bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the content and context of pain within paediatric rheumatology healthcare professional curricula in the UK: a summative content analysis
Authors: Lee Rebecca Rachael , McDonagh Janet E. , Connelly Mark , Peters Sarah , Cordingley Lis
Published: August 2021

Background

The curriculum for professionals working in paediatric rheumatology should include pain but it is unclear to what extent this currently occurs. The aim of this study was to identify pain-related curriculum content and the context in which pain is presented in educational and training documentation for healthcare professionals in this clinical speciality.

Methods

Core curricula documents from UK based professional organisations were identified in partnership with healthcare professionals. Documents were analysed using a summative content analysis approach. Key pain terms were quantified and weighted frequencies were used to explore narrative pain themes. Latent content was interpreted qualitatively to explore the context within which pain terms were positioned.

Results

Nine curriculum documents were identified and analysed from doctors, nurses, physiotherapists and occupational therapists specialising in paediatric rheumatology. Pain themes represented a mean percentage of 1.51% of text across all documents. Pain was rarely presented in the context of both inflammatory and non-inflammatory condition types despite being a common feature of each. Musculoskeletal pain was portrayed simply as a ‘somatic’ symptom, rather than as a complex phenomenon involving biological and psychosocial processes. Content around the assessment and management of pain was vague and inexplicit.

Conclusion

Current educational and training documentation in paediatric rheumatology do not include core pain topics. Curricula for these healthcare professionals would benefit from updates in contemporary pain theories and examples of in-context, evidence-based pain practices. This should be a priority starting point for optimising patient pain care in paediatric musculoskeletal healthcare.
Golimumab in juvenile idiopathic arthritis-associated uveitis unresponsive to Adalimumab
Authors: Lanz Sofia , Seidel Gerald , Skrabl-Baumgartner Andrea
Published: August 2021

Objective

To assess the efficacy of golimumab (GLM) as a treatment option for juvenile idiopathic arthritis (JIA)-associated uveitis refractory to adalimumab (ADA).

Methods

Retrospective single-centre study including patients with JIA receiving GLM for active uveitis after failing ADA. JIA- and uveitis-related data, including intraocular inflammation, best-corrected visual acuity, corticosteroid-sparing potential, and ocular complications were evaluated at start of GLM treatment, at 1 month and 3 months, and every 3 months thereafter during GLM administration. We further investigated the association of response to GLM with primary and secondary failure of ADA treatment.

Results

Ten patients were studied, all female (17 affected eyes, mean age 14.3 + 6.7 yrs., mean follow-up 25.2 + 21.7 mos). Two patients were switched to GLM because of primary non-response to ADA. Eight were switched because of loss of response (LOR).

In 5 of the latter LOR was associated with neutralizing anti-ADA-antibodies. Response to GLM was observed in all 8 patients with LOR, while the 2 patients with primary non-response to ADA also did not respond to GLM. Three of the 8 responders experienced LOR. At the end of follow-up 4 of the 5 remaining responders had achieved complete response. One had achieved partial response.

Conclusion

GLM is an efficacious therapeutic option in patients who experience LOR to ADA. Our data indicate that patients without primary response to ADA should be rather switched to a biologic agent with a different mode of action instead of further blocking the TNF-alpha pathway.
Breaking a dogma: acute anti-inflammatory treatment alters both post-lesional functional recovery and endogenous adaptive plasticity mechanisms in a rodent model of acute peripheral vestibulopathy
Authors: El Mahmoudi Nada , Rastoldo Guillaume , Marouane Emna , Péricat David , Watabe Isabelle , Tonetto Alain , Hautefort Charlotte , Chabbert Christian , Sargolini Francesca , Tighilet Brahim
Published: August 2021

Background

Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained spinning vertigo, spontaneous ocular nystagmus and oscillopsia, perceptual-cognitive, posturo-locomotor, and vegetative disorders. We assessed the effectiveness of acute corticotherapy, and the functional role of acute inflammation observed after sudden unilateral vestibular loss.

Methods

We used the rodent model of unilateral vestibular neurectomy, mimicking the syndrome observed in patients with APV. We treated the animals during the acute phase of the vestibular syndrome, either with placebo or methylprednisolone, an anti-inflammatory corticosteroid. At the cellular level, impacts of methylprednisolone on endogenous plasticity mechanisms were assessed through analysis of cell proliferation and survival, glial reactions, neuron’s membrane excitability, and stress marker. At the behavioral level, vestibular and posturo-locomotor functions’ recovery were assessed with appropriate qualitative and quantitative evaluations.

Results

We observed that acute treatment with methylprednisolone significantly decreases glial reactions, cell proliferation and survival. In addition, stress and excitability markers were significantly impacted by the treatment. Besides, vestibular syndrome’s intensity was enhanced, and vestibular compensation delayed under acute methylprednisolone treatment.

Conclusions

We show here, for the first time, that acute anti-inflammatory treatment alters the expression of the adaptive plasticity mechanisms in the deafferented vestibular nuclei and generates enhanced and prolonged vestibular and postural deficits. These results strongly suggest a beneficial role for acute endogenous neuroinflammation in vestibular compensation. They open the way to a change in dogma for the treatment and therapeutic management of vestibular patients.
CSF and serum inflammatory response and association with outcomes in spontaneous intracerebral hemorrhage with intraventricular extension: an analysis of the CLEAR-III Trial
Authors: Gusdon Aaron M. , Thompson Carol B. , Quirk Kendel , Mayasi Yunis M. , Avadhani Radhika , Awad Issam A. , Hanley Daniel F. , Ziai Wendy C.
Published: August 2021

Background

Intracerebral hemorrhage (ICH) results in a cascade of inflammatory cell activation with recruitment of peripheral leukocytes to the brain parenchyma and surrounding the hematoma. We hypothesized that in patients with ICH and intraventricular hemorrhage (IVH), a robust cerebrospinal fluid (CSF) inflammatory response occurs with leukocyte subtypes being affected by alteplase treatment and contributing to outcomes.

Methods

Serum and CSF cell counts from patients in the phase 3 Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III) trial were analyzed. CSF leukocytes were corrected for the presence of red blood cells. Trends in cell counts were plotted chronologically. Associations were evaluated between serum and CSF leukocyte subtypes and adjudicated functional outcome (modified Rankin Scale; mRS) at 30 and 180 days and bacterial infection according to treatment with intraventricular alteplase versus saline.

Results

A total of 279 and 292 patients had ≥3 differential cell counts from serum and CSF, respectively. CSF leukocyte subtypes evolved during IVH resolution with a significantly augmented inflammatory response for all subtypes in alteplase- compared to saline-treated patients. CSF leukocyte subtypes were not associated with detrimental effect on functional outcomes in the full cohort, but all were associated with poor 30-day outcome in saline-treated patients with IVH volume ≥20 mL. Higher serum lymphocytes were associated with good functional outcomes (mRS 0–3) in the entire cohort and saline-treated but not alteplase-treated group. Conversely, increased serum neutrophil-to-lymphocyte ratio (NLR) in the entire cohort and saline group was associated with worse functional outcomes. Higher median serum lymphocytes were associated with the absence of infection at 7 days.

Conclusions

Aseptic CSF inflammation after IVH involves all leukocyte subtypes. Serum lymphocytes may be associated with better outcomes by mitigating infection. Alteplase augments the inflammatory response without affecting outcomes.
Soluble tumor necrosis factor-alpha-induced hyperexcitability contributes to retinal ganglion cell apoptosis by enhancing Nav1.6 in experimental glaucoma
Authors: Cheng Shuo , Wang Hong-Ning , Xu Lin-Jie , Li Fang , Miao Yanying , Lei Bo , Sun Xinghuai , Wang Zhongfeng
Published: August 2021

Background

Neuroinflammation plays an important role in the pathogenesis of glaucoma. Tumor necrosis factor-alpha (TNF-α) is a major pro-inflammatory cytokine released from activated retinal glial cells in glaucoma. Here, we investigated how TNF-α induces retinal ganglion cell (RGC) hyperexcitability and injury.

Methods

Whole-cell patch-clamp techniques were performed to explore changes in spontaneous firing and evoked action potentials, and Na+ currents in RGCs. Both intravitreal injection of TNF-α and chronic ocular hypertension (COH) models were used. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the molecular mechanisms of TNF-α effects on RGCs.

Results

Intravitreal injection of soluble TNF-α significantly increased the spontaneous firing frequencies of RGCs in retinal slices. When the synaptic transmissions were blocked, more than 90% of RGCs still showed spontaneous firing; both the percentage of cells and firing frequency were higher than the controls. Furthermore, the frequency of evoked action potentials was also higher than the controls. Co-injection of the TNF-α receptor 1 (TNFR1) inhibitor R7050 eliminated the TNF-α-induced effects, suggesting that TNF-α may directly act on RGCs to induce cell hyperexcitability through activating TNFR1. In RGCs acutely isolated from TNF-α-injected retinas, Na+ current densities were upregulated. Perfusing TNF-α in RGCs of normal rats mimicked this effect, and the activation curve of Na+ currents shifted toward hyperpolarization direction, which was mediated through p38 MAPK and STAT3 signaling pathways. Further analysis revealed that TNF-α selectively upregulated Nav1.6 subtype of Na+ currents in RGCs. Similar to observations in retinas of rats with COH, intravitreal injection of TNF-α upregulated the expression of Nav1.6 proteins in both total cell and membrane components, which was reversed by the NF-κB inhibitor BAY 11-7082. Inhibition of TNFR1 blocked TNF-α-induced RGC apoptosis.

Conclusions

TNF-α/TNFR1 signaling induces RGC hyperexcitability by selectively upregulating Nav1.6 Na+ channels, thus contributing to RGC apoptosis in glaucoma.
Markov modelling of viral load adjusting for CD4 orthogonal variable and multivariate conditional autoregressive mapping of the HIV immunological outcomes among ART patients in Zimbabwe
Authors: Matsena Zingoni Zvifadzo , Chirwa Tobias F. , Todd Jim , Musenge Eustasius
Published: August 2021

Background

This study aimed to jointly model HIV disease progression patterns based on viral load (VL) among adult ART patients adjusting for the time-varying “incremental transients states” variable, and the CD4 cell counts orthogonal variable in a single 5-stage time-homogenous multistate Markov model. We further jointly mapped the relative risks of HIV disease progression outcomes (detectable VL (VL ≥ 50copies/uL) and immune deterioration (CD4 < 350cells/uL) at the last observed visit) conditional not to have died or become loss to follow-up (LTFU).

Methods

Secondary data analysis of individual-level patients on ART was performed. Adjusted transition intensities, hazard ratios (HR) and regression coefficients were estimated from the joint multistate model of VL and CD4 cell counts. The mortality and LTFU transition rates defined the extent of patients’ retention in care. Joint mapping of HIV disease progression outcomes after ART initiation was done using the Bayesian intrinsic Multivariate Conditional Autoregressive prior model.

Results

The viral rebound from the undetectable state was 1.78times more likely compared to viral suppression among patients with VL ranging from 50-1000copies/uL. Patients with CD4 cell counts lower than expected had a higher risk of viral increase above 1000copies/uL and death if their VL was above 1000copies/uL (state 2 to 3 (λ23): HR = 1.83 and (λ34): HR = 1.42 respectively). Regarding the time-varying effects of CD4 cell counts on the VL transition rates, as the VL increased, (λ12 and λ23) the transition rates increased with a decrease in the CD4 cell counts over time. Regardless of the individual’s VL, the transition rates to become LTFU decreased with a decrease in CD4 cell counts. We observed a strong shared geographical pattern of 66% spatial correlation between the relative risks of detectable VL and immune deterioration after ART initiation, mainly in Matabeleland North.

Conclusion

With high rates of viral rebound, interventions which encourage ART adherence and continual educational support on the barriers to ART uptake are crucial to achieve and sustain viral suppression to undetectable levels. Area-specific interventions which focus on early ART screening through self-testing, behavioural change campaigns and social support strategies should be strengthened in heavily burdened regions to sustain the undetectable VL. Sustaining undetectable VL lowers HIV transmission in the general population and this is a step towards achieving zero HIV incidences by 2030.
Functional analysis of a monoclonal antibody reactive against the C1C2 of Env obtained from a patient infected with HIV-1 CRF02_AG
Authors: Md Zahid Hasan , Kuwata Takeo , Takahama Shokichi , Kaku Yu , Biswas Shashwata , Matsumoto Kaho , Tamamura Hirokazu , Matsushita Shuzo
Published: August 2021

Background

Recent data suggest the importance of non-neutralizing antibodies (nnAbs) in the development of vaccines against HIV-1 because two types of nnAbs that recognize the coreceptor binding site (CoRBS) and the C1C2 region mediate antibody-dependent cellular-cytotoxicity (ADCC) against HIV-1-infected cells. However, many studies have been conducted with nnAbs obtained from subtype B-infected individuals, with few studies in patients with non-subtype B infections.

Results

We isolated a monoclonal antibody 1E5 from a CRF02_AG-infected individual and constructed two forms of antibody with constant regions of IgG1 or IgG3. The epitope of 1E5 belongs to the C1C2 of gp120, and 1E5 binds to 27 out of 35 strains (77 %) across the subtypes. The 1E5 showed strong ADCC activity, especially in the form of IgG3 in the presence of small CD4-mimetic compounds (CD4mc) and 4E9C (anti-CoRBS antibody), but did not show any neutralizing activity even against the isolates with strong binding activities. The enhancement in the binding of A32, anti-C1C2 antibody isolated from a patient with subtype B infection, was observed in the presence of 1E5 and the combination of 1E5, A32 and 4E9C mediated a strong ADCC activity.

Conclusions

These results suggest that anti-C1C2 antibodies that are induced in patients with different HIV-1 subtype infections have common functional modality and may have unexpected interactions. These data may have implications for vaccine development against HIV-1.

Graphical abstract
Metabolic phenotype of B cells from young and elderly HIV individuals
Authors: Frasca Daniela , Pallikkuth Suresh , Pahwa Savita
Published: August 2021

Background

HIV infection induces inflammaging and chronic immune activation (IA), which are negatively associated with protective humoral immunity. Similar to HIV, aging is also associated with increased inflammaging and IA. The metabolic requirements of B cell responses in HIV infected (HIV+) individuals are not known, although metabolic abnormalities have been reported in these individuals. How these metabolic abnormalities are exacerbated by aging is also not known.

Methods

B cells were isolated by magnetic sorting from the blood of young and elderly HIV + individuals, as well as from the blood of age-matched healthy controls. We evaluated the composition of the B cell pool by flow cytometry, the expression of RNA for pro-inflammatory and metabolic markers by qPCR and their metabolic status using a Seahorse XFp extracellular flux analyzer.

Results

In this study we have evaluated for the first time the metabolic phenotype of B cells from young and elderly HIV + individuals as compared to those obtained from age-matched healthy controls. Results show that the B cell pool of HIV + individuals is enriched in pro-inflammatory B cell subsets, expresses higher levels of RNA for pro-inflammatory markers and is hyper-metabolic, as compared to healthy controls, and more in elderly versus young HIV + individuals, suggesting that this higher metabolic phenotype of B cells is needed to support B cell IA. We have identified the subset of Double Negative (DN) B cells as the subset mainly responsible for this hyper-inflammatory and hyper-metabolic profile.

Conclusions

Our results identify a relationship between intrinsic B cell inflammation and metabolism in HIV + individuals and suggest that metabolic pathways in B cells from HIV + individuals may be targeted to reduce inflammaging and IA and improve B cell function and antibody responses.
The impact of visuospatial perception on distance judgment and depth perception in an Augmented Reality environment in patients after stroke: an exploratory study
Authors: Höhler Chiara , Rasamoel Nils David , Rohrbach Nina , Hansen John Paulin , Jahn Klaus , Hermsdörfer Joachim , Krewer Carmen
Published: August 2021

Background

Augmented Reality (AR)-based interventions are applied in neurorehabilitation with increasing frequency. Depth perception is required for the intended interaction within AR environments. Until now, however, it is unclear whether patients after stroke with impaired visuospatial perception (VSP) are able to perceive depth in the AR environment.

Methods

Different aspects of VSP (stereovision and spatial localization/visuoconstruction) were assessed in 20 patients after stroke (mean age: 64 ± 14 years) and 20 healthy subjects (HS, mean age: 28 ± 8 years) using clinical tests. The group of HS was recruited to assess the validity of the developed AR tasks in testing stereovision. To measure perception of holographic objects, three distance judgment tasks and one three-dimensionality task were designed. The effect of impaired stereovision on performance in each AR task was analyzed. AR task performance was modeled by aspects of VSP using separate regression analyses for HS and for patients.

Results

In HS, stereovision had a significant effect on the performance in all AR distance judgment tasks (p = 0.021,p = 0.002,p = 0.046) and in the three-dimensionality task (p = 0.003). Individual quality of stereovision significantly predicted the accuracy in each distance judgment task and was highly related to the ability to perceive holograms as three-dimensional (p = 0.001). In stroke-survivors, impaired stereovision had a specific deterioration effect on only one distance judgment task (p = 0.042), whereas the three-dimensionality task was unaffected (p = 0.317). Regression analyses confirmed a lacking impact of patients’ quality of stereovision on AR task performance, while spatial localization/visuoconstruction significantly prognosticated the accuracy in distance estimation of geometric objects in two AR tasks.

Conclusion

Impairments in VSP reduce the ability to estimate distance and to perceive three-dimensionality in an AR environment. While stereovision is key for task performance in HS, spatial localization/visuoconstruction is predominant in patients. Since impairments in VSP are present after stroke, these findings might be crucial when AR is applied for neurorehabilitative treatment. In order to maximize the therapy outcome, the design of AR games should be adapted to patients’ impaired VSP. 

Trial registration: The trial was not registered, as it was an observational study.
Discovery of metabolic biomarkers for gestational diabetes mellitus in a Chinese population
Authors: Lu Wenqian , Luo Mingjuan , Fang Xiangnan , Zhang Rong , Li Shanshan , Tang Mengyang , Yu Xiangtian , Hu Cheng
Published: August 2021

Background

Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, can lead to morbidity and mortality in both the mother and the infant. Metabolomics has provided new insights into the pathology of GDM and systemic analysis of GDM with metabolites is required for providing more clues for GDM diagnosis and mechanism research. This study aims to reveal metabolic differences between normal pregnant women and GDM patients in the second- and third-trimester stages and to confirm the clinical relevance of these new findings.

Methods

Metabolites were quantitated with the serum samples of 200 healthy pregnant women and 200 GDM women in the second trimester, 199 normal controls, and 199 GDM patients in the third trimester. Both function and pathway analyses were applied to explore biological roles involved in the two sets of metabolites. Then the trimester stage-specific GDM metabolite biomarkers were identified by combining machine learning approaches, and the logistic regression models were constructed to evaluate predictive efficiency. Finally, the weighted gene co-expression network analysis method was used to further capture the associations between metabolite modules with biomarkers and clinical indices.

Results

This study revealed that 57 differentially expressed metabolites (DEMs) were discovered in the second-trimester group, among which the most significant one was 3-methyl-2-oxovaleric acid. Similarly, 72 DEMs were found in the third-trimester group, and the most significant metabolites were ketoleucine and alpha-ketoisovaleric acid. These DEMs were mainly involved in the metabolism pathway of amino acids, fatty acids and bile acids. The logistic regression models for selected metabolite biomarkers achieved the area under the curve values of 0.807 and 0.81 for the second- and third-trimester groups. Furthermore, significant associations were found between DEMs/biomarkers and GDM-related indices.

Conclusions

Metabolic differences between healthy pregnant women and GDM patients were found. Associations between biomarkers and clinical indices were also investigated, which may provide insights into pathology of GDM.
In-flight transmission of wild-type SARS-CoV-2 and the outbreak potential of imported clusters of COVID-19: a review of published evidence
Authors: Kelly David , Bambury Niamh , Boland Mairin
Published: August 2021

International air travel has been highlighted as a concern since the beginning of the COVID-19 pandemic with respect to importation of cases. We summarise the available evidence for in-flight transmission of wild type SARS-CoV-2 during 2020, and for imported COVID-19 clusters to cause outbreaks. This paper provides a data baseline prior to the emergence of new mutations causing SARS-CoV-2 variants of concern, whose characteristics may increase the potential risk of in-flight transmission and imported outbreaks. The evidence on in-flight transmission of wild-type SARS-CoV-2 is limited, and is described in a small number of published reports. Most of the available evidence pertains to the early phase of the COVID-19 pandemic, during a period without non-pharmaceutical interventions such as distancing and in-flight mask wearing. There is considerable potential for outbreaks of COVID-19 from imported cases or clusters when public health guidance around quarantine of travellers and self-isolation of cases is not adhered to. Risks can be mitigated by measures such as: avoiding non-essential travel, targeted testing and quarantine of travellers from high incidence regions or regions of concern, managed quarantine processes, and protocols for rapid investigation and control of transmission from a possible variant of concern. Measures should be dynamically assessed and proportionate to the level of risk.

Graphical abstract
WHO/ISUP grading of clear cell renal cell carcinoma and papillary renal cell carcinoma; validation of grading on the digital pathology platform and perspectives on reproducibility of grade
Authors: Browning Lisa , Colling Richard , Verrill Clare
Published: August 2021

Background

There are recognised potential pitfalls in digital diagnosis in urological pathology, including the grading of dysplasia. The World Health Organisation/International Society of Urological Pathology (WHO/ISUP) grading system for renal cell carcinoma (RCC) is prognostically important in clear cell RCC (CCRCC) and papillary RCC (PRCC), and is included in risk stratification scores for CCRCC, thus impacting on patient management. To date there are no systematic studies examining the concordance of WHO/ISUP grading between digital pathology (DP) and glass slide (GS) images. We present a validation study examining intraobserver agreement in WHO/ISUP grade of CCRCC and PRCC.

Methods

Fifty CCRCCs and 10 PRCCs were graded (WHO/ISUP system) by three specialist uropathologists on three separate occasions (DP once then two GS assessments; GS1 and GS2) separated by wash-out periods of at least two-weeks. The grade was recorded for each assessment, and compared using Cohen’s and Fleiss’s kappa.

Results

There was 65 to 78% concordance of WHO/ISUP grading on DP and GS1. Furthermore, for the individual pathologists, the comparative kappa scores for DP versus GS1, and GS1 versus GS2, were 0.70 and 0.70, 0.57 and 0.73, and 0.71 and 0.74, and with no apparent tendency to upgrade or downgrade on DP versus GS. The interobserver kappa agreement was less, at 0.58 on DP and 0.45 on GS.

Conclusion

Our results demonstrate that the assessment of WHO/ISUP grade on DP is noninferior to that on GS. There is an apparent slight improvement in agreement between pathologists on RCC grade when assessed on DP, which may warrant further study.
Naloxone availability in independent community pharmacies in Georgia, 2019
Authors: Gilbert Lauren , Elliott Jennifer , Beasley Lauren , Oranu Ekene , Roth Kimberly , Nguyễn Jennifer
Published: August 2021

Background

Increasing the availability of naloxone among people who use opioids, and friends and family of past and present people who use opioids is a vitally important mission to reduce the occurrence of opioid-related overdose deaths. The purpose of this study was to determine the availability of naloxone in independent community pharmacies in Georgia. Secondary objectives include determining pharmacists’ knowledge regarding the standing order and ability to counsel regarding naloxone.

Methods

A cross-sectional study using a secret shopper approach with phone contact was conducted over a period of 10 months. The study was population based and was conducted at all independent pharmacies in the state of Georgia. All independent community pharmacies in the state of Georgia were contacted and asked the naloxone questions with a 96% response rate (n = 520).

Results

Five hundred fifty-eight independent community pharmacies were called, with a 96% response rate (n = 520 pharmacies). Two hundred-twenty pharmacies reported having naloxone in stock. Of the 335 pharmacists asked, 174 (51.9%) incorrectly said that a prescription was required. The mean (SD) cash price was $148.02 (27.40), with a range of $0 to $300. Of 237 pharmacists asked who had naloxone in stock or who stated they could get naloxone in stock, 212 stated that they could demonstrate how to use it, 8 stated they could not, and 17 said that they possibly could or were unsure how to use it.

Conclusions

This study provided insight into the limited availability of naloxone at independent community pharmacies in Georgia after the standing order was issued. The majority of pharmacists at independent pharmacies in Georgia were not using the publicly available state naloxone standing order. Additionally, the low availability of naloxone and its high cost for uninsured individuals are significant structural barriers for reducing opioid-related mortality.
Nomogram to predict collapse-free survival after core decompression of nontraumatic osteonecrosis of the femoral head
Authors: Zhao En-Ze , Liu Zun-Han , Zeng Wei-Nan , Ding Zi-Chuan , Luo Zhen-Yu , Zhou Zong-Ke
Published: August 2021

Background

Nontraumatic osteonecrosis of the femoral head (NONFH) is a devastating disease, and the risk factors associated with progression into collapse after core decompression (CD) remain poorly defined. Therefore, we aim to define risk factors associated with collapse-free survival (CFS) after CD of precollapse NONFH and to propose a nomogram for individual risk prediction.

Methods

According to the baseline characteristics, clinical information, radiographic evaluations, and laboratory examination, a nomogram was developed using a single institutional cohort of patients who received multiple drilling for precollapse NONFH between January 2007 and December 2019 to predict CFS after CD of precollapse NONFH. Furthermore, we usedCstatistics, calibration plot, and Kaplan-Meier curve to test the discriminative ability and calibration of the nomogram to predict CFS.

Results

One hundred and seventy-three patients who underwent CD for precollapse NONFH were retrospectively screened and included in the present study. Using a multiple Cox regression to identify relevant risk factors, the following risk factors were incorporated in the prediction of CFS: acute onset of symptom (HR, 2.78; 95% CI, 1.03–7.48;P= 0.043), necrotic location of Japanese Investigation Committee (JIC) C1 and C2 (HR, 3.67; 95% CI, 1.20–11.27;P= 0.023), necrotic angle in the range of 250–299°(HR, 5.08; 95% CI, 1.73–14.93;P= 0.003) and > 299° (HR, 9.96; 95% CI, 3.23–30.70;P< 0.001), and bone marrow edema (BME) before CD (HR, 2.03; 95% CI, 1.02-4.02;P= 0.042). TheCstatistics was 0.82 for CFS which revealed good discriminative ability and calibration of the nomogram.

Conclusions

Independent predictors of progression into collapse after CD for precollapse NONFH were identified to develop a nomogram predicting CFS. In addition, the nomogram could divide precollapse NONFH patients into prognosis groups and performed well in internal validation.
Atypical and rare cause of myocardial infarction: coronary subclavian steal syndrome (CSSS) treated by a carotid-subclavian bypass in a 71-year-old female patient
Authors: Walensi Mikolaj , Bernheim Johannes , Ulatowski Nikodemus , Piotrowski Michal , Karaindros Konstantinos , Juntermanns Benjamin , Mikat Christian , Heesen Roland , Hoffmann Johannes N.
Published: August 2021

Background

The coronary subclavian steal syndrome (CSSS) is a rare complication after coronary arterial bypass graft operations (CABG) using the left or right internal mammary artery ((L/R)IMA). It results from a retrograde blood flow from the IMA into the subclavian artery (SA) due to a stenosis or occlusion of the SA proximal to the IMA origin. This “steal phenomenon” leads to a decreased blood flow in the IMA and may result in myocardial ischemia (MIS) and even myocardial infarction (MIN). Treatment options include interventional and surgical therapy.

Case presentation

We report the case of a 71-year old woman, who suffered from an acute non-ST elevation myocardial infarction (NSTEMI) 11 years after LIMA-CABG surgery and who was treated successfully with a carotid-subclavian bypass (CSB) after failed interventional therapy.

Conclusion

CSB may be regarded as a viable treatment option for patients suffering CSSS in the case of MIS and even an acute MIN/NSTEMI, especially in the case of missing or failed interventional therapy attempts. Specialists in cardiothoracic and vascular surgery should be aware of possible CSSS conditions and know about appropriate diagnostic and therapeutic options.
Two large-scale forest scenario modelling approaches for reporting CO2 removal: a comparison for the Romanian forests
Authors: Blujdea Viorel N. B. , Sikkema Richard , Dutca Ioan , Nabuurs Gert-Jan
Published: August 2021

Background

Forest carbon models are recognized as suitable tools for the reporting and verification of forest carbon stock and stock change, as well as for evaluating the forest management options to enhance the carbon sink provided by sustainable forestry. However, given their increased complexity and data availability, different models may simulate different estimates. Here, we compare carbon estimates for Romanian forests as simulated by two models (CBM and EFISCEN) that are often used for evaluating the mitigation options given the forest-management choices.

Results

The models, calibrated and parameterized with identical or harmonized data, derived from two successive national forest inventories, produced similar estimates of carbon accumulation in tree biomass. According to CBM simulations of carbon stocks in Romanian forests, by 2060, the merchantable standing stock volume will reach an average of 377 m3 ha−1, while the carbon stock in tree biomass will reach 76.5 tC ha−1. The EFISCEN simulations produced estimates that are about 5% and 10%, respectively, lower. In addition, 10% stronger biomass sink was simulated by CBM, whereby the difference reduced over time, amounting to only 3% toward 2060.

Conclusions

This model comparison provided valuable insights on both the conceptual and modelling algorithms, as well as how the quality of the input data may affect calibration and projections of the stock and stock change in the living biomass pool. In our judgement, both models performed well, providing internally consistent results. Therefore, we underline the importance of the input data quality and the need for further data sampling and model improvements, while the preference for one model or the other should be based on the availability and suitability of the required data, on preferred output variables and ease of use.
The impact of a community based rehabilitation program in Afghanistan: a longitudinal analysis using propensity score matching and difference in difference analysis
Authors: Trani Jean-Francois , Vasquez-Escallon Juanita , Bakhshi Parul
Published: August 2021

Background

The 2006 United Nations Convention on the Rights of Persons with Disabilities states that the achievement of equal rights, empowerment and social inclusion of people with disabilities requires comprehensive rehabilitation services encompassing all components of the World Health Organization Community based rehabilitation (CBR) matrix: health, education, livelihood, social and empowerment. CBR programs specifically aim to deliver such comprehensive interventions. In the present study, we investigate the impact of a CBR program in Afghanistan on all these components.

Methods

We enrolled 1861 newly recruited CBR participants with disabilities in the study, from 169 villages between July 2012 and December 2013 as well as 1132 controls with disabilities randomly selected through a two-stage process within 6000 households from 100 villages in the same provinces but outside the catchment area of the CBR program. We interviewed them again after one (midline) and two (end-line) years in the study. Using propensity score matching and difference in difference analysis, we estimated the impact of the CBR on outcomes of interest, namely mobility, activities of daily living, communication, participation in social and community life, emotional well-being and employment.

Results

Three years on average into the CBR program, participants showed a significant and close to medium effect size reduction in emotional (Cohen’s d = − 0.48, 95%CI[− 0.58--0.38]), and social participation challenges (Cohen’s d = − 0.45, 95%CI[− 0.53−− 0.36]); small to medium effect size reduction in unemployment (Cohen’s d = − 0.21, 95%CI[− 0.33--0.10]), activities of daily living (Cohen’s d = − 0.26, 95%CI[− 0.35--0.18]), mobility (Cohen’s d = − 0.36, 95%CI[− 0.44--.29]) and communication challenges (Cohen’s d = − 0.38, 95%CI[− 0.46--0.3]).

Conclusions

Our study indicates that a CBR program may provide positive rehabilitation outcomes for persons with disabilities even in a conflict context, and improve overall well-being of all participants with disabilities, whatever their impairment, individual characteristics and the CBR matrix components considered.

Trial registration

ISRCTN, ISRCTN50214054. Registered August 5th 2020 - retrospectively registered
Comparison of 16S and whole genome dog microbiomes using machine learning
Authors: Lewis Scott , Nash Andrea , Li Qinghong , Ahn Tae-Hyuk
Published: August 2021

Background

Recent advances in sequencing technologies have driven studies identifying the microbiome as a key regulator of overall health and disease in the host. Both 16S amplicon and whole genome shotgun sequencing technologies are currently being used to investigate this relationship, however, the choice of sequencing technology often depends on the nature and experimental design of the study. In principle, the outputs rendered by analysis pipelines are heavily influenced by the data used as input; it is then important to consider that the genomic features produced by different sequencing technologies may emphasize different results.

Results

In this work, we use public 16S amplicon and whole genome shotgun sequencing (WGS) data from the same dogs to investigate the relationship between sequencing technology and the captured gut metagenomic landscape in dogs. In our analyses, we compare the taxonomic resolution at the species and phyla levels and benchmark 12 classification algorithms in their ability to accurately identify host phenotype using only taxonomic relative abundance information from 16S and WGS datasets with identical study designs. Our best performing model, a random forest trained by the WGS dataset, identified a species (Bacteroides coprocola) that predominantly contributes to the abundance of leuB, a gene involved in branched chain amino acid biosynthesis; a risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. This trend was not conserved when we trained the model using 16S sequencing profiles from the same dogs.

Conclusions

Our results indicate that WGS sequencing of dog microbiomes detects a greater taxonomic diversity than 16S sequencing of the same dogs at the species level and with respect to four gut-enriched phyla levels. This difference in detection does not significantly impact the performance metrics of machine learning algorithms after down-sampling. Although the important features extracted from our best performing model are not conserved between the two technologies, the important features extracted from either instance indicate the utility of machine learning algorithms in identifying biologically meaningful relationships between the host and microbiome community members. In conclusion, this work provides the first systematic machine learning comparison of dog 16S and WGS microbiomes derived from identical study designs.
Decision-making by medical officer in charge during major incidents: a qualitative study
Authors: Hugelius Karin , Rådestad Monica , Al-Dhahir H. , Kurland L.
Published: August 2021

Background

An incident command structure is commonly used to manage responses to major incidents. In the hospital incident command structure, the medical officer in charge (MOC) is in a key position. The decision-making process is essential to effective management, but little is known about which factors influence the process. Therefore, the current study aimed to describe factors influencing decision-making of MOCs.

Methods

A conventional content analysis was conducted based on 16 individual interviews with medical doctors who had been deployed as MOCs at Swedish hospitals during major incidents.

Results

The results showed that the decision-making and re-evaluation process was a comprehensive analysis influenced by three categories of factors: event factors, including consequences from the type of event, levels of uncertainty and the circumstances; organizational factors, including the doctor’s role, information management and the response to the event; and personal factors, such as competence, personality and mental preparedness.

Conclusions

Reliable and timely information management structure enabling the gathering and analysis of essential information, a clear command structure and appropriate personal qualities were essential and contributed to successful MOCs decision making in major incidents.
Discharge from the trauma centre: exposure to opioids, unmet information needs and lack of follow up—a qualitative study among physical trauma survivors
Authors: Finstad Jeanette , Røise Olav , Rosseland Leiv Arne , Clausen Thomas , Havnes Ingrid Amalia
Published: August 2021

Background

Physical trauma is associated with mortality, long-term pain and morbidity. Effective pain management is fundamental in trauma care and opioids are indispensable for treating acute pain; however, the use and misuse of prescribed opioids is an escalating problem. Despite this, few studies have been directed towards trauma patients in an early phase of rehabilitation with focusing on experiences and perspectives of health and recovery including pain and persistent use of prescribed opioids with abuse potential. To explore pre- and post-discharge trauma care experiences, including exposure to opioids, physical trauma survivors were recruited from a major trauma centre in Norway that provides the highest level of surgical trauma care.

Method

Qualitative exploratory study. Individual semi-structured interviews were conducted among 13 trauma patients with orthopedic injuries, known to be associated with severe pain, six weeks post-discharge. The interviews were recorded, transcribed verbatim, and thematically analyzed with an interdisciplinary approach.

Results

The overarching theme was that discharge from the trauma centre and the period that immediately followed were associated with feelings of insecurity. The three main themes that were identified as contributing to this was (a) unmet information needs about the injury, (b) exposure to opioids, and (c) lack of follow-up after discharge from the hospital. Participants experienced to be discharged with prescribed opioids, but without information about their addictive properties or tapering plans. This, and lack of attention to mental health and psychological impact of trauma, gave rise to unmet treatment needs of pain management and mental health problems during hospitalization and following discharge.

Conclusion

The findings from this study suggest that in addition to delivery of high-quality biomedical trauma care, health professionals should direct more attention to psychosocial health and safe pain management, including post-discharge opioid tapering and individually tailored follow-up plans for physical trauma survivors.
Myxofibrosarcoma harboring an MLH1 pathogenic germline variant associated with Muir-Torre syndrome: a case report
Authors: Nakagawa Makoto , Kobayashi Eisuke , Yamada Masayoshi , Watanabe Tomoko , Hirata Makoto , Tanabe Noriko , Ushiama Mineko , Sakamoto Hiromi , Sato Chiaki , Mori Taisuke , Yoshida Akihiko , Yoshida Teruhiko , Sugano Kokichi , Kawai Akira
Published: August 2021

Background

Muir–Torre syndrome (MTS), which accounts for a small subset (1–3 %) of Lynch syndrome (LS), is an autosomal dominant genetic disorder characterized by sebaceous gland or keratoacanthoma associated with visceral malignancies. Most families with MTS have pathogenic germline variants (PGV) in MSH2. Sarcomas are not common on the LS tumor spectrum, and sarcomas associated with MTS are extremely rare.

Case presentation

Here we report a myxofibrosarcoma of the abdominal wall in a 73-year-old man with a sebaceoma that occurred synchronically, leading to a diagnosis of MTS. The loss of MLH1 and PMS2 protein expression was detected in immunohistochemistry, and high-frequency microsatellite instability (MSI-H) was also confirmed. A germline genetic analysis revealed that he harbored the MLH1 PGV.

Conclusions

This is the first case of MSI-H myxofibrosarcoma with MTS in an MLH1 PGV carrier. Although rare, we should recognize that sarcomas can be part of the spectrum of LS and MTS.
Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock
Authors: Adda Imane , Lai Christopher , Teboul Jean-Louis , Guerin Laurent , Gavelli Francesco , Monnet Xavier
Published: August 2021

Background

Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a “fluid-like” effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR).

Methods

In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65–70 mmHg by default, 80–85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart–lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%.

Results

Norepinephrine was decreased from 0.32 [0.18–0.62] to 0.26 [0.13–0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7–20]% and Pms by 9 [4–19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9–19]% at the higher dose of norepinephrine and 11 [6–16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose.

Conclusions

Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.