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Background and purpose: As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy. Materials and methods: 62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months. Results: Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p < 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01-3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3-1.7, p < 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period. Conclusion: Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.
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BACKGROUND: Substantial resources are used in hospitals worldwide to counteract the ever-increasing incidence of vancomycin-resistant and vancomycin-variable Enterococcus faecium (VREfm and VVEfm), but it is important to balance patient safety, infection prevention, and hospital costs. AIM: To investigate the impact of ending VREfm/VVEfm screening and isolation at Odense University Hospital (OUH), Denmark, on patient and clinical characteristics, risk of bacteraemia, and mortality of VREfm/VVEfm disease at OUH. The burden of VREfm/VVEfm bacteraemia at OUH and the three collaborative hospitals in the Region of Southern Denmark (RSD) was also investigated. METHODS: A retrospective cohort study was conducted including first-time VREfm/VVEfm clinical isolates (index isolates) detected at OUH and collaborative hospitals in the period 2015-2022. The intervention period with screening and isolation was from 2015 to 2021, and the post-intervention period was 2022. Information about clinical isolates was retrieved from microbiological databases. Patient data were obtained from hospital records. FINDINGS: At OUH, 436 patients were included in the study, with 285 in the intervention period and 151 in the post-intervention period. Ending screening and isolation was followed by an increased number of index isolates. Besides a change in van genes, only minor non-significant changes were detected in all the other investigated parameters. Mortality within 30 days did not reflect the VREfm/VVEfm-attributable deaths, and in only four cases was VREfm/VVEfm infection the likely cause of death. CONCLUSION: Despite an increasing number of index isolates, nothing in the short follow-up period supported a reintroduction of screening and isolation.
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Bacteriemia , Infecção Hospitalar , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Enterococos Resistentes à Vancomicina , Humanos , Vancomicina , Hospitais Universitários , Enterococcus faecium/genética , Estudos Retrospectivos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologia , Enterococos Resistentes à Vancomicina/genética , Bacteriemia/epidemiologia , Dinamarca/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Infecções por Bactérias Gram-Positivas/microbiologiaRESUMO
Proton radiotherapy offers a dosimetric advantage compared to photon therapy in sparing normal tissue, but the clinical evidence for toxicity reductions in the treatment of head and neck cancer is limited. The Danish Head and Neck Cancer Group (DAHANCA) has initiated the DAHANCA 35 randomised trial to clarify the value of proton therapy (NCT04607694). The DAHANCA 35 trial is performed in an enriched population of patients selected by an anticipated benefit of proton therapy to reduce the risk of late dysphagia or xerostomia based on normal tissue complication probability (NTCP) modelling. We present our considerations on the trial design and a test of the selection procedure conducted before initiating the randomised study.
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Neoplasias de Cabeça e Pescoço , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Prótons , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Prótons/métodos , Fótons/uso terapêutico , Probabilidade , Radioterapia de Intensidade Modulada/métodos , Planejamento da Radioterapia Assistida por Computador , Dosagem RadioterapêuticaRESUMO
OBJECTIVE: Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration. METHOD: The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers. RESULTS: Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate. DISCUSSION: The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect. CONCLUSION: PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.
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Terapia de Reposição de Estrogênios , Embolia Pulmonar , Feminino , Humanos , Terapia de Reposição de Estrogênios/efeitos adversos , Acetato de Medroxiprogesterona , Estudos de Casos e Controles , Progestinas , Estrogênios , Administração Cutânea , Embolia Pulmonar/induzido quimicamente , Embolia Pulmonar/epidemiologia , Menopausa , Fatores de RiscoRESUMO
INTRODUCTION: The aim was to evaluate and compare the dosimetric effect and robustness towards day-to-day anatomical and setup variations in the delivered dose for photon and proton treatments of sinonasal cancer (SNC) patients. MATERIALS AND METHODS: Photon (VMAT) and proton (IMPT) plans were optimized retrospectively for 24 SNC patients. Synthetic CTs (synCT) were obtained by deforming the planning CT (pCT) to the anatomy of every daily cone-beam CT. Both VMAT and IMPT plans were recalculated on the synCTs. The recalculated daily dose was accumulated over the whole treatment on the pCT. Target coverage and dose to organs and risk (OARs) were evaluated for all patients for the nominal, daily and accumulated dose distribution. RESULTS: In general, dose to OARs farther away from the target, including brain, chiasm and contralateral optic nerve, was lower for proton plans than photon plans. Whereas, OARs in proximity of the target received a lower dose for photon plans. For proton plans, the target coverage (volume of CTV receiving 95% of prescribed dose), V95%, fell below 99% for 9/24 patients in one or more fractions. For photon plans, 4/24 patients had one or more fractions where V95% fell below 99%. For accumulated doses, V95% was below 99% only in two cases, but above 98% for all patients. CONCLUSION: Photon and proton treatment have different strengths regarding OAR sparing. The robustness was high for both treatment modalities. Patient selection for either proton or photon radiation therapy of SNC patients should be based on a case-by-case comparison.
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Neoplasias , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Órgãos em Risco , Prótons , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Estudos RetrospectivosRESUMO
OBJECTIVE: Most women experience vasomotor symptoms (VMS) around menopause that may affect quality of life negatively. Effective pharmacological treatment exists but is not recommended for all women, and there is a demand for alternatives to reduce symptoms and improve quality of life. The objective of this study was to investigate the effect of a resistance training intervention on health-related quality of life (HRQoL) in postmenopausal women with VMS. METHODS: This open randomized controlled trial included 65 postmenopausal women >45 years old with daily VMS. The participants were randomized to 15 weeks of resistance training three times per week or an untreated control group. The Women's Health Questionnaire (WHQ) and Short Form Health Survey (SF-36) were used to assess HRQoL at baseline and after 15 weeks. RESULTS: The resistance training group improved compared to the control group in the WHQ domains of VMS (p = 0.002), sleep problems (p = 0.003) and menstrual symptoms (p = 0.01) from baseline to post intervention. No significant between-group differences were found in SF-36 summary scores, or in any of the domains. CONCLUSION: In postmenopausal women with moderate to severe VMS, resistance training three times per week for 15 weeks improved menopause-specific HRQoL.
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Fogachos/terapia , Qualidade de Vida , Treinamento Resistido , Feminino , Humanos , Menopausa , Pessoa de Meia-Idade , Pós-MenopausaRESUMO
INTRODUCTION: Swedish National Diabetes Registry data show a correlation of improved glycemic control in people with type 1 diabetes (T1D) with increased use of diabetes technologies over the past 25 years. However, novel technologies are often associated with a high initial outlay. The aim of the present study was to evaluate the long-term cost-effectiveness of the advanced hybrid closed-loop (AHCL) MiniMed 780G system versus intermittently scanned continuous glucose monitoring (isCGM) plus self-injection of multiple daily insulin (MDI) or continuous subcutaneous insulin infusion (CSII) in people with T1D in Sweden. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0). Clinical data, including changes in glycated hemoglobin (HbA1c) and hypoglycemia rates, were sourced from observational studies and a randomized crossover trial. Modeled patients were assumed to receive the treatments for their lifetimes, with HbA1c kept constant following the application of treatment effects. Costs were accounted from a societal perspective and expressed in Swedish krona (SEK). Utilities and days off work estimates were taken from published sources. RESULTS: The MiniMed 780G system was associated with an improvement in life expectancy of 0.16 years and an improvement in quality-adjusted life expectancy of 1.95 quality-adjusted life years (QALYs) versus isCGM plus MDI or CSII. These clinical benefits were due to a reduced incidence and a delayed time to onset of diabetes-related complications. Combined costs were estimated to be SEK 727,408 (EUR 72,741) higher with MiniMed 780G, with treatment costs partially offset by direct cost savings from the avoidance of diabetes-related complications and indirect cost savings from the avoidance of lost workplace productivity. The MiniMed 780G system was associated with an incremental cost-effectiveness ratio of SEK 373,700 per QALY gained. CONCLUSIONS: Based on a willingness-to-pay threshold of SEK 500,000 per QALY gained, the MiniMed 780G system was projected to be cost-effective versus isCGM plus MDI or CSII for the treatment of T1D in Sweden.
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INTRODUCTION: The aim was to characterise patterns and predictability of aeration changes in the ipsilateral maxillary sinus during intensity-modulated radiotherapy (IMRT) for sinonasal cancer (SNC), and in a sample evaluate the dosimetric effects of aeration changes for both photon and proton therapy. MATERIALS AND METHODS: The study included patients treated with IMRT for SNC in a single institution in 2009-2017. The volume of air in the ipsilateral maxillary sinus was recorded in 1578 daily cone beam computer tomography (CBCT) from 53 patients. Patterns of changing air volumes were categorised as 'stable', increasing', 'decreasing', or 'erratic'. For the prediction analysis, categorisation was performed based both on the entire treatment course and the first five fractions (F1-5). Photon and proton therapy plans were generated for four patients, the one from each category with the largest aeration variation. Synthetic CT images were generated for each CBCT and all plans were recalculated on the daily synthetic CTs. RESULTS: The absolute volume of air varied considerably during the treatment course, ranging from 0 to 25.9 cm3. Changes within a single participant varied in the range of 0-18.7 cm3. In the categorisation of patterns, most patients had increasing aeration of the sinus. Generally, patterns of aeration could not be predicted from F1-5. Patients categorised as increasing in F1-5 had the best prediction, with 78% predicted correctly as increasing for the entire treatment course. The numeric correlation coefficients for target coverage and air volume were low for 3/4 scenarios (photons 0.03-0.23, protons 0.26-0.48). No straightforward correlation between the dosimetric effect and the volume changes could be detected in the sample test of four patients for neither photon nor proton therapy. CONCLUSION: The variation of aeration was large and unpredictable. No clear dosimetric consequences of the aeration variation were evident for neither IMRT nor proton therapy for the patients investigated.
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BACKGROUND: Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) clonal complex (CC) 398 may be transmitted and cause morbidity and mortality in hospitals. The economic cost of stopping hospital transmission of LA-MRSA CC398 is poorly described. Early detection of transmission may limit the extent of the intervention. AIM: To evaluate core genome multi-locus sequence typing (cgMLST) for detecting transmission chains and to estimate the costs for interventions to prevent further spread after discovery of hospital transmission of LA-MRSA CC398. METHODS: Five patients were involved in two episodes of transmission of LA-MRSA CC398 in a hospital. Standard interventions including MRSA screening of patients and healthcare workers were initiated. Whole genome sequences of the five isolates and 17 epidemiologically unrelated MRSA CC398 isolates from other hospitalized patients were analysed by single nucleotide polymorphism (SNP) comparisons and cgMLST. The economic costs of constraining transmission were calculated from relevant sources. FINDINGS: The five isolates suspected to be involved in hospital transmission clustered with ≤2 SNPs in the draft genome sequences with some distance to other isolates. cgMLST allocated the five isolates to the same type, which was different from all but two of the sporadic isolates. Furthermore, cgMLST separated the five transmission isolates from all other isolates. The economic costs of the outbreak interventions exceeded 11,000 per patient. CONCLUSION: LA-MRSA CC398 is transmittable in hospitals, and intervention against transmission may reach considerable costs. cgMLST is useful in surveillance of hospital transmission of LA-MRSA.
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Doenças dos Animais/transmissão , Infecção Hospitalar/microbiologia , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/epidemiologia , Doenças dos Animais/microbiologia , Animais , Infecção Hospitalar/epidemiologia , Dinamarca/epidemiologia , Surtos de Doenças , Custos de Cuidados de Saúde , Humanos , Gado/microbiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/economia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Sequenciamento Completo do GenomaRESUMO
OBJECTIVES: Sinonasal inverted papilloma (SIP) is a relatively rare disease, and its etiology is not understood. It is characterized by locally aggressive growth and a strong tendency to recur despite its benign histology. AIMS: The aim of this study was to identify the presence of human papilloma virus (HPV) and its surrogate marker p16 in SIP tissue samples from a regional cohort. MATERIAL AND METHODS: Subjects were identified from our regional center cohort of 88 SIP patients treated between 1984-2014. From these subjects, 54 were included in this study. Of these, 53 biopsies were analyzed with PCR, and 54 samples were immunohistochemically stained for p16. DNA was extracted from histopathologically verified SIP. Genotype screening for 13 high risk-, 5 oncogenic and 6 low risk HPV types was performed using the PapilloCheck® HPV-screening test. RESULTS: HPV analysis was successful for 38 of 53 samples. Of the 38 successfully analyzed samples, only 2 samples were positive for HPV 11. Notably, p16 was present in the epithelia in all samples, and in the papilloma lesions in 37 samples. CONCLUSION: Since only 2 out of 38 SIPs were positive for HPV (type 11), and at the same time p16 was positive in epithelia in all samples and in 37 of 38 papilloma lesions of the samples, it is concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP. We are currently planning a prospective, multicenter study in order to increase the study power and in order to be able to better evaluate the clinical implications of HPV-and p16 in SIP.
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Biomarcadores Tumorais/análise , Inibidor p16 de Quinase Dependente de Ciclina/análise , Recidiva Local de Neoplasia/química , Papiloma Invertido/química , Neoplasias dos Seios Paranasais/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/virologia , Papiloma Invertido/virologia , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/virologia , Neoplasias dos Seios Paranasais/virologia , Estudos Retrospectivos , Medição de Risco , Adulto JovemRESUMO
AIMS AND OBJECTIVES: To explore non-sedated mechanically ventilated patients' communication with nurses in the intensive care unit. BACKGROUND: Mechanically ventilated patients are temporarily voiceless, making interpersonal communication complex. Both nurses and patients find communication challenging and may experience negative emotions when communication fails. In Nordic countries, sedation protocols have changed to light/non-sedation, resulting in more patients being conscious and more clinical practitioners experiencing communication difficulties. DESIGN: The study was qualitative with a phenomenological-hermeneutic approach. Data were collected at two intensive care units in Denmark from January to April 2015. METHODS: Data collection consisted of interviews with patients, focus group interviews with nurses and field observations concerning nurse-patient communication. Data were analysed as one collective body of data using Ricoeur's theory of interpretation. FINDINGS: The main theme showed that communication is a movement between the two opposite feelings of comprehension and frustration. Sub-themes showed (1) the dynamics of power change when the patient is voiceless; (2) consciousness and voicelessness make caring difficult; and (3) the process of interpreting and structuring communication is situational. CONCLUSION: These findings are important in nursing care and provide perspectives on the shift from communication towards comprehension and, thus, away from frustration. A non-sedation protocol is a major change in clinical practice in relation to communication. It requires a new way of thinking where communication becomes an integrated part of care, and the nurse has to be constantly alert and adjust his or her communication strategies to the patient's changing needs and communication ability. RELEVANCE TO CLINICAL PRACTICE: Some nursing interventions may optimize communication: (1) systematic assessment of patients' communication; (2) education of nurses in Augmentative and Alternative Communication; (3) using communication tools when possible; and (4) securing time, continuity, empathy and patience in nursing care.
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Comunicação , Enfermagem de Cuidados Críticos/métodos , Hermenêutica , Relações Enfermeiro-Paciente , Respiração Artificial/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Dinamarca , Feminino , Grupos Focais , Humanos , Unidades de Terapia Intensiva , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pesquisa QualitativaRESUMO
BACKGROUND/OBJECTIVES: Low levels of orexin are associated with obesity and reduced physical activity in humans and animals. SUBJECTS/METHODS: Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) selectively activated orexin neurons in mouse lateral hypothalamus (LH) to measure effects on spontaneous physical activity (SPA). DREADD targeting was achieved by stereotaxic injection of AAV vectors into caudal lateral LH of heterozygous orexin-Cre or C57/B6J mice. In one set of studies, excitation of orexin neurons was examined (virus: AAV2-EF1a-DIO-hM3Dq-mCherry), and test sessions began 3-4 h after light cycle onset. In a study examining the inhibition of orexin neurons (virus: AAV2-hSyn-DIO-hM4Di-mCherry), testing began 15 min prior to dark cycle onset. Clozapine n-oxide (CNO; 1 or 5 mg/kg) or saline was injected intraperitoneally and time spent moving in open field chambers was recorded for 2 h. Follow-up studies in separate mouse cohorts quantified SPA in parallel with changes in energy expenditure (EE) and chow intake using indirect calorimetry chambers (SableSystem™). Following acclimation, testing sessions (saline and/or CNO) took place over the course of ~1 week, with injections administered every day. Changes in SPA, EE, chow intake, fecal boli, and body composition (EchoMRI™) were measured. Additional mice cohorts were fed a high-fat diet (HFD) and injected with CNO daily up to 10 days to assess the potential for orexin activation to prevent diet-induced obesity. RESULTS: Activation of orexin resulted in increases in SPA in male and female mice, and was accompanied by increases in energy expenditure without changes in overall chow intake. When orexin activation occurred in the context of high fat diet, weight gain and adiposity were significantly attenuated. SPA was decreased when DREADDs were used to inhibit orexin activity. CONCLUSION: These results demonstrate that orexin neurons play a critical role in mediating physical activity and suggest a novel therapeutic target for treating obesity.
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Adiposidade/efeitos dos fármacos , Neurotransmissores/metabolismo , Neurotransmissores/farmacologia , Orexinas/metabolismo , Orexinas/farmacologia , Adiposidade/fisiologia , Animais , Dieta Hiperlipídica , Feminino , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , TransfecçãoRESUMO
The surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010-2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.
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Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/epidemiologia , Monitoramento Epidemiológico , Vigilância da População/métodos , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Contagem de Colônia Microbiana , Dinamarca/epidemiologia , Enterocolite Pseudomembranosa/diagnóstico , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/microbiologia , Humanos , Reação em Cadeia da PolimeraseRESUMO
Acquisition of Legionnaires' disease is a serious complication of hospitalization. Rapid determination of whether or not the infection is caused by strains of Legionella pneumophila in the hospital environment is crucial to avoid further cases. This study investigated the use of whole-genome sequencing to identify the source of infection in hospital-acquired Legionnaires' disease. Phylogenetic analyses showed close relatedness between one patient isolate and a strain found in hospital water, confirming suspicion of nosocomial infection. It was found that whole-genome sequencing can be a useful tool in the investigation of hospital-acquired Legionnaires' disease.
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Infecção Hospitalar/microbiologia , Microbiologia Ambiental , Legionella pneumophila/classificação , Doença dos Legionários/microbiologia , Epidemiologia Molecular/métodos , Tipagem Molecular/métodos , Sequenciamento Completo do Genoma/métodos , Análise por Conglomerados , Humanos , Legionella pneumophila/genética , Legionella pneumophila/isolamento & purificação , Filogenia , Homologia de SequênciaRESUMO
Overweight and obesity result from an imbalance between caloric intake and energy expenditure, including expenditure from spontaneous physical activity (SPA). Changes in SPA and resulting changes in non-exercise activity thermogenesis (NEAT) likely interact with diet to influence risk for obesity. However, previous research on the relationship between diet, physical activity, and energy expenditure has been mixed. The neuropeptide orexin is a driver of SPA, and orexin neuron activity can be manipulated using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). We hypothesized that HFD decreases SPA and NEAT, and that DREADD-mediated activation of orexin neuron signaling would abolish this decrease and produce an increase in NEAT instead. To test these ideas, we characterized behaviors to determine the extent to which access to a high-fat diet (HFD) influences the proportion and probability of engaging in food intake and activity. We then measured NEAT following access to HFD and following a DREADD intervention targeting orexin neurons. Two cohorts of orexin-cre male mice were injected with an excitatory DREADD virus into the caudal hypothalamus, where orexin neurons are concentrated. Mice were then housed in continuous metabolic phenotyping cages (Sable Promethion). Food intake, indirect calorimetry, and SPA were automatically measured every second. For cohort 1 (n=8), animals were given access to chow, then switched to HFD. For cohort 2 (n=4/group), half of the animals were given access to HFD, the other access to chow. Then, among animals on HFD, orexin neurons were activated following injections of clozapine n-oxide (CNO). Mice on HFD spent significantly less time eating (p<0.01) and more time inactive compared to mice on chow (p<0.01). Following a meal, mice on HFD were significantly more likely to engage in periods of inactivity compared to those on chow (p<0.05). NEAT was decreased in animals on HFD, and was increased to the NEAT level of control animals following activation of orexin neurons with DREADDs. Food intake (kilocalories) was not significantly different between mice on chow and HFD, yet mice on chow expended more energy per unit of SPA, relative to that in mice consuming HFD. These results suggest that HFD consumption reduces SPA and NEAT, and increases inactivity following a meal. Together, the data suggest a change in the efficiency of energy expenditure based upon diet, such that SPA during HFD burns fewer calories compared to SPA on a standard chow diet.
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Dieta Hiperlipídica , Orexinas/metabolismo , Condicionamento Físico Animal/fisiologia , Termogênese/efeitos dos fármacos , Análise de Variância , Animais , Antipsicóticos/farmacologia , Calorimetria , Clozapina/análogos & derivados , Clozapina/farmacologia , Drogas Desenhadas/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/genética , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Orexinas/genética , Orexinas/farmacologia , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Superfície Celular/genética , Termogênese/genética , Fatores de Tempo , Transdução Genética , Proteína Vermelha FluorescenteRESUMO
The hypocretin/orexin system regulates, among other things, sleep and energy homeostasis. The system is likely regulated by both homeostatic and circadian mechanisms. Little is known about local differences in the regulation of hypocretin activity. The aim of this study was to establish an optimized peptide quantification method for hypocretin-1 extracted from different mouse brain areas and use this method for investigating circadian fluctuations of hypocretin-1 levels in these areas. The results show that hypocretin-1 peptide can be extracted from small pieces of intact tissue, with sufficient yield for measurements in a standard radioimmunoassay. Utilizing the optimized method, it was found that prepro-hypocretin mRNA and peptide show circadian fluctuations in the mouse brain. This study further demonstrates that the hypocretin-1 peptide level in the frontal brain peaks during dark as does prepro-hypocretin mRNA in the hypothalamus. However, in midbrain and brainstem tissue caudal to the hypothalamus, there was less circadian fluctuation and a tendency for higher levels during the light phase. These data suggest that regulation of the hypocretin system differs between brain areas.
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Encéfalo/metabolismo , Ritmo Circadiano , Orexinas/metabolismo , Radioimunoensaio/métodos , Animais , Feminino , Hipotálamo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Orexinas/genética , RNA Mensageiro/metabolismoRESUMO
STUDY QUESTION: Are Swedish women age 40-44 years with assumed early menopause 'undertreated' by hormone therapy (HT)? SUMMARY ANSWER: Many women with probable early menopause discontinue their HT after a short period of time. Thus, they fail to complete the recommended replacement up to age 51-52 years, the average age of menopause. WHAT IS KNOWN ALREADY: Spontaneous early menopause occurs in â¼5% of women age 40-45 years. Regardless of the cause, women who experience hormonal menopause due to bilateral oophorectomy before the median age of spontaneous menopause are at increased risk of cardiovascular disease, neurological disease, osteoporosis, psychiatric illness and even death. STUDY DESIGN, SIZE, DURATION: The study is descriptive, and epidemiological and was based on the use of national registers of dispensed drug prescriptions (HT) linking registers from the National Board of Health and Welfare and Statistics Sweden from 1 July 2005 until 31 December 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population consisted of 310 404 women, 40-44 years old on 31 December 2005 who were followed from 1 July 2005 until 31 December 2011. MAIN RESULTS AND THE ROLE OF CHANCE: Only 0.9% of women 40-44 years old started HT during the study period. A majority of these women used HT <1 year. LIMITATIONS, REASONS FOR CAUTION: We do not know the indications that led to the prescription of HT but assume that early onset of menopause was the main reason. Because of the study design-making a retrospective study of registers-we can only speculate on the reasons for most of the women in this group discontinuing HT. Another limitation of this study is that we have a rather short observation time. However, we have up to now only been able to collect and combine the data since July 2005. WIDER IMPLICATIONS OF THE FINDINGS: As the occurrence of spontaneous early menopause in women age 40-45 is reported to be â¼5%, the fact that <1% of Swedish women age 40-44 are prescribed HT, and can be shown also to have had the medication dispensed at a pharmacy suggests an unexpectedly low treatment rate. Some women with early menopause may have used combined contraceptives as supplementation therapy, but in Sweden HT is the recommended treatment for early menopause so any such women are not following this recommendation. Women who experience early menopause are at increased risk for overall morbidity and mortality, and can expect to benefit from HT until they have reached at least the median age of spontaneous menopause. It is therefore important to individualize the information given these women and to convey new knowledge in this area to gynaecologists and physicians in general as well as the recommendation that women in this group continue HT at least until the average age for spontaneous menopause is reached. STUDY FUNDING/COMPETING INTERESTS: No competing interests exist.
Assuntos
Terapia de Reposição de Estrogênios/métodos , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Hormônios/uso terapêutico , Menopausa Precoce , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Classe Social , Suécia , Resultado do TratamentoRESUMO
The King-Devick (K-D) test, a measure of processing speed, visual tracking, and saccadic eye movements, has shown promise as a supplemental screening test following concussion. However, limited normative data for this test have been published.The K-D test was administered to 185 professional ice hockey players as a preseason baseline test in seasons 2012-2013 and 2013-2014. Their average age was 23.8 years (median = 22.0 years, range = 16-40 years). The average K-D score was 40.0 s (SD = 6.1 s, range = 24.0-65.7 s). K-D test performance showed no association with age, education, or the number of self-reported previous concussions in this sample. The association between trials 1 and 2 of the K-D test was good (ICC = 0.92, Pearson = 0.93). Normative values of the K-D test for professional male ice hockey players are reported. K-D test performance did not vary by age, education, or concussion history in this study.
Assuntos
Atletas/psicologia , Concussão Encefálica/psicologia , Hóquei , Desempenho Psicomotor/fisiologia , Movimentos Sacádicos/fisiologia , Adolescente , Adulto , Cognição/fisiologia , Humanos , Masculino , Testes Neuropsicológicos , Valores de Referência , Adulto JovemRESUMO
OBJECTIVES: The use of hormone therapy (HT) for hot flushes has changed dramatically over the past five decades. In this cross-sectional questionnaire study, the aim was to describe the use of HT and alternative treatments and to study the frequency of hot flushes. A further aim was to compare data from the present questionnaire with data from previous studies made in the same geographic area. METHOD: A questionnaire was sent to a random sample of 2000 women aged 47-56 years living in Östergötland County, Sweden. The results were compared with findings from previous studies regarding use of HT, alternative treatment and hot flushes, and the number of HT prescriptions dispensed during the corresponding time using data derived from the Swedish Prescribed Drug Registry. RESULTS: The response rate was 66%. Six percent used HT, in line with prevalence data from the Swedish Prescribed Drug Registry. Alternative treatments were used by 10%. About 70% of postmenopausal women reported flushes and almost one-third of those with flushes stated that they would be positive to HT if therapy could be shown to be harmless, a view more often stated by women with severe complaints of hot flushes (67%). CONCLUSION: The use of HT and alternative treatments is low and many women suffer from flushes that could be treated. Women considered their knowledge of the climacteric period and treatment options as insufficient. Individualized information should be given and women with significant climacteric complaints, without contraindications, should be given the opportunity to try HT.