Form (36) Health Survey (SF-36) were used to identify changes in functional activities.

RESULTS: After EAW training, seated balance significantly improved in total-direction EPE and MXE (P < 0.01 and P < 0.017 respectively). The results of MFRT and sub-scales of physical functioning and role limitations due to physical health improved after EAW training but were not statistically significant.

CONCLUSIONS: EAW training may have the potential to improve seated balance for persons with chronic motor complete SCI. Due to the limitations of the study, such as small sample size and lack of a control group, further studies are needed to clarify the effect of improving seated balance through EAW training.

PMID:33712561 | DOI:10.1038/s41394-021-00384-8

BMJ Open. 2021 Mar 12;11(3):e043042. doi: 10.1136/bmjopen-2020-043042.

ABSTRACT

INTRODUCTION: Pressure ulcers are serious and potentially life-threatening problems across all age groups and across all medical specialties and care settings. The hospitalised elderly population is the most common group to develop pressure ulcers. This study aims to systematically review studies implementing pressure ulcer prevention strategies recommended in the Pressure Ulcer Prevention Practice Guidelines for the prevention of pressure ulcers among hospitalised elderly patients globally.

METHODS AND ANALYSIS: A systematic review of all studies that have assessed the use of pressure ulcer prevention strategies in hospital settings among hospitalised elderly patients shall be conducted. A comprehensive search of all published articles in Medline Ovid, Cumulative Index to Nursing and Allied Health Literature, PubMed, Embase, Cochrane library, Scopus and Web of Science will be done using terms such as pressure ulcers, prevention strategies, elderly patients and hospital. Studies will be screened for eligibility through title, abstract and full text by two independent reviewers. Study quality and risk of bias will be assessed using the Joanna Briggs Institute for Meta-Analysis of Statistics Assessment and Review Instrument. If sufficient data are available, a meta-analysis will be conducted to synthesise the effect size reported as OR with 95% CIs using both fixed and random effect models. I² statistics and visual inspection of the forest plots will be used to assess heterogeneity and identify the potential sources of heterogeneity. Publication bias will be assessed by visual inspections of funnel plots and Egger’s test.

ETHICS AND DISSEMINATION: No formal ethical approval or consent is required as no primary data will be collected. We aim to publish the research findings in a peer-reviewed scientific journal to promote knowledge transfer, as well as in conferences, seminars, congresses or symposia in a traditional manner.

PROSPERO REGISTRATION NUMBER: CRD42019129088.

PMID:33712523 | DOI:10.1136/bmjopen-2020-043042

J Nucl Med. 2021 Mar 12:jnumed.120.261866. doi: 10.2967/jnumed.120.261866. Online ahead of print.

ABSTRACT

Purpose: The aim of this study was to assess a) the impact of forced diuresis with early furosemide injection on the detection rate of local recurrence (LR) in prostate cancer (PC) patients with biochemical recurrence (BR) referred for ⁶⁸Ga-labelled Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (⁶⁸Ga-PSMA-11) Positron Emission Tomography/Computed Tomography (PET/CT) and b) whether intravenous administration of furosemide shortly after tracer injection increases renal wash-out of ⁶⁸Ga-PSMA-11 before it binds to the PSMA-receptor with possible influence on biodistribution and intensity of tracer uptake in organs with physiologic tracer accumulation. Materials and Methods: In a retrospective analysis two different groups with 220 prostate cancer patients each, referred for ⁶⁸Ga-PSMA-11 PET/CT because of biochemical recurrence after primary therapy, were compared: patients of group one (median prostate specific antigen (PSA): 1.30 ng/ml) receiving no preparation prior to imaging, whereas patients in group two (median PSA: 0.82 ng/ml) were injected with 20 mg furosemide and 500 ml sodium chloride (NaCl 0.9%) immediately after tracer injection. Presence of local recurrence was assessed visually. In addition, intensity of tracer accumulation in organs with physiologic tracer uptake was evaluated standardized uptake value. Results: The detection rate of lesions judged positive for local recurrence was significantly higher in patients receiving furosemide compared to patients without preparation: 56 cases (25.5%) vs 38 cases (17.3%), respectively (P = 0.048). Median maximum standardized uptake values (SUV_max) of organs with physiologic uptake of ⁶⁸Ga-PSMA-11 in group one and two were: urinary bladder (63.0 vs 8.9), kidney (55.6 vs 54.5), liver (9.9 vs 9.4), spleen (11.2 vs 11.9), small bowel (16.2 vs 17.1), parotid gland (19.2 vs 19.6), lacrimal gland (8.9 vs 10.9), blood pool activity (2.2 vs 2.3), muscle (1.0 vs 1.1) and bone (1.6 vs 1.6). Apart from bladder activity, no significant reduction of tracer accumulation was found in the patient group receiving furosemide. Conclusion: Injection of 20 mg furosemide at the timepoint of radiotracer administration significantly increases the detection rate of local recurrence in prostate cancer patients with biochemical recurrence referred for ⁶⁸Ga-PSMA-11 PET/CT. As intensity of ⁶⁸Ga-PSMA-11-uptake in organs with physiologic uptake is not significantly reduced, a negative impact of early furosemide injection on targeting properties and biodistribution of ⁶⁸Ga-PSMA-11 seems unlikely.

PMID:33712533 | DOI:10.2967/jnumed.120.261866

J Nucl Med. 2021 Mar 12:jnumed.120.259242. doi: 10.2967/jnumed.120.259242. Online ahead of print.

ABSTRACT

Objective: The aim of this study was to assess the added diagnostic value of contrast-enhanced CT (CECT) as compared to unenhanced CT (UECT) in PET/CT staging and treatment response assessment of ¹⁸FDG-avid lymphomas. Methods: 170 PET/UECT followed by CECT scans were prospectively performed for staging (n = 85) and for treatment response assessment (n = 85) of ¹⁸FDG-avid lymphomas, during a single session using an integrated 64-slice PET/CT scanner. CECT and UECT images were evaluated separately by two radiologists, whereas PET images by two nuclear physicians. Nodal and extranodal UECT and CECT findings were classified according to the Lugano criteria, and successively compared with PET/CT results, considered the gold standard. In the analysed groups, the agreement rate with the disease status determined via PET was calculated separately for UECT and CECT using Mc Nemar’s test on paired data. The added value of the contrast medium was shown by the agreement between the PET and CECT results and the lack of agreement between UECT and PET. Results: CECT enabled the identification of additional extranodal lesions (hepatic, muscular and gastric) in only 3 staging group cases (3.5%), indicating different stages as compared to UECT, whereas there was absolute agreement between CECT and UECT in terms of treatment response assessment. The added diagnostic value of CECT was lower than the established threshold for clinical relevance (15%). Mc Nemar’s test indicated no statistical significance in either group. The incidental findings detected by CECT but not UECT were important for clinical management, but not sufficient to alter lymphoma treatment strategy. Conclusion: According to our results, it might be possible to exclude CECT examination of ¹⁸FDG-avid lymphoma from staging and treatment response assessment, with the consequent advantages of reducing radiation exposure and potential contrast-related risks.

PMID:33712534 | DOI:10.2967/jnumed.120.259242

Br J Ophthalmol. 2021 Mar 12:bjophthalmol-2020-317969. doi: 10.1136/bjophthalmol-2020-317969. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: To assess epidemiological tumour features, risk factors, clinical management and outcome of eyelid squamous cell carcinoma (SCC) and changes thereof. Furthermore, we searched for validating predictors of the American Joint Committee on Cancer (AJCC) 8 classification system.

METHODS: We evaluated data of 117 patients with histologically proven eyelid SCC at a large tertiary German university centre between January 2009 and March 2020. This retrospective, monocentric analysis included descriptive statistics and non-parametric tests (p<0.05).

RESULTS: Histologically controlled excision and follow-up was performed in 88 (75.2%) patients. In the remaining patients with higher T-category, individual adjuvant therapy combinations were initiated. We found higher numbers of nodal metastasis and recurrence for male patients and higher T-category (p=0.035, p=0.008 and p=0.001, p<0.001). Recurrence rates proved higher for patients with multiple lesions (p=0.008). Disease-specific survival (DSS) was 95.7% at 2 and 94.9% at 5 years of follow-up. Six patients (5.1%) died from eyelid SCC with nodal metastasis and higher T-category being negative prognostic factors (p<0.001 and p=0.009). Mortality was associated with tumour location in the medial upper eyelid, nodal metastasis being more frequent (p=0.001 and p=0.009) and tumour of the lower eyelid alone as positive predictor (p=0.012). T category differed in 34 (29.1%) patients when comparing AJCC 7 and 8 (p<0.001). Changes in T category as per the AJCC 8 classification resulted in better prediction of DSS (p=0.024).

CONCLUSION: Special attention should be paid to male patients, tumour location in the upper medial eyelid and lymph node diagnostics. Prediction of DSS proved superior as per the AJCC 8 staging system.

PMID:33712477 | DOI:10.1136/bjophthalmol-2020-317969

J Epidemiol Community Health. 2021 Mar 12:jech-2020-215836. doi: 10.1136/jech-2020-215836. Online ahead of print.

ABSTRACT

BACKGROUND: Depression in the perinatal period, during pregnancy or within 1 year of childbirth, imposes a high burden on women with rippling effects through her and her child’s life course. Social support may be an important protective factor, but the complex bidirectional relationship with depression, alongside a paucity of longitudinal explorations, leaves much unknown about critical windows of social support exposure across the perinatal period and causal impacts on future depressive episodes.

METHODS: This study leverages marginal structural models to evaluate associations between longitudinal patterns of perinatal social support and subsequent maternal depression at 6 and 12 months postpartum. In a cohort of women in rural Pakistan (n=780), recruited in the third trimester of pregnancy and followed up at 3, 6 and 12 months postpartum, we assessed social support using two well-validated measures: the Multidimensional Scale of Perceived Social Support (MSPSS) and the Maternal Social Support Index (MSSI). Major depressive disorder was assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM IV).

RESULTS: High and sustained scores on the MSPSS through the perinatal period were associated with a decreased risk of depression at 12 months postpartum (0.35, 95% CI: 0.19 to 0.63). Evidence suggests the recency of support also matters, but estimates are imprecise. We did not find evidence of a protective effect for support based on the MSSI.

CONCLUSIONS: This study highlights the protective effect of sustained social support, particularly emotional support, on perinatal depression. Interventions targeting, leveraging and maintaining this type of support may be particularly important for reducing postpartum depression.

PMID:33712512 | DOI:10.1136/jech-2020-215836

J Investig Med. 2021 Mar 12:jim-2021-001800. doi: 10.1136/jim-2021-001800. Online ahead of print.

ABSTRACT

We performed a retrospective study of cardiology telemedicine visits at a large academic pediatric center between 2016 and 2019 (pre COVID-19). Telemedicine patient visits were matched to data from their previous in-person visits, to evaluate any significant differences in total charge, insurance compensation, patient payment, percent reimbursement and zero reimbursement. Miles were measured between patient’s home and the address of previous visit. We found statistically significant differences in mean charges of telemedicine versus in-person visits (2019US$) (172.95 vs 218.27, p=0.0046), patient payment for telemedicine visits versus in-person visits (2019US$) (11.13 vs 62.83, p≤0.001), insurance reimbursement (2019US$) (65.18 vs 110.85, p≤0.001) and insurance reimbursement rate (43% vs 61%, p=0.0029). Rate of zero reimbursement was not different. Mean distance from cardiology clinic was 35 miles. No adverse outcomes were detected. This small retrospective study showed cost reduction and a decrease in travel time for families participating in telemedicine visits. Future work is needed to enhance compensation for telemedicine visits.

PMID:33712521 | DOI:10.1136/jim-2021-001800

Eur Urol Focus. 2021 Mar 9:S2405-4569(21)00059-6. doi: 10.1016/j.euf.2021.03.002. Online ahead of print.

ABSTRACT

BACKGROUND: Open radical cystectomy (ORC) is still considered the reference approach for RC, although robot-assisted RC (RARC) has recently gained in popularity. There are literature reports on perioperative and oncologic outcomes of RARC, but functional outcomes and aspects related to health-related quality of life (HRQoL) remain unexplored.

OBJECTIVE: To report an interim analysis of 1-yr HRQoL outcomes from an ongoing randomised controlled trial comparing ORC and RARC with totally intracorporeal urinary diversion (iUD) (ClinicalTrials.gov NCT03434132).

DESIGN, SETTING, AND PARTICIPANTS: Patients with cT2-4N0M0 non-muscle-invasive bladder cancer or bacillus Calmette-Guérin failure who were candidates for cystectomy with curative intent without absolute contraindications to robotic surgery were included. A covariate adaptive randomisation based on the following variables was used: body mass index, American Society of Anesthesiologists score, preoperative haemoglobin level, cT stage, type of UD, and neoadjuvant chemotherapy.

INTERVENTION: ORC or RARC with iUD.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data from patient-reported European Organization for Research and Treatment of Cancer QoL questionnaires (QLQ-C30 and QLQ-BLM30) were collected at baseline and 1 yr. Continuous variables were compared using the Student t test.

RESULTS AND LIMITATIONS: At interim analysis, 51 patients (24 RARC, 27 ORC) were analysed. Overall, both groups reported significant worsening of body image and physical and sexual functions (all p ≤ 0.012). Patients receiving ORC were more likely to report significant 1-yr impairment of role functioning, symptoms scales and bowel symptoms (all p ≤ 0.048). Patients receiving RARC reported significant impairment of urinary symptoms and problems (p = 0.018).

CONCLUSIONS: This study suggests equivalence between RARC-iUD and ORC for most HRQoL domains. Notwithstanding, after 1 yr patients receiving ORC were more likely to experience a decline in role functioning and higher symptoms scale, while RARC-iUD patients were more likely to report significant increases in urinary symptoms and problems.

PATIENT SUMMARY: We analysed 1-year data for health-related quality of life from an ongoing trial comparing open and robotic surgery for removal of the bladder in patients with bladder cancer. Robotic surgery seems to provide benefits for most quality-of-life items on patient-reported questionnaires. This trial is registered at ClinicalTrial.gov as NCT03434132.

PMID:33712389 | DOI:10.1016/j.euf.2021.03.002

Appl Environ Microbiol. 2021 Mar 12:AEM.02753-20. doi: 10.1128/AEM.02753-20. Online ahead of print.

ABSTRACT

A controlled greenhouse study was performed to determine the effect of manure or compost amendments, derived during or in absence of antibiotic treatment of beef and dairy cattle, on radish taproot-associated microbiota and indicators of antibiotic resistance when grown in different soil textures. Bacterial beta-diversity, determined by 16S rRNA gene amplicon sequencing, bifurcated according to soil texture (p<0.001, R=0.501). There was a striking cross-effect in which raw manure from antibiotic-treated and antibiotic-free beef and dairy cattle added to loamy sand (LS) elevated relative (16S rRNA gene-normalized) (by 0.9-1.9 log₁₀) and absolute (per radish) (by 1.1-3.0 log₁₀) abundances of intI1 (an integrase gene and indicator of mobile multi-antibiotic resistance) on radishes at harvest compared to chemical fertilizer only control conditions (p<0.001). Radishes tended to carry fewer copies of intI1 and sul1 when grown in silty clay loam than LS. Composting reduced relative abundance of intI1 on LS-grown radishes (0.6-2.4 log₁₀ decrease vs corresponding raw manure; p<0.001). Effects of antibiotic use were rarely discernable. Heterotrophic plate count bacteria capable of growth on media containing tetracycline, vancomycin, sulfamethazine, or erythromycin tended to increase on radishes grown in turned composted antibiotic-treated dairy or beef control (no antibiotics) manures relative to the corresponding raw manure in LS (0.8-2.3 log₁₀ increase; p<0.001), suggesting that composting sometimes enriches cultivable bacteria with phenotypic resistance. This study demonstrates that combined effects of soil texture and manure-based amendments influence the microbiota of radish surfaces and markers of antibiotic resistance illuminating future research directions for reducing agricultural sources of antibiotic resistance.ImportanceIn working towards a comprehensive strategy to combat the spread of antibiotic resistance, potential farm-to-fork routes of dissemination are gaining attention. The effects of pre-harvest factors on the microbiota and corresponding antibiotic resistance indicators on the surfaces of produce commonly eaten raw is of special interest. Here we conducted a controlled greenhouse study, using radishes as a root vegetable grown in direct contact with soil, and compared the effects of manure-based soil amendments, antibiotic use in the cattle from which the manure was sourced, composting of the manure, and soil texture, with chemical fertilizer only as a control. We noted significant effects of amendment type and soil texture on the composition of the microbiota and genes used as indicators of antibiotic resistance on radish surfaces. The findings take a step towards identifying agricultural practices that aid in reducing carriage of antibiotic resistance and corresponding risks to consumers.

PMID:33712421 | DOI:10.1128/AEM.02753-20