Timely referral for device-aided therapy in Parkinson's disease. Development of a screening tool.

BACKGROUND: Timely referral of Parkinson's disease (PD) patients to specialized centers for treatment with device-aided therapies (DAT) is suboptimal. OBJECTIVE: To develop a screening tool for timely referral for DAT in PD and to compare the tool with the published 5-2-1 criteria. METHODS: A cross-sectional, observational study was performed in 8 hospitals in the catchment area of a specialized movement disorder center in the Northern part of the Netherlands. The target population comprised PD patients not yet on DAT visiting the outpatient clinic of participating hospitals. The primary outcome was apparent eligibility for referral for DAT based on consensus by a panel of 5 experts in the field of DAT. Multivariable logistic regression modelling was used to develop a screening tool for eligibility for referral for DAT. Potential predictors were patient and disease characteristics as observed by attending neurologists. RESULTS: In total, 259 consecutive PD patients were included, of whom 17 were deemed eligible for referral for DAT (point prevalence: 6.6%). Presence of response fluctuations and troublesome dyskinesias were the strongest independent predictors of being considered eligible. Both variables were included in the final model, as well as levodopa equivalent daily dose. Decision curve analysis revealed the new model outperforms the 5-2-1 criteria. A simple chart was constructed to provide guidance for referral. Discrimination of this simplified scoring system proved excellent (AUC after bootstrapping: 0.97). CONCLUSIONS: Awaiting external validation, the developed screening tool already appears promising for timely referral and subsequent treatment with DAT in patients with PD.

Advanced-Stage Parkinson's Disease: From Identification to Characterization Using a Nationwide Database.

Background: As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti-PD intensified therapy (IT) can serve as a proxy for increased burden of disease. Objective: To explore whether IT aligns with events reflecting advanced PD (APD) burden. Methods: This was a retrospective analysis of PD beneficiaries in the second-largest healthcare provider in Israel. Patients with PD diagnosed between January 2000 and June 2018 and treated with levodopa (l-dopa) ≥5 times/day and/or ≥1000 mg l-dopa equivalent daily dose were defined as the IT cohort (n = 2037). Treated patients with PD not fulfilling this criterion were defined as the nonintensified therapy (NIT) cohort (n = 3402). Point prevalence and 5- and 10-year cumulative incidence of IT were assessed. Baseline demographic and comorbidities, 1-year healthcare resource use, health costs, and time to clinical events were assessed and compared between cohorts. Results: IT was associated with significantly (P < 0.05) higher healthcare resource use compared with NIT. In turn, IT patients incurred higher healthcare costs (P < 0.001) and were at greater risk for mortality, hospitalization, disability, and device-aided therapy use (P < 0.001, for all comparisons). Conclusions: Treatment intensity can serve as an objective and robust indicator of more APD. This readily extractable marker can be easily integrated into electronic medical record alerts to actively target more advanced patients and to guide risk-appropriate care.

Guidelines for Parkinson's disease treatment: consensus from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology - motor symptoms / Diretrizes para o tratamento da doença de Parkinson: consenso do Departamento Científico de Transtornos do Movimento da Academia Brasileira de Neurologia - sintomas motores

ABSTRACT The treatment of Parkinson's disease (PD) is challenging, especially since it is considered highly individualized. The Brazilian Academy of Neurology has recognized the need to disseminate knowledge about the management of PD treatment, adapting the best evidence to the Brazilian reality. Thus, the main published treatment guidelines were reviewed based on the recommendations of group from the Movement Disorders Scientific Department of the Brazilian Academy of Neurology.

Resumo O tratamento da doença de Parkinson (DP) constitui um desafio, especialmente por ser considerado muito individualizado. A Academia Brasileira de Neurologia (ABN) identificou a necessidade de disseminar o conhecimento sobre o manejo do tratamento da DP, adaptando as melhores evidências à realidade brasileira. Assim, foi realizada uma revisão sobre as principais orientações de tratamento publicadas, baseada nas recomendações elaboradas por um grupo de especialistas em transtornos do movimento do departamento científico da ABN.

Adesão terapêutica ao uso de antiparkinsonianos em pessoas idosas e seus fatores associados: revisão integrativa / Antiparkinson drugs use and adherence in older adults and associated factors: an integrative review

Resumo Objetivos Identificar os fatores associados à adesão terapêutica ao uso de antiparkinsonianos em idosos com Doença de Parkinson (DP) por meio de uma revisão integrativa da literatura. Método Trata-se de uma revisão integrativa de literatura nos idiomas português, inglês, espanhol, nas bases de dados eletrônicas LILACS, MEDLINE - via PubMed, Web of Science e Scopus, sem restrição quanto ao tempo e desenho de estudo, realizada no período de agosto a setembro de 2021. A seleção dos estudos foi realizada de maneira independente por dois revisores e a validação final por um terceiro revisor. Resultados Após a aplicação dos critérios de elegibilidade, dos 460 estudos encontrados, foram incluídos cinco estudos que evidenciam taxas moderadas de adesão, variando de 35,3% a 66,8%, e apontam como principais fatores associados à menor adesão à terapia antiparkinsoniana: idade mais avançada, deficit cognitivo, maior comprometimento motor, multimorbidades, alteração nos regimes terapêuticos, depressão, polifarmácia, menor escolaridade, não brancos e sexo masculino. Foram fatores descritos para maior adesão: idade mais jovem, cor branca, sem modificação de regime terapêutico, maior nível de conhecimento sobre a DP, bom controle clínico, educação, ser casado, maior renda e nível de consciência. Conclusões A não adesão à terapêutica antiparkinsoniana é frequente e de dimensão multifatorial, sua compreensão torna-se relevante para subsidiar dados para a comunidade científica, objetivando a criação de políticas públicas e planejamento estratégico em serviços de saúde com o propósito de melhorar a qualidade de vida da pessoa idosa.

Abstract Objectives To identify factors associated with antiparkinson drugs use and adherence in older adults with Parkinson's disease (PD) through an integrative literature review. Method An integrative literature review involving a search for relevant publications in Portuguese, English, and Spanish on the electronic databases LILACS, MEDLINE - via PubMed, Web of Science and Scopus, without restriction regarding date or study design, was carried out during the period August-September 2021. The selection of studies was performed independently by two reviewers and the final validation conducted by a third reviewer. Results After applying the eligibility criteria, 5 of the 460 studies found were included in the review. Results showed moderate adherence rates (range 35.3-66.8%) and the main factors associated with lower adherence to antiparkinson therapy were older age, cognitive deficit, greater motor impairment, multimorbidities, change in therapy regimens, depression, polypharmacy, lower education, non-white ethnicity and male gender. Factors associated with greater adherence were younger age, white ethnicity, no change in therapy regimen, higher level of knowledge about PD, good clinical control, higher educational level, married status, higher income and greater level of awareness. Conclusions Non-adherence to antiparkinsonian therapy was frequent and multifactorial., Understanding this behavior is important to help inform the scientific community and devise public policies and strategic planning in health services for improving the quality of life of the older population.

Validation of 19-items wearing-off (WOQ-19) questionnaire to Portuguese / Validação do questionário de 19 itens de wearing-off (WOQ-19) para a língua portuguesa

ABSTRACT Background: The treatment of Parkinson disease with dopaminergic therapy improves functionality and quality of life. However, as the disease progresses, the wearing-off phenomenon develops. To improve the recognition of this phenomenon, the 19-item wearing-off questionnaire (WOQ-19) was developed. Objective: To translate and validate the WOQ-19 into Portuguese. Methods: The questionnaire was translated into Portuguese and, subsequently, back-translated into English and analyzed. The final version was tested in Parkinson disease patients for reliability through the test-retest paradigm and internal consistency. Also, sensitivity and specificity were obtained in different cut-off positive items. Results: The WOQ-19 showed good test stability, with an intraclass correlation coefficient of 0.877 (95%CI 0.690-0.951; p<0.001), and good internal consistency, with Cronbach alpha of 0.815. Two items of positive cut-off showed the best accuracy: 0.873 (95%CI 0.791-0.954). Sensitivity was 0.975 (95%CI 0.892-1) and specificity was 0.714 (95%CI 0.565-0.863). Conclusion: The Portuguese version of the WOQ-19 showed excellent diagnostic properties and can be used to diagnose wearing-off phenomena.

RESUMO Introdução: O tratamento da doença de Parkinson com terapia dopaminérgica melhora a funcionalidade e a qualidade de vida. Entretanto, com a progressão da doença, os fenômenos de flutuação motora e não motora se desenvolvem. Para melhorar o reconhecimento dessa situação, foi desenvolvido o questionário de 19 itens de wearing-off (WOQ-19) Objetivo: Traduzir e validar o questionário WOQ-19 para a língua portuguesa. Métodos: O questionário foi traduzido do inglês para o português. Em seguida, foi retrotraduzido para o inglês e analisado. A versão final foi testada em pacientes parkinsonianos com paradigma teste-reteste e consistência interna. A sensibilidade e especificidade foram medidas em relação a vários pontos de cortes de itens positivos. Resultados: O questionário apresenta boa estabilidade de teste, com coeficiente de correlação intraclasse de 0,877 (IC95% 0,690-0,951; p<0,001), e boa consistência interna, com alfa de Cronbach de 0,815. O ponto de corte com dois itens positivos teve a melhor acurácia: 0,873 (IC95% 0,791-0,954). A sensibilidade foi de 0,975 (IC95% 0,892-1) e a especificidade foi 0,714 (0,565-0,863). Conclusão: A versão em português do WOQ-19 mostrou excelentes propriedades diagnósticas e pode ser utilizada para diagnosticar as condições de flutuações motoras e não motoras na doença de Parkinson.

Physiological complexity of gait between regular and non-exercisers with Parkinson's disease.

BACKGROUND: Physiological complexity represents overall health of a system and its underlying capacity to adapt to stresses. The primary purpose of this study was to determine if physiological complexity of gait both ON and OFF anti-Parkinson medication differed between regular and non-exercisers with Parkinson's disease. METHODS: Twenty participants with idiopathic Parkinson's disease were enrolled in this cross-sectional study (regular exercisers n = 10, non-exercisers n = 10). Two data collection sessions were completed during a single visit, first after a 12-hour overnight withdrawal from anti-Parkinson medications (OFF), and again one-hour after taking anti-Parkinson medications (ON). During each session participants completed a 2-minute walking task at their preferred pace while wearing wireless inertial measurement units on each lower extremity segment (thigh, shank, foot). Multivariate multiscale entropy was calculated from the tri-axial accelerometer signals and converted to a complexity index for analysis. FINDINGS: Regular exercisers demonstrated significantly higher complexity indices ON and OFF anti-Parkinson medications compared to non-exercisers (ON F = 3.84 P = 0.02; OFF F = 3.61, P < 0.03). Regular exercisers did not significantly differ in complexity between OFF and ON states (most affected leg F = 0.15 P = 0.71; least affected leg F = 0.30 P = 0.60), but non-exercisers demonstrated significantly decreased complexity in the least affected leg OFF anti-Parkinson medications (F = 5.17 P < 0.04). INTERPRETATION: Enhanced gait complexity in the regular exercisers may indicate that ongoing exercise is a key ingredient contributing to health in persons with Parkinson's disease. Exercising on a regular basis with Parkinson's disease may augment one's ability to adapt to barriers encountered during gait regardless of medication state.

[Prescribing patterns of antiparkinson drugs in a group of Colombian patients, 2015].

INTRODUCTION: Parkinson's disease, whose prevalence in Colombia is 4.7 per 1,000 inhabitants, is a public health problem and a therapeutic challenge for health professionals. OBJECTIVE: To determine the prescribing patterns of antiparkinson drugs and the variables associated with its use in a population from Colombia. MATERIALS AND METHODS: We conducted a descriptive cross-sectional study. We selected patients who had been given antiparkinson drugs uninterruptedly between January 1st and March 31st, 2015 from a systematized database of approximately 3.5 million people affiliated to the Colombian health system. We included sociodemographic, pharmacologic and comedication variables. For the multivariate analysis, we used the IBM SPSS™-22 software. RESULTS: A total of 2,898 patients was included; the mean age was 65.1years, and 50.7% were men; 69.4% (n=2010) of people received monotherapy and 30.6% combination therapy with two to five antiparkinson drugs. The most frequently prescribed drugs were: levodopa 45.5% (n=1,318 patients), biperiden 23.1% (670), amantadine 18.3% (531) and pramipexole 16.3% (471). The most commonly used association was levodopa/carbidopa + entacapone (n=311; 10.7%). Multivariate analysis showed that being male (OR=1.56; 95%CI: 1.321-1.837), over 60 years (OR=1.41; 95%CI 1.112-1.782) and receiving treatment in the city of Barranquilla (OR=2.23; 95%CI 1.675-2.975) were statistically associated with a greater risk of using combination therapy; 68.2% (n=1,977) patients were given concomitant treatment with other drugs. CONCLUSIONS: Prescribing habits of drugs with high therapeutic value predominated, mainly in antiparkinson drugs monotherapy. Most were employed in the usual recommended doses. It is necessary to explore the clinical effectiveness of the medications studied and differentiate between disease and parkinsonian syndromes subtypes.

Prescribing patterns of antiparkinson drugs in a group of Colombian patients, 2015 / Patrones de prescripción de fármacos antiparkinsonianos en un grupo de pacientes de Colombia, 2015

Introduction: Parkinson's disease, whose prevalence in Colombia is 4.7 per 1,000 inhabitants, is a public health problem and a therapeutic challenge for health professionals. Objective: To determine the prescribing patterns of antiparkinson drugs and the variables associated with its use in a population from Colombia. Materials and methods: We conducted a descriptive cross-sectional study. We selected patients who had been given antiparkinson drugs uninterruptedly between January 1st and March 31st, 2015 from a systematized database of approximately 3.5 million people affiliated to the Colombian health system. We included sociodemographic, pharmacologic and comedication variables. For the multivariate analysis, we used the IBM SPSS™-22 software. Results: A total of 2,898 patients was included; the mean age was 65.1years, and 50.7% were men; 69.4% (n=2010) of people received monotherapy and 30.6% combination therapy with two to five antiparkinson drugs. The most frequently prescribed drugs were: levodopa 45.5% (n=1,318 patients), biperiden 23.1% (670), amantadine 18.3% (531) and pramipexole 16.3% (471). The most commonly used association was levodopa/carbidopa + entacapone (n=311; 10.7%). Multivariate analysis showed that being male (OR=1.56; 95%CI: 1.321-1.837), over 60 years (OR=1.41; 95%CI 1.112-1.782) and receiving treatment in the city of Barranquilla (OR=2.23; 95%CI 1.675-2.975) were statistically associated with a greater risk of using combination therapy; 68.2% (n=1,977) patients were given concomitant treatment with other drugs. Conclusions: Prescribing habits of drugs with high therapeutic value predominated, mainly in antiparkinson drugs monotherapy. Most were employed in the usual recommended doses. It is necessary to explore the clinical effectiveness of the medications studied and differentiate between disease and parkinsonian syndromes subtypes.

Introducción. La enfermedad de Parkinson, cuya prevalencia en Colombia es de 4,7 por 1.000 habitantes, constituye un problema de salud pública y un reto terapéutico para los profesionales de la salud. Objetivo. Determinar los patrones de prescripción de fármacos antiparkinsonianos y las variables asociadas con su utilización en una población colombiana. Materiales y métodos. Se hizo un estudio descriptivo de corte transversal. A partir de una base de datos de 3,5 millones de afiliados al sistema de salud, se seleccionaron pacientes con prescripción de medicamentos antiparkinsonianos de manera ininterrumpida entre el 1º de enero y el 31 de marzo de 2015. Se incluyeron variables sociodemográficas, farmacológicas y de medicación concomitante. El análisis multivariado se hizo con el programa IBM SPSS™-22. Resultados. Se hallaron 2.898 pacientes, con una edad media de 65,1 años, de los cuales el 50,7 % correspondía a hombres. El 69,4 % (n=2.010) de las personas recibía monoterapia y el 30,6 %, tratamiento combinado con dos a cinco medicamentos antiparkinsonianos. Los más prescritos eran la levodopa (45,5 %; n=1.318 pacientes), el biperideno (23,1 %; n=670), la amantadina (18,3 %; n=531) y el pramipexol (16,3 %; n=471). La asociación más utilizada fue la de levodopa-carbidopa y entacapone (n=311; 10,7 %). En el análisis multivariado se encontró que ser hombre (odds ratio, OR=1,56; IC95% 1,321-1,837), ser mayor de 60 años (OR=1,41; IC95% 1,112-1,782) y recibir tratamiento en Barranquilla (OR=2,23; IC95% 1,675-2,975), se asociaban con una mayor probabilidad de emplear el tratamiento combinado. Al 68,2 % (n=1.977) de los pacientes se les había prescrito tratamiento concomitante con otros medicamentos. Conclusión. Predominaron los hábitos de prescripción de medicamentos con gran valor terapéutico, principalmente en la monoterapia, la mayoría en las dosis usuales recomendadas. Es necesario explorar la efectividad clínica de las prescripciones estudiadas, y diferenciar entre la enfermedad y los subtipos de síndromes parkinsonianos.

The effect of pramipexole extended release on the levodopa equivalent daily dose in Lebanese Parkinson diseased patients.

OBJECTIVE: The objective of this study is to compute the potential benefit of Pramipexole ER on total levodopa equivalent dose (LED) and Unified Parkinson Disease Rating Score (UPDRS-III) compared to mono- or combined therapy of pramipexole IR and/or carbidopa/levodopa. METHODS: This is a retrospective observational study conducted in a specialized PD (Parkinson Disease) and movement disease center in Lebanon between January and December 2017. RESULTS: A total of 176 patient's record was reviewed. Pramipexole ER showed a significant difference on the mean changes in LED and UPDRS-III score. After 13 weeks of initiating Pramipexole ER, the mean decrease in LED was -49.42 mg for all patients (p < 0.001, CI 95% [35.28-63.55]) and the mean decrease in UPDRS-III score for all patients was -6 points (P< 0.001).According to the subgroup analysis, patients aged 65 years and below, the change in mean total LED from baseline (350.80 mg) was a decrease of 63.19 mg with a p<0.001, CI 95% [42.07-84.31]. In patients aged more than 65 years and shifted to mono or combined pramipexole ER therapy, the change in mean total LED from baseline (559.25 mg) was a decrease of 34.67 mg with a p<0.001 CI 95% [16.16-53.18]. In addition the results showed that in patients having an UPDRS-III score of less than or equal to 33, the change in mean total LED from baseline (436.73 mg) was a decrease of 56.76 mg (p<0.001; CI 95% [41.32-72.20]). However, in patients having an UPDRS-III score of more than 33 the change in mean total LED from baseline (545.06 mg) was a decrease of 2.96 mg with a p value < 0.844 CI 95% [27.32-33.15]. CONCLUSIONS: This study demonstrated the efficacy of Pramipexole ER on decreasing the total levodopa equivalent dose (LED).The role of health care professionals is to maintain the patient on the lowest effective levodopa equivalent daily dose and optimize the treatment therapy, thus decreasing the side effects that might arise from overdosing of antiparkinsonian drugs.

Fistulization of J-PEG Jejunal Tube into the Colon in a Patient Treated with Duodopa® Infusion: A Case Report.

The continuous delivery of a levodopa/carbidopa gel suspension (Duodopa®) into the small bowel through a jejunal tube inserted via percutaneous endoscopic gastrostomy represents a new treatment method in advanced Parkinson disease. Some severe device-related complications have been described in the last few years. Some of them are associated with phytobezoar formation at the pigtail of the catheter. We present the case of a Parkinson disease patient treated with the Duodopa infusion system complicated by jejunal tube fistulization into the colon. We suggest a possible treatment strategy for this complication, which has not been described in the literature to date.

Parkinson's disease, antiparkinson medicines, and driving.

INTRODUCTION: Parkinson's disease is a progressive neurodegenerative disorder with multiple motor and non-motor features. It is well known that the ability to drive safely is impaired in Parkinson's disease patients. While the impairing effects on psychomotor performance and vision are well established, there is uncertainty about the increased risk of road traffic accidents among drivers with Parkinson's disease. These issues, considering the progressive nature of Parkinson's disease, comorbidities and the profile of unwanted effects of the pharmacological treatments used, indicate that driving automobiles is a unique concern. AREAS COVERED: The Driving under the Influence of Drugs, Alcohol and Medicines (DRUID) categorization and specific advice for medications used in treating Parkinson's disease are presented. Expert commentary: Most medicines currently in use are considered DRUID category II: Likely to produce moderate effects on fitness to drive. Health professionals treating Parkinson's disease patients must be involved in providing proper advice and information to the patient, family and caregivers on the effects of the disorder and its medications on driving, and all possible actions should be undertaken to transition drivers with Parkinson's disease from driving to non-driving.

Non-oral Continuous Drug Delivery Techniques in Parkinson's Disease: For Whom, When, and How?

Continuous dopaminergic stimulation (CDS) has become one of the main concepts in present Parkinson's disease (PD) research. This is based on the assumption that CDS, or rather near CDS, is the normal striatal setting in a healthy individual. In PD, the degeneration of dopaminergic neurons leads to a reduced capacity to buffer dopamine, which could increase the vulnerability to a pulsatile administration of drugs. The term continuous drug delivery (CDD) describes the process of delivering drugs continuously with the aim of achieving CDS. There are three principal techniques for non-oral CDD: continuous subcutaneous apomorphine infusion CSAi), levodopa-carbidopa intestinal gel infusion (LCIGi), and transdermal rotigotine therapy. CDD has repeatedly been shown effective in the day-to-day treatment of PD patients. Although this review does not replace local guidelines regarding the use of the included non-oral CDD-based therapies, we have compiled the current base of evidence or consensus view with the intention of facilitating both the selection and the use in a clinical setting. The indications for CSAi and LCIGi are very similar and are centered around motor complications in advanced PD, whereas rotigotine has been proven effective both as a monotherapy in early PD and as an add-on to levodopa in advanced PD. Deep-brain stimulation is a relevant option for many of the patients with advanced PD, and we therefore also discuss its use in relation to the CDD-based techniques. Blinded and controlled trials have shown that non-oral CDD is an effective approach for the treatment of PD.