The Lessebo Effect in Disease Modification Trials in Parkinson's Disease.

BACKGROUND: The impact of expectation of benefit on outcomes is well established in Parkinson's disease (PD). A reduction of a treatment effect due to a perceived placebo allocation (lessebo effect) in randomized controlled trials (RCTs) was documented for symptomatic treatments. OBJECTIVES: To evaluate the lessebo effect in disease modification RCTs (DMT) in PD. METHODS: Subject-level meta-analyses of active treatment arms of DMT (n = 1149 subjects): FS-1, FS-TOO (probability of placebo allocation/P(placebo) = 0.33) and DATATOP, PRECEPT, QE2 (P(placebo) = 0.25). We tested the association between P(placebo) and time to dopaminergic treatment initiation using a marginal Cox proportional hazards model. RESULTS: The adjusted hazard ratio (P(placebo) = 0.25 vs. 0.33) for initiation of dopaminergic treatment was 1.15 (95% CI: 0.92-1.43). CONCLUSIONS: We did not observe the lessebo effect in DMT. The necessary use of a placebo (and no active comparator) is a limitation. The prospective measurement of expectation of benefit could help to evaluate the many impacts of placebo use. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Elucidating the key environmental parameters during the production of ectoines from biogas by mixed methanotrophic consortia.

Anaerobic digestion (AD) is a robust biotechnology for the valorisation of organic waste into biogas. However, the rapid decrease in renewable electricity prices requires alternative uses of biogas. In this context, the engineering of innovative platforms for the bio-production of chemicals from CH4 has recently emerged. The extremolyte and osmoprotectant ectoine, with a market price of ~1000€/Kg, is the industrial flagship of CH4-based bio-chemicals. This work aimed at optimizing the accumulation of ectoines using mixed microbial consortia enriched from saline environments (a salt lagoon and a salt river) and activated sludge, and biogas as feedstock. The influence of NaCl (0, 3, 6, 9 and 12 %) and Na2WO4 (0, 35 and 70 µg L-1) concentrations and incubation temperature (15, 25 and 35 °C) on the stoichiometry and kinetics of the methanotrophic consortia was investigated. Consortia enriched from activated sludge at 15 °C accumulated the highest yields of ectoine and hydroxyectoine at 6 % NaCl (105.0 ± 27.2 and 24.2 ± 5.4 mgextremolyte gbiomass-1, respectively). The consortia enriched from the salt lagoon accumulated the highest yield of ectoine and hydroxyectoine at 9 % NaCl (56.6 ± 2.5 and 51.0 ± 2.0 mgextremolyte gbiomass-1, respectively) at 25 °C. The supplementation of tungsten to the cultivation medium did not impact on the accumulation of ectoines in any of the consortia. A molecular characterization of the enrichments revealed a relative abundance of ectoine-accumulating methanotrophs of 7-16 %, with Methylomicrobium buryatense and Methylomicrobium japanense as the main players in the bioconversion of methane into ectoine.

Quantitative home-based assessment of Parkinson's symptoms: the SENSE-PARK feasibility and usability study.

BACKGROUND: Currently, assessment of symptoms associated with Parkinson's disease is mainly performed in the clinic. However, these assessments have limitations because they provide only a snapshot of the condition. METHODS: The feasibility and usability of an objective, continuous and relatively unobtrusive system (SENSE-PARK System), which consists of wearable sensors (three worn during the day and one worn at night), a smartphone-based App, a balance board and computer software, was tested 24/7 over 12 weeks in a study including 22 PD patients. During the first four weeks of the study, patients did not get feedback about their performance, during the last eight weeks they did. The study included seven clinical visits with standardized interviews, and regular phone contact. The primary outcome was the number of drop-outs during the study. As secondary outcomes, the Post-Study System Usability Questionnaire (PSSUQ), score and information obtained from the standardized interviews were used to evaluate the usability of the system. RESULTS: All patients completed the study. The participants rated the usability of the SENSE-PARK System with a mean score of 2.67 (±0.49) on the PSSUQ. The interviews revealed that most participants liked using the system and appreciated that it signaled changes in their health condition. CONCLUSIONS: This 12 week controlled study demonstrates that the acceptance level of PD patients using the SENSE-PARK System as a home-based 24/7 assessment is very good. Particular emphasis should be given to a user-friendly design. Motivation to wear such a system can be increased by providing direct feedback about the individual health condition.

Ectoines production from biogas in pilot bubble column bioreactors and their subsequent extraction via bio-milking.

Despite the potential of biogas from waste/wastewater treatment as a renewable energy source, the presence of pollutants and the rapid decrease in the levelized cost of solar and wind power constrain the use of biogas for energy generation. Biogas conversion into ectoine, one of the most valuable bioproducts (1000 €/kg), constitutes a new strategy to promote a competitive biogas market. The potential for a stand-alone 20 L bubble column bioreactor operating at 6% NaCl and two 10 L interconnected bioreactors (at 0 and 6% NaCl, respectively) for ectoine production from biogas was comparatively assessed. The stand-alone reactor supported the best process performance due to its highest robustness and efficiency for ectoine accumulation (20-52 mgectoine/gVSS) and CH4 degradation (up to 84%). The increase in N availability and internal gas recirculation did not enhance ectoine synthesis. However, a 2-fold increase in the internal gas recirculation resulted in an approximately 1.3-fold increase in CH4 removal efficiency. Finally, the recovery of ectoine through bacterial bio-milking resulted in efficiencies of >70% without any negative impact of methanotrophic cell recycling to the bioreactors on CH4 biodegradation or ectoine synthesis.

Influence of operational conditions on the performance of biogas bioconversion into ectoines in pilot bubble column bioreactors.

The application of biogas as a low-priced substrate for the production of ectoines constitutes an opportunity to decrease their production costs and to enhance the viability of anaerobic digestion. The influence of operational conditions on CH4-biogas biodegradation and on ectoines production yields was assessed in continuous pilot bubble column bioreactors. The rise in biomass concentration from 1 to 3 g L-1 resulted in a decrease in the specific ectoine content from 42 ± 8 to 30 ± 4 mgectoine gVSS-1. The concentration of Cu2+ and Mg2+ did not impact process performance, while the use of ammonium as N source resulted in low CH4 biodegradation and ectoine yields (13 ± 7 mgectoine gVSS-1). The increase in CH4 content from 4.5 to 9 %v·v-1 enhanced CH4 removal efficiency. Process operation at NaCl concentrations of 3 %w·w-1 instead of 6 %w·w-1 decreased the ectoine yield to 17 mgectoine gVSS-1. Finally, Methylomicrobiumburyatense was identified as the dominant species.

Utility of Huntington's Disease Assessments by Disease Stage: Floor/Ceiling Effects.

Introduction: An understanding of the clinimetric properties of clinical assessments, including their constraints, is critical to sound clinical study and trial design. Utilizing data from Enroll-HD-a global, prospective HD observational study and clinical research platform-we examined several well-established HD clinical assessments across all stages of disease for evidence of instrument constraints, specifically floor/ceiling effects, to inform selection of appropriate instruments for use in future studies/trials and identify gaps in instrument utility over the life-course of the disease. Material and Methods: Analyzing publicly available data from 6,614 HD gene-expansion carriers (HDGECs), we grouped participants into deciles based on baseline CAP score, which ranged from 26 to 229. We used descriptive statistics to characterize data distribution for 25 outcome measures (encompassing motor, function, cognition, and psychiatric/behavioral domains) in each CAP decile. A skewness statistic threshold of ±2 was defined a priori to indicate floor/ceiling effects. Results: We found evidence of floor/ceiling effects in the early premanifest stages of disease for most motor and function assessments (e.g., TMS, TFC) and select cognitive tasks (MMSE, Trail Making tests). Other cognitive assessments, and the HADS-SIS scales, performed well ubiquitously, with no evidence of floor/ceiling effects at any disease stage. Floor/ceiling effects were evident at every disease stage for certain assessments, including PBA-s measures. Ceiling effects were apparent for DCL from onset stages onwards, as expected. Discussion: Developing instruments sensitive to subtle differences in performance at the earlier stages of the disease spectrum, particularly in motor and function domains, is warranted.

Stress Hyperglycemia and Osteocalcin in COVID-19 Critically Ill Patients on Artificial Nutrition.

We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer (p = 0.004), and needed more frequently insulin infusion therapy (p = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy (p = 0.001) and glucose delivered through artificial nutrition (p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, p = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU (r = -0.476, p = 0.001) and at days 2 (r = -0.409, p = 0.007) and 3 (r = -0.351, p = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.

What happened after birth to pregnant women undergoing ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension?

The latest Brazilian Guidelines on ambulatory blood pressure monitoring (ABPM) consider an exam as a useful tool during pregnancy, especially during the first half of pregnancy. They also indicate that white coat hypertension as well as masked hypertension may occur in up to one-third of pregnancies. As white coat hypertension has a more favorable diagnosis than gestational hypertension, it remains associated with 50% of pregnancies and is not associated with complications. Elsewhere, 40% of pregnant women develop gestational hypertension. As per the guidelines, the guidance values should be the same for the general population. The aim of this study was to verify the blood pressure behavior after birth in pregnant women who underwent ABPM and whether ABPM in pregnant women may serve as a predictor of preeclampsia and abnormalities in newborns. Between 01 January 2017 and 31 December 2019, 117 ABPM routines in pregnant women were performed at Unicordis. Among them, 40 were requested for the diagnosis of hypertension, and 77 were requested for antihypertensive therapeutic assessment. The study population comprised pregnant women who underwent ABPM for the diagnosis of hypertension. We assessed a population that comprised 31 subjects who underwent ABPM, 17 of whom had normal results and 14 of whom had abnormal results. Of the 14 pregnant women with abnormal blood pressure behavior, only three (21%) had a physiological drop in blood pressure, seven had attenuated descent, and four did not have blood arterial descent. The age of the pregnant women ranged from 21 to 42 years. The gestational age at the beginning of ABPM ranged from 6 to 37 weeks. In the group with normal ABPM, two pregnant women (11.7%) developed preeclampsia during pregnancy. Additionally, in the group with abnormal ABPM, seven pregnant women (50%) developed preeclampsia during pregnancy. In the group with normal ABPM, three newborns had abnormalities (17.6%); in the group with abnormal ABPM, four newborns had abnormalities (28.5%). In the group with normal ABPM, two subjects developed hypertension after birth (11.7%). In the group with abnormal ABPM, ten subjects (71%) remained hypertensive following birth (Table 1). Conclusions: (1) the results show that the proportion of patients who presented with preeclampsia was higher among individuals with abnormal ABPM than that among individuals with normal ABPM. (2) The proportion of subjects with hypertension following birth was higher among individuals with abnormal ABPM than that among individuals with normal ABPM.

Infectious Complications in Home Parenteral Nutrition: A Systematic Review and Meta-Analysis Comparing Peripherally-Inserted Central Catheters with Other Central Catheters.

BACKGROUND: Home parenteral nutrition (HPN) has become a common therapy. There is still controversy regarding the possibility that peripherally inserted central catheters (PICCs) may diminish catheter-related blood stream infection (CRBSI) rates. METHODS: We searched the PubMed database for studies reporting the rates of CRBSI with HPN. Study selection was performed independently by three investigators. Disagreements were discussed and resolved by consensus or by arbitration by an author not involved in the search. The National Institutes of Health Quality Assessment Tools was used to assess the methodological quality of the studies. Meta-analyses were performed using MetaXL 5.3 with the quality effects model. RESULTS: Screening of the article titles and abstracts yielded 134 full text articles for evaluation. Only three prospective studies that included appropriate data were considered for the final analysis. The relative risk of the CRBSI rate was 0.41 (0.14-1.17) for PICC vs. tunneled catheters. The relative risk of the CRBSI rate was 0.16 (0.04-0.64) for PICC vs. ports. The relative risk of the thrombosis rate was 3.16 (0.20-49.67) for PICCs vs. tunneled. CONCLUSIONS: There is insufficient evidence to show a difference in CRBSI rates between PICCs and tunneled catheters. On the other hand, PICCs showed lower CRBSI rates than ports. There was also no difference in the rate of catheter-related thrombosis and mechanical complications.

Infectious complications in home parenteral nutrition: A long-term study with peripherally inserted central catheters, tunneled catheters, and ports.

OBJECTIVE: Home parenteral nutrition (HPN) has become a common therapy, with tunneled central venous catheters (CVCs) being the preferred route of administration. Peripherally inserted central catheters (PICCs) have been used increasingly, but whether they should be preferred over other types of CVCs is still controversial. The aim of this study was to evaluate catheter-related complications of CVC in patients receiving HPN. METHODS: All patients treated at our center for HPN from 2007 to 2017 were prospectively included. A specialized intravenous therapy team took care of these patients. Catheter-related bloodstream infections (CRBSI) were confirmed with positive, simultaneous, differential blood cultures drawn through the CVC and peripheral vein and then semiquantitative or quantitative culture of the catheter tip. RESULTS: In all, 151 patients received HPN during the 11-y study period. Of these patients, 95 were women (63%) and 55 were men (37%), with a mean age of 58 ± 13 y. Twenty-six were non-cancer patients (17%) and the remaining 125 patients had an underlying malignancy (83%). Regarding the CVC, 116 were PICCs, 18 Hickman, and 36 ports. Confirmed CRBSI per catheter-days showed 0.15 episodes per 1000 catheter-days for PICCs, 0.72 for Hickman, and 2.02 for ports. PICCs had less-confirmed CRBSIs per 1000 catheter-days than ports (φ = 0.54, P = 0.005), but no difference between PICCs and Hickman was found (φ = 0.32, P = 0.110). Confirmed episodes of CRBSI (2 versus 13%, χ2 = 6.625, P = 0.036) were more frequent with multilumen catheters. CONCLUSIONS: In our setting, single-lumen PICC and Hickman catheters showed low infectious complications.

[Intracavitary electrocardiogram (IC-ECG) guidance for peripherally inserted central catheter (PICC) placement]. / Colocación de catéteres centrales de inserción periférica (PICC) mediante control electrocardiográfico intracavitario (ECG-IC) de la punta del catéter.

INTRODUCTION: intracavitary electrocardiogram (IC-ECG) guidance has been recently proposed for peripherally inserted central catheter (PICC) placement since it may reduce the time of placement and avoid radiological control. OBJECTIVE: to evaluate IC-ECG compared to conventional radiological control. METHOS: prospective study of 532 consecutive patients. Those with arrhythmias or on antiarrhythmic drugs were excluded. In all cases, PICC tip placement was checked by IC-ECG guidance and by a chest X-ray, which was considered as the reference test. RESULTS: PICC placement with IC-ECG guidance was achieved in 96.8% of patients (applicability). PICC correct placement according to IC-ECG guidance was confirmed by chest X-ray in 94% of patients (accuracy). In 13 patients (2.7%) the catheter had to be repositioned after radiological control. The κ concordance index was 0.356 (p < 0.001). The IC-ECG sensitivity was 0.98, with a PPV of 0.97 and a positive likelihood ratio of 1.5. However, the specificity was only 0.35 with a NPV of 0.41 and a negative likelihood ratio of 0.06. CONCLUSION: PICC placement by IC-ECG guidance is plausible, safe, presents adequate indexes of validity and reliability, and allows reducing the time of catheter placement. However, radiological verification is still necessary, especially in cases of negative or uncertain ECG.

INTRODUCCIÓN: recientemente se ha planteado la posibilidad de comprobar la colocación de los catéteres centrales de inserción periférica (PICC) mediante control electrocardiográfico intracavitario (ECG-IC) ya que permitiría disminuir el tiempo de colocación y evitaría el control radiológico. OBJETIVO: evaluación de dicho método frente al control radiológico habitual. MÉTODOS: estudio prospectivo en el que se incluyeron 532 pacientes de forma consecutiva. Se excluyeron aquellos pacientes con arritmias o en tratamiento con fármacos antiarrítmicos. En todos los casos se comprobó la colocación de la punta del PICC mediante control ECG-IC y mediante la realización de una radiografía de tórax, que fue considerada método de referencia. RESULTADOS: la colocación del PICC gracias al control ECG-IC (aplicabilidad) fue del 96,8%. La correcta colocación del PICC gracias a la interpretación del ECG-IC se confirmó en un 94% de los casos con la radiografía de tórax (precisión). En 13 pacientes (2,7%) se requirió la recolocación del catéter tras el control radiológico. El índice κ de concordancia fue de 0,356 (p < 0,001). La sensibilidad del método ECG fue de 0,98, con un VPP de 0,97 y un cociente de probabilidad positivo de 1,5. Sin embargo, la especificidad fue solo del 0,35 con un VPN de 0,41 y un cociente de probabilidad negativo de 0,06. CONCLUSIÓN: la comprobación de la colocación de los PICC mediante ECG-IC es plausible, segura, presenta unos índices de validez/fiabilidad adecuados y permitiría disminuir el tiempo de colocación del catéter. Sin embargo, la comprobación radiológica sigue siendo necesaria, especialmente en los casos de ECG negativo o dudoso.

Efectiveness of long-term home parenteral nutrition with peripherally inserted central catheter: a case report / Eficacia de la nutrición parenteral domiciliaria de larga evolución con catéter de acceso periférico: a propósito de un caso

The use of home parenteral nutrition (HPN) in patients who can not obtain their nutritional requirements by the enteral route is increasing in recent years, allowing normalization lifestyle of patients. Neoplasm and mesenteric ischaemia are some of the diseases that most frequently require HPN in Spain. However, HPN is one of the cornerstones of the treatment of much less frequent illnesses as in the case of encapsulating peritoneal sclerosis. We present the case of a patient with encapsulating peritoneal sclerosis and HPN support for more than 7 years with a peripherally inserted central catheter (PICC) for over 6 years without complications and the autonomy to perform his normal business activity. Given the exceptional nature of the case we refer it to its publication.

El uso de la nutrición parenteral domiciliaria (NPD) en pacientes que no pueden alcanzar sus requerimientos nutricionales por la vía enteral está aumentando en los últimos años, permitiendo la normalización del estilo de vida de los pacientes. Entre las patologías que más frecuentemente precisan de la NPD en España destacan la neoplasia y la isquemia mesentérica. Sin embargo, la NPD constituye uno de los pilares básicos del tratamiento de enfermedades mucho menos frecuentes como es el caso de la esclerosis peritoneal encapsulante. A continuación presentamos el caso de un paciente diagnosticado de esclerosis peritoneal encapsulante con soporte NPD de más de 7 años de NPD con un catéter central de inserción periférica (PICC) para la NPD sin complicaciones y pudiendo realizar su actividad laboral habitual. Dado lo excepcional del caso lo remitimos para su publicación.

ROLE OF PARENTERAL NUTRITION IN ONCOLOGIC PATIENTS WITH INTESTINAL OCCLUSION AND PERITONEAL CARCINOMATOSIS.

INTRODUCTION AND AIMS: the precise role of parenteral nutrition in the management of oncologic patients with intestinal occlusion is not well defined yet. We aimed to identify the effects of parenteral nutrition in these patients regarding prognosis. MATERIAL AND METHODS: 55 patients with intestinal occlusion and peritoneal carcinomatosis were included. Parenteral nutrition aimed at 20-35 kcal/Kg/day, and 1.0 g/kg/day of amino-acids. Weight, body mass index, type of tumor, type of chemotherapy, and ECOG among others were recorded and analyzed. RESULTS: 69.1% of the patients had gastrointestinal tumors, 18.2% gynecologic and 12.7% others. Age was 60 ± 13y, baseline ECOG 1.5 ± 0.5 and body mass index 21.6 ± 4.3. Malnutrition was present in 85%. Survival from the start of parenteral nutrition was not significant when considering baseline ECOG (log rank = 0.593, p = 0.743), previous lines of chemotherapy (log rank = 2.117, p = 0.548), baseline BMI (log rank = 2.686, p = 0.261), or type of tumor (log rank = 2.066, p = 0.356). Survival in patients who received home parenteral nutrition after hospital discharge was higher than those who stayed in-hospital (log rank = 7.090, p = 0.008). Survival in patients who started chemotherapy during or after parenteral nutrition was higher than those who did not so (log rank = 17.316, p < 0.001). A total of 3.6% of patients presented catheter related infection without affecting survival (log rank = 0.061, p = 0.804). CONCLUSIONS: Parenteral nutrition in patients with advanced cancer and intestinal occlusion is safe, and in tho se who respond to chemotherapy, further administration of home parenteral nutrition together with chemotherapy may enhance prolonged survival.

Introducción y objetivos: el papel preciso de la nutrición parenteral en el manejo de los pacientes oncológicos con obstrucción intestinal no está bien definido todavía. El objetivo del presente trabajo es evaluar los efectos de la nutrición parenteral en este tipo de pacientes en cuanto al pronóstico. Material y métodos: fueron incluidos 55 pacientes con obstrucción intestinal y carcinomatosis peritoneal. La nutrición parenteral proporcionó 20-35 kcal/Kg/día y 1.0 g/kg/día de aminoácidos. El peso, el IMC, el tipo de tumor, el tipo de quimioterapia recibida y el ECOG, entre otras variables, fueron recogidas y analizadas. Resultados: un 69,1% de los pacientes presentaban tumors gastrointestinales, un 18,2% ginecológicos y otros tumores el 12,7% restante. La edad media fue de 60 ± 13 años, con un ECOG basal de 1,5 ± 0,5 y un IMC de 21,6 ± 4,3. La presencia de malnutrición fue de un 85%. La supervivencia desde el inicio de la nutrición parenteral no fue significativamente distinta entre los pacientes al considerar su ECOG basal (log rank = 0,593, p = 0,743), las líneas previas de quimioterapia recibida (log rank = 2,117, p = 0,548), el IMC basal (log rank = 2,686, p = 0,261), o el tipo de tumor (log rank = 2,066, p = 0,356). La supervivencia en los pacientes en que fue posible el alta hospitalaria con nutrición parenteral fue superior (log rank = 7,090, p = 0,008). La supervivencia en los pacientes en que se inició la quimioterapia durante o tras iniciar la nutrición parenteral fue también superior (log rank = 17,316, p < 0,001). Un total de 3,6% de los pacientes presentaron infección relacionada con el catéter sin afectar la supervivencia (log rank = 0,061, p = 0,804). Conclusión: la nutrición parenteral en los pacientes oncológicos con obstrucción intestinal y carcinomatosis peritoneal es segura y, en aquellos que responden a qui mioterapia, el uso de la nutrición parenteral domiciliaria, junto con en tratamiento antitumoral activo, aumentan la supervivencia.