Publications by authors named "Hughes J"

6,061 Publications

Reported sources of health inequities in Indigenous Peoples with chronic kidney disease: a systematic review of quantitative studies.

BMC Public Health 2021 07 23;21(1):1447. Epub 2021 Jul 23.

Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.

Background: To summarise the evidentiary basis related to causes of inequities in chronic kidney disease among Indigenous Peoples.

Methods: We conducted a Kaupapa Māori meta-synthesis evaluating the epidemiology of chronic kidney diseases in Indigenous Peoples. Systematic searching of MEDLINE, Google Scholar, OVID Nursing, CENTRAL and Embase was conducted to 31 December 2019. Eligible studies were quantitative analyses (case series, case-control, cross-sectional or cohort study) including the following Indigenous Peoples: Māori, Aboriginal and Torres Strait Islander, Métis, First Nations Peoples of Canada, First Nations Peoples of the United States of America, Native Hawaiian and Indigenous Peoples of Taiwan. In the first cycle of coding, a descriptive synthesis of the study research aims, methods and outcomes was used to categorise findings inductively based on similarity in meaning using the David R Williams framework headings and subheadings. In the second cycle of analysis, the numbers of studies contributing to each category were summarised by frequency analysis. Completeness of reporting related to health research involving Indigenous Peoples was evaluated using the CONSIDER checklist.

Results: Four thousand three hundred seventy-two unique study reports were screened and 180 studies proved eligible. The key finding was that epidemiological investigators most frequently reported biological processes of chronic kidney disease, particularly type 2 diabetes and cardiovascular disease as the principal causes of inequities in the burden of chronic kidney disease for colonised Indigenous Peoples. Social and basic causes of unequal health including the influences of economic, political and legal structures on chronic kidney disease burden were infrequently reported or absent in existing literature.

Conclusions: In this systematic review with meta-synthesis, a Kaupapa Māori methodology and the David R Williams framework was used to evaluate reported causes of health differences in chronic kidney disease in Indigenous Peoples. Current epidemiological practice is focussed on biological processes and surface causes of inequity, with limited reporting of the basic and social causes of disparities such as racism, economic and political/legal structures and socioeconomic status as sources of inequities.
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http://dx.doi.org/10.1186/s12889-021-11180-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299576PMC
July 2021

Get Outside! Promoting Adolescent Health through Outdoor After-School Activity.

Int J Environ Res Public Health 2021 07 6;18(14). Epub 2021 Jul 6.

Health & Human Performance, Eastern Oregon University, La Grande, OR 97850, USA.

Background: The Get Outside: After School Activity Program (GO-ASAP) exemplifies how a rural community can utilize its natural resources and community partnerships to promote adolescent health.

Methods: A qualitative descriptive inquiry was conducted using convenience sampling. Data were collected from students ( = 13/2018; = 13/2019) via focus group and art-based method (2018 only) and parent ( = 6/2018) focus group. Data were analyzed via qualitative content analysis using the applied theoretical frameworks of Social Cognitive Theory and Social Determination Theory.

Results: (1) Increasing Health-Related Competencies. Students increased their physical activity, improved their sleep, perceived less stress, and reported changes in dietary habits and electronic use. (2) Increasing Social Relatedness. Students made new friends, felt more connected, and spent less time home alone after school. (3) Increasing Autonomy and Intrinsic Motivation. Students recognized their emerging capabilities, and their increased confidence stimulated more action-oriented behavior. Parent-perceived changes support and mirror student reports.

Conclusion: Outdoor, nature-based, activity programs are a novel upstream approach to promote adolescent health, especially in rural communities where natural resources often exceed health-service resources and community partnerships are a way of life.
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http://dx.doi.org/10.3390/ijerph18147223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305783PMC
July 2021

Reactivation of a developmentally silenced embryonic globin gene.

Nat Commun 2021 07 21;12(1):4439. Epub 2021 Jul 21.

MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues.
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http://dx.doi.org/10.1038/s41467-021-24402-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295333PMC
July 2021

Large palindromes on the primate X Chromosome are preserved by natural selection.

Genome Res 2021 Aug 21;31(8):1337-1352. Epub 2021 Jul 21.

Whitehead Institute, Cambridge, Massachusetts 02142, USA.

Mammalian sex chromosomes carry large palindromes that harbor protein-coding gene families with testis-biased expression. However, there are few known examples of sex-chromosome palindromes conserved between species. We identified 26 palindromes on the human X Chromosome, constituting more than 2% of its sequence, and characterized orthologous palindromes in the chimpanzee and the rhesus macaque using a clone-based sequencing approach that incorporates full-length nanopore reads. Many of these palindromes are missing or misassembled in the current reference assemblies of these species' genomes. We find that 12 human X palindromes have been conserved for at least 25 million years, with orthologs in both chimpanzee and rhesus macaque. Insertions and deletions between species are significantly depleted within the X palindromes' protein-coding genes compared to their noncoding sequence, demonstrating that natural selection has preserved these gene families. The spacers that separate the left and right arms of palindromes are a site of localized structural instability, with seven of 12 conserved palindromes showing no spacer orthology between human and rhesus macaque. Analysis of the 1000 Genomes Project data set revealed that human X-palindrome spacers are enriched for deletions relative to arms and flanking sequence, including a common spacer deletion that affects 13% of human X Chromosomes. This work reveals an abundance of conserved palindromes on primate X Chromosomes and suggests that protein-coding gene families in palindromes (most of which remain poorly characterized) promote X-palindrome survival in the face of ongoing structural instability.
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http://dx.doi.org/10.1101/gr.275188.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327919PMC
August 2021

Temporal and regional variation in catch across an extensive coastal recreational fishery: Exploring the utility of survey methods to guide and assess spatio-temporal management initiatives.

PLoS One 2021 21;16(7):e0254388. Epub 2021 Jul 21.

Kewagama Research, Doonan, Queensland, Australia.

As global research into recreational fishing gains momentum due to the pursuit's biological, social and economic impacts, information on regional and temporal patterns of recreational exploitation will continue to enable objective assessment and development of management initiatives for exploited species. This paper demonstrates the utility of offsite survey methods in assessing spatial and temporal differences in recorded catches from a large, diffuse and heterogenous coastal recreational fishery. Using the estuarine recreational fishery that operates along the coast of New South Wales, Australia as a case study, survey data was employed to quantify annual (June 2013-May 2014) state-wide estuarine catch. Generalized linear mixed effects models were then applied to expanded catch estimates from surveyed households to examine the influence of zone and season on the kept and released numbers of snapper (Pagrus auratus), dusky flathead (Platycephalus fuscus) and bream (Acanthopagrus spp. complex comprised of A. butcheri, A. australis and their hybrids). For kept bream, significant differential seasonal effects were observed in all regions except the Mid-South Coast. For released bream, numbers were greatest in Sydney and during Summer and Winter. For kept snapper, the greatest harvest was recorded in the Mid-South Coast but season had no effect. Differential seasonal effects were found in each zone for released snapper. For kept dusky flathead, the greatest numbers were recorded in Sydney and the Mid-South Coast but season had no effect. We conclude by assessing some current spatial and temporal management initiatives in light of the uncovered patterns of recreational catch and consider the implications of these patterns in terms of future ecosystem-based management recommendations aimed at achieving ecological, social and economic sustainability in fisheries.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254388PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294510PMC
July 2021

Calculation algorithms and penumbra: Underestimation of dose in organs at risk in dosimetry audits.

Med Phys 2021 Jul 21. Epub 2021 Jul 21.

Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Purpose: The aim of this study is to investigate overdose to organs at risk (OARs) observed in dosimetry audits in Monte Carlo (MC) algorithms and Linear Boltzmann Transport Equation (LBTE) algorithms. The impact of penumbra modeling on OAR dose was assessed with the adjustment of MC modeling parameters and the clinical relevance of the audit cases was explored with a planning study of spine and head and neck (H&N) patient cases.

Methods: Dosimetric audits performed by the Australian Clinical Dosimetry Service (ACDS) of 43 anthropomorphic spine plans and 1318 C-shaped target plans compared the planned dose to doses measured with ion chamber, microdiamond, film, and ion chamber array. An MC EGSnrc model was created to simulate the C-shape target case. The electron cut-off energy E was set at 500, 200, and 10 keV, and differences between 1 and 3 mm voxel were calculated. A planning study with 10 patient stereotactic body radiotherapy (SBRT) spine plans and 10 patient H&N plans was calculated in both Acuros XB (AXB) v15.6.06 and Anisotropic Analytical Algorithm (AAA) v15.6.06. The patient contour was overridden to water as only the penumbral differences between the two different algorithms were under investigation.

Results: The dosimetry audit results show that for the SBRT spine case, plans calculated in AXB are colder than what is measured in the spinal cord by 5%-10%. This was also observed for other audit cases where a C-shape target is wrapped around an OAR where the plans were colder by 3%-10%. Plans calculated with Monaco MC were colder than measurements by approximately 7% with the OAR surround by a C-shape target, but these differences were not noted in the SBRT spine case. Results from the clinical patient plans showed that the AXB was on average 7.4% colder than AAA when comparing the minimum dose in the spinal cord OAR. This average difference between AXB and AAA reduced to 4.5% when using the more clinically relevant metric of maximum dose in the spinal cord. For the H&N plans, AXB was cooler on average than AAA in the spinal cord OAR (1.1%), left parotid (1.7%), and right parotid (2.3%). The EGSnrc investigation also noted similar, but smaller differences. The beam penumbra modeled by E  = 500 keV was steeper than the beam penumbra modeled by E  = 10 keV as the full scatter is not accounted for, which resulted in less dose being calculated in a central OAR region where the penumbra contributes much of the dose. The dose difference when using 2.5 mm voxels of the center of the OAR between 500 and 10 keV was 3%, reducing to 1% between 200 and 10 keV.

Conclusions: Lack of full penumbral modeling due to approximations in the algorithms in MC based or LBTE algorithms are a contributing factor as to why these algorithms under-predict the dose to OAR when the treatment volume is wrapped around the OAR. The penumbra modeling approximations also contribute to AXB plans predicting colder doses than AAA in areas that are in the vicinity of beam penumbra. This effect is magnified in regions where there are many beam penumbras, for example in the spinal cord for spine SBRT cases.
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http://dx.doi.org/10.1002/mp.15123DOI Listing
July 2021

Post-traumatic stress disorder is associated with alterations in evoked cortical activation during visual recognition of scenes.

Neuroimage Clin 2021 3;31:102752. Epub 2021 Jul 3.

National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, MD, USA; Behavioral Biology Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA. Electronic address:

We recorded magnetoencephalography data during a visual recognition task in participants with combat exposure (n = 40, age: 41.2 ± 7.2 years) to investigate the relationship between the evoked brain activity, behavioral performance, and the severity of their post-traumatic stress symptoms assessed using the PTSD Check List for DSM V version (PCL-5). In an initial study session, participants were presented with a series of images of outdoor scenes and were instructed to study the images for an upcoming recognition test. In a subsequent session, the original images were shown intermixed with novel images while participants performed the recognition task. PCL-5 scores were negatively correlated with discrimination performance and with the recognition accuracy for original images. During the recognition session, higher PCL-5 scores were associated with reduced relative power of the evoked response to original images from 100 ms to 300 ms following the image onset over a distributed brain network including the bilateral inferior frontal gyri, left middle frontal gyrus, left supramarginal gyrus, right precuneus and the bilateral superior temporal gyri. These findings indicate that the lower recognition performance in participants with higher PTSD symptom severity is associated with altered cortical activity in brain regions that are known to play a role in the elaboration on visual cues that supports recollection.
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http://dx.doi.org/10.1016/j.nicl.2021.102752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313740PMC
September 2021

Achieving Enrollment Outcomes by Aligning Applicant Recruitment and Selection with Unique Organizational Niches.

Am J Pharm Educ 2021 04 23;85(4):7743. Epub 2020 Dec 23.

University of Portland, School of Nursing, Portland, Oregon.

Several Doctor of Pharmacy programs have rescinded their requirement for applicants to complete the Pharmacy College Admissions Test, modified their requirements for prerequisite coursework, and reduced the minimum grade point average required for admission. As schools and colleges of pharmacy begin to use these and other more holistic approaches to recruitment and admission, the quantity and quality of students in the applicant pool will continue to shift. In alignment with their unique mission, values, and vision statements, pharmacy programs have also expanded aspects of their application and review process to increasingly focus on applicants' leadership skills, community service, teamwork, collaboration skills, and paid and volunteer work. These aspects allow them to look beyond a candidate's academic performance and instead emphasize skills and affective domain areas that are aligned with the Accreditation Council for Pharmacy Education standards and Center for the Advancement of Pharmacy Education outcomes. Ways in which pharmacy schools and colleges can refine their recruitment and admissions processes to better align with their unique curricular and programmatic niche areas are discussed.
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http://dx.doi.org/10.5688/ajpe7743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086607PMC
April 2021

USP9X Is Required to Maintain Cell Survival in Response to High-LET Radiation.

Front Oncol 2021 1;11:671431. Epub 2021 Jul 1.

Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, United Kingdom.

Ionizing radiation (IR) principally acts through induction of DNA damage that promotes cell death, although the biological effects of IR are more broad ranging. In fact, the impact of IR of higher-linear energy transfer (LET) on cell biology is generally not well understood. Critically, therefore, the cellular enzymes and mechanisms responsible for enhancing cell survival following high-LET IR are unclear. To this effect, we have recently performed siRNA screening to identify deubiquitylating enzymes that control cell survival specifically in response to high-LET α-particles and protons, in comparison to low-LET X-rays and protons. From this screening, we have now thoroughly validated that depletion of the ubiquitin-specific protease 9X (USP9X) in HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells using small interfering RNA (siRNA), leads to significantly decreased survival of cells after high-LET radiation. We consequently investigated the mechanism through which this occurs, and demonstrate that an absence of USP9X has no impact on DNA damage repair post-irradiation nor on apoptosis, autophagy, or senescence. We discovered that USP9X is required to stabilize key proteins (CEP55 and CEP131) involved in centrosome and cilia formation and plays an important role in controlling pericentrin-rich foci, particularly in response to high-LET protons. This was also confirmed directly by demonstrating that depletion of CEP55/CEP131 led to both enhanced radiosensitivity of cells to high-LET protons and amplification of pericentrin-rich foci. Our evidence supports the importance of USP9X in maintaining centrosome function and biogenesis and which is crucial particularly in the cellular response to high-LET radiation.
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http://dx.doi.org/10.3389/fonc.2021.671431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281306PMC
July 2021

Impact of the COVID-19 pandemic on adults with current and prior depression: initial findings from the longitudinal Texas RAD study.

J Affect Disord 2021 Nov 2;294:103-108. Epub 2021 Jul 2.

Center for Depression Research and Clinical Care, Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address:

Background: Emerging work has suggested worsening mental health in the general population during the COVID-19 pandemic, but there is minimal data on individuals with a prior history of depression.

Methods: Data regarding depression, anxiety and quality of life in adult participants with a history of a depressive disorder (n = 308) were collected before and during the COVID-19 pandemic. Mixed effects regression models were fit for these outcomes over the period May - August 2020, controlling for pre-pandemic depressive groups (none, mild, moderate-to-severe), demographic characteristics, and early COVID-19 related experiences (such as disruptions in routines, mental health treatment, and social supports).

Results: In pre-to-early pandemic comparisons, the 3 pre-pandemic depressive categories varied significantly in anxiety (F = 7.93, p < 0.0005) and psychological QOL (F = 8.57, p = 0.0003). The mildly depressed group (F = 6.01, p = 0.02) and moderate-to-severely depressed group (F = 38.51, p < 0.0001) had a significant reduction in anxiety. There were no changes among the groups in any outcome from May to August 2020. However, early impact on mental health care access and disruption in routines predicted worse outcomes during this time.

Limitations: Follow-up data were self-reported. Furthermore, the duration was a relatively short span into the pandemic.

Conclusions: Symptoms of depression, anxiety, and quality of life were generally stable from 2019 throughout August 2020 in adults with a history of depression. Disruption in mental health care access and routines in May 2020 predicted worse symptom outcomes through August 2020.
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http://dx.doi.org/10.1016/j.jad.2021.06.071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433599PMC
November 2021

A hybrid machine learning/pharmacokinetic approach outperforms maximum a posteriori Bayesian estimation by selectively flattening model priors.

CPT Pharmacometrics Syst Pharmacol 2021 Jul 16. Epub 2021 Jul 16.

InsightRX, San Francisco, California, USA.

Model-informed precision dosing (MIPD) approaches typically apply maximum a posteriori (MAP) Bayesian estimation to determine individual pharmacokinetic (PK) parameters with the goal of optimizing future dosing regimens. This process combines knowledge about the individual, in the form of drug levels or pharmacodynamic biomarkers, with prior knowledge of the drug PK in the general population. Use of "flattened priors" (FPs), in which the weight of the model priors is reduced relative to observations about the patient, has been previously proposed to estimate individual PK parameters in instances where the patient is poorly described by the PK model. However, little is known about the predictive performance of FPs and when to apply FPs in MIPD. Here, FP is evaluated in a data set of 4679 adult patients treated with vancomycin. Depending on the PK model, prediction error could be reduced by applying FPs in 42-55% of PK parameter estimations. Machine learning (ML) models could identify instances where FPs would outperform MAPs with a specificity of 81-86%, reducing overall root mean squared error (RMSE) of PK model predictions by 12-22% (0.5-1.2 mg/L) relative to MAP alone. The factors most indicative of the use of FPs were past prediction residuals and bias in past PK predictions. A more clinically practical minimal model was developed using only these two features, reducing RMSE by 5-18% (0.20-0.93 mg/L) relative to MAP. This hybrid ML/PK approach advances the precision dosing toolkit by leveraging the power of ML while maintaining the mechanistic insight and interpretability of PK models.
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http://dx.doi.org/10.1002/psp4.12684DOI Listing
July 2021

Promoting adaptive bone formation to prevent stress fractures in military personnel.

Eur J Sport Sci 2021 Jul 16:1-12. Epub 2021 Jul 16.

Army Health and Performance Research, Army Headquarters, Andover, UK.

Mechanical loading leads to adaptive bone formation - the formation of new bone on existing skeletal surfaces - which increases bone strength and fatigue resistance. The same mechanical loading can also cause microdamage to bone and development of a stress fracture through targeted remodelling. Stress fractures are common in military recruits and cause significant morbidity, lost training time, and discharge from military service. This narrative review proposes strategies to promote adaptive bone formation as a novel approach to mitigate the risk of stress fracture injuries during arduous military training. Exercise that is unaccustomed, dynamic, high-impact, multidirectional, intermittent, and includes extended rest periods to restore bone mechanosensitivity, is most osteogenic. New bone formation can take up to one year to mineralize, and so new exercise training programmes should be initiated well in advance of military activities with high risk of stress fracture. Bone mechanosensitivity is highest in adolescence, before puberty, and so increasing physical activity in youth is likely to protect skeletal health in later life, including for those in the military. Recent data show that adaptive bone formation takes place during initial military training. Adaptive bone formation can also be supported with adequate sleep, vitamin D, calcium, and energy availability. Further evidence on how strategies to promote adaptive bone formation affect stress fracture risk are required. Adaptive bone formation can be optimized with a range of training and nutritional strategies to help create a resilient skeleton, which may protect against stress fracture throughout military service.
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http://dx.doi.org/10.1080/17461391.2021.1949637DOI Listing
July 2021

Nonpharmacologic Pain Management Among Hospitalized Inpatients: A Randomized Waitlist-Controlled Trial of Standard Virtual Reality (CGI VR) Versus Video Capture VR (360 degrees 3D/Stereoscopic Video Capture VR).

Clin J Pain 2021 09;37(9):678-687

University of Minnesota, Minneapolis, MN.

Objectives: Nonpharmacologic pain management strategies are needed because of the growing opioid epidemic. While studies have examined the efficacy of virtual reality (VR) for pain reduction, there is little research in adult inpatient settings, and no studies comparing the relative efficacy of standard animated computer-generated imagery (CGI) VR to Video Capture VR (360 degrees 3D/stereoscopic Video Capture VR). Here, we report on a randomized controlled trial of the relative efficacy of standard CGI VR versus Video Capture VR (matched for content) and also compared the overall efficacy of VR to a waitlist control group.

Materials And Methods: Participants (N=103 hospitalized inpatients reporting pain) were randomized to 1 of 3 conditions: (1) waitlist control, (2) CGI VR, or (3) Video Capture VR. The VR and waitlist conditions were 10 minutes in length. Outcomes were assessed pretreatment, post-treatment, and after a brief follow-up.

Results: Consistent with hypotheses, both VR conditions reduced pain significantly more relative to the waitlist control condition (d=1.60, P<0.001) and pain reductions were largely maintained at the brief follow-up assessment. Both VR conditions reduced pain by ∼50% and led to improvements in mood, anxiety, and relaxation. Contrary to prediction, the Video Capture VR condition was not significantly more effective at reducing pain relative to the CGI VR condition (d=0.25, P=0.216). However, as expected, patients randomized to the Video Capture VR rated their experience as more positive and realistic (d=0.78, P=0.002).

Discussion: Video Capture VR was as effective as CGI VR for pain reduction and was rated as more realistic.
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http://dx.doi.org/10.1097/AJP.0000000000000958DOI Listing
September 2021

Critical shoulder angle does not influence retear rate after arthroscopic rotator cuff repair.

Knee Surg Sports Traumatol Arthrosc 2021 Jul 13. Epub 2021 Jul 13.

Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, 3200 South Water Street, Pittsburgh, PA, 15203, USA.

Purpose: The critical shoulder angle (CSA) has been implicated as a potential risk factor for failure following arthroscopic rotator cuff repair (RCR). However, there is conflicting evidence regarding the clinical usefulness of this measurement. Given these discrepancies and limited comparisons to clinical outcomes, the aim of the current study was to determine whether higher CSAs correlated with an increased retear rate after arthroscopic rotator cuff repair and to determine if any association between CSA and patient-reported outcomes (PROs) exists. It was hypothesized that there would be no correlation between CSA and retear rate or PROs after arthroscopic rotator cuff repair.

Methods: A total of 164 patients who underwent arthroscopic RCR were retrospectively reviewed. CSA was measured for each patient. Patients were then divided into a retear group of 18 patients and a non-retear group of 146 patients. Patient-reported outcomes (PROs), including PROMIS 10 score, American Shoulder and Elbow Surgeons (ASES) score, Brophy score, and visual analog pain scores (VAS) were recorded post-operatively.

Results: The average CSA was 31.2 ± 4.5° for the retear group and 32.2 ± 4.7° for the non-retear group (n.s.). No correlations were found between CSA and PROMIS score (n.s.), ASES score (n.s.), Brophy score (n.s.), or VAS (n.s.).

Conclusion: Critical shoulder angle had no correlation to retear rate or patient-reported outcomes. CSA should not be used as a clinical predictor to assess rotator cuff retear risk after arthroscopic RCR.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1007/s00167-021-06652-2DOI Listing
July 2021

Widespread cis- and trans-regulatory evolution underlies the origin, diversification, and loss of a sexually dimorphic fruit fly pigmentation trait.

J Exp Zool B Mol Dev Evol 2021 Jul 12. Epub 2021 Jul 12.

Department of Biology, University of Dayton, Dayton, Ohio, USA.

Changes in gene expression are a prominent feature of morphological evolution. These changes occur to hierarchical gene regulatory networks (GRNs) of transcription factor genes that regulate the expression of trait-building differentiation genes. While changes in the expression of differentiation genes are essential to phenotypic evolution, they can be caused by mutations within cis-regulatory elements (CREs) that drive their expression (cis-evolution) or within genes for CRE-interacting transcription factors (trans-evolution). Locating these mutations remains a challenge, especially when experiments are limited to one species that possesses the ancestral or derived phenotype. We investigated CREs that control the expression of the differentiation genes tan and yellow, the expression of which evolved during the gain, modification, and loss of dimorphic pigmentation among Sophophora fruit flies. We show these CREs to be necessary components of a pigmentation GRN, as deletion from Drosophila melanogaster (derived dimorphic phenotype) resulted in lost expression and lost male-specific pigmentation. We evaluated the ability of orthologous CRE sequences to drive reporter gene expression in species with modified (Drosophila auraria), secondarily lost (Drosophila ananassae), and ancestrally absent (Drosophila willistoni) pigmentation. We show that the transgene host frequently determines CRE activity, implicating trans-evolution as a significant factor for this trait's diversity. We validated the gain of dimorphic Bab transcription factor expression as a trans-change contributing to the dimorphic trait. Our findings suggest an amenability to change for the landscape of trans-regulators and begs for an explanation as to why this is so common compared to the evolution of differentiation gene CREs.
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http://dx.doi.org/10.1002/jez.b.23068DOI Listing
July 2021

Clinical Performance Status and Technical Factors Affecting Outcomes from Percutaneous Transhepatic Biliary Interventions; A Multicentre, Prospective, Observational Cohort Study.

Cardiovasc Intervent Radiol 2021 Jul 12. Epub 2021 Jul 12.

Department of Interventional Radiology, Oxford University Hospitals NHS Foundation Trust, oxford, UK.

Purpose: The purpose of this study was to evaluate the predictive value of a 'Modified Karnofsky Scoring System' on outcomes and provide real-world data regarding the UK practice of biliary interventions.

Materials And Methods: A prospective multi-centred cohort study was performed. The pre-procedure modified Karnofsky score, the incidence of sepsis, complications, biochemical improvement and mortality were recorded out to 30 days post procedure.

Results: A total of 292 patients (248 with malignant lesions) were suitable for inclusion in the study. The overall 7 and 30 day mortality was 3.1% and 16.1%, respectively. The 30 day sepsis rate was 10.3%. In the modified Karnofsky 'high risk' group the 7 day mortality was 9.7% versus 0% for the 'low risk' group (p = 0.002), whereas the 30 day mortality was 28.8% versus 13.3% (p = 0.003). The incidence of sepsis at 30 days was 19% in the high risk group versus 3.3% at the low risk group (p = 0.001) CONCLUSION: Percutaneous biliary interventions in the UK are safe and effective. Scoring systems such as the Karnofsky or the modified Karnofsky score hold promise in allowing us to identify high risk groups that will need more careful consideration and enhanced patient informed consent but further research with larger studies is warranted in order to identify their true impact on patient selection and outcomes post biliary interventions.
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http://dx.doi.org/10.1007/s00270-021-02888-0DOI Listing
July 2021

Truthfulness and the person living with dementia: Embedded intentions, speech acts and conforming to the reality.

Authors:
Julian C Hughes

Bioethics 2021 Jul 10. Epub 2021 Jul 10.

Bristol Medical School (PHS), Bristol Population Health Science Institute, University of Bristol, Bristol, United Kingdom of Great Britain and Northern Ireland.

Highly reputable bodies have said that lying is to be avoided when speaking with people living with dementia, unless it cannot be. And yet, the evidence is that many professionals looking after people who live with dementia have been lying to them. I wish to consider an underlying philosophical justification for the moral position that allows lying under some circumstances whilst still condemning it generally. It can seem difficult to ignore the immorality of lying, but thinkers have developed arguments to get around the absolute prohibition. I shall argue that in concrete circumstances the object and the intended end of an action are not as clearly distinct as has been presumed. Further, looking at how language functions allows us to appeal to speech acts and to see the illocutionary force of a statement as way to broaden its purview. We need not think that the only options are between lying and not lying; there is also the possibility, in exigent circumstances, of 'conforming to the reality', which would allow a more nuanced account of moral acts, where the intentional nature of the act is no longer to lie. There are, thus, extreme concrete circumstances where not to speak the truth may be excusable, even if regrettable.
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http://dx.doi.org/10.1111/bioe.12923DOI Listing
July 2021

Feasibility study for a high-k temperature fluctuation diagnostic based on soft x-ray imaging.

Rev Sci Instrum 2021 May;92(5):053537

Plasma Science and Fusion Center, MIT, Cambridge, Massachusetts 02139, USA.

A new pseudolocal tomography algorithm is developed for soft X-ray(SXR) imaging measurements of the turbulent electron temperature fluctuations (δ T) in tokamaks and stellarators. The algorithm overcomes the constraints of limited viewing ports on the vessel wall (viewing angle) and limited number of lines of sight (LOS). This is accomplished by increasing the number of LOS locally in a region of interest. Numerical modeling demonstrates that the wavenumber spectrum of the turbulence can be reliably reconstructed, with an acceptable number of viewing angles and LOS and suitable low SNR detectors. We conclude that a SXR imaging diagnostic for measurements of turbulent δ T using a pseudolocal reconstruction algorithm is feasible.
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http://dx.doi.org/10.1063/5.0043819DOI Listing
May 2021

Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes.

Prev Med 2021 Jul 7:106714. Epub 2021 Jul 7.

Vermont Center on Behavior and Health, University of Vermont, Burlington, VT, USA.

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.
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http://dx.doi.org/10.1016/j.ypmed.2021.106714DOI Listing
July 2021

Improved Outcomes Following Arthroscopic Superior Capsular Reconstruction May Not Be Associated With Changes in Shoulder Kinematics: An In Vivo Study.

Arthroscopy 2021 Jul 6. Epub 2021 Jul 6.

Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.A.

Purpose: To determine the in vivo effects of superior capsule reconstruction (SCR) on glenohumeral kinematics during abduction and to compare those kinematics results with patient-reported outcomes, range of motion, and strength.

Methods: Dynamic biplane radiography was used to image 10 patients with irreparable rotator cuff tears while performing scapular plane abduction pre- and 1-year post-surgery. Shoulder kinematics were determined by matching subject-specific computed tomography-based bone models to the radiographs using a validated tracking technique.

Results: No change was detected in static acromiohumeral distance (-0.7 ± 2.1 mm; P = .35); however, average dynamic acromiohumeral distance decreased (2.7 ± 1.2 mm to 2.3 ± 1.0 mm; P = .035) from pre- to 1-year post-surgery, respectively. The humeral head position was 0.5 ± 0.5 mm more superior 1-year post-surgery compared with pre-surgery (P = .01). Glenohumeral abduction increased from pre-surgery (150 ± 20°) to 1-year post-surgery (165 ± 10°) (P = .04) and all patient-reported outcomes improved from pre-surgery to 1-year post-surgery (all P < .002). A more posterior shift in humeral head position was associated with improved American Shoulder and Elbow Surgeons Shoulder Score from pre-surgery to 1-year post-surgery (r = 0.71, P = .02).

Conclusions: These data suggest that SCR may not depress the humeral head during functional abduction, as previously postulated, and postoperative improvements in subjective and clinical outcomes may be affected by mechanisms other than changes in shoulder kinematics.

Clinical Relevance: In vivo kinematics changes after SCR are small and do not correspond to previously postulated changes.
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http://dx.doi.org/10.1016/j.arthro.2021.06.018DOI Listing
July 2021

'You can't start a car when there's no petrol left': a qualitative study of patient, family and clinician perspectives on implantable cardioverter defibrillator deactivation.

BMJ Open 2021 07 6;11(7):e048024. Epub 2021 Jul 6.

Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK

Objective: To explore the attitudes towards implantable cardioverter defibrillator (ICD) deactivation and initiation of deactivation discussions among patients, relatives and clinicians.

Design: A multiphase qualitative study consisting of in situ hospital ICD clinic observations, and semistructured interviews of clinicians, patients and relatives. Data were analysed using a constant comparative approach.

Setting: One tertiary and two district general hospitals in England.

Participants: We completed 38 observations of hospital consultations prior to ICD implantation, and 80 interviews with patients, family members and clinicians between 2013 and 2015. Patients were recruited from preimplantation to postdeactivation. Clinicians included cardiologists, cardiac physiologists, heart failure nurses and palliative care professionals.

Results: Four key themes were identified from the data: the current status of deactivation discussions; patients' perceptions of deactivation; who should take responsibility for deactivation discussions and decisions; and timing of deactivation discussions. We found that although patients and doctors recognised the importance of advance care planning, including ICD deactivation at an early stage in the patient journey, this was often not reflected in practice. The most appropriate clinician to take the lead was thought to be dependent on the context, but could include any appropriately trained member of the healthcare team. It was suggested that deactivation should be raised preimplantation and regularly reviewed. Identification of trigger points postimplantation for deactivation discussions may help ensure that these are timely and inappropriate shocks are avoided.

Conclusions: There is a need for early, ongoing and evolving discussion between ICD recipients and clinicians regarding the eventual need for ICD deactivation. The most appropriate clinician to instigate deactivation discussions is likely to vary between patients and models of care. Reminders at key trigger points, and routine discussion of deactivation at implantation and during advance care planning could prevent distressing experiences for both the patient and their family at the end of life.
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http://dx.doi.org/10.1136/bmjopen-2020-048024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261879PMC
July 2021

From gateways to multilinear connections: A qualitative longitudinal investigation of the relationships between vaping and smoking among adolescent users.

Int J Drug Policy 2021 Jul 3;97:103341. Epub 2021 Jul 3.

College of Life Sciences, University of Leicester, Leicester, LE1 7RH, UK.

Background: The international growth of e-cigarette use has been accompanied by a corresponding concern that e-cigarettes will act as a 'gateway' to smoking and the use of other drugs. Taking these concerns as our point of departure, we explore the relationships between vaping and smoking among a cohort of young people.

Methods: Qualitative longitudinal methods with a diverse sample of 36 14-18-year olds from the UK city of Leicester. A total of 66 depth interviews conducted across two phases separated by 6-12 months. The interviews were recorded, transcribed verbatim and thematically analysed.

Findings: We highlight a complex 'tangle' of connections between substances/risk behaviours recounted to us by our adolescent study participants, including multiple and multilinear relationships between vaping and smoking. These findings problematise some of the core axioms of the notion of gateways as an explanatory model of causality and sequential connection between smoking and vaping. They also throw into question gateway logics more fundamentally. While many of our study participants themselves consciously invoked ideas of 'gateway effects', the accounts they produced repeatedly disrupted the logics of connection (between e-cigarettes and smoking; one set of behaviours and another) presupposed in gateway theory and our own early lines of questioning. Accordingly, we explore how cultural understandings of gateway effects are invoked by users in accounting for their vaping and smoking behaviours, noting the potential influence of these ideas upon the very processes they are understood to apprehend.

Conclusion: Our findings suggest there is a case to be made to reinforce the distinctiveness of tobacco and e-cigarettes in the life-worlds of young people to avoid naturalising a 'gateway' logic of connection that might ultimately inform the associative logic of young users themselves, and potentially the development of their usage careers.
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http://dx.doi.org/10.1016/j.drugpo.2021.103341DOI Listing
July 2021

Decision-Making Capacity, Opioid Use Disorder, and the 3-Stage Model of Addiction.

Mayo Clin Proc 2021 08 3;96(8):2040-2042. Epub 2021 Jul 3.

Department of Internal Medicine, Program in Addiction Medicine, Yale School of Medicine, New Haven, CT; VA Connecticut Healthcare System, West Haven, CT. Electronic address:

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http://dx.doi.org/10.1016/j.mayocp.2021.04.020DOI Listing
August 2021

Failure rates and clinical outcomes after treatment for long-head biceps brachii tendon pathology: a comparison of three treatment types.

JSES Int 2021 Jul 10;5(4):630-635. Epub 2021 May 10.

Department of Orthopaedic Surgery, UPMC Freddie Fu Sports Medicine Center, University of Pittsburgh, Pittsburgh, PA, USA.

Hypothesis/background: Treatment options for the biceps brachii tendon include tenotomy, arthroscopic tenodesis, and open tenodesis. Few studies to date have compared all treatment options in the context of a rotator cuff repair.

Methods: A retrospective review of 100 patients who underwent arthroscopic supraspinatus repair between 2013 and 2018 with a minimum of one-year follow-up was performed. Patients were separated into the following 4 groups: (1) 57 had isolated supraspinatus repair with no biceps tendon surgery (SSP); (2) 16 had supraspinatus repair and biceps tenotomy; (3) 18 had supraspinatus repair and arthroscopic biceps tenodesis; (4) 9 had supraspinatus repair and an open biceps tenodesis (SSP + OT). The primary outcome was operative time. The secondary outcomes were cost analysis, complications, patient-reported outcome measures, range of motion, and strength testing.

Results: The operative time for the SSP + OT group was significantly longer than that of the SSP group ( < .05) but was not significantly longer than that of the other groups. The cost for the SSP group was significantly less than the cost for the SSP + OT and supraspinatus repair and arthroscopic biceps tenodesis groups ( < .05 for both), whereas the cost for the supraspinatus repair and biceps tenotomy group was significantly less than the cost for the SSP + OT group ( < .05). There were no significant differences between groups for complications, all patient-reported outcome measues, all range of motion, and all strength parameters.

Discussion/conclusion: Operative time is the longest in open biceps tenodesis and is significantly longer than that of isolated supraspinatus repair. No significant differences in operative times or costs were identified in patients undergoing arthroscopic vs. open biceps tenodesis. All patients, irrespective of the type of biceps tendon procedure, had excellent clinical and functional outcomes at least one year after surgery. There was no difference in clinical or functional outcomes, or complications, among the 4 groups.
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http://dx.doi.org/10.1016/j.jseint.2021.04.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245991PMC
July 2021

Pharmacists' and pharmacy technicians' scopes of practice in the management of minor ailments at community pharmacies in Indonesia: a cross-sectional study.

Pharm Pract (Granada) 2021 Apr-Jun;19(2):2295. Epub 2021 May 26.

PhD. Adjunct Professor. Pharmacy, Curtin Medical School, Curtin University. Perth, WA (Australia).

Background: Managing minor ailments in community pharmacy is an evolving pharmacy service in developing countries. Defined scopes of practice for pharmacy staff are essential for the safe management of minor ailments. Limited research exists regarding the perceptions of Indonesian pharmacists' and pharmacy technicians' scopes of practice in providing minor ailments management services.

Objective: To evaluate pharmacists' and pharmacy technicians' understanding of their scopes of practice, perceived competency and factors influencing the delivery of minor ailments services in Indonesian community pharmacies.

Methods: Cross-sectional surveys were conducted during January-February 2020 of pharmacists and pharmacy technicians attending seminars conducted by relevant Indonesian Associations in Central Java, Indonesia. Percentage of common responses (PCR) described similarity of perceived scopes of practice for pharmacists and pharmacy technicians. Univariate and multivariate analyses identified associations of scopes of practice with pharmacy characteristics.

Results: A total of 185 pharmacists and 142 pharmacy technicians participated. Pharmacy technicians performed minor ailment consultations, however, if considered beyond their scope of practice, they referred the patient to the pharmacist (T=120/142, 84.5%). Vaginal thrush, bacterial conjunctivitis, gastro-oesophageal reflux disease, and acute pain were minor ailments perceived only within a pharmacist's scope (PCR above 60%). Of 34 minor ailments, 11 showed PCR values between 40-60% overlapping pharmacists and pharmacy technicians perceived scopes of practice (allergy/rash, back pain, cold sores, dermatitis, diarrhoea, eczema, hayfever, haemorrhoids, rheumatism, sore throat, and superficial wounds). Back pain, cold sores, dermatitis, and sore throat associated pharmacists' scope of practice with years of practice experience (p-value<0.05). Pharmacy technicians perceived their scopes of practice to be wider than perceived by pharmacists.

Conclusions: Discordance between pharmacists' and pharmacy technicians' perceived scopes of minor ailments management highlights the need for clearly defined scopes of practice for each professional group. Each professional group must practise within their competence to ensure safe pharmacy practices.
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http://dx.doi.org/10.18549/PharmPract.2021.2.2295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216711PMC
May 2021

Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.

J Neurosurg 2021 Jul 2:1-10. Epub 2021 Jul 2.

1Department of Neurosurgery and.

Objective: The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors' a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies.

Methods: The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality.

Results: Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23-88 years). The median follow-up was 8.5 months (range 0.1-231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months.

Conclusions: Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.
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http://dx.doi.org/10.3171/2020.12.JNS202517DOI Listing
July 2021

Ethical challenges faced when there is a mismatch between guidelines, patient autonomy and clinical practice.

Br J Hosp Med (Lond) 2021 Jun 30;82(6):1-4. Epub 2021 Jun 30.

Vice Dean, Faculty of Pain Medicine, Royal College of Anaesthetists, London, UK.

This editorial reviews the ethical day-to-day challenges faced by pain specialists when managing each patient's unique requirements, in light of guidelines, clinical practice and interpretation of evidence relating to the assessment and management of chronic pain.
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http://dx.doi.org/10.12968/hmed.2021.0315DOI Listing
June 2021

Anti-NMDA receptor encephalitis and brain atrophy in children and adults: A quantitative study.

Clin Imaging 2021 Oct 1;78:296-300. Epub 2021 Jun 1.

Department of Neurology, Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, United States of America; Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States of America. Electronic address:

Purpose: To determine whether brain atrophy was present in patients with anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE) using qualitative and quantitative analyses of brain magnetic resonance imaging (MRI) and to explore clinical differences in patients with anti-NMDARE with or without brain atrophy.

Methods: A retrospective observational study encompassing the serologic, cerebrospinal fluid, and brain MRI data of 23 patients with anti-NMDARE was conducted. Median patient age was 14 years (interquartile range [IQR], 12 years). The cohort included 15 children (<18 years old) and 8 adults (≥18 years old). There were 6 male and 17 female patients. Imaging analysis involved 2 expert readers' observations of MRIs and automated volumetric quantification using NeuroQuant (CorTechs Labs, Inc.) software.

Results: Of 23 pediatric and adult patients, 11 patients had 14 brain MRIs that were quantitatively analyzed. Quantitative NeuroQuant volumetric analysis showed atrophy in 9 of 14 MRIs for 7 of 11 patients compared to age-controlled normative data. In these 9 MRIs, atrophy was present in the temporal lobes (n = 9), cerebral cortex (n = 3), and cerebellum (n = 3). Qualitative analysis of 59 MRIs (23 patients) revealed volume loss in 6 patients: 5 with global cerebral and temporal lobe volume loss and 1 with temporal lobe volume loss. No patient showed cerebellar volume loss on qualitative analysis. Mean length of stay in the intensive care unit was not significantly different for patients with or without quantitative volume loss (3.5 [5.2] vs 27.4 [23.4] days; p = 0.08).

Conclusions: In this cohort of patients with anti-NMDARE, quantitative volumetric analysis showed brain atrophy, particularly affecting the temporal lobes, in 64% (7/11) of the patients. Qualitative analysis showed brain atrophy in 26% (6/23). These findings highlight the increased sensitivity of quantitative methods for volume loss detection. Larger studies are needed.
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http://dx.doi.org/10.1016/j.clinimag.2021.05.028DOI Listing
October 2021

Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data.

Elife 2021 06 29;10. Epub 2021 Jun 29.

Division of Infection and Immunity, University College London, London, United Kingdom.

Background: Rapid identification and investigation of healthcare-associated infections (HCAIs) is important for suppression of SARS-CoV-2, but the infection source for hospital onset COVID-19 infections (HOCIs) cannot always be readily identified based only on epidemiological data. Viral sequencing data provides additional information regarding potential transmission clusters, but the low mutation rate of SARS-CoV-2 can make interpretation using standard phylogenetic methods difficult.

Methods: We developed a novel statistical method and sequence reporting tool (SRT) that combines epidemiological and sequence data in order to provide a rapid assessment of the probability of HCAI among HOCI cases (defined as first positive test >48 hr following admission) and to identify infections that could plausibly constitute outbreak events. The method is designed for prospective use, but was validated using retrospective datasets from hospitals in Glasgow and Sheffield collected February-May 2020.

Results: We analysed data from 326 HOCIs. Among HOCIs with time from admission ≥8 days, the SRT algorithm identified close sequence matches from the same ward for 160/244 (65.6%) and in the remainder 68/84 (81.0%) had at least one similar sequence elsewhere in the hospital, resulting in high estimated probabilities of within-ward and within-hospital transmission. For HOCIs with time from admission 3-7 days, the SRT probability of healthcare acquisition was >0.5 in 33/82 (40.2%).

Conclusions: The methodology developed can provide rapid feedback on HOCIs that could be useful for infection prevention and control teams, and warrants further prospective evaluation. The integration of epidemiological and sequence data is important given the low mutation rate of SARS-CoV-2 and its variable incubation period.

Funding: COG-UK HOCI funded by COG-UK consortium, supported by funding from UK Research and Innovation, National Institute of Health Research and Wellcome Sanger Institute.
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http://dx.doi.org/10.7554/eLife.65828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285103PMC
June 2021
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