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BACKGROUND: Emergency department (ED) crowding is a major patient safety concern and has a negative impact on healthcare systems and healthcare providers. We hypothesized that it would be feasible to control crowding by employing a multifaceted approach consisting of systematically fast-tracking patients who are mostly not in need of a hospital stay as assessed by an initial nurse and treated by decision competent physicians. METHODS: Data from 120,901 patients registered in a secondary care ED from the 4tth quarter of 2021 to the 1st quarter of 2024 was drawn from the electronic health record's data warehouse using the SAP Web Intelligence tool and processed in the Python programming language. Crowding was compared before and after ED transformation from a uniform department into a high flow (α) and a low flow (ß) section with patient placement in gurneys/chairs or beds, respectively. Patients putatively not in need of hospitalization were identified by nurse, placed in in the α setting and assessed and treated by decision competent physicians. Incidence of crowding, number of patients admitted per day and readmittances within 72 h following ED admission before and after changes were determined. Values are number of patients, mean ± SEM and mean differences with 95% CIs. Statistical significance was ascertained using Student's two tailed t-test for unpaired values. RESULTS: Before and after ED changes crowding of 130% amounted to 123.8 h and 19.3 h in the latter. This is a difference of -104.6 ± 23.9 h with a 95% CI of -159.9 to -49.3, Δ% -84 (p = 0.002). There was the same amount of patients / day amounting to 135.8 and 133.5 patients / day Δ% = -1.7 patients 95% CI -6.3 to 1.6 (p = 0.21). There was no change in readmittances within 72 h before and after changes amounting to 9.0% versus 9.5%, Δ% = 0.5, 95%, CI -0.007 to 1.0 (p > 0.052). CONCLUSION: It appears feasible to abate crowding with unchanged patient admission and without an increase in readmittances by fast-track assessment and treatment of patients who are not in need of hospitalization.
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Aglomeración , Servicio de Urgencia en Hospital , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , HospitalizaciónRESUMEN
3D cancer cell cultures have enabled new opportunities for replacing compound testing in experimental animals. However, most solid tumors are composed of multiple cell types, including fibroblasts. In this study we developed multicellular tumor heterospheroids composed of cancer and fibroblasts cell lines. We developed heterospheroids by combining HT-29, MCF-7, PANC-1 or SW480 with 1BR.3.G fibroblasts, which we have previously reported support spheroid formation. We also tested fibroblast cell lines, MRC-5, GM00498 and HIF, but 1BR.3.G was found to best form heterospheroids with morphological similarity to in vivo tumor tissue. The architectural organization of heterospheroids was based on histological examination using immunohistochemistry. We found that HT-29 and MCF-7 cells developed spheroids with the cancer cells surrounding the fibroblasts, whereas PANC-1 cells interspersed with the fibroblasts and SW480 cells were surrounded by fibroblasts. The fibroblasts also expressed collagen-1 and FAP-α, and whole transcriptomic analysis (WTA) showed abundant ECM- and EMT-related expression in heterospheroids, thus reflecting a representative tumor-like microenvironment. The WTA showed that PANC-1 heterospheroids possess a strong EMT profile with abundant Vimentin and CDH2 expression. Drug testing was evaluated by measuring cytotoxicity of 5FU and cisplatin using cell viability and apoptosis assays. We found no major impact on the cytotoxicity when fibroblasts were added to the spheroids. We conclude that the cancer cell lines together with fibroblasts shape the architectural organization of heterospheroids to form tumor-like morphology, and we propose that the various 3D tumor structures can be used for drug testing directed against the cancer cells as well as the fibroblasts.
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Importance: Up to 20% of patients develop chronic pain after total knee arthroplasty (TKA), yet there is a scarcity of effective interventions for this population. Objective: To evaluate whether neuromuscular exercise and pain neuroscience education were superior to pain neuroscience education alone for patients with chronic pain after TKA. Design, Setting, and Participants: A superiority randomized clinical trial was conducted at 3 outpatient clinics at Aalborg University Hospital in Denmark. Participants with moderate-to-severe average daily pain intensity and no signs of prosthesis failure at least 1 year after primary TKA were included. Participant recruitment was initiated on April 12, 2019, and completed on October 31, 2022. The 12-month follow-up was completed on March 21, 2023. Interventions: The study included 24 sessions of supervised neuromuscular exercise (2 sessions per week for 12 weeks) and 2 total sessions of pain neuroscience education (6 weeks between each session) or the same pain neuroscience education sessions alone. The interventions were delivered in groups of 2 to 4 participants. Main Outcomes and Measures: The primary outcome was change from baseline to 12 months using the mean score of the Knee Injury and Osteoarthritis Outcome Score, covering the 4 subscales pain, symptoms, activity of daily living, and knee-related quality of life (KOOS4; scores range from 0 to 100, with higher scores indicating better outcomes). The outcome assessors and statistician were blinded. All randomized participants were included in the intention-to-treat analysis. Results: Among the 69 participants (median age, 67.2 years [IQR, 61.2-71.9 years]; 40 female [58%]) included in the study, 36 were randomly assigned to the neuromuscular exercise and pain neuroscience education group, and 33 to the pain neuroscience education-alone group. The intention-to-treat analysis showed no between-group difference in change from baseline to 12 months for the KOOS4 (7.46 [95% CI, 3.04-11.89] vs 8.65 [95% CI, 4.67-12.63] points; mean difference, -1.33 [95% CI, -7.59 to 4.92]; P = .68). Among the 46 participants who participated in the 12-month assessment in the 2 groups, 16 (34.8%) experienced a clinically important improvement (a difference of ≥10 points on the KOOS4) with no between-group difference. No serious adverse events were observed. Conclusions and Relevance: In this randomized clinical trial, the results demonstrated that neuromuscular exercises and pain neuroscience education were not superior to pain neuroscience education alone in participants with chronic pain after TKA. Approximately one-third of the participants, regardless of intervention, experienced clinically important improvements. Future studies should investigate which patient characteristics indicate a favorable response to exercises and/or pain neuroscience education. Trial Registration: ClinicalTrials.gov Identifier: NCT03886259.
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Artroplastia de Reemplazo de Rodilla , Dolor Crónico , Terapia por Ejercicio , Educación del Paciente como Asunto , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/rehabilitación , Femenino , Masculino , Dolor Crónico/etiología , Anciano , Persona de Mediana Edad , Terapia por Ejercicio/métodos , Educación del Paciente como Asunto/métodos , Neurociencias/educación , Dinamarca , Dolor Postoperatorio/etiología , Dimensión del Dolor , Osteoartritis de la Rodilla/cirugía , Resultado del Tratamiento , Manejo del Dolor/métodosRESUMEN
OBJECTIVES: Currently, gout management, particularly urate-lowering therapy (ULT), is often suboptimal. Nurses successfully manage various diseases including gout. As gout prevalence is rising, and rheumatologists and general practitioners face shortages, a new approach is imperative. This real-life prospective cohort study evaluated the effectiveness of nurse-led care employing a treat-to-target strategy for gout management over a 2-year period. METHODS: All consecutively confirmed gout patients were included. The nurse-led clinic provided a structured treatment plan with consultations, patient leaflets, telephone contacts and laboratory monitoring. After a year of nurse-led care, patients transitioned to continued care in general practice. Follow-up data were complete through registries. The primary outcome was achieving target p-urate levels (<0.36 mmol/L) at 2 years after diagnosis. Secondary outcomes included treatment continuation and achievement of target p-urate levels in specific subgroups. The results were compared with patients diagnosed in the same clinic but followed up in 'usual care'. RESULTS: In the nurse-led group (n=114), 83% achieved target p-urate levels and ULT was continued by 98%. This trend persisted across various patient subgroups. Only 44% of patients in usual care achieved target p-urate and with insufficient doses of allopurinol . Nurse-led care involved an average of two visits and three telephone contacts over 336 days. The 2-year mortality rate was 15%. CONCLUSIONS: Nurse-led gout care, employing a targeted approach, was associated with a very high uptake of and adherence to ULT. The encouraging results were not achieved in usual care although a direct comparison might be influenced by selection bias.
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Supresores de la Gota , Gota , Ácido Úrico , Humanos , Gota/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Ácido Úrico/sangre , Estudios Prospectivos , Supresores de la Gota/uso terapéutico , Supresores de la Gota/administración & dosificación , Resultado del Tratamiento , Pautas de la Práctica en Enfermería , Alopurinol/uso terapéutico , Manejo de la EnfermedadRESUMEN
OBJECTIVES: Management of patients with chronic musculoskeletal pain (CMP) remains a challenge in general practice. The general practitioner (GP) often experiences diagnostic uncertainty despite frequently referring patients with CMP to specialized departments. Therefore, it remains imperative to gain insights on how to optimize and reframe the current setup for the management of patients with CMP. The objective was to explore GP's perspectives on the challenges, needs, and visions for improving the management of patients with CMP. METHODS: A qualitative study with co-design using the future workshop approach. Eight GPs participated in the future workshop (five females). Insights and visions emerged from the GP's discussions and sharing of their experiences in managing patients with CMP. The audio-recorded data were subjected to thematic text analysis. RESULTS: The thematic analysis revealed four main themes, including (1) challenges with current pain management, (2) barriers to pain management, (3) the need for a biopsychosocial perspective, and (4) solutions and visions. All challenges are related to the complexity and diagnostic uncertainty for this patient population. GPs experienced that the patients' biomedical understanding of their pain was a barrier for management and underlined the need for a biopsychosocial approach when managing the patients. The GPs described taking on the role of coordinators for their patients with CMP but could feel ill-equipped to handle diagnostic uncertainty. An interdisciplinary unit was recommended as a possible solution to introduce a biopsychosocial approach for the examination, diagnosis, and management of the patient's CMP. CONCLUSIONS: The complexity and diagnostic uncertainty of patients with CMP warrants a revision of the current setup. Establishing an interdisciplinary unit using a biopsychosocial approach was recommended as an option to improve the current management for patients with CMP.
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Medicina General , Médicos Generales , Dolor Musculoesquelético , Femenino , Humanos , Dolor Musculoesquelético/diagnóstico , Dolor Musculoesquelético/terapia , Médicos Generales/psicología , Manejo del Dolor , IncertidumbreRESUMEN
Global spread of multidrug-resistant, hospital-adapted Staphylococcus epidermidis lineages underscores the need for new therapeutic strategies. Here we show that many S. epidermidis isolates belonging to these lineages display cryptic susceptibility to penicillin/ß-lactamase inhibitor combinations under in vitro conditions, despite carrying the methicillin resistance gene mecA. Using a mouse thigh model of S. epidermidis infection, we demonstrate that single-dose treatment with amoxicillin/clavulanic acid significantly reduces methicillin-resistant S. epidermidis loads without leading to detectable resistance development. On the other hand, we also show that methicillin-resistant S. epidermidis is capable of developing increased resistance to amoxicillin/clavulanic acid during long-term in vitro exposure to these drugs. These findings suggest that penicillin/ß-lactamase inhibitor combinations could be a promising therapeutic candidate for treatment of a high proportion of methicillin-resistant S. epidermidis infections, although the in vivo risk of resistance development needs to be further addressed before they can be incorporated into clinical trials.
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Penicilinas , Infecciones Estafilocócicas , Humanos , Penicilinas/farmacología , Penicilinas/uso terapéutico , Inhibidores de beta-Lactamasas/farmacología , Staphylococcus epidermidis , Infecciones Estafilocócicas/tratamiento farmacológico , Ácido Clavulánico/farmacología , Ácido Clavulánico/uso terapéutico , Amoxicilina/farmacología , Amoxicilina/uso terapéutico , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Infectious diseases are major health care challenges globally and a prevalent cause of admission to emergency departments. Epidemiologic characteristics and outcomes based on population level data are limited. The Database of Community Acquired Infections in Eastern Denmark (DCAIED) 2018-2021 was established with the aim to explore and estimate the population characteristics, and outcomes of patients suffering from community acquired infections at the emergency departments in the Capital Region and the Zealand Region of Denmark using data from electronic medical records. Adult patients (≥18 years) presenting to the emergency department with suspected or confirmed infection are included in the cohort. Presence of sepsis and organ failure are assessed using modified criteria from the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). During the inclusion period from January 2018 to January 2022, 2,241,652 adult emergency department visits have been registered. Of these, 451,825 were unique encounters of which 60,316 fulfilled criteria of suspected infection and 28,472 fulfilled sepsis criteria and 8,027 were defined as septic shock. The database covers the entire Capital and Zealand Region of Denmark with an uptake area of 2.6 million inhabitants and includes demographic, laboratory and outcome indicators, with complete follow-up. The database is well-suited for epidemiological research for future national and international collaborations.
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Immunodeficient mice engrafted with psoriatic human skin are widely used for the preclinical evaluation of new drug candidates. However, the T-cell activity, including the IL23/IL17 pathway, declines in the graft over time after engraftment, which likely affects the study data. Here, we investigated whether the T-cell activity could be sustained in xenografted psoriatic skin by local stimulation of T cells or systemic injection of autologous CD4 + T cells. We surgically transplanted human psoriatic skin from 5 untreated patients onto female NOG mice. Six days after surgery, mice received an intraperitoneal injection of autologous human CD4+ T cells, a subcutaneous injection under the grafts of a T-cell stimulation cocktail consisting of recombinant human IL2, human IL23, antihuman CD3, and antihuman CD28, or saline. Mice were euthanized 21 d after surgery and spleens and graft biopsies were collected for analysis. Human T cells were present in the grafts, and 60% of the grafts maintained the psoriatic phenotype. However, neither local T-cell stimulation nor systemic injection of autologous CD4+ T cells affected the protein levels of human IL17A, IL22, IFN γ, and TNF α in the grafts. In conclusion, NOG mice seem to accept psoriatic skin grafts, but the 2 approaches studied here did not affect human T-cell activity in the grafts. Therefore, NOG mice do not appear in this regard to be superior to other immunodeficient mice used for psoriasis xenografts.
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Psoriasis , Linfocitos T , Humanos , Ratones , Femenino , Animales , Xenoinjertos , Piel/patología , Psoriasis/tratamiento farmacológico , Psoriasis/patología , Linfocitos T CD4-PositivosRESUMEN
Prophages of the ΦSa3int family are commonly found in human-associated strains of Staphylococcus aureus where they encode factors for evading the human innate immune system. In contrast, they are usually absent in livestock-associated methicillin-resistant S. aureus (LA-MRSA) strains where the phage attachment site is mutated compared to the human strains. However, ΦSa3int phages have been found in a subset of LA-MRSA strains belonging to clonal complex 398 (CC398), including a lineage that is widespread in pig farms in Northern Jutland, Denmark. This lineage contains amino acid changes in the DNA topoisomerase IV and the DNA gyrase encoded by grlA and gyrA, respectively, which have been associated with fluoroquinolone (FQ) resistance. As both of these enzymes are involved in DNA supercoiling, we speculated that the mutations might impact recombination between the ΦSa3int phage and the bacterial chromosome. To examine this, we introduced the FQ resistance mutations into S. aureus 8325-4attBLA that carry the mutated CC398-like bacterial attachment site for ΦSa3int phages. When monitoring phage integration and release of Φ13, a well-described representative of the ΦSa3int phage family, we did not observe any significant differences between the FQ-resistant mutant and the wild-type strain. Thus our results suggest that mutations in grlA and gyrA do not contribute to the presence of the ΦSa3int phages in LA-MRSA CC398.
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Human immune system (HIS) mouse models can be valuable when cross-reactivity of drug candidates to mouse systems is missing. However, no HIS mouse models of psoriasis have been established. In this study, it was investigated if imiquimod (IMQ) induced psoriasis-like skin inflammation was driven by human immune cells in human FMS-related tyrosine kinase 3 ligand (hFlt3L) boosted (BRGSF-HIS mice). BRGSF-HIS mice were boosted with hFlt3L prior to two or three topical applications of IMQ. Despite clinical skin inflammation, increased epidermal thickness and influx of human immune cells, a human derived response was not pronounced in IMQ treated mice. However, the number of murine neutrophils and murine cytokines and chemokines were increased in the skin and systemically after IMQ application. In conclusion, IMQ did induce skin inflammation in hFlt3L boosted BRGSF-HIS mice, although, a limited human immune response suggest that the main driving cellular mechanisms were of murine origin.
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Dermatitis , Psoriasis , Humanos , Ratones , Animales , Imiquimod/efectos adversos , Piel , Psoriasis/tratamiento farmacológico , Inflamación/inducido químicamente , Modelos Animales de EnfermedadRESUMEN
Xenografting of psoriasis skin onto immune deficient mice has been widely used to obtain proof-of-principle of new drug candidates. However, the lack of human T-cell activity in the grafts limits the use of the model. Here, we show that xenografting of lesional skin from psoriasis patients onto human IL-2 NOG mice results in increased numbers of human CD3+ cells in the grafts, axillary lymph nodes and blood from human IL-2 NOG mice compared to C.B-17 scid and NOG mice. In addition, disease relevant human cytokine levels were higher in graft lysates and serum from human IL-2 NOG mice. However, the epidermis was lacking and no efficacy of ustekinumab, a human anti-P40 antibody targeting both IL-12 and IL-23, was shown. Thus, despite the sustained T-cell activity, the model needs further investigations and validation to capture more aspects of psoriasis.
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Interleucina-2 , Psoriasis , Humanos , Ratones , Animales , Trasplante Heterólogo , Linfocitos T/patología , Piel/patología , Psoriasis/patologíaRESUMEN
ABSTRACT: Evidence and gap maps (EGMs) can be used to identify gaps within specific research areas and help guide future research agendas and directions. Currently, there are no EGMs within the broad domain of chronic musculoskeletal (MSK) pain in adults. The aim of this study was to create a contemporary EGM of interventions and outcomes used for research investigating chronic MSK pain. This EGM was based on systematic reviews of interventions published in scientific journals within the past 20 years. Embase, PubMed, the Cochrane Library, and PsycINFO were used to retrieve studies for inclusion. The quality of the included reviews was assessed using AMSTAR-II. Interventions were categorised as either physical, psychological, pharmacological, education/advice, interdisciplinary, or others. Outcomes were categorised using the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) recommendations. Of 4299 systematic reviews, 457 were included. Of these, 50% were rated critically low quality, 25% low quality, 10% moderate quality, and 15% rated high quality. Physical interventions (eg, exercise therapy) and education were the most common interventions reported in 80% and 20% of the studies, respectively. Pain (97%) and physical functioning (87%) were the most reported outcomes in the systematic reviews. Few systematic reviews used interdisciplinary interventions (3%) and economic-related outcomes (2%). This contemporary EGM revealed a low proportion of high-quality evidence within chronic MSK pain. This EGM clearly outlines the lack of high-quality research and the need for increased focus on interventions encompassing the entire biopsychosocial perspective.
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Dolor Crónico , Dolor Musculoesquelético , Adulto , Humanos , Dolor Crónico/terapia , Dolor Crónico/psicología , Terapia por Ejercicio/métodos , Dolor Musculoesquelético/diagnóstico , Dolor Musculoesquelético/terapia , Dimensión del Dolor , Literatura de Revisión como AsuntoRESUMEN
BACKGROUND: We aimed to identify important components of, and practical resources relevant for inclusion in, a toolkit to aid exercise delivery for people with hip/knee osteoarthritis. METHOD: An online international multi-disciplinary survey was conducted across 43 countries (139 clinicians, 44 people with hip/knee osteoarthritis and 135 osteoarthritis researchers). Participants were presented with the seeding statement 'Practical resources to aid the implementation of exercise for people with hip/knee osteoarthritis should ' and asked to provide up to 10 open text responses. Responses underwent refinement and qualitative content analysis to create domains and categories. RESULTS: Refinement of 551 open text responses yielded 72 unique statements relevant for analysis. Statements were organised into nine broad domains, suggesting that resources to aid exercise delivery should: (1) be easily accessible; (2) be of high quality; (3) be developed by, and for, stakeholders; (4) include different ways of delivering information; (5) include different types of resources to support exercise and non-exercise components of self-management; (6) include resources on recommended exercises and how to perform/progress them; (7) include tools to support motivation and track progress; (8) include resources to enable tailoring of the programme to the individual and; (9) facilitate access to professional and peer support. CONCLUSION: Our findings identified important components of, and practical resources to include within, a toolkit to aid delivery of exercise for people with hip/knee osteoarthritis. These findings have implications for exercise providers and lay the foundation for the development of a toolkit to help ensure exercise provision aligns with current international recommendations.
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Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/rehabilitación , Osteoartritis de la Cadera/rehabilitación , Terapia por Ejercicio , Ejercicio Físico , Articulación de la RodillaRESUMEN
OBJECTIVES: Patient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to establish research priorities for chronic musculoskeletal (MSK) pain by engaging with people living with chronic MSK pain, relatives to people living with chronic MSK pain, healthcare professionals (HCP), and researchers working with chronic MSK pain. METHODS: This JLA-PSP included a nation-wide survey in Denmark, an interim prioritisation, and an online consensus building workshop. The information gained from this was the basis for developing the final list of specific research priorities within chronic MSK pain. RESULTS: In the initial survey, 1010 respondents (91% people living with chronic MSK pain/relatives, 9% HCPs/researchers) submitted 3121 potential questions. These were summarised into 19 main themes and 36 sub-themes. In the interim prioritisation exercise, 51% people living with pain/relatives and 49% HCPs/researchers reduced the list to 33 research questions prior to the final priority setting workshop. 23 participants attended the online workshop (12 people/relatives, 10 HCPs, and 1 researcher) who reached consensus for the most important research priorities after two rounds of discussion of each question. CONCLUSIONS: This study identified several specific research questions generated by people living with chronic MSK pain, relatives, HCPs, and researchers. The stakeholders proposed prioritization of the healthcare system's ability to support patients, focus on developing coherent pathways between sectors and education for both patients and HCP. These research questions can form the basis for future studies, funders, and be used to align research with end-users' priorities.
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Dolor Musculoesquelético , Humanos , Dolor Musculoesquelético/terapia , Investigación Participativa Basada en la Comunidad , Prioridades en Salud , Conducta Cooperativa , DinamarcaRESUMEN
BACKGROUND: Household pets can carry meticillin-resistant Staphylococcus aureus (MRSA) introduced to the home by their human companions. Specific factors promoting pet carriage of this pathogen have not been fully elucidated. OBJECTIVE: This study evaluated MRSA cultured from pets and the home environment in households where a human infected with MRSA had been identified, and aimed to determine potential risk factors for pet MRSA carriage. MATERIALS AND METHODS: Humans diagnosed with community-associated MRSA (CA-MRSA) skin or soft-tissue infection (SSTI) in the mid-Atlantic United States were identified. One hundred forty-two dogs and cats from 57 affected households were identified of which 134 (94.4%) pets and the household environment were sampled for bacterial culture, PCR confirmation and spa-typing for MRSA strain determination. Samples were obtained 3 months later from 86 pets. RESULTS: At baseline, 12 (9.0%) pets carried MRSA. Potential risk factors associated with carriage included pet bed (environmental) MRSA contamination, flea infestation and prior antimicrobial use in the pet. Pets tended to carry human-adapted MRSA strains and spa-types of MRSA isolates cultured from pets were concordant with strains cultured from the home environment in seven of eight homes (87.5%) at baseline. CONCLUSIONS AND CLINICAL RELEVANCE: Results may inform risk-based veterinary clinical recommendations and provide evidence for selective pet testing as a possible alternative to early removal of pets from the homes of humans infected with MRSA. MRSA contamination of the home environment is likely an important risk factor for pet MRSA carriage, and household interventions should be considered to reduce risk of MRSA carriage in exposed pets.
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Enfermedades de los Gatos , Enfermedades de los Perros , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Animales , Humanos , Gatos , Perros , Meticilina , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/veterinaria , Infecciones Estafilocócicas/microbiología , Enfermedades de los Gatos/epidemiología , Enfermedades de los Gatos/microbiología , Portador Sano/veterinaria , Portador Sano/microbiología , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/microbiología , Factores de Riesgo , Mascotas/microbiologíaRESUMEN
OBJECTIVES: Existing equipment for quantitative sensory testing is generally expensive and not easily applicable in a clinical setting thus simple bed-side devices are warranted. Pressure hyperalgesia is a common finding in patients with musculoskeletal pain and an experimental model is delayed-onset muscle soreness (DOMS). DOMS is characterised by muscle hyperalgesia and some studies report facilitation of temporal summation of pain. This study aimed to detect DOMS induced muscle hyperalgesia and temporal summation of pain using a newly developed bed-side quantitative sensory testing device to deliver standardised pressure. METHODS: Twenty-two healthy participants participated in two sessions with the second session approximately 48 h after baseline. Pressure pain intensities were assessed from the gastrocnemius muscle with four probes calibrated to apply 2, 4, 6 and 8 kg, respectively. Temporal summation of pain (10 stimuli delivered at 0.5 Hz using the 6 kg probe) intensities were assessed from the same location. DOMS was evoked in the gastrocnemius muscle by an eccentric exercise. Sleepiness and physical activity were measured with the Epworth Sleepiness Scale and the Global Physical Activity Questionnaire to investigate if they were associated with the quantitative sensory testing measures. RESULTS: Pressure pain intensity was significantly increased 48 h after induction of DOMS when compared to baseline for all four probes (p<0.05). Temporal summation of pain was not statistically significant affected by DOMS and sleep quality and physical activity did not associate with any of the measures. CONCLUSIONS: This study introduces a simple, bed-side assessment tool for the assessment of pressure pain intensity and hence hyperalgesia and temporal summation of pain.
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Hiperalgesia , Umbral del Dolor , Humanos , Dimensión del Dolor , Hiperalgesia/diagnóstico , Umbral del Dolor/fisiología , Somnolencia , MialgiaRESUMEN
Introduction: International travel has been a major determinant for the introduction of pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) into naïve geographic areas. MRSA clonal complex 239 (CC239) is a highly virulent clone that is predominant in Asia. The objective of this study was to determine the geographic origin of MRSA CC239 isolates recovered from Danish cases with or without a history of international travel during 2004-2016. Materials and methods: Human MRSA isolates with spa types t030 and t037 (n = 60) were obtained from the National Reference Laboratory for Antimicrobial Resistance. For each case, the following data were collected from notification forms: sex, age, isolation year, specimen source (screening swab or clinical sample), infection type, and international travel history. All isolates were whole-genome sequenced, and a comparative genome and phylogenetic analysis was performed. Results: The majority of isolates originated from skin and soft tissue (SST) infections and screening swabs. In 31 out of 60 cases reported international travel to different parts of the world. Fifty-four isolates belonged to CC239, including sequence type 239 (ST239) (n = 43), ST241 (n = 5), ST4377 (n = 2), ST4378 (n = 1), ST1465 (n = 1), ST343 (n = 1), and ST592 (n = 1). The majority of the CC239 MRSA isolates (40/54) belonged to well-known geographic clades, including the Asian (n = 12), Serbian (n = 11), South American (n = 2), and Turkish (n = 15). Most MRSA ST239 isolates belonging to the highly virulent Asian clade carried sasX and were recovered from individuals who had travelled to Asia, Africa and the Middle East. Conclusion: Our data reveal multiple introductions of MRSA CC239 into Denmark through international travel, which highlights the importance of continued genomic surveillance of MRSA in persons returning from international travel to areas where MRSA is endemic.
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OBJECTIVES: The main objective was to investigate 5-year outcomes in patients with knee osteoarthritis, randomised to one of two non-surgical treatments. SETTING: Two outpatient clinics. PARTICIPANTS: At baseline, 100 patients with radiographic and symptomatic knee osteoarthritis not found eligible for knee replacement (KR) were included. Main exclusion criteria were average score above 75 of the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales pain, symptoms, function of daily living and quality of life; KOOS4 and average knee pain the previous week greater than 60 mm on a 100 mm visual analogue scale. INTERVENTIONS: Patients were randomised to supervised non-surgical treatment consisting of patient education, supervised exercise, weight loss, insoles, and pain medication (the MEDIC treatment) or written advice. The 12-week MEDIC treatment included patient education, neuromuscular exercise, insoles and a dietary weight loss programme and/or pain medication if needed and written advice consisted of two leaflets. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was 5-year mean change for KOOS4. Secondary outcomes included KOOS subscales, self-reported health, usage of pain medication and self-reported physical activity. RESULTS: Thirty-nine (78%) and 36 (72%) from the MEDIC and written advice groups responded at 5 years. There were no between-group differences in KOOS4 (difference 5.3 (95% CI -1.5 to 12.1) or any secondary outcomes. However, the 95% CI included the minimal clinically important difference for the main outcome.Seventy-six percent of the MEDIC group and 66% of the written advice group experienced clinically important improvements in KOOS4.Fifteen patients (30%) from the MEDIC group and 17 (34%) from the written advice group received KR in the index knee. Undergoing KR did not result in a statistically significant greater improvement in KOOS4 (difference 6.1 (95% CI -1.1 to 13.4). CONCLUSIONS: No statistically significant differences between supervised non-surgical treatment and written advice were demonstrated at 5 years. Most patients experienced clinically important improvements, irrespective of initial treatment strategy or KR. TRIAL REGISTRATION NUMBER: NCT01535001; ClinicalTrials.gov.
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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/cirugía , Calidad de Vida , Estudios de Seguimiento , Dolor/cirugíaRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA), a major human pathogen, uses the prophage-encoded tarP gene as an important immune evasion factor. TarP glycosylates wall teichoic acid (WTA) polymers, major S. aureus surface antigens, to impair WTA immunogenicity and impede host defence. However, tarP phages appear to be restricted to only a few MRSA clonal lineages, including clonal complexes (CC) 5 and 398, for unknown reasons. We demonstrate here that tarP-encoding prophages can be mobilized to lysogenize other S. aureus strains. However, transfer is largely restricted to closely related clones. Most of the non-transducible clones encode tarM, which generates a WTA glycosylation pattern distinct from that mediated by TarP. However, tarM does not interfere with infection by tarP phages. Clonal complex-specific Type I restriction-modification systems were the major reasons for resistance to tarP phage infection. Nevertheless, tarP phages were found also in unrelated S. aureus clones indicating that tarP has the potential to spread to distant clonal lineages and contribute to the evolution of new MRSA clones.
RESUMEN
The European Commission requested scientific and technical assistance in the preparation of a EU-wide baseline survey protocol for a European Union (EU) coordinated monitoring programme on the prevalence of methicillin-resistant Staphylococcus Aureus (MRSA) in pigs. The objective of the survey is to estimate the MRSA prevalence in batches of fattening pigs at slaughter at both European and national levels, with a 95% level of confidence and a level of precision of 10% considering an expected prevalence of 50%. The survey protocol defines the target population, the sample size for the survey, sample collection requirements, the analytical methods (for isolation, identification, phenotypic susceptibility testing and further genotypic testing of MRSA isolates), the data reporting requirements and the plan of analysis. The samples are to be analysed according to the laboratory protocols available on the European Union Reference Laboratory (EURL-AR) website. Generalised linear models will be used to estimate proportion (with 95% confidence intervals) of batches of slaughter pigs tested positive to MRSA. The necessary data to be reported by the EU Member States to support this baseline survey are presented in three data models. The results of the survey should be reported using the EFSA data collection framework.