RESUMEN
BACKGROUND: Endocrinopathic, or hyperinsulinaemia-associated laminitis (HAL) is a common and debilitating equine foot disease, and although no pharmacological treatments are registered, several are under development. To evaluate the effect of such treatments, an accurate and consistent method is needed to track the clinical signs of laminitis over time, and the natural history of the disease, in terms of a 'normal' pattern of improvement, needs to be understood. This study examined the improvement pattern in clinical cases of naturally-occurring HAL subjected to a range of best-practice interventions, using two different scoring methods. Eighty horses and ponies with suspected HAL were enrolled in a study conducted at 16 veterinary practices across Germany. The severity of laminitis was assessed by independent veterinarians using both the traditional Obel method and a modified Obel method developed by Meier and colleagues. Assessments were made on the day of diagnosis (d 0), then on days 4, 9, 14, 25 and 42 during the intervention period. Pain medications were withheld for 24 h prior to clinical examination in all cases. RESULTS: Time to marked improvement from laminitis varied between individuals, but was difficult to monitor accurately using the Obel method, with the median grade being 2/4 on days 0 and 4, then 0/4 from d 9 onwards. More subtle changes could be identified using the Meier method, however, and the median scores were seen to follow the form of an exponential decay model in most horses, improving from 8/12 on d 0, to 0/12 on d 25. Within this composite scoring method, considerable variation was observed in the rate of improvement of individual clinical signs, with the average time taken for each sign to reach a median score of 0 ranging from 4 days (foot lift and weight shifting) to 25 days (gait when turned in a circle) across all 80 horses. CONCLUSIONS: The Meier method provides a reliable and consistent method for monitoring the clinical status of horses with HAL, and despite the variability, the pattern of improvement described here should provide a useful benchmark against which individual cases and new treatments can be assessed.
Asunto(s)
Enfermedades del Pie/veterinaria , Enfermedades de los Caballos/patología , Hiperinsulinismo/veterinaria , Índice de Severidad de la Enfermedad , Animales , Progresión de la Enfermedad , Femenino , Alemania , Pezuñas y Garras/patología , Caballos , Cojera Animal , MasculinoRESUMEN
Most of the microbial degradation in oil reservoirs is believed to take place at the oil-water transition zone (OWTZ). However, a recent study indicates that there is microbial life enclosed in microliter-sized water droplets dispersed in heavy oil of Pitch Lake in Trinidad and Tobago. This life in oil suggests that microbial degradation of oil also takes place in water pockets in the oil-bearing rock of an oil leg independent of the OWTZ. However, it is unknown whether microbial life in water droplets dispersed in oil is a generic property of oil reservoirs rather than an exotic exception. Hence, we took samples from three heavy-oil seeps, Pitch Lake (Trinidad and Tobago), the La Brea Tar Pits (California, USA), and an oil seep on the McKittrick oil field (California, USA). All three tested oil seeps contained dispersed water droplets. Larger droplets between 1 and 10 µl revealed high cell densities of up to 109 cells ml-1 Testing for ATP content and LIVE/DEAD staining showed that these populations consist of active and viable microbial cells with an average of 60% membrane-intact cells and ATP concentrations comparable to those of other subsurface ecosystems. Microbial community analyses based on 16S rRNA gene amplicon sequencing revealed the presence of known anaerobic oil-degrading microorganisms. Surprisingly, the community analyses showed similarities between all three oil seeps, revealing common OTUs, although the sampling sites were thousands of kilometers apart. Our results indicate that small water inclusions are densely populated microhabitats in heavy oil and possibly a generic trait of degraded-oil reservoirs.IMPORTANCE Our results confirmed that small water droplets in oil are densely populated microhabitats containing active microbial communities. Since these microhabitats occurred in three tested oil seeps which are located thousands of kilometers away from each other, such populated water droplets might be a generic trait of biodegraded oil reservoirs and might be involved in the overall oil degradation process. Microbial degradation might thus also take place in water pockets in the oil-bearing oil legs of the reservoir rock rather than only at the oil-water transition zone.
Asunto(s)
Archaea/aislamiento & purificación , Bacterias/aislamiento & purificación , Microbiota , Yacimiento de Petróleo y Gas/microbiología , Microbiología del Agua , Archaea/clasificación , Bacterias/clasificación , California , Lagos , Los Angeles , ARN de Archaea/análisis , ARN Bacteriano/análisis , ARN Ribosómico 16S/análisis , Trinidad y Tobago , Agua/químicaRESUMEN
Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.
Asunto(s)
Distrofina/genética , Mutación del Sistema de Lectura , Edición Génica/métodos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , ARN Guía de Kinetoplastida/genética , Animales , Modelos Animales de Enfermedad , Exones , Femenino , Regulación de la Expresión Génica , Terapia Genética , Genoma , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Espectrometría de Masas , Músculo Esquelético/metabolismo , Músculos/metabolismo , Mioblastos/metabolismo , Miocitos Cardíacos/metabolismo , Proteoma , PorcinosRESUMEN
Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected samples on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.
Asunto(s)
Adiponectina/metabolismo , Enfermedades del Pie/veterinaria , Péptido 1 Similar al Glucagón/sangre , Pezuñas y Garras/patología , Inflamación/veterinaria , Factor I del Crecimiento Similar a la Insulina/metabolismo , Adiponectina/genética , Animales , Carbohidratos de la Dieta/efectos adversos , Enfermedades del Pie/inducido químicamente , Péptido 1 Similar al Glucagón/metabolismo , Enfermedades de los Caballos/inducido químicamente , Enfermedades de los Caballos/metabolismo , Caballos , Inflamación/inducido químicamente , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/genéticaRESUMEN
OBJECTIVES: Conducting manual surveillance of non-ventilator-associated hospital-acquired pneumonia (nvHAP) using ECDC (European Centre for Disease Prevention and Control) surveillance criteria is very resource intensive. We developed and validated a semi-automated surveillance system for nvHAP, and describe nvHAP incidence and aetiology at our hospital. METHODS: We applied an automated classification algorithm mirroring ECDC definition criteria to distinguish patients 'not at risk' from patients 'at risk' for suffering from nvHAP. 'At risk'-patients were manually screened for nvHAP. For validation, we applied the reference standard of full manual evaluation to three validation samples comprising 2091 patients. RESULTS: Among the 39 519 University Hospital Zurich inpatient discharges in 2017, the algorithm identified 2454 'at-risk' patients, reducing the number of medical records to be manually screened by 93.8%. From this subset, nvHAP was identified in 251 patients (0.64%, 95%CI: 0.57-0.73). Sensitivity, negative predictive value, and accuracy of semi-automated surveillance versus full manual surveillance were lowest in the validation sample consisting of patients with HAP according to the International Classification of Diseases (ICD-10) discharge diagnostic codes, with 97.5% (CI: 93.7-99.3%), 99.2% (CI: 97.9-99.8%), and 99.4% (CI: 98.4-99.8%), respectively. The overall incidence rate of nvHAP was 0.83/1000 patient days (95%CI: 0.73-0.94), with highest rates in haematology/oncology, cardiac and thoracic surgery, and internal medicine including subspecialties. CONCLUSIONS: The semi-automated surveillance demonstrated a very high sensitivity, negative predictive value, and accuracy. This approach significantly reduces manual surveillance workload, thus making continuous nvHAP surveillance feasible as a pivotal element for successful prevention efforts.
Asunto(s)
Automatización/métodos , Monitoreo Epidemiológico , Neumonía Asociada a la Atención Médica/epidemiología , Neumonía Asociada a la Atención Médica/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Suiza/epidemiología , Adulto JovenRESUMEN
BACKGROUND: A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 µIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo (n = 10-12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. RESULTS: Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 µIU/mL in wk. 0, to 119 ± 19 µIU/mL (P = 0.015) and 117 ± 15 µIU/ml (P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin Cmax in this group was not significantly lower than in controls at wk-8 (P = 0.061), it was lower at wk-16 (P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin Cmax returned to 199 ± 36 µIU/mL in the treated group, with no rebound effect. CONCLUSIONS: Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them.
Asunto(s)
Enfermedades de los Caballos/tratamiento farmacológico , Hiperinsulinismo/veterinaria , Nitrilos/uso terapéutico , Animales , Enfermedades de los Caballos/sangre , Caballos , Hiperinsulinismo/sangre , Hiperinsulinismo/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Distribución Aleatoria , Resultado del TratamientoRESUMEN
PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45â¯Gy (1.8â¯Gy per fraction) administered either to the partial breast (nâ¯= 42) or mastectomy scar (nâ¯= 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (pâ¯= 0.045), lower Tcategory (pâ¯= 0.019), and N0 category (pâ¯= 0.005). N0 was also superior to N+ with respect to outfield recurrences (pâ¯= <0.001) and breast cancer-specific survival (pâ¯= 0.025). Acute and late skin toxicity was generally low (Asunto(s)
Neoplasias de la Mama/radioterapia
, Fraccionamiento de la Dosis de Radiación
, Recurrencia Local de Neoplasia/radioterapia
, Radioterapia Adyuvante
, Reirradiación
, Adulto
, Anciano
, Neoplasias de la Mama/mortalidad
, Neoplasias de la Mama/patología
, Terapia Combinada/métodos
, Femenino
, Estudios de Seguimiento
, Humanos
, Mastectomía
, Mastectomía Segmentaria
, Persona de Mediana Edad
, Recurrencia Local de Neoplasia/mortalidad
, Recurrencia Local de Neoplasia/patología
, Estadificación de Neoplasias
, Pronóstico
, Planificación de la Radioterapia Asistida por Computador
, Estudios Retrospectivos
, Tasa de Supervivencia
RESUMEN
As surveillance of hospital-acquired pneumonia (HAP) is very resource intensive, alternatives for HAP surveillance are needed urgently. This study compared HAP rates according to routine discharge diagnostic codes of the International Classification of Diseases, 10th Revision (ICD-10; ICD-HAP) with HAP rates according to the validated surveillance definitions of the Hospitals in Europe Link for Infection Control through Surveillance (HELICS/IPSE; HELICS-HAP) by manual retrospective re-evaluation of patient records. The positive predictive value of ICD-HAP for HELICS-HAP was 0.35, and sensitivity was 0.59. Therefore, the currently available ICD-10-based routine discharge data do not allow reliable identification of patients with HAP.
Asunto(s)
Infección Hospitalaria/epidemiología , Monitoreo Epidemiológico , Clasificación Internacional de Enfermedades , Neumonía/epidemiología , Europa (Continente)/epidemiología , Humanos , Valor Predictivo de las Pruebas , Encuestas y CuestionariosRESUMEN
AIM: The aim of the study was to assess the predictors of ocular surface squamous neoplasia (OSSN) and conjunctival squamous cell carcinoma (SCC) among Ugandan patients. MATERIALS AND METHODS: Patients presenting for removal of ocular surface lesions received human immunodeficiency virus (HIV) testing, completed questionnaires about demographic, behavioral, and historical potential risk factors for conjunctival neoplasia, and had lesions examined for interpalpebral versus other locations, rough versus smooth texture, and number of feeder vessels. Biopsies were classified pathologically using standard definitions classified OSSN and SCC. HIV rates were calculated for patients: with OSSN, SCC, and benign lesions. Potential risk factors and gross findings were tested for abilities to predict OSSN and SCC. RESULTS: One hundred and ninety-five patients presented with 212 lesions in 203 eyes. Nearly 34% of the patients were more than 60 years old, 67% were peasants, 88% spent more than 20 h/week outdoors, and only 10% wore sun protection. No potential risk factors predicted neoplasia. HIV prevalence was 17.1% among patients with OSSN compared to 11.1% among those without OSSN; 42.9% among SCC patients compared to 12.0% among those without SCC. Rough tumor surface (adjusted odds ratio [aOR] = 4.4 and 95% confidence interval [CI]: 2.2-9.1), six or more feeder vessels (aOR = 2.6, 95% CI: 1.3-5.2), and interpalpebral tumor location (aOR = 3.3, 95% CI: 1.5-7.1) predicted OSSN. Only a rough tumor surface (aOR = 34.6, 95% CI: 7.8-153.4) predicted SCC. CONCLUSION: HIV infection remained a risk factor for OSSN and particularly, SCC, but less so than in the past. Lesions' rough surface, six or more feeder vessels, and interpalpebral location increased OSSN risk. Only a rough tumor surface increased risk for SCC.
Asunto(s)
Carcinoma de Células Escamosas/epidemiología , Neoplasias de la Conjuntiva/epidemiología , Neoplasias del Ojo/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Adolescente , Adulto , Anciano , Biopsia , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de la Conjuntiva/diagnóstico , Neoplasias del Ojo/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
The aim of this study was to investigate the relationship between laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 µIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 laminitis in 14 ponies (38%). The ponies that developed laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) µIU/mL for laminitis cases, compared to 216 (148-316) µIU/mL for ponies who did not develop laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (µIU/mL) was <50; 35% (8/23) if insulin was 50 to 195; and 86% (6/7) if insulin was >195 µIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.
Asunto(s)
Carbohidratos de la Dieta/efectos adversos , Enfermedades del Pie/veterinaria , Prueba de Tolerancia a la Glucosa , Enfermedades de los Caballos/inducido químicamente , Inflamación/veterinaria , Hormona Adrenocorticotrópica/sangre , Animales , Glucemia , Carbohidratos de la Dieta/administración & dosificación , Femenino , Enfermedades del Pie/inducido químicamente , Pezuñas y Garras/patología , Caballos , Inflamación/patología , Insulina/sangre , Masculino , Enfermedades de la Hipófisis/veterinariaRESUMEN
The objective of this study is to apply therapeutic drug monitoring (TDM) as an objective tool to monitor the switch from infliximab innovator (INX) to infliximab biosimilar (INB) in our diverse rheumatic cohort in daily clinical practice. All rheumatic patients on INX treatment (Remicade®) and ≥18 years were switched to INB (Inflectra®) as part of routine care, but in a controlled setting. Patients were monitored by taking blood samples just before the first infusion of INB (T1), and after the second (T2), fourth (T3), and seventh (T4) infusion of INB. T4 reflects the patients' status after â¼12 months. Infliximab trough levels, antibodies-to-infliximab (ATI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and validated disease activity scores (if possible) were measured. Our population consisted of 27 patients with seven different rheumatic diseases who had received INX for 143 (58-161) months (median (IQR)). Half of the patients (52%) received concomitant immunosuppressives. We found widely varying infliximab levels, with only 56% within the proposed therapeutic range of 1-5 µg/mL. One patient had very high ATI levels (>880 au/mL), and two had low ATI levels (≤30 au/mL). After switching to INB, seven patients (26%) discontinued the therapy, partially due to subjective reasons. No difference in infliximab levels, CRP levels, and disease activity scores was found between the four time points (p ≥ 0.2460). In conclusion, no pharmacokinetic or clinical differences were found between INX and INB in our diverse rheumatic cohort. TDM is a helpful tool to monitor patients switching from INX to INB.
Asunto(s)
Antirreumáticos/administración & dosificación , Biosimilares Farmacéuticos/administración & dosificación , Monitoreo de Drogas , Infliximab/administración & dosificación , Enfermedades Reumáticas/tratamiento farmacológico , Anciano , Proteína C-Reactiva/análisis , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: The best practice for the organization of follow-up care in oncology is under debate, due to growing numbers of cancer survivors. Understanding survivors' preferences for follow-up care is elementary for designing patient-centred care. Based on data from prostate cancer and melanoma survivors, this study aims to identify: 1) preferences for follow-up care providers, for instance the medical specialist, the oncology nurse or the general practitioner; 2) characteristics associated with these preferences and 3) the preferred care provider to discuss cancer-related problems. MATERIAL AND METHODS: Survivors diagnosed with prostate cancer (N = 535) and melanoma (N = 232) between 2007 and 2013 as registered in The Netherlands Cancer Registry returned a questionnaire (response rate was 71% and 69%, respectively). A latent class cluster model analysis was used to define preferences and a multinomial logistic regression analysis was used to identify survivor-related characteristics associated with these preferences. RESULTS: Of all survivors, 29% reported no preference, 40% reported a preference for the medical specialist, 20% reported a preference for both the medical specialist and the general practitioner and 11% reported a preference for both the medical specialist and the oncology nurse. Survivors who were older, lower/intermediate educated and women were more likely to have a preference for the medical specialist. Lower educated survivors were less likely to have a preference for both the medical specialist and the general practitioner. Overall, survivors prefer to discuss diet, physical fitness and fatigue with the general practitioner, and hereditary and recurrence with the medical specialist. Only a small minority favored to discuss cancer-related problems with the oncology nurse. CONCLUSION: Survivors reported different preferences for follow-up care providers based on age, education level, gender and satisfaction with the general practitioner, showing a need for tailored follow-up care in oncology. The results indicate an urgency to educate patients about transitions in follow-up care.
Asunto(s)
Cuidados Posteriores , Melanoma/mortalidad , Neoplasias de la Próstata/mortalidad , Sobrevivientes , Anciano , Estudios Transversales , Femenino , Personal de Salud , Humanos , Masculino , Melanoma/terapia , Persona de Mediana Edad , Educación del Paciente como Asunto , Prioridad del Paciente , Neoplasias de la Próstata/terapia , Sistema de RegistrosRESUMEN
One of the key advantages of adaptive licensing (AL) is to align the licensing of new medicines more closely with patient needs for earlier access to beneficial treatments. From an innovators perspective, "earlier" market access may seem an obvious incentive to gain earlier revenue generation. However, this is offset with an "earlier" start to patent and regulatory protection periods, which, depending on the technology, disease, population, and timing of subsequent asset protection periods, can present a conflict.
Asunto(s)
Tecnología Biomédica/legislación & jurisprudencia , Industria Farmacéutica/legislación & jurisprudencia , Accesibilidad a los Servicios de Salud/legislación & jurisprudencia , Propiedad Intelectual , Unión Europea , Necesidades y Demandas de Servicios de Salud , Humanos , Factores de TiempoRESUMEN
RATIONALE AND OBJECTIVES: To prospectively compare high-pitch computed tomography (HPCT) under free breathing (FB) with standard-pitch CT (SPCT) under breath-hold (BH) for detection of pulmonary embolism (PE). MATERIALS AND METHODS: One hundred consecutive patients (47 females; mean age 58.7 ± 16.6) randomly underwent HPCT-FB (n = 50) or SPCT-BH (n = 50). Radiation doses were documented. One reader measured pulmonary artery attenuation and noise; mean signal-to-noise ratio (SNR) was calculated. Two readers assessed image quality, diagnostic confidence for detection of PE, motion artifacts, assessability of anatomical structures, and presence of transient interruption of contrast as sign of Valsalva maneuver. Inter-reader agreement was calculated. RESULTS: Radiation dose was significantly lower in HPCT compared to SPCT (2.68 ± 0.60 mGy vs 6.01 ± 2.26 mGy; P < .001). Mean pulmonary artery attenuation and image noise were significantly higher in HPCT (attenuation: 479 Hounsfield unit (HU) vs 343HU; P < .001; noise: 16 HU vs 10 HU; P < .001) whereas SNR was similar between groups (34 HU vs 38 HU; P = .258). HPCT had significantly higher diagnostic confidence for PE detection (P = .048), less cardiac and breathing artifacts (P < .001), better assessability of anatomical structures, and fewer cases of transient interruption of contrast (P < .001) compared to the SPCT. CONCLUSIONS: HPCT-FB allows for a significant reduction of breathing and motion artifacts compared to SPCT-BH. Diagnostic confidence, assessability of vascular and bronchial structures, as well as SNR are maintained.
Asunto(s)
Tomografía Computarizada Multidetector/métodos , Embolia Pulmonar/diagnóstico por imagen , Artefactos , Contencion de la Respiración , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Dosis de Radiación , Respiración , Relación Señal-RuidoRESUMEN
OBJECTIVES: In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. METHODS: In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. RESULTS: At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. CONCLUSIONS: In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA.
Asunto(s)
Artritis Reumatoide/diagnóstico , Articulaciones de la Mano/patología , Sinovitis/diagnóstico , Adulto , Anciano , Artralgia/diagnóstico , Estudios de Casos y Controles , Femenino , Articulaciones de la Mano/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Óptica , Proyectos Piloto , Índice de Severidad de la Enfermedad , Análisis Espectral , UltrasonografíaRESUMEN
The authors studied chromosomal aberrations in blood lymphocytes of 100 miners in coal mines of Kuznetsk coal field, with underground length of service over 15 years. Reference data were collected by cytogenetic analysis in a group of workers with long length of service in Kemerovo thermal power plant, contacting coal dust (n = 104) and in healthy males of the same age group, residents of Kemerovo city, without occupational contact with mutagenes (n = 194). The miners appeared to have maximal frequency of structural chromosomal injuries--5.37%. In the workers of thermal power plant, this value was considerably lower than in the miners (4.23%; p < 0.01), but not exceeding the values obtained in the reference groups (1.07%; p < 0.0001). Analysis of qualitative spectrum of chromosomal structural changes revealed that the miners have higher frequency of both chromosomal and chromatid type aberrations. Differences in chromosomal aberrations frequency between the miners and the thermal power plant workers are mostly due to chromosomal type aberrations. This points to significant role of chemical and radiation factors contribution into chromosomal mutagenesis in miners.
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Aberraciones Cromosómicas/inducido químicamente , Minas de Carbón , Daño del ADN/efectos de los fármacos , Polvo , Linfocitos/efectos de los fármacos , Enfermedades Profesionales/inducido químicamente , Exposición Profesional/efectos adversos , Adulto , Humanos , Incidencia , Masculino , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/genética , Siberia/epidemiologíaRESUMEN
Endoscopic hemostasis is the daily challenge that must be mastered by gastroenterologists. An emergency colonoscopy is the procedure of choice for lower gastrointestinal bleeding because of the diagnostic and therapeutic potential. Colonoscopy should be performed after oral preparation with 4-6 l polyethylene glycol solution within 12 h. In the case of massive hematochezia, colonoscopy without oral preparation employinga mechanical pump is possible and is not associated with a higher rate of complications. Many different endoscopic techniques are available (injection therapy, hemoclips, thermal coagulation, topical hemostatic substances). The suitable and most effective method must be chosen depending on the source of bleeding.
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Enfermedades del Colon/etiología , Enfermedades del Colon/terapia , Colonoscopía/métodos , Cuidados Críticos/métodos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Enfermedades del Recto/terapia , Técnicas Hemostáticas , Humanos , Polietilenglicoles/administración & dosificación , Enfermedades del Recto/etiología , Irrigación TerapéuticaRESUMEN
AIM: To investigate the value of advanced virtual monoenergetic image reconstruction (mono-plus) from dual-energy computed tomography (CT) for improving the contrast of CT pulmonary angiography (CTPA). MATERIALS AND METHODS: Forty consecutive patients (25 women, mean 62.5 years, range 28-87 years) underwent 192-section dual-source CTPA with dual-energy CT (90/150 SnkVp) after the administration of 60 ml contrast media (300 mg iodine/ml). Conventional virtual monochromatic images at 60 keV and 17 mono-plus image datasets from 40-190 keV (in 10 keV steps) were reconstructed. Subjective image quality (artefacts, subjective noise) was rated. Attenuation was measured in the pulmonary trunk and in the right lower lobe pulmonary artery; noise was measured in the periscapular musculature. The signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were calculated for each patient and dataset. Comparisons between monochromatic images and mono-plus images were performed by repeated measures analysis of variance (ANOVA) with post-hoc Bonferroni correction. RESULTS: Interreader agreement was good to excellent for subjective image quality (ICC: 0.616-0.889). As compared to conventional 60 keV images, artefacts occurred less (p=0.001) and subjective noise was rated lower (p<0.001) in mono-plus 40 keV images. Noise was lower (p<0.001), and the SNR and CNR in the pulmonary trunk and right lower lobe pulmonary artery were higher (both, p<0.001) in mono-plus 40 keV images compared to conventional monoenergetic 60 keV images. Transient interruption of contrast (TIC) was found in 14/40 (35%) of patients, with subjective contrast being similar 8/40 (20%) or higher 32/40 (80%) in mono-plus 40 keV as compared to conventional monoenergetic 60 keV images. CONCLUSIONS: Compared to conventional virtual monoenergetic imaging, mono-plus images at 40 keV improve the contrast of dual-energy CTPA.
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Procesamiento de Imagen Asistido por Computador/normas , Arteria Pulmonar/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Artefactos , Medios de Contraste , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Yodo , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Imagen Radiográfica por Emisión de Doble Fotón/métodos , Imagen Radiográfica por Emisión de Doble Fotón/normas , Estudios Retrospectivos , Relación Señal-Ruido , Tomografía Computarizada por Rayos X/métodos , Tomografía Computarizada por Rayos X/normasRESUMEN
ACCESSIBLE SUMMARY: Studies have indicated that individuals who are homeless access hospital emergency departments more frequently and may have different needs than individuals who are housed. Successful interventions have been developed and tested to reduce discharge to homelessness for psychiatric inpatients but have not been similarly tested for discharge from emergency departments. This study was developed to provide baseline data on this issue to inform future emergency department interventions. Findings from the current study suggest that discharge from emergency departments to homelessness happens frequently in London, Canada. Participants are unlikely to spontaneously disclose their housing/homelessness issue when first entering the emergency department, which may result in services that do not adequately meet their complex needs. Screening for housing issues is necessary within emergency departments and psychiatric crisis teams as housing issues may be a reason for accessing care or contribute to the presenting condition. Nurses are in an ideal position to evaluate housing needs among emergency department patients. Services outside of the emergency department are also needed to address housing issues, particularly outside of regular office hours. ABSTRACT: Individuals who have mental health issues and are homeless or in housing crisis have been found to access emergency departments more frequently than individuals with stable housing. While emergency departments primarily focus on medical issues, homeless individuals may require psychosocial support as well. This study examined issues around housing crises and emergency department use for individuals with mental illness in Canada. Collecting baseline data about these issues is important to inform subsequent interventions. Administrative data from a hospital emergency department and psychiatric crisis service were collected, and five individuals accessing the emergency department for psychiatric reasons were interviewed. Results indicated that individuals with an identified housing crisis accessed the emergency department 930 times in 6 months. None of the interview participants identified housing as the primary reason for accessing the emergency department, but all noted that housing was a contributing stressor. Future research is needed to examine ways in which discharge to homelessness from emergency departments can be avoided and identify alternative services to address housing concerns, particularly for individuals with mental illness. Crisis service and emergency department staff, especially nurses, can play an important role in screening for housing issues and connecting individuals to outside services.