Category: Statistics

Methods Mol Biol. 2022;2526:241-257. doi: 10.1007/978-1-0716-2469-2_18.

ABSTRACT

Reshaping of the chromatin landscape under oxidative stress is of paramount importance for mounting an effective stress response. Unbiased systemic identification and quantification of histone marks is crucial for understanding the epigenetic component of plant responses to adverse environmental conditions. We describe a detailed method for isolation of plant histones and subsequent bottom-up proteomics approach for characterization of acetylation and methylation status. By performing label-free quantitative mass spectrometry analysis, relative abundances of histone marks can be statistically compared between experimental conditions.

PMID:35657525 | DOI:10.1007/978-1-0716-2469-2_18

J Occup Rehabil. 2022 Jun 3. doi: 10.1007/s10926-022-10048-5. Online ahead of print.

ABSTRACT

Purpose This study sought to determine patterns of opioid use among workers with a compensated lower limb injury, factors associated with opioid use, and how opioid use is associated with time loss duration. Methods Claims and medication data were provided by the workers’ compensation regulator of Victoria, Australia, for claims lodged 2008-2018 from workers aged 15+ years with a lower limb injury. Descriptive statistics showed the number and prevalence of each opioid type (weak/strong) by demographic, claim and injury predictors. Binary and multinomial logistic regression determined the likelihood of any opioid use, and use of strong, weak or a combination of strong and weak opioids by predictors. Cox regression determined the effect of each opioid type on duration of time loss, controlling for predictors. Results There were 51,334 claims and of these 23.6% were dispensed opioids (9.2% for strong opioids only, 6.6% for weak opioids only and 7.8% for a combination). Weak opioids, on average, were dispensed 15 days earlier than strong opioids. Time loss claims and workers with fractures or hip injuries were most likely to be dispensed opioids. All opioids were associated with increased duration of time loss, with those dispensed both weak and strong opioids having the longest duration of time loss. Conclusions Any opioid use was associated with longer time loss duration, with increasing opioid strength having a greater effect. Review of pain management methods should be undertaken to reduce opioid use, which may have a positive impact on duration of time loss and long-term function.

PMID:35657441 | DOI:10.1007/s10926-022-10048-5

J Patient Rep Outcomes. 2022 Jun 3;6(1):59. doi: 10.1186/s41687-022-00464-9.

ABSTRACT

BACKGROUND: The Patient-Reported Outcome Measurement Information System^® (PROMIS^®) was developed to reliably measure health-related quality of life using the patient’s voice. To achieve these aims, PROMIS utilized Item Response Theory methods in its development, validation and implementation. PROMIS measures are typically scored using a specific method to calculate scores, called Expected A Posteriori estimation. BODY: Expected A Posteriori scoring methods are flexible, produce accurate scores and can be efficiently calculated by statistical software. This work seeks to make Expected A Posteriori scoring methods transparent and accessible to a larger audience through description, graphical demonstration and examples. Further applications and practical considerations of Expected A Posteriori scoring are presented and discussed. All materials used in this paper are made available through the R Markdown reproducibility framework and are intended to be reviewed and reused. Commented statistical code for the calculation of Expected A Posteriori scores is included.

CONCLUSION: This work seeks to provide the reader with a summary and visualization of the operation of Expected A Posteriori scoring, as implemented in PROMIS. As PROMIS is increasingly adopted and implemented, this work will provide a basis for making psychometric methods more accessible to the PROMIS user base.

PMID:35657454 | DOI:10.1186/s41687-022-00464-9

Insights Imaging. 2022 Jun 3;13(1):94. doi: 10.1186/s13244-022-01234-3.

ABSTRACT

BACKGROUND: Majority of research and commercial efforts have focussed on use of artificial intelligence (AI) for fracture detection in adults, despite the greater long-term clinical and medicolegal implications of missed fractures in children. The objective of this study was to assess the available literature regarding diagnostic performance of AI tools for paediatric fracture assessment on imaging, and where available, how this compares with the performance of human readers.

MATERIALS AND METHODS: MEDLINE, Embase and Cochrane Library databases were queried for studies published between 1 January 2011 and 2021 using terms related to ‘fracture’, ‘artificial intelligence’, ‘imaging’ and ‘children’. Risk of bias was assessed using a modified QUADAS-2 tool. Descriptive statistics for diagnostic accuracies were collated.

RESULTS: Nine eligible articles from 362 publications were included, with most (8/9) evaluating fracture detection on radiographs, with the elbow being the most common body part. Nearly all articles used data derived from a single institution, and used deep learning methodology with only a few (2/9) performing external validation. Accuracy rates generated by AI ranged from 88.8 to 97.9%. In two of the three articles where AI performance was compared to human readers, sensitivity rates for AI were marginally higher, but this was not statistically significant.

CONCLUSIONS: Wide heterogeneity in the literature with limited information on algorithm performance on external datasets makes it difficult to understand how such tools may generalise to a wider paediatric population. Further research using a multicentric dataset with real-world evaluation would help to better understand the impact of these tools.

PMID:35657439 | DOI:10.1186/s13244-022-01234-3

J Chem Theory Comput. 2022 Jun 3. doi: 10.1021/acs.jctc.2c00207. Online ahead of print.

ABSTRACT

Widely applicable, modified Green-Kubo expressions for the local diffusion coefficient (D_l) are obtained using linear response theory. In contrast to past definitions in use, these expressions are statistical mechanical results. Molecular simulations of systems with anisotropic diffusion and an inhomogeneous density profile confirm the validity of the results. Diffusion coefficients determined from different expressions in terms of currents and velocity correlations agree in the limit of large systems. Furthermore, they apply to arbitrarily small local regions, making them readily applicable to nanoscale and inhomogeneous systems where knowledge of D_l is important.

PMID:35657378 | DOI:10.1021/acs.jctc.2c00207

Int J Cancer. 2022 Jun 3. doi: 10.1002/ijc.34143. Online ahead of print.

ABSTRACT

Little is known about risk factors for progression of high-grade anal intraepithelial neoplasia (AIN) to anal squamous cell carcinoma (ASCC). In this large, population-based study, we assess the role of factors related to immune status for the risk of ASCC among individuals from the general population with a diagnosis of AIN3. Individuals diagnosed with AIN3 during 1985-2016 were identified in the Danish Pathology Registry and followed for subsequent development of ASCC. The study population was linked to the National Patient Registry, the Danish Prescription Registry, and the Danish HIV Cohort Study for information on autoimmune disease, genital warts, and HIV status. To study the progression rate, Cox regression models with hazard ratios (HR) and 95% confidence intervals (CI) were applied with time since AIN3 as the underlying time scale and with adjustment for age at AIN3 diagnosis, year of AIN3 diagnosis, and sex. The study population comprised 1,222 individuals with AIN3 contributing 12,824 person-years of follow-up. Ninety-seven individuals (7.9%) developed ASCC. Individuals registered with an autoimmune disease or genital warts before and/or after the AIN3 diagnosis had an increased rate of progression to ASCC compared with individuals without these conditions. People living with HIV had a higher progression rate than HIV-negative individuals (HR = 4.25; 95% CI: 1.87-9.65) with the highest progression rate among those with CD4 count <200 cells/μl. These associations may be caused by an interplay between HPV infection and immunosuppression.

PMID:35657350 | DOI:10.1002/ijc.34143

Int J Cancer. 2022 Jun 3. doi: 10.1002/ijc.34148. Online ahead of print.

ABSTRACT

Risk of colorectal cancer (CRC) increases in relatives of patients with CRC. The extent to which this is attributable to genetic predisposition or shared environment is unclear. We explored this question using nationwide cohorts from Denmark, Finland and Sweden. From 1977-2013, we identified 359,879 individuals with a CRC diagnosis and 2,258,870 of their relatives who we followed for CRC incidence. We calculated standardised incidence ratios (SIR) and 95% confidence intervals (CI) for CRC in individuals with an affected relative. We used nationwide household and pedigree data along with national SIR estimates to calculate risk ratios (RR) for the contribution of shared household environment, childhood environment, and genetic relationship to CRC risk in those with an affected relative. SIR of CRC was increased for individuals with an affected relative, across all countries and ages. For those with an affected parent, the SIR was 1.65 (95% CI: 1.61-1.69), 1.98 (95% CI: 1.87-2.09), for those with an affected sibling, and 2.14 (95% CI: 1.84-2.49) for those with an affected halfsibling. In those <65 years old, shared childhood (RR: 1.41, 95% CI: 1.26-1.57) and household (RR: 2.08, 95% CI: 1.25-3.46) environments were significantly greater contributors to familial risk of CRC than genetics (RR: 0.88, 95% CI: 0.53-1.46). This large-scale Nordic population-based study of excess risk of CRC among relatives of those with CRC addresses the difficult disentangling of shared environment from genetic predisposition in the heritability of CRC. We found shared environment to be the most important contributor to CRC risk.

PMID:35657349 | DOI:10.1002/ijc.34148

ACS Appl Mater Interfaces. 2022 Jun 3. doi: 10.1021/acsami.2c05761. Online ahead of print.

ABSTRACT

Active pharmaceutical ingredients (APIs) typically consist of solid therapeutic particles that may acquire electrostatic charge during milling and grinding operations. This may result in the agglomeration of particles, thereby reducing the flowability and affecting the homogeneity of the drug formulation. Electrostatic charge build-up may also lead to fire explosions. To avoid charge build-up, APIs are often coated with polymers. In this paper, atomic layer deposition (ALD) using metal oxides such as Al₂O₃ and TiO₂ on APIs, namely, palbociclib and pazopanib HCl, has been utilized to demonstrate a uniform coating that results in a significant reduction in the surface charge of the drug particles. Kelvin probe force microscopy (KPFM) shows a 4-fold decrease in the surface contact potential of uncoated pazopanib HCl (2.3 V) to 0.52 and 0.82 V in TiO₂-and Al₂O₃-coated APIs, respectively. Also, the ζ potential indicated a 4-fold decrease in the surface charge on coating pazopanib HCl, i.e., from -32.9 mV to -7.51 and -8.51 mV in Al₂O₃ and TiO₂, respectively. Surface morphology, thermal stability, dissolution studies, and cytotoxicity of the drug particles after coating were also examined. Thermal analysis indicated no change in the melting temperature (T_m) after coating. ALD coating was found to be uniform and conformal as observed in images obtained from scanning electron microscopy (SEM) and scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDS). The rate of dissolution was found to be delayed by the coating, and thus ALD offers slower drug release. Coating APIs with TiO₂ and Al₂O3 did not induce statistically significant cytotoxicity compared to the uncoated samples. The results presented in this study demonstrate that ALD coating can be used to reduce surface charge build-up and enhance the bulk properties of the drug particles without affecting their physicochemical properties.

PMID:35656880 | DOI:10.1021/acsami.2c05761

Hand (N Y). 2022 Jun 3:15589447221093676. doi: 10.1177/15589447221093676. Online ahead of print.

ABSTRACT

BACKGROUND: Stenosing flexor tenosynovitis is commonly treated by injection of corticosteroids into the flexor tendon sheath. However, there is no consensus in the literature regarding the optimal technique, specifically when not utilizing ultrasound guidance. Here, we present a cadaver study in which 3 common techniques of flexor sheath injection were compared with regard to their accuracy and safety profiles.

METHODS: Fifteen fresh-frozen cadaver hands (60 digits) were evenly divided into 3 groups (20 digits per group). Digits in each group were injected with methylene blue dye using 1 of the 3 techniques (palmar-to-bone, palmar supra-tendinous, and mid-axial). The fingers were then dissected and were inspected for location of dye, as well as injury to tendon or digital nerves.

RESULTS: The mid-axial technique demonstrated the greatest accuracy with the highest rate of all intra-sheath injection, 15 of 20 digits (75%), while the palmar-to-bone technique produced the most combined intra- and extra-sheath injections, 13 of 20 digits, (65%) and the palmar supra-tendinous technique resulted in the most all extra-sheath injections, 9 of 20 digits (45%). The difference in rates of all intra-sheath injection was significant (P = .01). The mid-axial technique also produced the fewest intra-tendinous injections 0 of 20, although this result did not reach statistical significance (P = .15).

CONCLUSIONS: Compared to other common non-image guided flexor tendon sheath injection techniques, the mid-axial injection technique was found to be the most accurate in producing all intra-sheath injection and least likely to result in intra-tendinous injection.

PMID:35656857 | DOI:10.1177/15589447221093676

Hand (N Y). 2022 Jun 3:15589447221093671. doi: 10.1177/15589447221093671. Online ahead of print.

ABSTRACT

BACKGROUND: Upper-extremity limb loss has been associated with serious psychological sequelae. Despite advancements in surgical procedures and prostheses for upper limb amputees, it is critical to recognize the psychosocial component of these patients’ care. Although the role of psychological factors in outcomes is increasingly acknowledged, little is known about the prevalence of depression and post-traumatic stress disorder (PTSD) in the civilian population after traumatic upper-extremity amputation.

METHODS: In this retrospective observational single-center study, adult patients evaluated for traumatic upper limb amputations from 2016 to 2019 completed the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, Visual Analogue Scale, the Center for Epidemiologic Studies Depression Scale, and the Primary Care PTSD Screen during visits. All data underwent descriptive statistical analysis.

RESULTS: Thirty-nine adult patients treated for upper-extremity traumatic amputation completed patient-reported outcomes (PROs) questionnaires. The median final follow-up time for our cohort was 17 months from amputation. Twenty patients (51%) screened positive for depression and 27 (69%) for PTSD during follow-up. The median time from amputation to first positive screening was 6.5 months for depression and 10 months for PTSD. The physical component score of Veterans RAND 12-Item Health Survey (VR-12) was significantly worse for patients with depression. The Median DASH and mental component score of VR-12 were significantly worse for patients with PTSD.

CONCLUSION: Upper-extremity limb loss has a significant impact on mental health, which in turn affects PROs. The high prevalence of depression and PTSD in traumatic upper-extremity amputees underscores the necessity for screening and multidisciplinary treatment.

PMID:35656852 | DOI:10.1177/15589447221093671