Clinical trials for cognition in Parkinson's disease: Where are we and how can we do better?

BACKGROUND: Cognitive impairment is common in Parkinson's disease (PD) and has a substantial impact on quality of life. Despite numerous trials targeting various PD features, we still lack effective treatments for cognition beyond cholinesterase inhibitors. OBJECTIVE: To identify the gaps in recent clinical trials with cognitive outcomes in PD and consider areas for improvement. METHODS: We examined recent clinical trials with cognitive outcomes in PD registered on ClinicalTrials.gov, excluding trials without cognitive outcomes, non-interventional studies, and in atypical Parkinsonian disorders. Included trials were categorized by treatment approach (investigational medicinal product, behavioral, physical activity, device-based). Details of trial design and outcomes were collected. RESULTS: 178 trials at different stages of trial completion were considered. 46 trials were completed, 25 had available results. Mean follow-up duration was 29.9 weeks. Most common cognitive measure was Montreal Cognitive Assessment. Most were performed in North America or Europe. Majority of the participants identified as non-Hispanic and White. Only eight trials showed improvement in cognition, none showed improvement beyond four months. These included trials of international medicinal products, cognitive and physical interventions and devices. GRADE certainty levels ranged from Moderate to Very Low. Only mevidalen had a Moderate certainty for potential clinical effectiveness. CONCLUSIONS: Amongst a large number of trials for cognition in PD, only a small proportion were completed. Few showed significant improvement, with no proven long-lasting effects. Trial design, lack of enrichment for at-risk groups, short follow-up duration, insensitive outcome measures likely contribute to lack of detectable benefit and should be considered in future trials.

Spotlight on non-motor symptoms and Covid-19.

The Coronavirus Disease 2019 (Covid-19) pandemic has profoundly affected the quality of life (QoL) and health of the general population globally over the past 2 years, with a clear impact on people with Parkinson's Disease (PwP, PD). Non-motor symptoms have been widely acknowledged to hold a vital part in the clinical spectrum of PD, and, although often underrecognized, they significantly contribute to patients' and their caregivers' QoL. Up to now, there have been numerous reports of newly emerging or acutely deteriorating non-motor symptoms in PwP who had been infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), while some of these symptoms, like fatigue, pain, depression, anxiety and cognitive impairment, have also been identified as part of the long-COVID syndrome due to their persistent nature. The subjacent mechanisms, mediating the appearance or progression of non-motor symptoms in the context of Covid-19, although probably multifactorial in origin, remain largely unknown. Such mechanisms might be, at least partly, related solely to the viral infection per se or the lifestyle changes imposed during the pandemic, as many of the non-motor symptoms seem to be prevalent even among Covid-19 patients without PD. Here, we summarize the available evidence and implications of Covid-19 in non-motor PD symptoms in the acute and chronic, if applicable, phase of the infection, with a special reference on studies of PwP.

Evaluation of the effect of bilateral subthalamic nucleus deep brain stimulation on fatigue in Parkinson's Disease as measured by the non-motor symptoms scale.

BACKGROUND: Fatigue is a common and disabling non-motor symptom (NMS) in Parkinson's disease (PD) patients. However, the effect of subthalamic nucleus (STN) deep brain stimulation (DBS) on fatigue has not been widely studied. OBJECTIVE: To determine the effect of STN DBS on fatigue in PD patients, measured by the Non-motor symptoms scale (NMSS). METHODS: Cross-sectional analysis of 50 patients with PD who underwent STN DBS at King's College Hospital and Salford Royal Hospital with fatigue scores (measured by question number 4 from domain 2 (sleep/fatigue) of the NMSS as the primary outcome measure. Secondary outcome measures included the PD Sleep Scale (PDSS), Scales for Outcome in PD (SCOPA)-motor examination, activities of daily living, motor complications, Hoehn and Yahr (HY) stage and changes in Levodopa Equivalent Daily Dose (LEDD). RESULTS: 50 patients with a mean follow-up period of 1.98 ± 1.36 years were studied. Significant improvement in median fatigue scores (4.00 (0.75-9.00) to 1.00 (0.00-4.50); p = .001) was observed. In addition, improvements in question 5 (sleep maintenance and fragmentation; 8.00 (4.00-12.00) to 0.00 (0.00-4.00); p < .001) and in domain 2 total score (sleep/fatigue; 20.00 (8.75-27.25) to 6.00 (0.75-16.00); p < .001) were also significant, together with improvements in NMSS total score, SCOPA scores and HY stage (p ≤ .02). Moreover, LEDD but especially dopamine agonists LEDD was significantly reduced after DBS (310.00 (0.00-480.00) to 150.00 (0.00-300.00); p < .020). CONCLUSIONS: Even though open label and not using a validated fatigue scale, this observational analysis suggest that fatigue improves significantly after STN DBS with persisting benefits at two years follow-up.

Nonmotor symptom burden grading as predictor of cognitive impairment in Parkinson's disease.

BACKGROUND: Identifying predictors of incident cognitive impairment (CI), one of the most problematic long-term outcomes, in Parkinson's disease (PD) is highly relevant for personalized medicine and prognostic counseling. The Nonmotor Symptoms Scale (NMSS) provides a global clinical assessment of a range of NMS, reflecting NMS burden (NMSB), and thus may assist in the identification of an "at-risk" CI group based on overall NMSB cutoff scores. METHODS: To investigate whether specific patterns of PD NMS profiles predict incident CI, we performed a retrospective longitudinal study on a convenience sample of 541 nondemented PD patients taking part in the Nonmotor Longitudinal International Study (NILS) cohort, with Mini-Mental State Examination (MMSE), NMSS, and Scales for Outcomes in PD Motor Scale (SCOPA Motor) scores at baseline and last follow-up (mean 3.2 years) being available. RESULTS: PD patients with incident CI (i.e., MMSE score ≤ 25) at last follow-up (n = 107) had severe overall NMSB level, significantly worse NMSS hallucinations/perceptual problems and higher NMSS attention/memory scores at baseline. Patients with CI also were older and with more advanced disease, but with no differences in disease duration, dopamine replacement therapy, sex, and comorbid depression, anxiety, and sleep disorders. CONCLUSIONS: Our findings suggest that a comprehensive baseline measure of NMS and in particular hallucinations and perceptual problems assessed with a validated single instrument can be used to predict incident CI in PD. This approach provides a simple, holistic strategy to predict future CI in this population.

Identifying and responding to fatigue and apathy in Parkinson's disease: a review of current practice.

Introduction: Fatigue and apathy are two key non-motor symptoms in Parkinson's disease (PD), with documented negative impact on Quality of life (QoL) and a frequent burden for caregivers.Areas covered: In this review, the authors comment on the latest pathophysiology, clinical phenomenology, the most frequently used scales for fatigue and apathy in PD with a focus on available therapeutic strategies.Expert opinion:The identification of fatigue and apathy in PD is mainly hampered by the lack of a clear consensus on these subjective symptoms. The pathophysiological processes remain unclear, and the large variation in prevalence is likely due to the heterogeneous PD populations and the lack of an enriched cohort of people with fatigue and/or apathy as main symptoms. Treatment strategies, and especially level 1 evidence for specific treatments for fatigue and apathy in PD, remain scarce. The best evidence to date is doxepin, rasagiline and levodopa infusion therapy (for fatigue), and rivastigmine (for apathy). Further efforts should be made to properly identify these two major symptoms in PD, to correctly detect those who may benefit most from tailored personalized interventions.

Drooling in Parkinson's Disease: Prevalence and Progression from the Non-motor International Longitudinal Study.

Sialorrhoea in Parkinson's disease (PD) is an often neglected yet key non-motor symptom with impact on patient quality of life. However, previous studies have shown a broad range of prevalence figures. To assess prevalence of drooling in PD and its relationship to quality of life, we performed a retrospective analysis of 728 consecutive PD patients who had a baseline and follow-up assessment as part of the Non-motor International Longitudinal Study (NILS), and for whom drooling presence and severity were available, assessed through the Non-Motor Symptoms Scale (NMSS). In addition, we analysed the prevalence of associated dysphagia through self-reported outcomes. Quality of life was assessed through the PDQ-8 scale. Baseline (disease duration 5.6 years) prevalence of drooling was 37.2% (score ≥ 1 NMSS question 19), and after 3.27 ± 1.74 years follow-up, this was 40.1% (p = 0.17). The prevalence of drooling increased with age (p < 0.001). The severity of drooling, however, did not change (p = 0.12). While in 456 patients without drooling at baseline, only 16% (n = 73) had dysphagia (question 20 of the NMSS), in those with drooling this was 34.3% (p < 0.001). At follow-up, the number of patients with dysphagia had increased, 20.4% with no drooling had dysphagia, and 43.6% with drooling had dysphagia. Both at baseline and follow-up, drooling severity was significantly positively associated with quality of life (PDQ-8; r = 0.199; p < 0.001). In moderately advanced PD patients, subjective drooling occurs in over one-third of patients and was significantly associated with decreased quality of life. Dysphagia occurred significantly more often in patients with drooling.

Entrenamiento en Conducta Pro- Social y Asertiva en Observadores de Bullying escolar / Training in Pro-Social and Assertive Behavior in School Bullying Observers

El estudio permite identificar el efecto del entrenamiento a observadores en conductas pro-sociales y asertivas en el bullying escolar en un colegio de la ciudad de Bogotá ubicado en la localidad de Bosa. Se tomaron 64 estudiantes entre 12-14 años de 6°, 7° y 8°grado de secundaria, seleccionados mediante muestreo por conglomerados. El diseño fue cuasi-experimental pre-test pos-test con grupo control. Se aplicó el Cuestionario sobre Intimidación y Maltrato entre Iguales- INSEBULL (Avilés y Elices, 2007) seleccionando la población y homogenizando los grupos, se vincularon participantes mediante asignación aleatoria en grupos. Se aplicó la Escala de habilidades pro-sociales para adolescentes EHPA (Morales y Suárez, 2011) y la Escala de comportamiento asertivo para niños (CABS) (Wood, 1978), a partir de lo anterior se desarrolló el entrenamiento al GE, evaluándolo a través del pos-test del INSEBULL, EPHA y CABS. Los resultados permiten rechazar la hipótesis de trabajo establecida para el estudio, y se acepta la hipótesis nula, la cual especifica que el entrenamiento en observadores en conductas pro-sociales y asertivas no establece diferencias significativas en sus medidas, por lo cual no se observa cambios en la dinámica del fenómeno del Bullying Escolar

The study allows us to identify the effect of observer training on pro-social and assertive behaviors in school bullying in a school in the city of Bogotá located in the town of Bosa. 64 students were taken between 12-14 years of 6th, 7th and 8th grade of high school, selected by sampling by conglomerates. The design was quasi-experimental pre-test post-test with control group. The Questionnaire on Intimidation and Maltreatment between Equals was applied- INSEBULL (Avilés & Elices, 2007) selecting the population and homogenizing the groups, participants were linked by random assignment in groups. The Scale of pro-social skills for adolescents EHPA (Morales & Suárez, 2011) and the Assertive Behavior Scale for Children (CABS) (Wood, 1978) was applied, from the above the GE training was developed, evaluating it through the post-test of the INSEBULL, EPHA and CABS. The results allow to reject the hypothesis of work established for the study, and the null hypothesis is accepted, which specifies that the training in observers in pro-social and assertive behaviors does not establish significant differences in their measurements, for which no changes are observed. in the dynamics of the phenomenon of School Bullying

A new technique of "double-A" bilateral flaps based on perforators for the treatment of sacral defects.

BACKGROUND: Myocutaneous and fasciocutaneous flaps can provide stable coverage of sacral defects. For neurologically intact patients, sensate innervated gluteal artery perforator flaps are the ideal solution. For patients with spinal cord injury, soft-tissue coverage can be performed with a variety of noninnervated flaps. METHODS: Between 1997 and 2004, the authors operated on 30 patients, 21 men and nine women, using bilateral gluteal distal fasciocutaneous and proximal musculocutaneous vertical vector rotation-advancement flaps, based on perforators with V-Y closures. The ages of the patients ranged from 32 to 74 years. Twenty-five patients had spinal cord injuries and all had sacral pressure sores extending to the bone. Three patients had low-grade malignant tumors (sacral chordomas); one had a sacral radiation-induced necrosis and two senile patients with large sacral defects had chronic renal failure and multiple sclerosis. No comorbidities were found in the sample. RESULTS: All the lesions were closed successfully. After follow-up of 1 to 8 years, 27 patients never required repeated surgery after wound complications. Three patients had infection and partial dehiscence of the flaps that healed after reoperation with V-Y readvancement; three died as a result of their primary diseases. CONCLUSIONS: This flap design has been used only in selected cases because, after its elevation, use of other gluteal-based flaps for future sacral reconstructions may not be possible. Five neurologically intact patients were found to have good sensitive protection of the flaps and adequate cushion contour after surgery because the authors conserved the gluteal arteries, perforators, and their corresponding sensory nerves.

La Evaluación de las necesidades en la relación de pareja: validación de un instrumento / Assessment of needs in the marital relationship: An instrument validity

Para evaluar la satisfacción de las necesidades de pareja se hace necesario el uso de instrumentos, motivo por el cual el desarrollo de esta investigación, en donde se validó el instrumento “Inventario de Necesidades de Pareja” elaborado en su fase inicial por Castro y Rojas (1994), con ocho áreas; afectiva, de comunicación, independencia, sexual, social financiera, rol, crianza de los hijos, para evaluar la importancia de cada área y su nivel de satisfacción.El primer pilotaje se aplicó a una muestra de 31 parejas, 3 de las cuales estaban en terapia de pareja. El segundo a 49,9 en proceso terapéutico por “conflicto marital”. La validación se aplicó a 149 parejas, de las cuales 21 asistían a consulta. El análisis factorial en ésta última fase, arrojó 6 factores para ambas muestras que fueron denominadas. “Necesidades Afectivas”, “Sexualidad”, “Manejo de finanzas”, “Relaciones Sociales”, “Roles en el Hogar” y “Responsabilidad con los hijos “. La confiabilidad fue: Factor 1,0.95; 2, 0.91; 3, 0.86; 4, 0.79 y 6, 0.92. El instrumento presentó validez de contracto y de contenido. Los factores evidenciaron una buena educación muestral (KMO=0.949) y una buena esfericidad (Chi-cuadrado = 6766,339; gl = 496; Sig = 0.000). Las puntuaciones brutas de cada área se convirtieron a puntuaciones estándar (T), con media 50 y desviación 10, mediante un proceso de transformación lineal, lo que permitió el establecimiento de grados de satisfacción por cada factor. Al realizar el análisis de los ítemes de importancia frente a los de satisfacción, se halló que los factores de importancia son diferentes a los de satisfacción y se encontró que en ninguno de los dos casos los puntajes en una escala son predoctores de los puntajes en la otra

Alteraciones del esmalte dental después de repetidos procesos de cementación de brackets ortodónticos: estudio in vitro / Enamel surface alterations after repeated processes of bonding orthodontic brackets: an in vitro study

Antecedentes: el estudio de las alteraciones en el esmalte dental de pacientes sometidos a tratamientos de ortodoncia, es de gran interés en el ámbito odontológico por la fijación de aparatología al esmalte; ello incluye las técnicas de cementación y la descementación, lo que puede resultar agresivo para la estructura de este tejido. Objetivo: el objetivo de este estudio descriptivo in vitro fue examinar la estructura superficial del esmalte dental después de haberse sometido a repetidos procesos de cementación de brackets ortodónticos, y evaluar los cambios que se producen, por medio de microscopía electrónica de barrido. Métodos: se tomaron 40 premolares sanos y sin tratamiento ortodóntico previo, que requerían extracción terapéutica, los cuales se mantuvieron en saliva artificial. La estructura superficial del esmalte se sometió a magnificación para descartar posibles daños durante el proceso de exodoncia. Se realizó profilaxis previa y se procedió a dividir los dientes en 4 grupos de 10 cada uno: grupo I o grupo control, y grupos II, III y IV con uno, dos y tres procesos de cementación y descementación, respectivamente. La evaluación se hizo analizando las fotografías obtenidas por MEB; se observó la presencia o ausencia de alteraciones de la superficie del esmalte, tales como rasgaduras, grietas y fracturas. Los datos fueron analizados con estadísticas descriptivas y la prueva del Chi2. Resultados: se obtuvo que a mayor cantidad de procesos de cementacion de brackets, mayor fue el deterioro de la superficie del esmalte dental. Conclusiones: se sugiere que el deterioro de la superficie del esmalte dentario se incrementa con el número de procesos de cementación

Manejo de la historía clínica por el personal médico y de enfermería de la fundación hospitalaria San Vicente de Paúl. Medellín, Antioquia. 1995 / The use of the clinical records by the medical and nursing staff from th eSan Vicente de Paul hospital fundation.. Medellín-Antioquia 1995

A través de una investigación descriptiva se pretende analizar el manejo de la historia clínica del personal médico y de enfermería de la Fundación Hospitalaria San Vicente de Paúl, con el fin de hacer sugerencias para mejorar los registros clínicos de dicha institución. Se tomó una muestra no probabilística de las historias y una muestra probabilística para el personal que labora en la institución; se escogieron los encuestados de manera aleatoria simple y se encontró que sólo el 13,2 por ciento tiene ordenada la historia clínica; la actualización del plan de cuidados fue diligenciado en un 100 por ciento y no se puede diferenciar entre la nota del personal auxiliar y profesional de enfermería. En cuanto a los conocimientos del personal sobre las normas de manejo de la historia clínica, el 96 por ciento dice conocerlas, el 21,3 por ciento finaliza las notas de evolución con nombre, apellidos y código, el 85,4 por ciento conoce la forma de corregir errores en la historia clínica y el 79,8 por ciento conoce los usos de la historia clínica. Se sugirió: 1) estandarizar el conocimiento del personal sobre el ordenamiento y diligenciamiento correcto de la historia clínica, 2) implementar un programa de vigilancia y control dirigido por el comité de historias clínicas, y 3) fomentar el buen diligenciamiento de las notas del personal por medio de cursos, seminarios y estímulos.