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Importance: Finding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies. Objective: To evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF. Design, Setting, and Participants: This blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis. Exposure: Skin biopsy for detection of phosphorylated α-synuclein. Main Outcomes: Rates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy. Results: Of 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected. Conclusions and Relevance: In this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.
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Piel , Sinucleinopatías , alfa-Sinucleína , Anciano , Femenino , Humanos , Masculino , alfa-Sinucleína/análisis , Biopsia , Estudios Transversales , Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/patología , Atrofia de Múltiples Sistemas/diagnóstico , Atrofia de Múltiples Sistemas/patología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/patología , Sinucleinopatías/diagnóstico , Sinucleinopatías/patología , Fosforilación , Piel/química , Piel/patología , Insuficiencia Autonómica Pura/diagnóstico , Insuficiencia Autonómica Pura/patología , Reproducibilidad de los Resultados , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Método Simple Ciego , Estudios ProspectivosRESUMEN
(1) Background: The aim was to perform a literature review on customized subperiosteal implants (CSIs) and provide clinical guidelines based on the results of an expert consensus meeting held in 2023. (2) Methods: A literature search was performed in Pubmed (MEDLINE) in July 2023, including case series and cohort studies with a minimum follow-up of 6 months that analyzed totally or partially edentulous patients treated with CSIs. Previously, an expert consensus meeting had been held in May 2023 to establish the most relevant clinical guidelines. (3) Results: Six papers (four case series and two retrospective cohort studies) were finally included in the review. Biological and mechanical complication rates ranged from 5.7% to 43.8% and from 6.3% to 20%, respectively. Thorough digital planning to ensure the passive fit of the CSI is mandatory to avoid implant failure. (4) Conclusions: CSIs are a promising treatment option for rehabilitating edentulous patients with atrophic jaws; they seem to have an excellent short-term survival rate, a low incidence of major complications, and less morbidity in comparison with complex bone grafting procedures. As the available data on the use of CSIs are very scarce, it is not possible to establish clinical recommendations based on scientific evidence.
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BACKGROUND: There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity. OBJECTIVES: The objective was to determine if P2B001 (a fixed, low-dose, extended-release [ER] combination of pramipexole 0.6 mg and rasagiline 0.75 mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole-ER. METHODS: This was a 12-week, double-blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole-ER 0.6 mg or rasagiline-ER 0.75 mg), or commercial doses of pramipexole-ER titrated to optimal dose (1.5-4.5 mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole-ER. RESULTS: P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II + III scores were -2.66 (95% CI, -4.33 to -1.00) versus pramipexole-ER 0.6 mg (P = 0.0018) and - 3.30 (95% CI, -4.96 to -1.63) versus rasagiline-ER 0.75 mg (P < 0.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole-ER (mean, 3.2 mg), but significantly less worsening in daytime-sleepiness (ESS treatment difference: -2.66 [95% CI, -3.50 to -1.81]; P < 0.0001). P2B001 was well-tolerated with fewer sleep-related and dopaminergic adverse events than titrated doses of pramipexole-ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects. CONCLUSIONS: P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole-ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once-daily P2B001 as initial therapy for patients with early PD. © 2023 International Parkinson and Movement Disorder Society.
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Indanos , Enfermedad de Parkinson , Humanos , Pramipexol , Enfermedad de Parkinson/tratamiento farmacológico , Antiparkinsonianos/efectos adversos , Somnolencia , Benzotiazoles/uso terapéutico , Método Doble CiegoRESUMEN
Introduction: IPX203 is a novel oral extended-release (ER) formulation of carbidopa (CD) and levodopa (LD) developed to address the short half-life and limited area for absorption of LD in the gastrointestinal tract. This paper presents the formulation strategy of IPX203 and its relationship to the pharmacokinetics (PK) and pharmacodynamic profile of IPX203 in Parkinson's disease (PD) patients. Methods: IPX203 was developed with an innovative technology containing immediate-release (IR) granules and ER beads that provides rapid LD absorption to achieve desired plasma concentration and maintaining it within the therapeutic range for longer than can be achieved with current oral LD formulations. The PK and pharmacodynamics of IPX203 were compared with IR CD-LD in a Phase 2, open-label, rater-blinded, multicenter, crossover study in patients with advanced PD. Results: Pharmacokinetic data showed that on Day 15, LD concentrations were sustained above 50% of peak for 6.2 h with IPX203 vs. 3.9 h with IR CD-LD (P = 0.0002). Pharmacodynamic analysis demonstrated that mean MDS-UPDRS Part III scores prior to administration of the first daily dose were significantly lower among patients receiving IPX203 than IR CD-LD (LS mean difference -8.1 [25.0], P = 0.0255). In a study conducted in healthy volunteers, a high-fat, high-calorie meal delayed plasma LD Tmax by 2 h, and increased Cmax and AUCtau by approximately 20% compared with a fasted state. Sprinkling capsule contents on applesauce did not affect PK parameters. Conclusion: These data confirm that the unique design of IPX203 addresses some of the limitations of oral LD delivery.
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BACKGROUND: Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD. OBJECTIVE: To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation. DESIGN: Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791). SETTING: Outpatient. PATIENTS: 150 patients with PD and constipation. INTERVENTION: ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period. MEASUREMENTS: The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]). RESULTS: The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary end points included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016). LIMITATION: Longer treatment periods need to be investigated in future studies. CONCLUSION: ENT-01 was safe and significantly improved constipation. PRIMARY FUNDING SOURCE: Enterin, Inc.
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Demencia , Enfermedad de Parkinson , Humanos , Resultado del Tratamiento , Estreñimiento , Defecación , Método Doble CiegoRESUMEN
INTRODUCTION: In a pivotal study, apomorphine sublingual film (APL; KYNMOBI®) was an effective and generally well-tolerated on-demand treatment of "OFF" episodes in patients with Parkinson's disease (PD), approved across the dose range of 10-30 mg. Pharmacokinetics and comparative bioavailability of APL and two subcutaneous (SC) apomorphine formulations (SC-APO [APOKYN®] and SC-APO-GO [APO-go® PEN]) were evaluated in a randomized, three-way crossover, open-label study (NCT03292016). METHODS: Patients with PD and "OFF" episodes received an open-label randomized sequence of single doses of SC-APO and SC-APO-GO at the currently prescribed dose (2/3/4/5 mg) and APL doses with similar plasma exposure (15/20/25/30 mg) with ≥ 1-day washout between formulations. Plasma pharmacokinetics of apomorphine and apomorphine sulfate (major inactive metabolite) were measured 0-6 h postdose. RESULTS: Median time to maximum plasma concentration (tmax) of apomorphine was 0.63-0.75 h for APL and 0.25-0.38 h for SC-APO and SC-APO-GO. Geometric mean maximum plasma concentration (Cmax) of apomorphine was 4.31-11.2 ng/ml across APL doses and was generally lower compared with SC apomorphine formulations within dose groups. Area under the concentration-time curve from time 0 to infinity (AUC∞) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was ~ 17% of SC apomorphine by AUC∞; SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC∞ and Cmax, respectively). Apomorphine sulfate exposure was ~ three-fold higher for APL versus SC-APO and SC-APO-GO by AUC∞ and Cmax. CONCLUSION: In patients with PD and "OFF" episodes, APL demonstrated lower Cmax and relative bioavailability but similar exposures (AUCs) versus SC apomorphine within the approved dose range. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03292016.
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FAT1, which encodes a protocadherin, is one of the most frequently mutated genes in human cancers1-5. However, the role and the molecular mechanisms by which FAT1 mutations control tumour initiation and progression are poorly understood. Here, using mouse models of skin squamous cell carcinoma and lung tumours, we found that deletion of Fat1 accelerates tumour initiation and malignant progression and promotes a hybrid epithelial-to-mesenchymal transition (EMT) phenotype. We also found this hybrid EMT state in FAT1-mutated human squamous cell carcinomas. Skin squamous cell carcinomas in which Fat1 was deleted presented increased tumour stemness and spontaneous metastasis. We performed transcriptional and chromatin profiling combined with proteomic analyses and mechanistic studies, which revealed that loss of function of FAT1 activates a CAMK2-CD44-SRC axis that promotes YAP1 nuclear translocation and ZEB1 expression that stimulates the mesenchymal state. This loss of function also inactivates EZH2, promoting SOX2 expression, which sustains the epithelial state. Our comprehensive analysis identified drug resistance and vulnerabilities in FAT1-deficient tumours, which have important implications for cancer therapy. Our studies reveal that, in mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, progression, invasiveness, stemness and metastasis through the induction of a hybrid EMT state.
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Cadherinas/deficiencia , Transición Epitelial-Mesenquimal/genética , Eliminación de Gen , Metástasis de la Neoplasia/genética , Neoplasias/genética , Neoplasias/patología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Cadherinas/genética , Cadherinas/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Progresión de la Enfermedad , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Humanos , Receptores de Hialuranos/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mesodermo/metabolismo , Mesodermo/patología , Ratones , Metástasis de la Neoplasia/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Fenotipo , Fosfoproteínas/análisis , Fosfoproteínas/metabolismo , Proteómica , Factores de Transcripción SOXB1/metabolismo , Transducción de Señal , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Factores de Transcripción/metabolismo , Proteínas Señalizadoras YAP , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Familia-src Quinasas/metabolismoRESUMEN
Nasal amputation and nasomaxillary defects, need to reconstruct the internal lining, osteochondral structure, and external coating of the nose. Authors report a 70-year-old male and a 65-year-old female treated for nasomaxillary defects (Brown JS, Shaw RJ. The Lancet Oncology 2010;11:1001-1008) due to squamous cell carcinoma (SCC) where the tip of the nose was preserved. A new custom design of the radial forearm free flap (RFFF) consisting on a subcutaneous tissue (SCT) component, a skin paddle for the internal nasal vault lining, and a skin paddle for the external nasal skin coating was raised to treat both total thickness nasal defects. The dimension of each skin paddle corresponds to the defect measurements. The skin incisions of the custom design correspond to those of a conventional RFFF. The SCT component was harvested in a subcutaneous plane continuously with the skin island for the internal nasal lining which is drawn on the ulnar skin of the forearm. The component for the external nasal coating was drawn on the radial skin area of the flap. No postoperative complications and a satisfactory outcome was reported after 1 year of follow-up. This new custom design of the RFFF is described for reconstruction of nasomaxillary defects when the tip of the nose is preserved.
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Colgajos Tisulares Libres , Neoplasias Nasales , Procedimientos de Cirugía Plástica , Anciano , Femenino , Antebrazo/cirugía , Humanos , Masculino , Neoplasias Nasales/cirugía , Radio (Anatomía)RESUMEN
OBJECTIVE: The aim of this study was to investigate whether the use of a thrombin-fibrinogen biosponge (TachoSil) has any advantage in tongue healing. STUDY DESIGN: A retrospective study with 30 patients treated with partial glossectomy (below half a tongue) was designed. We compared the results from a group using the biosponge (n =15 patients) and a control group (nâ¯=â¯15). Variables taken into consideration were bolus clearance, frenulum flexibility, and oral transit time. With these parameters, we formulated a "tongue remaining functional" (TRF) scale to assess tongue functionality after the surgery. We also evaluated long-term quality of life by using the Functional Intraoral Glasgow Scale (FIGS). RESULTS: In this study, TRF score, bolus clearance, oral transit time, and frenulum flexibility were significantly improved in the biosponge group. However, there were no differences between the 2 groups in the FIGS scores. CONCLUSIONS: The use of the biosponge in this pilot study showed positive long-term effects in lingual healing and functionality after partial glossectomies.
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Fibrinógeno , Glosectomía , Trombina , Lengua , Cicatrización de Heridas , Combinación de Medicamentos , Fibrinógeno/uso terapéutico , Humanos , Proyectos Piloto , Calidad de Vida , Estudios Retrospectivos , Trombina/uso terapéutico , Lengua/cirugíaRESUMEN
Desde el modelo de los determinantes sociales de la salud y el enfoque de equidad, la Dirección General de Salud Pública de Madrid ha desarrollado la metodología de los mapas de la vulnerabilidad en salud para facilitar a los equipos sociosanitarios la planificación, la priorización y la intervención en salud en un territorio. A partir de la selección de las zonas básicas de salud con peores indicadores de vulnerabilidad en salud, se inicia un proceso de relación con los actores clave del territorio a fin de identificar conjuntamente áreas prioritarias de intervención y desarrollar un plan de acción consensuado. Se presentan el desarrollo de esta experiencia y su conexión con los modelos teóricos del mapeo en activos, los sistemas de georreferenciación integrados en salud y las intervenciones de salud comunitaria (AU)
The Public Health General Directorate of Madrid has developed a health vulnerability mapping methodology to assist regional social health teams in health planning, prioritisation and intervention based on a model of social determinants of health and an equity approach. This process began with the selection of areas with the worst social indicators in health vulnerability. Then, key stakeholders of the region jointly identified priority areas of intervention and developed a consensual plan of action. We present the outcomes of this experience and its connection with theoretical models of asset-based community development, health-integrated georeferencing systems and community health interventions (AU)
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Humanos , Determinantes Sociales de la Salud/clasificación , Vulnerabilidad en Salud , Servicios de Salud Comunitaria/tendencias , Grupos de Riesgo , Análisis Espacial , Disparidades en el Estado de Salud , Política de SaludRESUMEN
BACKGROUND: The ANCHOR-CD prospective observational registry study evaluated the effectiveness of abobotulinumtoxinA in adult idiopathic cervical dystonia (CD) in clinical practice. METHODS: Adults with CD were eligible. Treating physicians determined abobotulinumtoxinA dose and treatment interval. The primary endpoint was patient response rate (Toronto Western Spasmodic Torticollis Rating Scale [TWSTRS] score reduction≥25% and Patient Global Impression of Change [PGIC] score of +2 or +3 at Week 4 of Cycle 1). RESULTS: 350 patients enrolled (75% women; mean age 59±13.6years; 27.4% botulinum neurotoxin-naive) and 347 received at least 1 treatment. The median abobotulinumtoxinA dose for Cycle 1 was 500 Units. At Week 4, the responder rate was 30.6% (n=304) and the TWSTRS total score decreased 27.4% from baseline. PGIC of at least "Much improved" was documented in 43.6% of patients and maintained in Cycles 2 through 4 (43.3%, 48.9%, and 52.8%, respectively). A total of 39 adverse events (31 study drug-related) were reported in 17 patients (5%); the most common were dysphagia (n=6), muscle weakness (n=4), and neck pain (n=3). CONCLUSION: This study confirmed the beneficial effect of abobotulinumtoxinA on CD in routine clinical practice as measured by improvements in TWSTRS and PGIC. No new safety concerns were identified.
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Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Tortícolis/tratamiento farmacológico , Toxinas Botulínicas Tipo A/efectos adversos , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Dolor de Cuello/tratamiento farmacológico , Dolor de Cuello/etiología , Fármacos Neuromusculares/efectos adversos , Sistema de Registros , Tortícolis/complicaciones , Resultado del Tratamiento , Estados UnidosRESUMEN
Objective Report a modification of the "rescue flap" technique using a direct endonasal approach with a partial superior septectomy for approaching pituitary tumors developed in our institution. Design Prospective study. Setting Hospital Universitario "Dr. José Eleuterio González," Universidad Autónoma de Nuevo León. Main Outcome Measures Since April 2015, we have performed 19 cases employing a direct endonasal approach with partial superior septectomy. Results and a technical note are described below. Results Nineteen patients were included in this report. Six patients presented transoperatory cerebrospinal fluid (CSF) leak, so a nasoseptal rescue flap was harvested. No patients developed postoperative CSF leak in this group. Two patients were submitted to a second surgical procedure. Nasoseptal flap was harvested without complications. In both patients, the size of the flap was enough to cover the dural defect and avoid CSF leak. Conclusion Direct endonasal approach with a partial posterior septectomy allows enough exposition of the sphenoidal sinus while preserving the nasoseptal septum with the possibility of a successful rescue flap when needed.
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BACKGROUND: Midface advancement is a keystone intervention in the treatment plan of syndromic hypoplasia of the midface. Although earlier authors had been using a combination of smaller incisions to acquire enough access to perform the different osteotomies, Tessier popularized the bicoronal incision. This approach can be time-consuming however and leaves an ear-to-ear scar. The authors describe an endoscopically assisted piezo-electric Le Fort III osteotomy performed through minimal invasive access. The cutaneous incision was limited to a single-short mid-glabellar vertical scar (8âmm) to perform the nasofrontal and septum osteotomy. Further osteotomies are performed through a 1.5âcm intraoral incision and a transconjunctival approach with a retrocaruncular extension. A lateral canthotomy was avoided to lower the risk of postoperative eyelid malposition. METHODS: A feasibility study using 2 fresh nonfrozen cadaver heads. CONCLUSION: The minimally invasive Le Fort III approach is feasible and efficacious for clinical use in a cadaveric setup.
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Asimetría Facial/cirugía , Huesos Faciales/cirugía , Osteotomía Le Fort/métodos , Cadáver , Endoscopía , Estudios de Factibilidad , Femenino , Humanos , MasculinoRESUMEN
The Public Health General Directorate of Madrid has developed a health vulnerability mapping methodology to assist regional social health teams in health planning, prioritisation and intervention based on a model of social determinants of health and an equity approach. This process began with the selection of areas with the worst social indicators in health vulnerability. Then, key stakeholders of the region jointly identified priority areas of intervention and developed a consensual plan of action. We present the outcomes of this experience and its connection with theoretical models of asset-based community development, health-integrated georeferencing systems and community health interventions.
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Determinantes Sociales de la Salud , Anciano , Femenino , Humanos , Masculino , España , Salud UrbanaRESUMEN
BACKGROUND: Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of â¼6 hours. OBJECTIVE: To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting. METHODS: Patients had ≥2.5 hours/day of "off" time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided. RESULTS: Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily "off" time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE. CONCLUSIONS: Among PD patients with substantial "off" time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.
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Antiparkinsonianos/administración & dosificación , Carbidopa/administración & dosificación , Levodopa/administración & dosificación , Evaluación de Resultado en la Atención de Salud , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Antiparkinsonianos/efectos adversos , Antiparkinsonianos/farmacología , Carbidopa/efectos adversos , Carbidopa/farmacología , Catecoles/administración & dosificación , Catecoles/efectos adversos , Catecoles/farmacología , Estudios Cruzados , Método Doble Ciego , Esquema de Medicación , Combinación de Medicamentos , Femenino , Humanos , Levodopa/efectos adversos , Levodopa/farmacología , Masculino , Persona de Mediana Edad , Nitrilos/administración & dosificación , Nitrilos/efectos adversos , Nitrilos/farmacología , Resultado del TratamientoRESUMEN
PURPOSE: Many types of soft tissue grafts have been used for grafting or prelaminating bone flaps for intraoral lining reconstruction. The best results are achieved when prelaminating free flaps with mucosal grafts. We suggest a new approach to obtain keratinized mucosa over a fibula flap using full-thickness, engineered, autologous oral mucosa. PATIENTS AND METHODS: We report on a pilot study for grafting fibula flaps for mandibular and maxilla reconstruction with full-thickness tissue-engineered autologous oral mucosa. We describe 2 different techniques: prelaminating the fibula flap and second-stage grafting of the fibula after mandibular reconstruction. Preparation of the full-thickness tissue-engineered oral mucosa is also described. RESULTS: The clinical outcome of the tissue-engineered intraoral lining reconstruction and response after implant placement are reported. A peri-implant granulation tissue response was not observed when prelaminating the fibula, and little response was observed when intraoral grafting was performed. CONCLUSION: Tissue engineering represents an alternative method by which to obtain sufficient autologous tissue for reconstructing mucosal oral defects. The full-thickness engineered autologous oral mucosa offers definite advantages in terms of reconstruction planning, donor site morbidity, and quality of the intraoral soft tissue reconstruction, thereby restoring native tissue and avoiding peri-implant tissue complications.
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Trasplante Óseo/métodos , Colgajos Tisulares Libres/trasplante , Mandíbula/cirugía , Maxilar/cirugía , Mucosa Bucal/trasplante , Procedimientos de Cirugía Plástica/métodos , Ingeniería de Tejidos/métodos , Aumento de la Cresta Alveolar/métodos , Autoinjertos/trasplante , Carcinoma Mucoepidermoide/cirugía , Técnicas de Cultivo de Célula , Implantación Dental Endoósea/métodos , Femenino , Fibroblastos/fisiología , Peroné/trasplante , Estudios de Seguimiento , Humanos , Arcada Edéntula/cirugía , Queratinocitos/fisiología , Masculino , Neoplasias Mandibulares/cirugía , Persona de Mediana Edad , Mucosa Bucal/citología , Proyectos Piloto , Andamios del Tejido , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to evaluate a multimodality approach to sentinel lymph node biopsy (SLNB) detection with lymphoscintigraphy and single-photon emission computed tomography (SPECT)/computed tomography (CT). When combined with intraoperative imaging by a portable gamma camera (PGC), improved SLNB accuracy and detection rate may result. MATERIAL AND METHODS: A total of 42 patients selected for SLNB in node-negative T1 and T2 oral squamous cell carcinoma were retrospectively analyzed. The detection protocol consisted of preoperative lymphoscintigraphy and SPECT/CT performed the day before surgery. Intraoperative sentinel lymph node (SLN) detection was done with the aid of a PGC in association with hand-held gamma probe. RESULTS: All SLN detected in the preoperative study could be harvested except for one case. A total of 131 SLN were resected. This number was higher than the SLN depicted on lymphoscintigraphy (119 SLNs) and SPECT/CT (123 SLNs). Sublingual SLNs were observed in two cases (4.76%). These SLNs were detected by SPECT/CT but not by lymphoscintigraphy. Five (3.8%) additional SLNs not previously visualized on lymphoscintigraphy or on SPECT/CT were detected intraoperatively with the aid of the PGC. Positive SLNs were detected in eight cases (19%). Micrometastases were detected in five cases (62%) and macrometastases in three cases (38%). CONCLUSION: The SLNB detection protocol described contributes to more accurate study and detection.
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Carcinoma de Células Escamosas/diagnóstico por imagen , Neoplasias de la Boca/diagnóstico por imagen , Biopsia del Ganglio Linfático Centinela/métodos , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Humanos , Metástasis Linfática , Imagen Multimodal , Ganglio Linfático Centinela/patología , Biopsia del Ganglio Linfático Centinela/instrumentación , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/instrumentaciónRESUMEN
Pseudoaneurysm of the superficial temporal artery is an uncommon complication of a blunt trauma. It usually presents as a pulsating mass in the frontotemporal area a few weeks after the injury. Doppler ultrasonography, angiography, or computed tomographic angiography can aid or confirm the diagnosis. The treatment of choice is the surgical resection of the pseudoaneurysm and ligation of the vessels. We report a case of a pseudoaneurysm of the frontal branch of the superficial temporal artery and review the literature.
Asunto(s)
Accidentes por Caídas , Aneurisma Falso/etiología , Arterias Temporales/lesiones , Anciano , Aneurisma Falso/diagnóstico , Aneurisma Falso/cirugía , Femenino , HumanosRESUMEN
OBJECTIVES: To describe the population targeted for the rapid HIV testing program delivered via socio-culturally adapted services in primary care centers and to assess factors associated with uptake of first-time testing. METHODS: This was a descriptive cross-sectional study. We analyzed consultations between April 29, 2010 and May 31, 2012. We assessed the differences in age, origin, education, and sexual history between men who have sex with men (MSM), heterosexual men (HM), and women, using a two-sided independent t-test and Chi-square statistics. Factors associated with first-time testing were analyzed by logistic regression. RESULTS: Of 1940 consultations, 45.1% were HM, 25.4% MSM, and 29.5% women; 35.4% were immigrants, 2.5% were or had been sex workers, and 15.4% had visited one. The test was reactive in 2.1%. Up to 44.2% had never been tested. The probability of being tested for the first time increased in HM, women, populations from the Indian Subcontinent, those with no casual sexual partners, those whose partner's serostatus was unknown, and those with no history of other sexually transmitted infections. CONCLUSIONS: This program managed to reach a high proportion of vulnerable people. First time HIV testing rates were high.