RESUMO
Increasing levels of physical inactivity is a global burden for mankind and is also an emerging problem in companion dogs. In both humans and dogs, insufficient physical activity is associated with increased risk for noncommunicable diseases and impaired quality of life (QoL). The aim of the current pilot study was to evaluate effects of a joint outdoor exercise program for dog owners (n = 22) and dogs (n = 22) with focus on QoL and body measurements. Results indicate that an eight-week exercise intervention alone, with a target distance of at least 2 km twice a week, may be sufficient to significantly increase self-reported QoL and acceptance of bodily appearance in dog owners despite no reductions in body measurements. In dogs, a significantly reduced body condition score (BCS) was registered, despite no considerable changes in feeding. The increased owner motivation for continued joint exercise suggests potential for lifestyle changes, which could be investigated in future studies including control groups and long-term follow-ups. The importance of the human-animal bond as a success factor for increased mutual physical activity and health benefits in both dog owners and dogs is recommended to be studied in a more in-depth manner.
Assuntos
Exercício Físico , Qualidade de Vida , Cães , Animais , Projetos Piloto , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Vínculo Humano-Animal , Animais de Estimação/psicologia , Condicionamento Físico Animal , PropriedadeRESUMO
Over 200,000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually. Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC.
Assuntos
Predisposição Genética para Doença/genética , Neoplasias da Próstata/genética , Cromossomo X , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Cromossômico , Marcadores Genéticos , Genótipo , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Linhagem , Receptores Androgênicos/genéticaRESUMO
It is well accepted that strain and strain rate deformation parameters are not only a measure of intrinsic myocardial contractility but are also influenced by changes in cardiac load and structure. To date, no information is available on the relative importance of these confounders. This study was designed to investigate how strain and strain rate, measured by Doppler echocardiography, relate to the individual factors that determine cardiac performance. Echocardiographic and conductance measurements were simultaneously performed in mice in which individual determinants of cardiac performance were mechanically and/or pharmacologically modulated. A multivariable analysis was performed with radial and circumferential strains and peak systolic radial and circumferential strain rates as dependent parameters and preload recruitable stroke work (PRSW), arterial elastance (E(a)), end-diastolic pressure, and left ventricular myocardial volume (LVMV) as independent factors representing myocardial contractility, afterload, preload, and myocardial volume, respectively. Radial strain was most influenced by E(a) (ß = -0.58, R(2) = 0.34), whereas circumferential strain was strongly associated with E(a) and moderately with LVMV (ß = 0.79 and -0.52, respectively, R(2) = 0.54). Radial strain rate was related to both PRSW and LVMV (ß = 0.79 and -0.62, respectively, R(2) = 0.50), whereas circumferential strain rate showed a prominent correlation only with PRSW (ß = -0.61, R(2) = 0.51). In conclusion, strain (both radial and circumferential) is not a good surrogate measure of intrinsic myocardial contractility unless the strong confounding influence of afterload is considered. Strain rate is a more robust measure of contractility that is less influenced by changes in cardiac load and structure. Thus, peak systolic strain rate is the more relevant parameter to assess myocardial contractile function noninvasively.
Assuntos
Hipertrofia Ventricular Esquerda/fisiopatologia , Contração Miocárdica , Infarto do Miocárdio/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Animais , Fenômenos Biomecânicos , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Dobutamina/farmacologia , Ecocardiografia Doppler , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Contração Miocárdica/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico por imagem , Valor Preditivo dos Testes , Estresse Mecânico , Fatores de Tempo , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda/efeitos dos fármacos , Pressão VentricularRESUMO
The present study investigated if acetyl salicylic acid (ASA) and terbutaline in combination increased the clinical pregnancy rate in patients undergoing in vitro fertilisation (IVF)/intra-cytoplasmic sperm injection (ICSI). A randomised controlled trial was designed, in which 167 patients were randomised to taking ASA for 9 weeks after embryo transfer and terbutaline around the time of embryo transfer as adjuvant medication. A total of 112 patients were randomised to no adjuvant medication. The clinical pregnancy rate per controlled ovarian hyperstimulation was 30.5% in the intervention group and 42.0% in the control group. This difference was not statistically significant, and we conclude that ASA and terbutaline in combination do not increase the clinical pregnancy rate after IVF/ICSI treatment.
Assuntos
Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Injeções de Esperma Intracitoplásmicas , Terbutalina/uso terapêutico , Adulto , Quimioterapia Combinada , Transferência Embrionária , Feminino , Fertilização in vitro , Humanos , Análise de Intenção de Tratamento , Gravidez , Taxa de GravidezRESUMO
BACKGROUND: Patients with metastatic castration resistant prostate cancer (mCRPC) are at risk of symptomatic skeletal events (SSE). Bone health agents (BHA, ie bisphosphonates and denosumab) and new life-prolonging drugs (LPDs) can delay SSEs. The aim of this study is to investigate the use of BHAs in relation to SSEs in treated real-world mCRPC population. PATIENTS AND METHODS: We included patients from the CAPRI registry who were treated with at least one LPD and diagnosed with bone metastases prior to the start of first LPD (LPD1). Outcomes were SSEs (external beam radiation therapy (EBRT) to the bone, orthopedic surgery, pathologic fracture or spinal cord compression) and SSE-free survival (SSE-FS) since LPD1. RESULTS: One-thousand nine hundred and twenty-three patients were included with a median follow-up from LPD1 of 16.7 months. Fifty-two percent (n = 996) started BHA prior or within 4 weeks after the start of LPD1 (early BHA). In total, 41% experienced at least one SSE. SSE incidence rate was 0.29 per patient year for patients without BHA and 0.27 for patients with early BHA. Median SSE-FS from LPD1 was 12.9 months. SSE-FS was longer in patients who started BHA early versus patients without BHA (13.2 vs. 11.0 months, P = .001). CONCLUSION: In a real-world population we observed an undertreatment with BHAs, although patients with early BHA use had lower incidence rates of SSEs and longer SSE-FS. This finding was irrespective of type of SSE and presence of risk factors. In addition to LPD treatment, timely initiation of BHAs is recommended in bone metastatic CRPC-patients with both pain and/or opioid use and prior SSE.
Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Densidade Óssea , Neoplasias Ósseas/secundário , Países Baixos/epidemiologia , Neoplasias de Próstata Resistentes à Castração/patologiaRESUMO
BACKGROUND: In 2004 docetaxel was the first life-prolonging drug (LPD) registered for metastatic castration-resistant prostate cancer (mCRPC) patients. Between 2011 and 2014 new LPDs for mCRPC (cabazitaxel, abiraterone, enzalutamide, and radium-223) were introduced in the Netherlands. The objective of this study is to assess the impact of the introduction of new LPDs on treatment patterns and overall survival (OS) over time. PATIENTS AND METHODS: CRPC patients diagnosed in the years 2010-2016 in the observational, retrospective CAPRI registry (20 hospitals) were included and followed up to 2018. Two subgroups were analyzed: treatment-naïve patients (subgroup 1, n = 3600) and post-docetaxel patients (subgroup 2, n = 1355). RESULTS: In both subgroups, the use of any LPD increased: from 57% (2010-2011) to 69% (2014-2015) in subgroup 1 and from 65% (2011-2012) to 79% (2015-2016) in subgroup 2. Chemotherapy as first mCRPC-treatment (i.e., docetaxel) and first post-docetaxel treatment (i.e., cabazitaxel or docetaxel rechallenge) decreased (46-29% and 20-9% in subgroup 1 and 2, respectively), while the use of androgen-receptor targeting treatments (ART) increased from 11% to 39% and 46% to 64% in subgroup 1 and 2, respectively. In subgroup 1, median OS (mOS) from diagnosis CRPC increased from 28.5 months to 31.0 months (p = 0.196). In subgroup 2, mOS from progression on docetaxel increased from 7.9 months to 12.5 months (p < 0.001). After multiple imputations of missing values, in multivariable cox-regression analysis with known prognostic parameters, the treatment period was independent significant for OS in subgroup 1 (2014-2015 vs. 2010-2011 with HR 0.749, p < 0.001) and subgroup 2 (2015-2016 vs. 2011-2012 with HR 0.811, p = 0.037). CONCLUSION: Since 2010, a larger proportion of mCRPC patients was treated with LPDs, which was related to an increased mOS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/mortalidade , Neoplasias de Próstata Resistentes à Castração/mortalidade , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Androstenos/administração & dosagem , Benzamidas/administração & dosagem , Docetaxel/administração & dosagem , Seguimentos , Humanos , Masculino , Nitrilas/administração & dosagem , Feniltioidantoína/administração & dosagem , Prognóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagemRESUMO
BACKGROUND: Cross resistance between androgen-receptor targeting therapies (ARTs) (abiraterone acetate plus prednisone [ABI+P] or enzalutamide [ENZ]) for treatment of metastatic castration-resistant prostate cancer (mCRPC) may affect responses to second ART (ART2). OBJECTIVE: To establish treatment duration and prostate-specific antigen (PSA) response of ART2 in real-world mCRPC patients treated with or without other life-prolonging drugs (LPDs; ie, docetaxel, cabazitaxel, or radium-223) between ART1 and ART2. DESIGN, SETTING, AND PARTICIPANTS: Castration-resistant prostate cancer patients, diagnosed between 2010 and 2016 were retrospectively registered in Castration-resistant Prostate Cancer Registry (CAPRI). Patients treated with both ARTs were clustered into two subgroups: ART1>ART2 or ART1>LPD>ART2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Outcomes were ≥50% PSA response and treatment duration of ART2. Descriptive statistics and binary logistic regression after multiple imputations were performed. RESULTS AND LIMITATIONS: A total of 273 patients were included with a median follow-up of 8.4 mo from ART2. Patients with ART1>ART2 were older and had favourable prognostic characteristics at ART2 baseline compared with patients with ART1>LPD>ART2. No differences between ART1>ART2 and ART1>LPD>ART2 were found in PSA response and treatment duration. Multivariate analysis suggested that PSA response of ART2 was less likely in patients with visceral metastases (odds ratio [OR] 0.143, p=0.04) and more likely in patients with a relatively longer duration of androgen-deprivation treatment (OR 1.028, p=0.01) and with ABI + P before ENZ (OR 3.192, p=0.02). A major limitation of this study was missing data, a common problem in retrospective observational research. CONCLUSIONS: The effect of ART2 seems to be low, with a low PSA response rate and a short treatment duration irrespective of interposed chemotherapy or radium-223, especially in patients with short time on castration, visceral disease, and ENZ before ABI+P. PATIENT SUMMARY: We observed no differences in outcomes of patients treated with sequential abiraterone acetate plus prednisone (ABI+P) and enzalutamide (ENZ) with or without interposed chemotherapy or radium-223. In general, outcomes were lower than those in randomised trials, questioning the additional effect of second treatment with ABI+P or ENZ in daily practice.
Assuntos
Preparações Farmacêuticas , Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios , Androgênios , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Sistema de Registros , Estudos RetrospectivosRESUMO
The agent of African relapsing fever, Borrelia crocidurae, causes reversible multiple organ damage. We hypothesize that this damage is caused when the spirochete forms aggregate with erythrocytes in vivo, creating rosettes that plug the microcirculatory system. To test this hypothesis, we compared testicular microcirculation over an extended time period in two groups of rats: one experimentally inoculated with B. crocidurae, the other with the nonerythrocyte rosette-forming Borrelia hermsii. In the B. crocidurae group, erythrocyte rosettes formed during spiro-chetemia blocked precapillary blood vessels and reduced the normal pattern of microcirculatory blood flow. After spirochetemia, erythrocyte rosettes disappeared and flow was normalized. Decreased blood flow and focal vascular damage with increased permeability and interstitial bleeding adjacent to the erythrocyte microemboli induced cell death in seminiferous tubules. Interestingly, we found that B. crocidurae could penetrate the tubules and remain in the testis long after the end of spirochetemia, suggesting that the testis can serve as a reservoir for this bacteria in subsequent relapses. The group infected with B. hermsii displayed normal testicular blood flow and vasomotion at all selected time points, and suffered no testicular damage. These results confirmed our hypothesis that the erythrocyte rosettes produce vascular obstruction and are the main cause of histopathology seen in model animal and human infections.
Assuntos
Infecções por Borrelia/patologia , Febre Recorrente/patologia , Testículo/lesões , Animais , Barreira Hematotesticular , Borrelia/genética , Borrelia/isolamento & purificação , Borrelia/patogenicidade , Infecções por Borrelia/sangue , Infecções por Borrelia/microbiologia , Morte Celular , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Febre Recorrente/sangue , Febre Recorrente/microbiologia , Túbulos Seminíferos/microbiologia , Túbulos Seminíferos/patologia , Espermatozoides/citologia , Testículo/irrigação sanguínea , Testículo/patologiaRESUMO
Despite its high prevalence, very little is known regarding genetic predisposition to prostate cancer. A genome-wide scan performed in 66 high-risk prostate cancer families has provided evidence of linkage to the long arm of chromosome 1 (1q24-25). Analysis of an additional set of 25 North American and Swedish families with markers in this region resulted in significant evidence of linkage in the combined set of 91 families. The data provide strong evidence of a major prostate cancer susceptibility locus on chromosome 1.
Assuntos
Mapeamento Cromossômico , Cromossomos Humanos Par 1 , Genes , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Repetições de Dinucleotídeos , Ligação Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , América do Norte , Oncogenes , Linhagem , Fatores de Risco , Estatísticas não Paramétricas , SuéciaRESUMO
BACKGROUND: South Africa did not meet its Millennium Development Goals with regard to the reduction in maternal and under-5 mortality. Furthermore, many birthing women do not receive intrapartum care with empathy and endure disrespect-ful and abusive care. OBJECTIVES: To implement a multicomponent, context-specific intervention package to change the complex interplay between preventable maternal and perinatal mortality and morbidity and poor clinical governance and supervision in midwife-led labour units. METHODS: A mixed-methods intervention study was conducted in Tshwane District, South Africa, in 10 midwife-led obstetric units (MOUs), from which a purposive sample consisting of five units was selected for the intervention. The intervention took place in three phases: (i) baseline measurement; (ii) implementation of the so-called 'CLEVER' intervention package in the five intervention units, based on the results of the first phase; and (iii) a review of health systems improvements and perinatal outcomes. The intervention had three pillars: (i) feedback of the baseline measurement to the intervention units to raise awareness and solicit participation; (ii) health systems strengthening; and (iii) intensive weekly engagement for 3 months, with further monthly support afterwards. Observation of barriers during baseline activities contributed to the health systems strengthening and improvement strategies during implementation. RESULTS: Perinatal outcome indicators for the year before the intervention were compared with data for the year in which the intervention took place and the year after the intervention. Significant declines were observed in in-facility fresh stillbirths, meconium aspiration and birth asphyxia in the intervention MOUs from 2015 to 2017. The control group showed some decline during the period owing to support from district clinical specialist team members. CONCLUSIONS: CLEVER as a context-specific, multicomponent, clinically focused intervention package may have contributed to improved perinatal morbidity and mortality rates in MOUs.
RESUMO
BACKGROUND: The institutional maternal mortality ratio (iMMR) in South Africa (SA) is still unacceptably high. A key recommendation from the National Committee on Confidential Enquiries into Maternal Deaths has been to improve the availability and quality of care for women suffering obstetric emergencies. OBJECTIVES: To determine whether there was a change in the number of maternal deaths and in the iMMR over time that could be attributed to the training of >80% of healthcare professionals by means of a specifically designed emergency obstetric care (EmOC) training programme. METHODS: A before-and-after study was conducted in 12 healthcare districts in SA, with the remaining 40 districts serving as a comparison group. Twelve 'most-in-need' healthcare districts in SA were selected using a composite scoring system. Multiprofessional skills-and-drills workshops were held off-site using the Essential Steps in Managing Obstetric Emergencies and Emergency Obstetric Simulation Training programme. Eighty percent or more of healthcare professionals providing maternity care in each district were trained between October 2012 and March 2015. Institutional births and maternal deaths were assessed for the period January 2011 - December 2016 and a before-and-after-training comparison was made. The number of maternal deaths and the iMMR were used as outcome measures. RESULTS: A total of 3 237 healthcare professionals were trained at 346 workshops. In all, 1 248 333 live births and 2 212 maternal deaths were identified and reviewed for cause of death as part of the SA confidential enquiries. During the same period there were 5 961 maternal deaths and 5 439 870 live births in the remaining 40 districts. Significant reductions of 29.3% in the number of maternal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.66 - 0.77) and 17.5% in the number of maternal deaths from direct obstetric causes (RR 0.825, 95% CI 0.73 - 0.93) were recorded. When comparing the percentage change in iMMR for equivalent before-and-after periods, there was a greater reduction in all categories of causes of maternal death in the intervention districts than in the comparison districts. CONCLUSIONS: Implementing a skills-and-drills EmOC training package was associated with a significant reduction in maternal deaths.
Assuntos
Parto Obstétrico/métodos , Educação Médica Continuada/métodos , Educação Continuada em Enfermagem/métodos , Serviços Médicos de Emergência/métodos , Morte Materna/prevenção & controle , Complicações do Trabalho de Parto/terapia , Treinamento por Simulação , Competência Clínica , Parto Obstétrico/mortalidade , Emergências , Feminino , Humanos , Morte Materna/tendências , Complicações do Trabalho de Parto/mortalidade , Gravidez , Melhoria de Qualidade/tendências , Indicadores de Qualidade em Assistência à Saúde/tendências , África do SulRESUMO
The symmetry of the rider is highly relevant, and in the equestrian community it is generally thought that a symmetrical rider has a better possibility to influence the horse in an optimal way. The aim of the study was to analyse and compare frontal plane kinematics of the core body segments in ten riders while riding and while rocking a balance chair from side-to-side. It was hypothesized that the riders were asymmetrical in relation to their intersegmental strategies when comparing between left and right directions and that individual riders would display the same postural strategies when riding and when rocking the balance chair. Ten moderately-skilled riders wore a full-body marker set that was tracked by a motion capture system as they rocked a balance chair from side to side. Inertial measurement units attached to the head, trunk and pelvis were used to measure the segmental movements while riding in left and right directions. Roll rotation data for head, trunk and pelvis were averaged over available strides/cycles. Results from mixed models showed that the riders were asymmetric when comparing riding in left vs right directions, for example the trunk was rotated 19° to the right on the right circle and 14° to the left on the left circle, on average. Riders adopted the same asymmetrical posture whether they were riding in the left or right direction on straight lines, circles or leg yielding. A significant relationship was found between postural asymmetries when riding and when rocking the balance chair, one degree of pelvis or head roll asymmetry on the chair predicted 2.4 (SE 0.9) degrees of asymmetry while riding. Future studies may investigate the value of seated, off-horse postural training for improving rider symmetry and thereby equestrian performance.
RESUMO
The ability to predict new chemical entity performance using in vivo animal models has been under investigation for more than two decades. Pharmaceutical companies use their own strategies to make decisions on the most appropriate formulation starting early in development. In this paper the biopharmaceutical decision trees available in four EFPIA partners (Bayer, Boehringer Ingelheim, Bristol Meyers Squibb and Janssen) were discussed by 7 companies of which 4 had no decision tree currently defined. The strengths, weaknesses and opportunities for improvement are discussed for each decision tree. Both pharmacokineticists and preformulation scientists at the drug discovery & development interface responsible for lead optimization and candidate selection contributed to an overall picture of how formulation decisions are progressed. A small data set containing compound information from the database designed for the IMI funded OrBiTo project is examined for interrelationships between measured physicochemical, dissolution and relative bioavailability parameters. In vivo behavior of the drug substance and its formulation in First in human (FIH) studies cannot always be well predicted from in vitro and/or in silico tools alone at the time of selection of a new chemical entity (NCE). Early identification of the risks, challenges and strategies to prepare for formulations that provide sufficient preclinical exposure in animal toxicology studies and in FIH clinical trials is needed and represents an essential part of the IMI funded OrBiTo project. This article offers a perspective on the use of in vivo models and biopharmaceutical decision trees in the development of new oral drug products.
Assuntos
Produtos Biológicos/química , Biofarmácia/métodos , Química Farmacêutica/métodos , Desenvolvimento de Medicamentos/métodos , Animais , Disponibilidade Biológica , Árvores de Decisões , Descoberta de Drogas/métodos , HumanosRESUMO
BACKGROUND: Cabazitaxel has been shown to improve overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel in the TROPIC trial. However, trial populations may not reflect the real-world population. We compared patient characteristics and outcomes of cabazitaxel within and outside trials (standard of care, SOC). PATIENTS AND METHODS: mCRPC patients treated with cabazitaxel directly after docetaxel therapy before 2017 were retrospectively identified and followed to 2018. Patients were grouped on the basis of treatment within a trial or SOC. Outcomes included OS and prostate-specific antigen (PSA) response. RESULTS: From 3616 patients in the CAPRI registry, we identified 356 patients treated with cabazitaxel, with 173 patients treated in the second line. Trial patients had favorable prognostic factors: fewer symptoms, less visceral disease, lower lactate dehydrogenase, higher hemoglobin, more docetaxel cycles, and longer treatment-free interval since docetaxel therapy. PSA response (≥ 50% decline) was 28 versus 12%, respectively (P = .209). Median OS was 13.6 versus 9.6 months for trial and SOC subgroups, respectively (hazard ratio = 0.73, P = .067). After correction for prognostic factors, there was no difference in survival (hazard ratio = 1.00, P = .999). Longer duration of androgen deprivation therapy treatment, lower lactate dehydrogenase, and lower PSA were associated with longer OS; visceral disease had a trend for shorter OS. CONCLUSION: Patients treated with cabazitaxel in trials were fitter and showed outcomes comparable to registration trials. Conversely, those treated in daily practice showed features of more aggressive disease and worse outcome. This underlines the importance of adequate estimation of trial eligibility and health status of mCRPC patients in daily practice to ensure optimal outcomes.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Taxoides/administração & dosagem , Idoso , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Humanos , L-Lactato Desidrogenase/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Países Baixos , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Estudos Retrospectivos , Padrão de Cuidado , Análise de Sobrevida , Taxoides/efeitos adversos , Resultado do TratamentoRESUMO
Poorly functioning health systems and local health systems barriers affect many women giving birth in low- and middle-income countries. The district clinical specialist teams in South Africa are uniquely positioned to provide facilitation and mentoring during interventions for improving the weak primary healthcare system. To ensure success, four key principles should be considered during scale-up of interventions: systems thinking and awareness of contexts and barriers; a focus on sustainability; harnessing factors known to enhance scalability; and respect for human rights and equity. Asking the right questions about the responsibilities of health systems at the micro-, meso- and macro-levels will benefit scale-up processes and sustain innovative pathways to high-quality obstetric care in communities.
Assuntos
Acessibilidade aos Serviços de Saúde , Serviços de Saúde Materna/organização & administração , Obstetrícia , Análise de Sistemas , Atenção à Saúde/organização & administração , Atenção à Saúde/normas , Países em Desenvolvimento , Feminino , Equidade em Saúde , Direitos Humanos , Humanos , Ciência da Implementação , Serviços de Saúde Materna/normas , Gravidez , Avaliação de Programas e Projetos de Saúde , Qualidade da Assistência à Saúde , Respeito , África do SulRESUMO
BACKGROUND: Poor emergency obstetric care has been shown by national confidential enquiries into maternal deaths to contribute to a number of maternal deaths in South Africa. OBJECTIVES: To assess whether a structured training course can improve knowledge and skills and whether this can influence the capacity of a healthcare facility to provide basic and comprehensive emergency obstetric care signal functions. METHODS: A baseline survey was conducted to assess the seven basic emergency obstetric and neonatal care signal functions in 51 community health centres (CHCs) and the nine comprehensive emergency care signal functions in 62 district hospitals (DHs). A re-assessment was conducted 1 year after saturation training had been provided in each district. The delegates were trained using a structured training programme (Essential Steps in Managing Obstetric Emergencies, ESMOE) and their knowledge and skills were tested before and after the training. Saturation training was considered to have been achieved once 80% of the healthcare professionals involved in maternity care had been trained. RESULTS: There was a significant improvement in the knowledge and skills of doctors, namely by 16.8% and 32.8%, respectively, of advanced midwives by 13.7% and 29.0%, and of professional nurses with midwifery by 16.1% and 31.2%. The seven basic emergency care functions improved from 60.8% to 67.8% in the CHCs and from 90.7% to 92.5% in the DHs before and after training. If the two signal functions that are not within the scope of practice of professional nurses with midwifery are excluded (viz. assisted delivery and manual vacuum aspiration), the functionality of CHCs increased from 85.1% to 94.9%. CONCLUSIONS: The ESMOE training programme improved knowledge and skills, but there was a modest improvement in the functionality of the facilities. Improvement in functionality requires changes in the structure of the health system, including changing the scope of practice of professional nurses with midwifery and employing more advanced midwives in CHCs.
Assuntos
Competência Clínica , Conhecimentos, Atitudes e Prática em Saúde , Serviços de Saúde Materna/normas , Obstetrícia/normas , Médicos/normas , Centros Comunitários de Saúde/normas , Parto Obstétrico/estatística & dados numéricos , Emergências , Feminino , Pessoal de Saúde/educação , Pessoal de Saúde/normas , Hospitais de Distrito , Humanos , Recém-Nascido , Morte Materna/prevenção & controle , Serviços de Saúde Materna/estatística & dados numéricos , Tocologia/normas , Tocologia/estatística & dados numéricos , Obstetrícia/educação , Médicos/organização & administração , Médicos/estatística & dados numéricos , Gravidez , África do SulRESUMO
REASONS FOR PERFORMING STUDY: No studies have been published on effects of treatment with a defocused beam carbon dioxide (CO2) laser on equine skin histology. A better understanding of this will help to define how lasers should be used, in order to reduce potential side effects. OBJECTIVE: To describe the acute effects of different doses of defocused CO2 laser, ranging from therapeutic to surgical levels, on equine skin. METHODS: Defocused CO2 laser was administered to the skin in the hamstrings (91 J/cm2), fetlock (137 J/cm2) and loin (450 J/cm2) areas of 13 Standardbred horses. The acute effects on skin histology were examined 90 min after the end of therapy. RESULTS: Mild changes with focal spongiosis and subepidermal clefts were found after 91 J/cm2 irradiation and more severe changes with diffuse subepidermal clefts after the 137 J/cm2 dose. A homogeneous eosinophilic acellular zone of dermis and destruction of adnexal structures, and significant thinning of the epidermis was observed after the 450 J/cm2 dose. CONCLUSIONS: The present study indicates acute dose-dependent changes in equine skin histology after laser treatment Severe tissue damage was induced using a 450 J/cm2 dose. POTENTIAL RELEVANCE: To reduce the potential side effects of defocused CO2 laser treatment, the laser parameters must be carefully evaluated. Caution should be taken if doses higher than 91 J/cm2 (16 W, 4 min, and 42 cm2) are used in irradiation of equine skin.
Assuntos
Procedimentos Cirúrgicos Dermatológicos , Cavalos/cirurgia , Terapia a Laser/veterinária , Lasers , Pele/patologia , Animais , Dióxido de Carbono , Relação Dose-Resposta à Radiação , Feminino , Terapia a Laser/instrumentação , Terapia a Laser/métodos , Lasers/efeitos adversos , Masculino , Pele/efeitos da radiaçãoRESUMO
Lameness detection can be challenging in dogs, as reflected in the reported low inter-rater agreement when visually assessing lameness. The aim of this study was to use an inertial sensor-based system to detect and quantify induced distal and proximal limb disturbances mimicking supporting and swinging limb lameness in dogs trotting on a treadmill by measuring vertical head and pelvic movement symmetry. Ten clinically sound dogs were equipped with inertial measurement units that were attached to the head, pelvis and right distal forelimb. Vertical head and pelvic movement symmetry were measured while dogs trotted on a treadmill, before and after the induction of moderate support or swinging fore- and hindlimb lameness. Four symmetry variables were calculated: the differences in displacement between the two lowest and between the two highest values of the head and pelvis per stride, respectively. These variables were defined as minimum head difference (HDmin), maximum head difference (HDmax), minimum pelvic difference (PDmin) and maximum pelvic difference (PDmax). Induction of supporting forelimb and hindlimb lameness produced significant changes in HDmin and PDmin, respectively. Swinging forelimb and hindlimb lameness produced significant changes in HDmax and PDmax, respectively. Additional compensatory ipsilateral forelimb and contralateral hindlimb movements were detected. Based on our findings, inertial sensor-based systems can be used to detect and quantify induced moderate lameness and differentiate between supporting and swinging limb lameness in dogs trotting on a treadmill. Further studies are needed to evaluate this method in dogs presented for clinical lameness evaluation and in overground locomotion.
Assuntos
Acelerometria/veterinária , Doenças do Cão/diagnóstico , Coxeadura Animal/diagnóstico , Acelerometria/instrumentação , Animais , Cães , Feminino , Marcha , MasculinoRESUMO
Compensatory limb loading has been studied in lame dogs; however, little is known about how these compensations relate to motion of the head and pelvis, assessment of which is an important component of lameness examinations. The aim of this study was to describe the patterns of vertical head and pelvic motion symmetry at the trot in dogs with induced supporting limb lameness in the forelimbs or hind limbs. Ten sound dogs were trotted on a treadmill before and after temporary induction of moderate lameness (grade 2/5) in each limb. Reflective markers were located on the head, pelvis and right forelimb, and kinematic data were captured with a motion capture system. Upper body symmetry parameters were calculated, including differences in the highest (HDmax) and in the lowest (HDmin) positions of the head, and in the highest (PDmax) and in the lowest (PDmin) positions of the mid-pelvis, with a value of zero indicating symmetry. The head was lowered more during the sound limb stance phase and lowered less during the lame limb stance phase in supporting forelimb lameness (HDmin: 4.6mm in dogs when sound, -18.3mm when left limb lameness was induced and 20.5mm when right limb lameness was induced). The mid-pelvis was lowered more during the sound limb stance phase and lowered and lifted less during the lame limb stance phase in supporting hind limb lameness (PDmin: 1mm in dogs when sound, -10.1mm in left limb lameness and 8.4mm in right limb lameness). The hip of the lame side, measured at the level of the greater trochanter, had an increased downwards displacement during the lame limb swing phase (-21mm in left hind limb lameness, P=0.005; 23.4mm in right hind limb lameness, P=0.007). Asymmetry in the lowering of the head or mid-pelvis is a more sensitive indicator of supporting forelimb and hind limb lameness, respectively, than asymmetry in the raising of the head. Increased displacement of the hip ('hip drop' of the lame side during its swing phase) is a good indicator of hind limb lameness in dogs.
Assuntos
Doenças do Cão/fisiopatologia , Marcha , Cabeça/fisiologia , Membro Posterior/fisiopatologia , Pelve/fisiologia , Animais , Fenômenos Biomecânicos , Cães , Teste de Esforço , Feminino , Membro Anterior/fisiopatologia , Coxeadura Animal/fisiopatologia , MasculinoRESUMO
The development of safety and quality standards for equestrian surfaces needs to be based on objective, repeatable measurements which allow comparisons between surfaces. These measurements should incorporate the assessment of surface performance by riders. This study provides data from objective and subjective assessment of functional properties of high-level show jumping competition and warm-up arenas. Twenty-five arenas in nine international show jumping events were evaluated by mechanical in-situ testing with a surface tester, rider assessments using visual analogue scales (198 riders provided 749 arena evaluations), descriptions of arena constructions and by laboratory tests of surface material. Mixed models were used to present subjective evaluation of rider perception of the functional properties for each arena while controlling for rider and event. The association between objective and subjective assessments were also explored creating mixed models, controlling for rider and event. Mechanical measurements of impact firmness, and to a lesser extent cushioning and grip, had a significant positive association with the riders' perception. Responsiveness as assessed by the Orono biomechanical surface tester (OBST) was negatively associated with the riders' perceptions, which suggests riders and the OBST had different concepts of this functional property and that further developments of the OBST might be necessary. Objectively measured uniformity showed no useful association with riders' perception. Even though arena assessments were made by top level riders, a substantial inter-rider variation was demonstrated.