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Trauma ◽  
2021 ◽  
pp. 146040862110324
Bernard Kreps ◽  
Stefano Malinverni ◽  
Emma Carles ◽  
Magali Bartiaux ◽  
Pierre Youatou Towo

Introduction Pain is a frequent complaint in the emergency department and should be measured and treated according to the existing protocols. The intranasal route offers several advantages over the oral or intravenous routes. The aim of the study was to evaluate the efficacy and safety of intranasal sufentanil as the primary opioid for acute pain in the emergency department. Materials and methods This was a prospective open-label sequential study in patients who presented to the emergency department with severe non-visceral pain. The control group was treated according to the current standard of care including oral or intravenous opioids whereas the intervention group was treated according to a modified protocol, including intranasal sufentanil as the only opioid. Pain intensity was measured at different time points. The occurrence of side effects, the placement of intravenous lines and the need for additional analgesia were also recorded. Results Pain intensity in the two groups was not comparable at baseline (8.5; IQR 8–10 in the intervention group vs 7.9; IQR 7–9.4 in the control group; p = .026). However, the median reduction of the pain score was significantly larger in the intervention group compared to the control group after 15 minutes (2.5; IQR 1.2 – 4 vs 1.6; IQR 1–2.4; p = .005) and after 30 min (4; IQR 3–5.7 vs 3.1; IQR 2–4.4; p = .02). No significant difference in pain scores between the two groups was observed after 60 min from baseline. Conclusions Patients receiving intranasal sufentanil for severe pain achieved better pain relief at 15 min and 30 min compared to those receiving standard care. Vertigo, nausea, vomiting and diaphoresis were side effects more frequently observed in the sufentanil group. No differences in pain relief were observed after 30 and 60 min from baseline.

2021 ◽  
Vol 11 (1) ◽  
Darren Shu Jeng Ting ◽  
Eunice Tze Leng Goh ◽  
Venkatesh Mayandi ◽  
Joanna M. F. Busoy ◽  
Thet Tun Aung ◽  

AbstractBacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC = 12.5–25.0 μg/ml (5.2–10.4 μM)] and S. epidermidis [MIC = 12.5 μg/ml (5.2 μM)], and moderate efficacy against P. aeruginosa [MIC = 25-50 μg/ml (10.4–20.8 μM)]. CaD23 (at 25 μg/ml or 2× MIC) killed all the bacteria within 30 min, which was 8 times faster than amikacin (25 μg/ml or 20× MIC). After 10 consecutive passages, S. aureus (ATCC SA29213) did not develop any antimicrobial resistance (AMR) against CaD23 whereas it developed significant AMR (i.e. a 32-fold increase in MIC) against amikacin, a commonly used treatment for BK. Pre-clinical murine studies showed that CaD23 (0.5 mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log10 CFU/ml) while not impeding corneal epithelial wound healing. In conclusion, rational hybridization of human-derived HDPs has led to generation of a potentially efficacious and safe topical antimicrobial agent for treating Gram-positive BK, with no/minimal risk of developing AMR.

2021 ◽  
Xiang Zhang ◽  
Yingchang Wang ◽  
xiaojuan Lv ◽  
Fangfang Wang ◽  
Qiong Zhou ◽  

Abstract BackgroundTo evaluate the clinical benefit of concurrent chemoradiotherapy in combination with H101 injection for the treatment of locally advanced cervical cancer (LACC) patients.MethodsThe patients, all diagnosed with stage IIB or III cervical cancer according to The International Federation of Gynecology and Obstetrics (FIGO) stage (2009) with tumor length ≥6cm were enrolled at Zhejiang Cancer Hospital from July 2015 to April 2017. All patients received concurrent chemoradiotherapy (CCRT) in combination with intratumoral H101 injection before and during external beam radiotherapy (EBRT). The parameters recorded and analyzed included progression-free survival (PFS), overall survival (OS), tumor regression after EBRT and side effects, which were compared to another group of patients with similar characteristics treated with CCRT alone.ResultsTwenty patients were treated with CCRT in combination with intratumoral H101 injection and another group of 20 patients treated with CCRT alone was selected as control. The median follow-up time was 38 months (range 10-58 months). The 3-year local, regional, and overall PFS rates were 95% vs 66.6%(p = 0.02), 95% vs 62.5%(p = 0.029), and 65% vs 43.8%(p = 0.19), for H101 group and control group respectively. The 3-year (OS) was 74.3% vs 54.5%(p = 0.098), respectively. The median reduction of tumor length and volume for H101 group and control group were 37.7% vs 28.7%(p = 0.016) and 75.1% vs 62.4%(p = 0.001), respectively. The major adverse event related to H101 was fever.ConclusionCCRT in combination with intratumoral H101 injection is effective in treating LACC, and has an acceptable safety profile.Trial registrationThe study was registered at Chinese Clinical Trail Registry (ChiCTR-OPC-15006142).

2021 ◽  
Vera Porwollik ◽  
Susanne Rolinski ◽  
Jens Heinke ◽  
Werner von Bloh ◽  
Sibyll Schaphoff ◽  

Abstract. Land management practices can reduce the environmental impact of agricultural land use and production, improve productivity, and transform cropland into carbon sinks. We applied the global vegetation model LPJmL5.0-tillage-cc with a modified representation of cover crop practices. We assessed simulated responses to cover crop practices on agroecosystem components in comparison to bare soil fallow between two consecutive primary crops’ growing seasons on global cropland for a simulation period of 50 years. With cover crops and tillage, we obtained annual global median soil carbon sequestration rates of 0.52 and 0.48 t C ha−1 yr−1 for the first and last decades of the entire simulation period, respectively. We found that cover crops with tillage reduced annual nitrogen leaching rates from cropland soils by a median of 39 % and 54 % but also the productivity of the following main crop by average of 1.6 % and 2 % for the two analyzed decades. Largest reduction of productivity were found for rice, modestly lowered for maize and wheat, whereas soybean yield revealed an almost homogenous positive response to cover crop practices during fallow periods. Further, the results suggest that no-tillage is a suitable complementary practice to cover crops, enhancing their environmental benefits and reducing potential trade-offs with the main crop productivity due to their impacts on soil nitrogen and water dynamics. For cover crops applied in conjunction with no-tillage across the mapped Conservation Agriculture cropland area for the period 1974–2010, we estimated a cumulative soil carbon net-accumulation of 1.4 PgC, an annual median reduction of soil nitrogen leaching by 57 %, as well as mostly enhanced yields of the following main crop. The spatial heterogeneity of simulated impacts of cover crops on the variables assessed here was related to the time period since the introduction of the management practice as well as to environmental and agronomic conditions of the cropland. This study supports findings of other studies, highlighting the substantial potential contribution of cover crop practices to the sustainable development of arable production.

2021 ◽  
Vol 12 ◽  
Ronald M. Harper ◽  
Dieter Hertling ◽  
Ashley Curtis ◽  
Eberhardt K. Sauerland ◽  
Christopher M. De Giorgio

Cerebellar stimulation reduces seizures in animals and in humans with drug-resistant epilepsy. In a pilot safety and feasibility study, we applied continuous cutaneous vibratory stimulation (limb proprioceptive cerebellar stimulation) to foot limb proprioceptive receptors to activate cerebellar, pontine, and thalamic structures in drug-resistant epilepsy patients for 8-h nocturnally up to 6-months after a 4-week pre-treatment control baseline. Seizure frequency was evaluated during the baseline control period, and at 6, 12, and 24 weeks after the control recordings. Five-subjects completed at least the first 6-week treatment. At 12-weeks, the median reduction in seizure frequency was −27.8% (mean reduction = −22.3%). Two subjects continued for 24 weeks, with a decline of −44.1 and −45.4%. This pilot study provides support for further clinical studies into the safety and efficacy of limb proprioceptive cerebellar stimulation for epilepsy.

2021 ◽  
Vol 26 (6) ◽  
pp. 615-623
Claire Arbitre ◽  
Yves Pastore ◽  
Benoit Bailey ◽  
Niina Kleiber ◽  
Nancy Robitaille ◽  

OBJECTIVE The aim of this study was to review the use of patient-controlled analgesia (PCA) in sickle cell disease (SCD) for pediatric patients with vaso-occlusive crisis (VOC) in our institution and to compare the effect of early vs late PCA start on pain relief and LOS. METHODS This retrospective study included all pediatric patients treated with PCA for a severe VOC from 2010 to 2016. “Early-PCA” was defined as start of PCA within 48 hours of arrival. Time to reach adequate analgesia was defined as the time to reach 2 consecutive pain scores less than 5/10 at 4-hour interval. RESULTS During the study period, 46 patients presented 87 episodes of VOC treated with PCA. Sixty-three patients with VOC were treated with Early-PCA and 24 with Late-PCA. Both groups were comparable except for median pain score at admission; the Early-PCA group had higher scores: 9.0/10 vs 7.0/10. Time to reach adequate analgesia could be evaluated only in a subset of patients (n = 32) but was shorter in the Early-PCA group with a median difference of 41.0 hours (95% CI −82.0 to −6.0). Early-PCA was associated with a median reduction in LOS of 3.4 days (95% CI −4.9 to −1.9). There was no difference between the 2 groups in terms of side effects and occurrence of acute chest syndrome during hospitalization. CONCLUSIONS In this study, a reduced time to reach adequate analgesia and LOS was noted in the Early-PCA group for severe VOC. A prospective study is required to confirm these results.

2021 ◽  
Carolina Ureta ◽  
Santiago Ramírez-Barahona ◽  
Óscar Calderón-Bustamante ◽  
Pedro Cruz-Santiago ◽  
Carlos Gay ◽  

Abstract Global warming1, is reshaping the distribution of biodiversity across the world and can lead to the occurrence of large-scale singular events, such as the melting of polar ice sheets2,3. The potential impacts of such a melting event on species persistence across taxonomic groups – in terms of magnitude and geographic extent – remain unexplored. Here we assess impacts on biodiversity of global warming and melting of Greenland’s ice sheet on the distribution of 21,146 species of vascular plants and tetrapods across twelve megadiverse countries. We show that high global warming would lead to widespread reductions in species’ geographic ranges (median range loss, 35–78%), which are magnified (median range loss, 95–99%) with the added contribution of Greenland’s melting and its potentially large impact on oceanic circulation and regional climate changes. Our models project a decline in the geographical extent of species hotspots across countries (median reduction, 48–95%) and a substantial alteration of species composition in the near future (mean temporal dissimilarity, 0.26–0.89). These results imply that, in addition to global warming, the influence of Greenland’s melting can lead to the collapse of biodiversity across the globe, providing an added domino in its cascading effects.

2021 ◽  
Vol 23 (1) ◽  
Roger Hesselstrand ◽  
Jörg H. W. Distler ◽  
Gabriela Riemekasten ◽  
Dirk M. Wuttge ◽  
Marie Törngren ◽  

Abstract Objectives To evaluate the changes in disease-related biomarkers and safety of paquinimod, an oral immunomodulatory compound, in patients with systemic sclerosis (SSc). Methods In this open-label, single-arm, multicenter study, SSc patients with a rapidly progressive disease received paquinimod for 8 weeks. Blood and skin biopsies were collected at baseline, during treatment, and at follow-up for the analyses of type I interferon (IFN) activity, chemokine (C-C motif) ligand 2 (CCL2), and the number of myofibroblasts. The safety of paquinimod was evaluated throughout the study. Results Nine SSc patients were enrolled and completed the study treatment with paquinimod at 3 mg/day for 8 weeks. After the treatment, a reduction of type I IFN activity in the plasma from one patient with elevated baseline IFN activity was recorded. A trend towards reduced IFN activity in the skin after treatment was also observed in patients. The serum level of CCL2 was reduced in 7 of 9 patients after paquinimod treatment. There was a median reduction of 10% of the number of myofibroblasts in skin biopsies at week 8 compared to baseline. No change in modified Rodnan skin score and quality of life was detected in the study. Reported adverse events (AEs) were mild to moderate and expected with the most common being arthralgia (n = 3) and headache (n = 3), and C-reactive protein (CRP) increase. Conclusions Analysis of biomarkers before and after treatment suggest reduced type I IFN activity and reduced number of myofibroblasts in lesional skin. Paquinimod was overall well tolerated with mild to moderate and expected AEs. Trial registration, NCT01487551. Registered on 7 September 2011

H Hartley ◽  
S Lane ◽  
B Pizer ◽  
L Bunn ◽  
B Carter ◽  

Abstract Purpose To report the course of ataxia in children up to 2 years post-operatively, following surgical resection of a posterior fossa tumour (PFT). Methods Thirty-five children, (median age 9 years, range 4–15) having resection of PFT, were assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Brief Ataxia Rating Scale (BARS) and the mobility domain of the Paediatric Evaluation of Disability Index (PEDI-m) at initial post-operative period (baseline), 3 months, 1 year and 2 years post-operatively. Results Baseline median scores of the SARA and BARS were 8.5 (range 0–35.5), and 7 (0–25) respectively. Ataxia improved at 3 months (median SARA and BARS reduction 3.5 and 4, respectively). Additional gradual improvements in SARA were recorded at 1 (median reduction 2) and 2 years post-operatively (median reduction 0.5). Median baseline PEDI-m was 54.75 (range 15.2–100) with improvement at 3 months (median increase 36.95) and small improvement at 1 year (median increase 2.5) and 2 years (median increase 5.8). Children with medulloblastoma and midline tumours (median baseline SARA 10 and 11, respectively) demonstrated more severe ataxia than children with low-grade gliomas and unilateral tumours (median baseline SARA 7.5 and 6.5, respectively). Conclusion The largest improvement in ataxia scores and functional mobility scores is demonstrated within the first 3 months post-operatively, but ongoing gradual improvement is observed at 2 years. Children with medulloblastoma and midline tumour demonstrated higher ataxia scores long term.

Alyson K. Baker ◽  
Andrew L. Beardsley ◽  
Brian D. Leland ◽  
Elizabeth A. Moser ◽  
Riad L. Lutfi ◽  

AbstractNoninvasive ventilation (NIV) is a common modality employed to treat acute respiratory failure. Most data guiding its use is extrapolated from adult studies. We sought to identify clinical predictors associated with failure of NIV, defined as requiring intubation. This single-center retrospective observational study included children admitted to pediatric intensive care unit (PICU) between July 2014 and June 2016 treated with NIV, excluding postextubation. A total of 148 patients was included. Twenty-seven (18%) failed NIV. There was no difference between the two groups with regard to age, gender, comorbidities, or etiology of acute respiratory failure. Those that failed had higher admission pediatric risk of mortality (p = 0.01) and pediatric logistic organ dysfunction (p = 0.002) scores and higher fraction of inspired oxygen (FiO2; p = 0.009) at NIV initiation. Failure was associated with lack of improvement in tachypnea. At 6 hours of NIV, the failure group had worsening tachypnea with a median increase in respiratory rate of 8%, while the success group had a median reduction of 18% (p = 0.06). Multivariable Cox's proportional hazard models revealed FiO2 at initiation and worsening respiratory rate at 1- and 6-hour significant risks for failure of NIV. Failure was associated with a significantly longer PICU length of stay (success [2.8 days interquartile range (IQR): 1.7, 5.5] vs. failure [10.6 days IQR: 5.6, 13.2], p < 0.001). NIV can be successfully employed to treat acute respiratory failure in pediatric patients. There should be heightened concern for NIV failure in hypoxemic patients whose tachypnea is unresponsive to NIV. A trend toward improvement should be closely monitored.

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