Category: Statistics

J Med Imaging Radiat Oncol. 2022 Feb 16. doi: 10.1111/1754-9485.13382. Online ahead of print.

ABSTRACT

INTRODUCTION: Clinical and biochemical assessment and biopsies can miss clinically significant prostate cancers (csPCa) in up to 20% of patients and diagnose clinically insignificant tumours leading to overtreatment. This retrospective study analyses the accuracy of ¹⁸ F-DCFPyL PET/CT in detecting csPCa as a primary diagnostic tool and directly compares it with mpMRI prostate in treatment-naive patients. The two modalities are then correlated to determine whether they are better in combination, than either alone.

METHODS: This is a retrospective dual-institution study of patients who underwent contemporaneous MRI and PSMA-PET between January 2017 and March 2020 with histologic confirmation. The images were re-reviewed and concordance between modalities assessed. Results were compared with histopathology to determine the ability of MRI and PSMA-PET to detect csPCA.

RESULTS: MRI and PSMA-PET detected the same index lesion in 90.8% of cases with a kappa of 0.82. PET detected an additional 6.2% of index lesions which were MRI occult. MRI detected an additional 3.1% which were PET occult. No additional csPCa was identified on pathology which was not seen on imaging. The sensitivity of PSMA-PET in detecting csPCa is 96.7% and that of MRI is 93.4% with no statistically significant difference between the two (P = 0.232). Both modalities detected all four cases of non-csPCa with these being considered false positives.

CONCLUSION: Both mpMRI and 18F-DCFPyL-PSMA-PET/CT have high sensitivity for detecting csPCa with high agreement between modalities. There were no synchronous csPCa lesions detected on pathology that were not detected on imaging too.

PMID:35170858 | DOI:10.1111/1754-9485.13382

Ann Clin Transl Neurol. 2022 Feb 16. doi: 10.1002/acn3.51525. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate whether herpes zoster (HZ) was associated with subsequent increased risk of dementia diagnosis.

METHODS: We conducted a historical cohort study using primary care electronic health records from the Clinical Practice Research Datalink in the United Kingdom. Individuals with incident HZ aged ≥40 years from 2000 to 2017 were matched with up to four individuals without HZ by age, sex, primary care practise and calendar time. The primary outcome was a new diagnosis of all-cause dementia. We used the Cox proportional hazards regression adjusting for demographic, lifestyle and clinical confounders to assess any association between HZ and dementia. We investigated interactions with sex, frailty index and antiviral treatment and conducted various sensitivity analyses.

RESULTS: The cohort comprised 177,144 individuals with HZ and 706,901 matched unexposed individuals (median age 65 years (IQR 55.1-75.0), 40% male) followed for a median duration of 4.6 years (IQR 2.0-8.1). In total, 26,585 (3%) patients had an incident dementia diagnosis recorded and 113,056 patients died (12.8%). HZ was associated with a small reduction in dementia diagnosis (adjusted HR 0.92 (95% CI 0.89-0.95)), occurring predominantly in frail individuals and females. For patients who were fit (578,115, 65%), no association was seen (adjusted HR 0.97, 95% CI 0.92-1.02). There was no association between HZ and a composite outcome of dementia or death (adjusted HR 1.00, 95% CI 0.99-1.02). Dementia risk did not vary by prescription of antiviral agents. Sensitivity analyses showed consistent results.

INTERPRETATION: HZ was not associated with increased dementia diagnosis in a UK primary care-based cohort.

PMID:35170873 | DOI:10.1002/acn3.51525

Plant Genome. 2022 Feb 16:e20194. doi: 10.1002/tpg2.20194. Online ahead of print.

ABSTRACT

Genomic selection (GS) is a predictive methodology that trains statistical machine-learning models with a reference population that is used to perform genome-enabled predictions of new lines. In plant breeding, it has the potential to increase the speed and reduce the cost of selection. However, to optimize resources, sparse testing methods have been proposed. A common approach is to guarantee a proportion of nonoverlapping and overlapping lines allocated randomly in locations, that is, lines appearing in some locations but not in all. In this study we propose using incomplete block designs (IBD), principally, for the allocation of lines to locations in such a way that not all lines are observed in all locations. We compare this allocation with a random allocation of lines to locations guaranteeing that the lines are allocated to the same number of locations as under the IBD design. We implemented this benchmarking on several crop data sets under the Bayesian genomic best linear unbiased predictor (GBLUP) model, finding that allocation under the principle of IBD outperformed random allocation by between 1.4% and 26.5% across locations, traits, and data sets in terms of mean square error. Although a wide range of performance improvements were observed, our results provide evidence that using IBD for the allocation of lines to locations can help improve predictive performance compared with random allocation. This has the potential to be applied to large-scale plant breeding programs.

PMID:35170851 | DOI:10.1002/tpg2.20194

Clin Exp Ophthalmol. 2022 Feb 16. doi: 10.1111/ceo.14060. Online ahead of print.

ABSTRACT

BACKGROUND: Aim of this study was to evaluate the efficacy of a novel algorithm to customise overminus lens (OML) therapy in intermittent exotropia (IXT) based on clinical factors associated with control of the deviation.

METHODS: Clinical parameters in IXT vary among individuals. Based on individual’s physiological factors, an algorithm was developed. Children aged between four and fifteen years with IXT were randomised into OML and observation groups. Participants in the observation group were corrected for any significant refractive error. IXT control score, angle of deviation, refraction, axial length and stereopsis were examined at baseline and follow up ranging between six and fifteen months and compared. Compliance and tolerance to OML was determined by a symptom survey.

RESULTS: The OML power ranged between -1.00D and – 6.25D. Of the total 141 participants (mean age 6.8 ± 2.5 year), 77 were in the OML and 66 were in observation group. IXT control score improved (mean difference – 2.5 ± 1.1; p < 0.001) and angle of deviation reduced (6.9 ± 7.2pd; p < 0.001) significantly in the OML group only. Compliance rate to OML wear was 80%; 90% never or rarely experienced asthenopia symptoms. Slightly greater myopic shift (-0.36 ± 0.53D vs -0.18 ± 0.55D) and change in axial length (0.17 mm vs 0.14 mm) were observed in the OML group, but these differences were not statistically significant.

CONCLUSIONS: A customised overminus lens, calculated using this novel algorithm was effective in improving distance control, angle of deviation and stereopsis. Glasses wear was highly tolerable. This article is protected by copyright. All rights reserved.

PMID:35170837 | DOI:10.1111/ceo.14060

Genet Epidemiol. 2022 Feb 16. doi: 10.1002/gepi.22442. Online ahead of print.

NO ABSTRACT

PMID:35170805 | DOI:10.1002/gepi.22442

Genet Epidemiol. 2022 Feb 16. doi: 10.1002/gepi.22444. Online ahead of print.

ABSTRACT

Large-scale sequencing and genotyping data provide an opportunity to integrate external samples as controls to improve power of association tests. However, due to the systematic differences between genotyped samples from different studies, naively aggregating the controls could lead to inflation in Type I error rates. There has been recent effort to integrate external controls while adjusting for batch effect, such as the integrating External Controls into Association Test (iECAT) and its score-based single variant tests. Building on the original iECAT framework, we propose an iECAT-Score region-based test that increases power for rare-variant tests when integrating external controls. This method assesses the systematic batch effect between internal and external samples at each variant and constructs compound shrinkage score statistics to test for the joint genetic effect within a gene or a region, while adjusting for covariates and population stratification. Through simulation studies, we demonstrate that the proposed method controls for Type I error rates and improves power in rare-variant tests. The application of the proposed method to the association studies of age-related macular degeneration (AMD) from the International AMD Genomics Consortium and UK Biobank revealed novel rare-variant associations in gene DXO. Through the incorporation of external controls, the iECAT methods offer a powerful suite to identify disease-associated genetic variants, further shedding light on future directions to investigate roles of rare variants in human diseases.

PMID:35170803 | DOI:10.1002/gepi.22444

Environ Toxicol Chem. 2022 Feb 16. doi: 10.1002/etc.5309. Online ahead of print.

ABSTRACT

This project has generated a workflow based on non-target analysis (NTA) using Compound Discoverer (CD) v. 3.1 to characterize a set of source-discriminating compounds identified from water samples from locations in South Florida, particularly those describing a freshwater environment (Everglades-based), urban impacted areas (septic tank driven), and coastal (Biscayne Bay) endmembers in and around the Charles Deering Estate property in the Village of Palmetto Bay. Waters from an interconnected managed canal system were assessed to evaluate the influence of localized emissions. Septic tank effluents influence the water in many Southeast Florida environments due to their diminished onsite treatment capacity based on the limestone dominated geology and canal systems providing a relatively unobstructed connection pathway. Through a combination of high-resolution mass spectrometry (HRMS) and statistical analyses a set of tracers and indicators was determined (azelaic acid, decanophenone, galaxolidone, methyl violet, monoolein, metoprolol, and 1-stearoylglycerol). Tentatively identified compounds were generally assigned to various categories such as dyes, personal care products (PCPs), and pharmaceuticals. The NTA CD 3.1 compound data presented as Principal Component Analysis and Kendrick Mass Defect plots showed apparent differences between wastewater influenced sites and non-wastewater influenced sites along with the ranked “Top10” compounds found at each location. Waters from different locations were also compared using the presence of sucralose to further inform the NTA. The most septic influenced site contained 3,594 ± 94 ng/L of sucralose with concentrations declining steadily reaching the lowest concentrations in Biscayne Bay of 122 ± 94 ng/L. The sucralose concentrations provided further evidence of septic influence on this system. Sucralose was determined to be a conservative tracer between the freshwater and coastal sources and complimentary to other probable unique tracers of septic tank effluent identified by the NTA. This article is protected by copyright. All rights reserved.© 2022 SETAC.

PMID:35170796 | DOI:10.1002/etc.5309

J Ultrasound Med. 2022 Feb 16. doi: 10.1002/jum.15960. Online ahead of print.

ABSTRACT

OBJECTIVES: Ultrasound is useful in predicting arteriovenous fistula (AVF) maturation, which is essential for hemodialysis in end-stage renal disease patients. We developed ultrasound software that measures circumferential vessel wall strain (distensibility) using conventional ultrasound Digital Imaging and Communications in Medicine (DICOM) data. We evaluated user-induced variability in measurement of arterial wall distensibility and upon finding considerable variation we developed and tested 2 methods for semiautomated measurement.

METHODS: Ultrasound scanning of arteries of 10 subjects scheduled for AVF surgery were performed. The top and bottom of the vessel wall were tracked using the Kanade-Lucas-Tomasi (KLT) feature-tracking algorithm over the stack of images in the DICOM cine loops. The wall distensibility was calculated from the change of vessel diameter over time. Two semiautomated methods were used for comparison.

RESULTS: The location of points selected by users for the cine loops varied significantly, with a maximum spread of up to 120 pixels (7.8 mm) for the top and up to 140 pixels (9.1 mm) for the bottom of the vessel wall. This variation in users’ point selection contributed to the variation in distensibility measurements (ranging from 5.63 to 41.04%). Both semiautomated methods substantially reduced variation and were highly correlated with the median distensibility values obtained by the 10 users.

CONCLUSIONS: Minimizing user-induced variation by standardizing point selection will increase reproducibility and reliability of distensibility measurements. Our recent semiautomated software may help expand use in clinical studies to better understand the role of vascular wall compliance in predicting the maturation of fistulas.

PMID:35170801 | DOI:10.1002/jum.15960

J Adv Nurs. 2022 Feb 15. doi: 10.1111/jan.15178. Online ahead of print.

ABSTRACT

AIM: To evaluate the effectiveness of a nurse-led smartphone-based self-management programme (NSSMP) on improving self-efficacy, promoting diabetes self-care, increasing health-related quality of life (HRQoL) and decreasing HbA1c, acute complications and unplanned medical consultation for people with poorly controlled type 2 diabetes compared with a nurse-led diabetic service (NDS).

DESIGN: A two-arm randomized controlled trial with repeated measures was conducted.

METHODS: Participants were recruited from June 2018 to September 2020. Eligible participants were assigned to either the intervention or control group randomly. Participants assigned to intervention group received the 6-month NSSMP, while those in the control group received existing NDS provided by the study hospital. Outcomes were measured at baseline, and at 3 and 6 months from baseline.

RESULTS: A total of 114 participants were recruited. There were no significant interactions between group and time for all the outcomes except for blood glucose testing activities (F = 4.742, p = .015). Both groups had reduced HbA1c over 6 months. The intervention group had a lower HbA1c than the control group at follow-ups, but the differences were not statistically significant. None of the participants had acute diabetes complications at follow-up. Similarly, the differences in the number of unplanned medical consultation at 6-month follow-up between two groups were statistically insignificant.

CONCLUSION: The NSSMP is as effective as existing NDS provided by the study hospital in improving most of the outcomes. NSSMP can liberate valuable time for nurses to provide care to critically ill patients and supports healthcare resource constraints in the current COVID-19 pandemic.

IMPACT: The existing diabetes service is labour intensive as nurses are required to deliver education, follow-up telephone calls to trace blood sugar monitoring and provide therapeutic consultations and necessary referrals. The outbreak of COVID-19 pandemic has added further strain on the overworked professionals. NSSMP provides an alternative programme that is just as effective, to reduce nurses’ workload by delegating them back to the individuals through self-management strategies. This enables nurses to increase contact time with patients, and individuals to take onus of their disease through increased self-efficacy, facilitated by technology.

CLINICAL TRIAL: This study is registered under clinical registration number NCT03088475.

PMID:35170786 | DOI:10.1111/jan.15178

Lasers Surg Med. 2022 Feb 16. doi: 10.1002/lsm.23524. Online ahead of print.

ABSTRACT

BACKGROUND: A previous multi-center clinical study of low energy (20% power), single-pass helium plasma dermal resurfacing (HPDR) showed positive results but did not fully reveal the true potential of this novel technology. A second multi-center clinical study, reported herein, was therefore undertaken to evaluate efficacy and safety of high energy (40%), double pass HPDR for treatment of facial rhytids (ClinicalTrials.gov Identifier: NCT04185909).

METHODS: Fifty-five eligible subjects seeking improvement in facial rhytids were enrolled for study at one of four investigational sites. All subjects underwent full-face HPDR treatment. The forehead, nose, cheeks, and peri-oral treatment zones were treated at 40% power with two passes whereas the peri-orbital and jawline/mandibular zones were treated at 20% power (up to 40% for jawline/mandibular zone) and one or two passes. Photographic images of the face were captured using the VISIA-CR system. Three-month posttreatment Fitzpatrick Wrinkle and Elastosis Scale (FWS) scores were compared to baseline scores as determined by blinded independent photographic reviewers (IPRs) and study investigators.

RESULTS: Blinded IPRs and study investigators observed a ≥1-point FWS improvement in 100% of subjects with mean change in IPR FWS from baseline to the 90-day visit of -3.6 (±1.2). 96.4% of subjects indicated “improvement” in appearance at the 90-day visit utilizing the modified Global Aesthetic Improvement Scale. Evaluation of VISIA-CR data revealed statistically significant improvements in wrinkles, brown spots, and pore counts. Overall, 269 Adverse Events in 55 subjects were reported; most were mild-moderate in severity (99.3%), anticipated (86.2%), and of relatively short duration with most having resolved within 30 days (60.6%) of treatment.

CONCLUSION: Treatment of facial rhytids with high energy, double pass HPDR as detailed herein enables a marked improvement in FWS that parallels or surpasses competing technologies. VISIA-CR analysis demonstrates additional improvements in skin quality with statistically significant quantitative improvements in brown spots and enlarged pores as well as wrinkles. Effective rhytid effacement combines with high subject satisfaction and few unanticipated adverse events for a reasonable benefit-risk ratio.

PMID:35170772 | DOI:10.1002/lsm.23524