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OBJECTIVE: Frequent presenters to the Emergency Department (ED) are known to have complex physical, behavioural and social needs. The study aimed to analyse the system's behaviour to generate new insights into ED high utilisers with complex mental health issues. METHODS: A retrospective cohort study of the ED presentations of 200 high utilisers during a 12-month period was conducted. Analyses included psychiatric diagnoses, re-presentation rates, cost-benefit analysis of services and patient journey maps to illustrate the patient experience. RESULTS: The profiled high utilisers represented nearly a quarter of total ED mental health presentations and were more likely to be single and unemployed. Diagnostically, Borderline Personality Disorder and Schizophrenia predominated. The re-presentation rate was high (70% within 28 days) and mental health attributable costs represented nearly three quarters of total health costs. CONCLUSION: The study revealed a disintegrated service system for ED high utilisers with mental health issues, resulting in suboptimal clinical outcomes and substantial costs. To deliver value-based mental healthcare our lessons were; (1) stabilise the system's interaction with the patient by ensuring service responses are consistent with their enhanced management plan (2) all the system's parts channel the patient into various support services including psychological treatment with one therapist.KEY POINTSThe top 200 high utilisers presented to emergency 1928 times within 12 monthsThe re-presentation rate amongst the study's cohort was high (70% within 28 days)A high prevalence of BPD and schizophrenia was noted for this cohortThe study reveals a disintegrated service system for ED high utilisers, resulting in suboptimal clinical outcomes and substantial costs for the serviceA need for early identification, consistency in service responses and various support services to be provided by the hospital including psychological treatment.
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Servicio de Urgencia en Hospital , Utilización de Instalaciones y Servicios , Trastornos Mentales , Pacientes , Servicio de Urgencia en Hospital/estadística & datos numéricos , Utilización de Instalaciones y Servicios/estadística & datos numéricos , Humanos , Trastornos Mentales/terapia , Pacientes/psicología , Pacientes/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
OBJECTIVE: Intrathecal baclofen therapy (ITB) has been used in the treatment of spasticity and dystonia. In our pediatric movement disorder clinic, we noted a delay in referral of patients for consideration of ITB. Often, only after years of failed medical therapy, a baclofen pump is considered. This study attempts to investigate the prevalence, length and causes of the delay. METHODS: A retrospective, outcome analysis was performed. We conducted a survey of 30 pediatric patients who received baclofen pumps between the ages of 5 and 23. Patients were divided into two groups (before and after ITB approval by the US Food and Drug Administration in 1996) (FDA/Center for Drug Evaluation and Research, 2014; Ridley and Rawlins, J Neurosci Nurs 38:72-82, 2006; Medical Advisory Secretariat, Ont Health Technol Assess Ser 5:1-93, 2005). Information was collected regarding their onset of spasticity, attempted treatments, pump referral, satisfaction, and resulting change in the quality of life. RESULTS: There was a delay in referral in most cases investigated. Average time to baclofen pump implantation, after initial onset of spasticity, was 5.14 years (group A) and 11.7 years (group B). Out of the subjects who reported diminished effects or no effect of pharmacological treatment, 93 % of these respondents reported that ITB had a dramatic long-lasting effect on their spasticity. Of 30 patients, 28 reported effectiveness of ITB, and 26 of 30 subjects reported an improved quality and ease of life. CONCLUSION: Despite the limitations of this subjective retrospective analysis of outcomes and delay in referral, the opinions of the parents and caregivers should be considered. Earlier referral for ITB therapy may better treat severe spasticity in pediatric patients.
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Baclofeno/uso terapéutico , Relajantes Musculares Centrales/uso terapéutico , Espasticidad Muscular/tratamiento farmacológico , Derivación y Consulta , Adolescente , Niño , Preescolar , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Adulto JovenRESUMEN
Coexisting psychiatric and medical conditions, environmental and contextual factors, inadequate diagnosis and treatment, medication non-adherence, and issues such as low self-esteem, hopelessness and cognitive reactivity, can play a role in difficult-to-treat depression. A reduction in symptoms due to pharmacological treatment does not equate with full recovery, and some level of rehabilitation is often required. The evidence base for psychosocial therapies in difficult-to-treat depression is small, with the research heavily weighted toward biological treatments. Nevertheless, combining psychological treatments with pharmacotherapy is likely to improve rates of recovery in difficult-to-treat depression. Psychological therapies can be useful in modifying health beliefs, treating comorbid anxiety and other disorders, dealing with contextual factors, and activating patients to facilitate their recovery. Effective treatment requires a multidisciplinary team involving a general practitioner and psychologist, and sometimes a psychiatrist. Effective communication and active engagement of patients and families is essential.
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Trastorno Depresivo Resistente al Tratamiento/terapia , Terapia Cognitivo-Conductual , Comorbilidad , Trastorno Depresivo Resistente al Tratamiento/epidemiología , Terapia Familiar , Humanos , Atención Plena , Grupo de Atención al Paciente , Cooperación del Paciente , Autoimagen , Resultado del TratamientoRESUMEN
Vascular anomalies are malformations or tumors of the blood or lymphatic vasculature and can be life-threatening. Although molecularly targeted therapies can be life-saving, identification of the molecular etiology is often impeded by lack of accessibility to affected tissue samples, mosaicism or insufficient sequencing depth. In a cohort of 356 participants with vascular anomalies, including 104 with primary complex lymphatic anomalies (pCLAs), DNA from CD31+ cells isolated from lymphatic fluid or cell-free DNA from lymphatic fluid or plasma underwent ultra-deep sequencing thereby uncovering pathogenic somatic variants down to a variant allele fraction of 0.15%. A molecular diagnosis, including previously undescribed genetic causes, was obtained in 41% of participants with pCLAs and 72% of participants with other vascular malformations, leading to a new medical therapy for 63% (43/69) of participants and resulting in improvement in 63% (35/55) of participants on therapy. Taken together, these data support the development of liquid biopsy-based diagnostic techniques to identify previously undescribed genotype-phenotype associations and guide medical therapy in individuals with vascular anomalies.
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Anomalías Linfáticas , Malformaciones Vasculares , Humanos , Mutación , Pruebas Genéticas/métodos , Malformaciones Vasculares/diagnóstico , Malformaciones Vasculares/genética , Malformaciones Vasculares/terapia , Alelos , Anomalías Linfáticas/genética , GenómicaRESUMEN
Peyer's patches (PP), a key component of the gut-associated lymphoid tissue, serve as the primary inductive sites for intestinal immunity. In the present study, we addressed the hypothesis that the morphological features of PP innervation are consistent with an immunomodulatory role for the enteric nervous system. Laser scanning confocal microscopy was used to collect images through large tissue volumes, yielding a three-dimensional perspective of the neuronal network superimposed on PP follicles from porcine jejunum and human ileum. Peptidergic nerve fibers were found in close apposition to immunocytes within PP subepithelial domes and the adjacent villi. The results suggest that nerve fibers in PP may participate in neuroimmune cross-talk within individual antigen-sampling sites as well as integrate information across multiple antigen-sampling sites.
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Sistema Nervioso Entérico/anatomía & histología , Mucosa Intestinal/inmunología , Mucosa Intestinal/inervación , Neuroinmunomodulación , Ganglios Linfáticos Agregados/inervación , Animales , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunidad Mucosa , Inmunohistoquímica , Masculino , Microscopía Confocal , PorcinosRESUMEN
Enteric neural activity modulates active transepithelial ion transport in the intestine. We investigated the neural circuits mediating neurogenic secretion in mucosal explants from porcine ileum. Transmural electrical stimulation increased short-circuit current, a measure of active ion transport, by 35+/-2 microA/cm2. The neuronal Na+ channel blocker saxitoxin, the muscarinic cholinergic receptor antagonist atropine, the 5-hydroxytryptamine3 receptor antagonist tropisetron, and the cyclooxygenase inhibitor indomethacin inhibited this response. In addition, tropisetron inhibited the atropine-resistant portion of the response, and both atropine and indomethacin attenuated the saxitoxin-resistant component. Neurogenic secretion in porcine ileum appears to be mediated by tryptaminergic and prostanoid-sensitive cholinergic pathways.
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Acetilcolina/farmacología , Íleon/efectos de los fármacos , Prostaglandinas/farmacología , Serotonina/farmacología , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Ácido 8,11,14-Eicosatrienoico/farmacología , Animales , Atropina/farmacología , Estimulación Eléctrica , Femenino , Íleon/inervación , Íleon/metabolismo , Técnicas In Vitro , Indoles/farmacología , Indometacina/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inervación , Mucosa Intestinal/metabolismo , Transporte Iónico/efectos de los fármacos , Masculino , Saxitoxina/farmacología , Serotoninérgicos/farmacología , Antagonistas de la Serotonina/farmacología , Porcinos , Tropisetrón , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: Selective dorsal rhizotomy (SDR) is often recommended for children with spastic paraparesis and cerebral palsy. SDR reduces spasticity in the lower extremities for these children with spastic paraplegia. However, SDR is infrequently recommended for adults with spasticity. Spastic diplegia in adult patients can be due to stroke, brain or spinal cord injury from trauma, infection, toxic-metabolic disorders, and other causes. Although rarely considered, SDR is an option for adult patients with spastic diplegia as well. CASE DESCRIPTION: The authors describe a patient who underwent a SDR with a successful postoperative outcome. This man suffered a hypertensive and hemorrhagic stroke secondary to intravenous drug abuse at age 46. A SDR was performed after two failed intrathecal baclofen pump placements due to recurrent infections, likely resulting from his immunocompromised status. The patient underwent lumbar laminectomies and dorsal rhizotomies at levels L1-S1 bilaterally. Postoperatively, the patient's spasticity was significantly reduced. His Ashworth spasticity score decreased from 4/5 to 1/5, and the reduction in tone has been durable over 3 years. CONCLUSION: SDR in older patients with spastic paraparesis may be considered as a treatment option.
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AIMS: In a rabbit denudation model, assess impact of strut thickness on arterial healing by comparing endothelial cell coverage and strut tissue coverage after implantation of bare metal stents of varying thickness; evaluate the effect of an everolimus-eluting stent. METHODS AND RESULTS: Strut tissue coverage and endothelialisation were assessed 14 and 21 days after implantation with scanning electron microscopy quantitation methods and immunostaining against the endothelial cell marker PECAM-1 (CD-31). At 14 days, strut tissue coverage was higher with the stainless steel Liberté stent (88%, 97 µm) versus Express (77%, 132 µm). The platinum chromium Element stent with the thinnest strut (81 µm) had the highest level (95%). By 21 days endothelialisation was complete for all. The everolimus-eluting Element stent had a 1-week delay in luminal endothelialisation but was >89% by 21 days; strut endothelial coverage was >79% in 80% (4/5) of animals, with total strut tissue coverage >95%. CONCLUSIONS: This study demonstrated that strut thickness affects strut tissue coverage post stent implantation and the addition of an everolimus-eluting polymer introduces a short delay in endothelialisation. The results highlight the need to control for aspects of stent design such as strut thickness when comparing across drug-eluting stent platforms.
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Angioplastia Coronaria con Balón , Vasos Coronarios/patología , Stents Liberadores de Fármacos , Células Endoteliales/patología , Inmunosupresores/administración & dosificación , Sirolimus/análogos & derivados , Stents , Animales , Cromo , Vasos Coronarios/ultraestructura , Células Endoteliales/fisiología , Everolimus , Femenino , Metales , Microscopía Electrónica de Rastreo , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Platino (Metal) , Diseño de Prótesis , Conejos , Sirolimus/administración & dosificaciónRESUMEN
OBJECTIVE: Diabetes leads to protein kinase C (PKC)-beta overactivation and microvascular dysfunction, possibly resulting in disordered skin microvascular blood flow (SkBF) and other changes observed in diabetic peripheral neuropathy (DPN) patients. We investigate the effects of the isoform-selective PKC-beta inhibitor ruboxistaurin mesylate on neurovascular function and other measures of DPN. RESEARCH DESIGN AND METHODS: Endothelium-dependent and C fiber-mediated SkBF, sensory symptoms, neurological deficits, nerve fiber morphometry, quantitative sensory and autonomic function testing, nerve conduction studies, quality of life (using the Norfolk Quality-of-Life Questionnaire for Diabetic Neuropathy [QOL-DN]), and adverse events were evaluated for 20 placebo- and 20 ruboxistaurin-treated (32 mg/day) DPN patients (aged > or =18 years; with type 1 or type 2 diabetes and A1C < or =11%) during a randomized, double-masked, single-site, 6-month study. RESULTS: Endothelium-dependent (+78.2%, P < 0.03) and C fiber-mediated (+56.4%, P < 0.03) SkBF at the distal calf increased from baseline to end point. Significant improvements from baseline within the ruboxistaurin group were also observed for the Neuropathy Total Symptom Score-6 (NTSS-6) (3 months -48.3%, P = 0.01; end point -66.0%, P < 0.0006) and the Norfolk QOL-DN symptom subscore and total score (end point -41.2%, P = 0.01, and -41.0, P = 0.04, respectively). Between-group differences in baseline-to-end point change were observed for NTSS-6 total score (placebo -13.1%; ruboxistaurin -66.0%, P < 0.03) and the Norfolk QOL-DN symptom subscore (placebo -4.0%; ruboxistaurin -41.2%, P = 0.041). No significant ruboxistaurin effects were demonstrated for the remaining efficacy measures. Adverse events were consistent with those observed in previous ruboxistaurin studies. CONCLUSIONS: In this cohort of DPN patients, ruboxistaurin enhanced SkBF at the distal calf, reduced sensory symptoms (NTSS-6), improved measures of Norfolk QOL-DN, and was well tolerated.
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Neuropatías Diabéticas/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Indoles/uso terapéutico , Maleimidas/uso terapéutico , Microcirculación/fisiología , Proteína Quinasa C/antagonistas & inhibidores , Flujo Sanguíneo Regional/efectos de los fármacos , Piel/irrigación sanguínea , Anciano , Velocidad del Flujo Sanguíneo , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/diagnóstico , Femenino , Humanos , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Placebos , Proteína Quinasa C beta , Grupos RacialesRESUMEN
Enteric neurotransmitters can modulate the biodefensive functions of the intestinal mucosa, but their role in mucosal interactions with enteropathogens is not well defined. Here we tested the hypothesis that norepinephrine (NE) modulates interactions between enterohemorrhagic Escherichia coli O157:H7 (EHEC) and the colonic epithelium. Mucosal sheets from porcine distal colon were mounted in Ussing chambers. Drugs and an inoculum of either Shiga toxin-negative or -positive EHEC were added to the contraluminal and luminal bathing medium, respectively. After 90 min, adherent bacteria were quantified by an adherence assay and by immunohistochemical methods; short-circuit current (I(sc)) was measured continuously to assess changes in active ion transport. NE-treated tissues exhibited concentration-dependent increases in I(sc) and EHEC adherence. NE did not alter adherence of a rodent-adapted, noninfectious E. coli strain or two porcine-adapted non-O157 E. coli strains. The actions of NE on EHEC adherence but not I(sc) were prevented by the alpha-adrenergic antagonist yohimbine and the PKA activator Sp-8-bromoadenosine-3',5'-cyclic monophosphorothioate. Like NE, the PKA inhibitor Rp-8-bromoadenosine-3',5'-cyclic monophosphorothioate or indirectly acting sympathomimetic agents increased EHEC adherence. Nerve fibers immunoreactive for the NE-synthesizing enzymes tyrosine hydroxylase and dopamine beta-hydroxylase appeared to innervate the colonic epithelium. EHEC-like immunoreactivity on the colonic surface had the appearance of bacterial microcolonies and increased after NE treatment by a phentolamine-sensitive mechanism. Through interactions with alpha(2)-adrenergic receptors, NE appears to increase EHEC adherence to the colonic mucosa. Changes in sympathetic neural outflow may alter intestinal susceptibility to infection.