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OBJECTIVES: There have been significant advances in the medical management of severe postpartum hemorrhage (sPPH) over recent decades, which is reflected in numerous published guidelines. To date, many of the currently available national and international guidelines recommend recombinant factor VIIa (rFVIIa) to be used only at a very late stage in the course of sPPH, as a "last resort", before or after hysterectomy. Based on new safety data, rFVIIa has recently been approved by the European Medicines Agency (EMA) and Swissmedic for use in sPPH, if uterotonics are insufficient to achieve hemostasis, which in fact is significantly earlier in the course of postpartum hemorrhage (PPH). We therefore aimed to develop expert consensus guidance as a step toward standardizing care with the use of rFVIIa for clinicians managing women experiencing life-threatening sPPH. METHODS: The consensus process consisted of one face-to-face meeting with a group of nine experts, including eight obstetrician-gynecologists and a hematologist highly experienced in sPPH care in tertiary care perinatal centers. The panel was representative of multidisciplinary expertise in the European obstetrics community and provided consensus opinion in answer to pre-defined questions around clinical practice with rFVIIa in the management of sPPH. Recommendations have been based on current national and international guidelines, extensive clinical experience, and consensus opinion, as well as the availability of efficacy and new safety data. RESULTS: The expert panel developed 17 consensus statements in response to the 13 pre-defined questions on the use of rFVIIa in the management of sPPH including: available efficacy and safety data and the need for interdisciplinary expertise between obstetricians, anesthesiologists, and hematologists in the management of sPPH. Based on novel data, the experts recommend: (1) earlier administration of rFVIIa in patients with sPPH who do not respond to uterotonic administration to optimize the efficacy of rFVIIa; (2) the importance of hematological parameter prerequisites prior to the administration of rFVIIa to maximize efficacy; and (3) continued evaluation or initiation of further invasive procedures according to standard practice. Furthermore, recommendations on the timing of rFVIIa treatment within the sPPH management algorithm are outlined in a range of specified clinical scenarios and settings, including vaginal delivery, cesarean section, and smaller birthing units before transfer to a tertiary care center. The panel agreed that according to available, and new data, as well as real-world experience, there is no evidence that the use of rFVIIa in patients with sPPH increases the risk of thromboembolism. The authors acknowledge that there is still limited clinical effectiveness data, as well as pharmacoeconomic data, on the use of rFVIIa in sPPH, and recommend further clinical trials and efficacy investigation. CONCLUSIONS: This expert panel provides consensus guidance based on recently available data, clinical experience, and expert opinion, augmented by the recent approval of rFVIIa for use in sPPH by the EMA. These consensus statements are intended to support clinical care for sPPH and may help to provide the impetus and a starting point for updates to existing clinical practice guidelines.
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Hemorragia Pós-Parto , Humanos , Feminino , Gravidez , Hemorragia Pós-Parto/tratamento farmacológico , Cesárea , Fator VIIa/uso terapêutico , Período Pós-Parto , Proteínas RecombinantesRESUMO
Post-mortem computed tomography (PMCT) imaging is gaining popularity and acceptance for use alongside forensic autopsies of children, predominantly to aid in the detection of traumatic injuries. Recent research on this topic has provided a breadth of new information regarding the appropriate usage, imaging guidance, and diagnostic accuracy for the identification of different paediatric pathologies. Additionally, advanced CT imaging techniques, such as PMCT angiography or ventilated PMCT, have been trialled, and post-mortem micro-CT is now being used in specialist centres for the assessment of subtle fractures in extracted bone specimens. Various image post-processing methods (e.g., three-dimensional printing from PMCT imaging data) are being used for the illustration of injuries in the medicolegal setting to a lay audience and provide another avenue for the future of forensic radiology research. In this review, the evidence-based principles and benefits of post-mortem imaging for forensic investigation in childhood deaths are presented, with a particular focus on PMCT and current practices. Variations in forensic imaging strategies around the world, published diagnostic accuracy rates, and expected normal post-mortem imaging findings are discussed, as well as potential future applications and research in this area.
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Fraturas Ósseas , Humanos , Criança , Autopsia/métodos , Patologia Legal/métodos , Processamento de Imagem Assistida por Computador , Microtomografia por Raio-XRESUMO
Each year, approximately 70 million people suffer traumatic brain injury, which has a significant physical, psychosocial and economic impact for patients and their families. It is recommended in the UK that all patients with traumatic brain injury and a Glasgow coma scale ≤ 8 should be transferred to a neurosurgical centre. However, many patients, especially those in whom neurosurgery is not required, are not treated in, nor transferred to, a neurosurgical centre. This review aims to provide clinicians who work in non-neurosurgical centres with a summary of contemporary studies relevant to the critical care management of patients with traumatic brain injury. A targeted literature review was undertaken that included guidelines, systematic reviews, meta-analyses, clinical trials and randomised controlled trials (published in English between 1 January 2017 and 1 July 2022). Studies involving key clinical management strategies published before this time, but which have not been updated or repeated, were also eligible for inclusion. Analysis of the topics identified during the review was then summarised. These included: fundamental critical care management approaches (including ventilation strategies, fluid management, seizure control and osmotherapy); use of processed electroencephalogram monitoring; non-invasive assessment of intracranial pressure; prognostication; and rehabilitation techniques. Through this process, we have formulated practical recommendations to guide clinical practice in non-specialist centres.
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Lesões Encefálicas Traumáticas , Lesões Encefálicas , Humanos , Lesões Encefálicas Traumáticas/terapia , Unidades de Terapia Intensiva , Cuidados Críticos , Escala de Coma de GlasgowRESUMO
BACKGROUND: The use of oral opioids as standard treatment after cesarean delivery has been linked to persistent use in opioid-naïve women in the USA. In Denmark, the use of opioids after cesarean delivery is typically restricted to in-hospital use. The aim of this study was to estimate the incidence of persistent postpartum opioid use in Denmark and compare the incidence by mode of delivery. METHODS: This was a national cohort study of all women giving birth in Denmark in 2016, with one-year follow-up. Data from Danish registries were retrieved and combined using each woman's unique identification number. Persistent use of opioids was defined as ≥3 redeemed opioid prescriptions 31-365â¯days postpartum. RESULTS: A total of 62 520 births were included in the cohort: 49 859 vaginal deliveries, 5310 intrapartum cesarean deliveries, and 7351 pre-labor cesarean deliveries. For all births, persistent postpartum opioid use occurred in 85 (140 in 100 000) women of whom 36 (42%) had opioid use during pregnancy. The incidence of persistent opioid use was highest in the pre-labor cesarean delivery cohort (n=27; 360 in 100 000) and lowest in the intrapartum cesarean delivery cohort (n=3, 60 in 100 000; P<0.001). Women taking opioids during pregnancy were at increased risk of persistent opioid use (odds ratio 63.3; 95% CI 43.9 to 91.4). CONCLUSIONS: Women giving birth in Denmark, where use of post-discharge opioid treatment is generally restricted, have a low risk of developing persistent use of opioids, with very few women seeking additional analgesic treatment from their general practitioner.
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Assistência ao Convalescente , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor Pós-Operatória/tratamento farmacológico , Alta do Paciente , Período Pós-Parto , GravidezRESUMO
AIM: To identify clinical, medical and psychosocial predictors of venous leg ulcer recurrence within 12 months of healing. METHODS: A multi-site study was conducted in Australia in community and hospital outpatient settings. Adults with venous leg ulcers were recruited within 4 weeks of healing and data were collected on preventative treatments and health, medical, clinical and psychosocial factors. Follow-up data on recurrences were collected every 3 months until ulcer recurrence, or until 12 months after healing pending which occurred first. Factors associated with time to recurrence were analysed using a Cox proportional hazards regression model. DESIGN: Secondary data analysis of a multi-site, prospective longitudinal study to validate a risk assessment tool for recurrence. RESULTS: A sample of 143 participants was recruited (51% male, Mage = 73 years, SD 13.6). Almost half (49.6%) had an ulcer recurrence within 12 months, with a mean time to ulcer recurrence of 37 weeks (SE 1.63, 95% CI 33.7-40.1). Factors measured at the time of healing that were significant independent predictors of recurrence were: prescribed antidepressant medications (p = .035), presence of haemosiderosis (p = .006), decreased mobility (longer sitting times) (p = .007) and lower social support scale scores (p = .002). Participants who wore compression systems providing 20 mmHg or higher for at least 5 days/week were less likely to recur, although not reaching statistical significance (p = .06). CONCLUSION: Results provide evidence that antidepressant medications, haemosiderosis, decreased mobility and lack of social support are risk factors associated with ulcer recurrence; therefore, these variables are modifiable and could guide early intervention.
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Hemossiderose , Úlcera da Perna , Úlcera Varicosa , Adulto , Idoso , Antidepressivos , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Recidiva , Apoio Social , Úlcera Varicosa/tratamento farmacológicoRESUMO
BACKGROUND: Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)-17A and IL-17F, which is currently under investigation for treatment of moderate-to-severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL-17 inhibitors for psoriasis. OBJECTIVES: To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies. METHODS: Forty-nine patients with moderate-to-severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28. RESULTS: At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte-related gene products such as CXCL1 (C-X-C motif chemokine ligand 1), IL-8 (encoded by the CXCL8 gene), CCL20 (C-C motif chemokine 20), IL-36γ and IL-17C were profoundly normalized to levels associated with nonlesional skin. CONCLUSIONS: Here, inhibition of IL-17F in addition to IL-17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials.
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Psoríase , Transcriptoma , Anticorpos Monoclonais Humanizados , Método Duplo-Cego , Humanos , Psoríase/tratamento farmacológico , Psoríase/genética , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Samples of rock from the Tomtor Nb - REE (rare-earth elements) deposit (Russia) have been investigated by Raman micro-spectroscopy using visible 532 nm wavelength excitation. Raman spectra of different samples of this rock confirm their composition as calcites and other carbonates such as rhodochrosite, and mixed solid solution phases (Ca, Mn, Fe, Mg, Ba, Sr, REE)(CO3). An association between cyanobacteria and the apatite crystals has been noted Cyanobacteria exhibited Raman modes at 1520-1517 cm-1 located in the double bonds of the central part of the polyene chain of carotenoids. A slight shift of this mode in the apatite-containing samples are dependent upon the compositions of carotenoids, the ratio of the rare earth elements adsorbed by cyanobacteria as well as their interaction with the environment. Laser-induced photoluminescence of REE and Mn+2, obtained as an analytical artifact in the Raman spectra, has been observed in most cases with significant spectral intensity. The luminescence emission of Mn 2+, Sm3+, Eu 3+, Pr3+, Ho3+, Er 3+ in the spectra of the apatite-containing samples obtained with 532 nm excitation can be attributed both to apatite and to other mineral phases with a low concentration which contain these elemental ions. The results obtained in this study allowed us to confirm that the biogenic presence of the cyanobacterial mat had a significant impact on the formation of the unique Nb-REE Tomtor deposit.
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Cianobactérias , Análise Espectral Raman , Carbonatos/análise , Minerais , Fosfatos , Federação RussaRESUMO
BACKGROUND: The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting. OBJECTIVE: Robust characterization of the underlying HS mechanisms and detection of the involved skin compartments. METHODS: Hidradenitis suppurativa/acne inversa molecular taxonomy and key signalling pathways were studied by whole transcriptome profiling. Dysregulated genes were detected by comparing lesional and non-lesional skin obtained from female HS patients and matched healthy controls using the Agilent array platform. The differential gene expression was confirmed by quantitative real-time PCR and targeted protein characterization via immunohistochemistry in another set of female patients. HS-involved skin compartments were also recognized by immunohistochemistry. RESULTS: Alterations to key regulatory pathways involving glucocorticoid receptor, atherosclerosis, HIF1α and IL17A signalling as well as inhibition of matrix metalloproteases were detected. From a functional standpoint, cellular assembly, maintenance and movement, haematological system development and function, immune cell trafficking and antimicrobial response were key processes probably being affected in HS. Sixteen genes were found to characterize HS from a molecular standpoint (DEFB4, MMP1, GJB2, PI3, KRT16, MMP9, SERPINB4, SERPINB3, SPRR3, S100A8, S100A9, S100A12, S100A7A (15), KRT6A, TCN1, TMPRSS11D). Among the proteins strongly expressed in HS, calgranulin-A, calgranulin-B and serpin-B4 were detected in the hair root sheath, koebnerisin and connexin-32 in stratum granulosum, transcobalamin-1 in stratum spinosum/hair root sheath, small prolin-rich protein-3 in apocrine sweat gland ducts/sebaceous glands-ducts and matrix metallopeptidase-9 in resident monocytes. CONCLUSION: Our findings highlight a panel of immune-related drivers in HS, which influence innate immunity and cell differentiation in follicular and epidermal keratinocytes as well as skin glands.
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Hidradenite Supurativa/genética , Hidradenite Supurativa/imunologia , Imunidade Inata , Adulto , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase em Tempo Real , Pele/citologia , TranscriptomaRESUMO
Staphylococcus aureus (S. aureus) is a challenging bacterial pathogen which can cause a range of diseases, from mild skin infections, to more serious and invasive disease including deep or organ space surgical site infections, life-threatening bacteremia, and sepsis. S. aureus rapidly develops resistance to antibiotic treatments. Despite current infection control measures, the burden of disease remains high. The most advanced vaccine in clinical development is a 4 antigen S. aureus vaccine (SA4Ag) candidate that is being evaluated in a phase 2b/3 efficacy study in patients undergoing elective spinal fusion surgery (STaphylococcus aureus suRgical Inpatient Vaccine Efficacy [STRIVE]). SA4Ag has been shown in early phase clinical trials to be generally safe and well tolerated, and to induce high levels of bactericidal antibodies in healthy adults. In this review we discuss the design of SA4Ag, as well as the proposed clinical development plan supporting licensure of SA4Ag for the prevention of invasive disease caused by S. aureus in elective orthopedic surgical populations. We also explore the rationale for the generalizability of the results of the STRIVE efficacy study (patients undergoing elective open posterior multilevel instrumented spinal fusion surgery) to a broad elective orthopedic surgery population due to the common pathophysiology of invasive S. aureus disease and commonalties of patient and procedural risk factors for developing postoperative S. aureus surgical site infections.
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Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/imunologia , Infecções Estafilocócicas/prevenção & controle , Vacinas Antiestafilocócicas/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Antígenos de Bactérias/administração & dosagem , Bacteriemia/prevenção & controle , Ensaios Clínicos como Assunto , Procedimentos Cirúrgicos Eletivos , Humanos , Procedimentos Ortopédicos , Staphylococcus aureus , Infecção da Ferida Cirúrgica/microbiologiaRESUMO
In 2020, the ESA ExoMars and NASA Mars 2020 missions will be launched to Mars to search for evidence of past and present life. In preparation for these missions, terrestrial analog samples of rock formations on Mars are studied in detail in order to optimize the scientific information that the analytical instrumentation will return. Desert varnishes are thin mineral coatings found on rocks in arid and semi-arid environments on Earth that are recognized as analog samples. During the formation of desert varnishes (which takes many hundreds of years), organic matter is incorporated, and microorganisms may also play an active role in the formation process. During this study, four complementary analytical techniques proposed for Mars missions (X-ray diffraction [XRD], Raman spectroscopy, elemental analysis, and pyrolysis-gas chromatography-mass spectrometry [Py-GC-MS]) were used to interrogate samples of desert varnish and describe their capacity to sustain life under extreme scenarios. For the first time, both the geochemistry and the organic compounds associated with desert varnish are described with the use of identical sets of samples. XRD and Raman spectroscopy measurements were used to nondestructively interrogate the mineralogy of the samples. In addition, the use of Raman spectroscopy instruments enabled the detection of ß-carotene, a highly Raman-active biomarker. The content and the nature of the organic material in the samples were further investigated with elemental analysis and methylated Py-GC-MS, and a bacterial origin was determined to be likely. In the context of planetary exploration, we describe the habitable nature of desert varnish based on the biogeochemical composition of the samples. Possible interference of the geological substrate on the detectability of pyrolysis products is also suggested. Key Words: Desert varnish-Habitability-Raman spectroscopy-Py-GC-MS-XRD-ExoMars-Planetary science. Astrobiology 17, 1123-1137.
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Clima Desértico , Exobiologia/métodos , Marte , Minerais/análise , Pintura/análise , Planeta Terra , Exobiologia/instrumentação , Cromatografia Gasosa-Espectrometria de Massas/instrumentação , Cromatografia Gasosa-Espectrometria de Massas/métodos , Minerais/química , Voo Espacial , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Difração de Raios X/instrumentação , Difração de Raios X/métodosRESUMO
OBJECTIVE: Chronic wounds are costly and affect approximately 1-2% of the population. Venous disease is responsible for about 60% of all chronic leg ulcers and these ulcers can be debilitating, with evidence of a decreased quality of life. Unfortunately, up to 30% of venous leg ulcers (VLUs) fail to heal, despite best practice treatment. This study aimed to identify risk factors associated with delayed healing in participants with VLUs and in particular, whether psychosocial factors play a part in this process. METHOD: A secondary analysis was conducted of a large data set of clinical, wound healing, health, social, economic and psychological data collected in previous prospective studies of participants with VLUs. Generalised linear mixed modelling was used to identify independent predictors of failure to heal after 24 weeks. RESULTS: We recruited 247 participants with 318 VLUs from hospital and community settings. Findings revealed that four early predictors were independently significantly associated with failure to heal by 24 weeks. These were: participants who lived alone (OR 2.3, 95%CI [1.13-4.61], p=0.03); had less than 25% reduction in ulcer area within two weeks of treatment (OR 10.07, 95%CI [4.60-22.19], p<0.001); had higher ulcer severity scores (OR 5.1, 95%CI [2.33-11.88], p=0.001); and participants who were not treated with high level compression therapy (i.e.>30 mmHg) at the time of assessment (OR 4.18, 95% CI [1.95-8.97], p=0.002). CONCLUSION: Identified risk factors offer an opportunity for clinicians to determine realistic outcomes for their patients and to guide decisions on early referral and implementation of tailored adjunctive interventions. Additionally, findings from this study suggest health professionals need to assess and address not only clinical risk factors but also social risk factors, when planning interventions to promote healing.
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Bandagens Compressivas , Úlcera Varicosa/terapia , Cicatrização/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Autocuidado , Falha de TratamentoRESUMO
BACKGROUND: Chronic leg ulcers, remaining unhealed after 4-6 weeks, affect 1-3% of the population, with treatment costly and health service resource intensive. Venous disease contributes to approximately 70% of all chronic leg ulcers and these ulcers are often associated with pain, reduced mobility and a decreased quality of life. Despite evidence-based care, 30% of these ulcers are unlikely to heal within a 24-week period and therefore the recognition and identification of risk factors for delayed healing of venous leg ulcers would be beneficial. AIM: To review the available evidence on risk factors for delayed healing of venous leg ulcers. METHODS: A review of the literature in regard to risk factors for delayed healing in venous leg ulcers was conducted from January 2000 to December 2013. Evidence was sourced through searches of relevant databases and websites for resources addressing risk factors for delayed healing in venous leg ulcers specifically. RESULTS: Twenty-seven studies, of mostly low-level evidence (Level III and IV), identified risk factors associated with delayed healing. Risk factors that were consistently identified included: larger ulcer area, longer ulcer duration, a previous history of ulceration, venous abnormalities and lack of high compression. Additional potential predictors with inconsistent or varying evidence to support their influence on delayed healing of venous leg ulcers included: decreased mobility and/or ankle range of movement, poor nutrition and increased age. DISCUSSION: Findings from this review indicate that a number of physiological risk factors are associated with delayed healing in venous leg ulcers and that social and/or psychological risk factors should also be considered and examined further. CONCLUSION: The findings from this review can assist health professionals to identify prognostic indicators or risk factors significantly associated with delayed healing in venous leg ulcers. This will facilitate realistic outcome planning and inform implementation of appropriate early strategies to promote healing.
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Úlcera Varicosa/fisiopatologia , Cicatrização/fisiologia , Articulação do Tornozelo/fisiologia , Dieta , Nível de Saúde , Humanos , Estilo de Vida , Prognóstico , Fatores de Risco , Fatores Socioeconômicos , Úlcera Varicosa/complicaçõesRESUMO
BACKGROUND: Patient perceived quality of recovery is an important outcome after surgery and should be measured in clinical trials. Quality of recovery after surgery and general anaesthesia can be measured by the QoR-15. A high score indicates a good recovery and the score ranges from 0 to 150. The aim of this study was to translate the QoR-15 questionnaire into Danish and do a full psychometric evaluation of the Danish version. METHODS: A translation and cultural adaption of the original version of the QoR-15 into a Danish version, the QoR-15D, was performed. After obtaining consent, patients undergoing elective abdominal, orthopaedic or gynaecological surgery under general anaesthesia were included. Patients completed the QoR-15D before surgery and on the first postoperative day. The validity, reliability, responsiveness and clinical feasibility of the QoR-15D were evaluated. RESULTS: One hundred and forty patients returned their pre- and postoperative questionnaire successfully giving a completion rate of 56%. The postoperative QoR-15 score was negatively correlated with duration of surgery (ρ = -0.21, 95% CI: -0.04 to -0.36, P < 0.02) and postoperative stay (ρ = -0.28, 95% CI: -0.12 to -0.43, P < 0.01). Postoperative QoR-15D scores were inversely related to the extent of surgery: minor, intermediate or major (127 ± 22, 106 ± 29 and 96 ± 24, respectively, P < 0.01). Cronbach's alpha and split-half reliability was 0.90 and 0.88. Test-retest reliability was 0.99 (95% CI: 0.94-1.00). Cohen's effect size was 1.13 and the standardized response mean was 0.82. CONCLUSION: The QoR-15D has preserved the validity, excellent reliability, high degree of responsiveness and the clinical feasibility of the original English version.
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Período de Recuperação da Anestesia , Anestesia Geral , Satisfação do Paciente , Inquéritos e Questionários/normas , Traduções , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Idioma , Masculino , Pessoa de Meia-Idade , Países Baixos , Psicometria , Reprodutibilidade dos Testes , Adulto JovemRESUMO
BACKGROUND: In early postpartum haemorrhage (PPH), a low concentration of fibrinogen is associated with excessive subsequent bleeding and blood transfusion. We hypothesized that pre-emptive treatment with fibrinogen concentrate reduces the need for red blood cell (RBC) transfusion in patients with PPH. METHODS: In this investigator-initiated, multicentre, double-blinded, parallel randomized controlled trial, we assigned subjects with severe PPH to a single dose of fibrinogen concentrate or placebo (saline). A dose of 2 g or equivalent was given to all subjects independent of body weight and the fibrinogen concentration at inclusion. The primary outcome was RBC transfusion up to 6 weeks postpartum. Secondary outcomes were total blood loss, total amount of blood transfused, occurrence of rebleeding, haemoglobin <58 g litre(-1), RBC transfusion within 4 h, 24 h, and 7 days, and as a composite outcome of 'severe PPH', defined as a decrease in haemoglobin of >40 g litre(-1), transfusion of at least 4 units of RBCs, haemostatic intervention (angiographic embolization, surgical arterial ligation, or hysterectomy), or maternal death. RESULTS: Of the 249 randomized subjects, 123 of 124 in the fibrinogen group and 121 of 125 in the placebo group were included in the intention-to-treat analysis. At inclusion the subjects had severe PPH, with a mean blood loss of 1459 (sd 476) ml and a mean fibrinogen concentration of 4.5 (sd 1.2) g litre(-1). The intervention group received a mean dose of 26 mg kg(-1) fibrinogen concentrate, thereby significantly increasing fibrinogen concentration compared with placebo by 0.40 g litre(-1) (95% confidence interval, 0.15-0.65; P=0.002). Postpartum blood transfusion occurred in 25 (20%) of the fibrinogen group and 26 (22%) of the placebo group (relative risk, 0.95; 95% confidence interval, 0.58-1.54; P=0.88). We found no difference in any predefined secondary outcomes, per-protocol analyses, or adjusted analyses. No thromboembolic events were detected. CONCLUSIONS: We found no evidence for the use of 2 g fibrinogen concentrate as pre-emptive treatment for severe PPH in patients with normofibrinogenaemia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: http://clinicaltrials.gov/show/NCT01359878. Published protocol: http://www.trialsjournal.com/content/pdf/1745-6215-13-110.pdf.
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Fibrinogênio/uso terapêutico , Hemorragia Pós-Parto/tratamento farmacológico , Método Duplo-Cego , Transfusão de Eritrócitos , Feminino , Fibrinogênio/efeitos adversos , Hemostasia , Humanos , Hemorragia Pós-Parto/sangue , Gravidez , Resultado do TratamentoRESUMO
Sandhoff disease (SD) is caused by deficiency of N-acetyl-ß-hexosaminidase (Hex) resulting in pathological accumulation of GM2 ganglioside in lysosomes of the central nervous system (CNS) and progressive neurodegeneration. Currently, there is no treatment for SD, which often results in death by the age of five years. Adeno-associated virus (AAV) gene therapy achieved global CNS Hex restoration and widespread normalization of storage in the SD mouse model. Using a similar treatment approach, we sought to translate the outcome in mice to the feline SD model as an important step toward human clinical trials. Sixteen weeks after four intracranial injections of AAVrh8 vectors, Hex activity was restored to above normal levels throughout the entire CNS and in cerebrospinal fluid, despite a humoral immune response to the vector. In accordance with significant normalization of a secondary lysosomal biomarker, ganglioside storage was substantially improved, but not completely cleared. At the study endpoint, 5-month-old AAV-treated SD cats had preserved neurological function and gait compared with untreated animals (humane endpoint, 4.4±0.6 months) demonstrating clinical benefit from AAV treatment. Translation of widespread biochemical disease correction from the mouse to the feline SD model provides optimism for treatment of the larger human CNS with minimal modification of approach.
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Terapia Genética , Doença de Sandhoff/terapia , Animais , Gatos , Dependovirus/genética , Dependovirus/imunologia , Progressão da Doença , Gangliosídeos/metabolismo , Vetores Genéticos , Humanos , Imunidade Humoral , Injeções Intraventriculares , Doença de Sandhoff/patologia , Transdução Genética , Resultado do Tratamento , beta-N-Acetil-Hexosaminidases/biossíntese , beta-N-Acetil-Hexosaminidases/genéticaRESUMO
This study is primarily focused on proving the potential of miniaturized Raman systems to detect any biomolecular and mineral signal in natural geobiological samples that are relevant for future application of the technique within astrobiologically aimed missions on Mars. A series of evaporites of varying composition and origin from two extremely dry deserts were studied, namely Atacama and Mojave. The samples represent both dry evaporitic deposits and recent evaporitic efflorescences from hypersaline brines. The samples comprise halite and different types of sulfates and carbonates. The samples were analysed in two different ways: (i) directly as untreated rocks and (ii) as homogenized powders. Two excitation wavelengths of miniaturized Raman spectrometers were compared: 532 and 785 nm. The potential to detect carotenoids as biomarkers on Mars compared with the potential detection of carbonaceous matter using miniaturized instrumentation is discussed.
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OBJECTIVE: Exercise has the potential to offer a range of health benefits in addition to improving healing outcomes for people with venous leg ulcers (VLUs). However, despite evidence-based recommendations, most of these individuals do not engage in regular exercise. The aim of this study was to gain an understanding of the perspectives of adults with VLUs, in relation to exercise. METHOD: This was a qualitative design using semi-structured interviews and discussions. Ten participants with venous leg ulceration volunteered to participate. Recruitment was through a specialist wound clinic. Verbatim data were collected by an experienced moderator using a semi-structured guide. Data saturation was reached after three group discussions and two interviews. A random selection of transcripts was sent back to the participants for verification. Thematic content analysis was used to determine major themes and categories. Two transcripts were independently analysed, categories and themes independently developed, cross checked and found comparable. Remaining transcripts were analysed using the developed categories and codes. RESULTS: Regardless of their current exercise routine, participants reported exercising before venous leg ulceration and expressed an interest in either becoming active or maintaining an active lifestyle. Overall, four themes emerged from the findings: i) participant understanding of the relationship between chronic venous insufficiency and exercise patterns; ii) fear of harm impacts upon positive beliefs and attitudes to exercise; iii) perceived factors limit exercise; and iv) structured management facilitates exercise. CONCLUSION: The value of exercise in improving outcomes in VLUs lies in its capacity to promote venous return and reduce the risk of secondary conditions in this population. Despite motivation and interest in being exercise active, people with VLUs report many obstacles. Further exploration of mechanisms that assist this patient population and promote understanding about management of barriers, coupled with promotion of enabling factors, is vital for improving their exercise participation.