On the inner dynamics between Fossil fuels and the carbon market: a combination of seasonal-trend decomposition and multifractal cross-correlation analysis.

This study examines the inner dynamics of multifractality between the carbon market (EU ETS) and four major fossil fuel energy markets: Brent Crude Oil (BRN), Richards Bay Coal (RBC), UK Natural Gas (NGH2), and FTSE350 electricity index (FTSE350) from January 04, 2016, to March 04, 2022. First, we decompose the daily price changes by applying seasonal and trend decomposition using loess (STL). Then, we examine the inner dynamics of multifractality and cross-correlation by employing multifractal detrended fluctuation analysis (MFDFA) and multifractal detrended cross-correlation analysis (MFDCCA) using the remaining components of the return series. Our findings reveal that all series and the cross-correlations of carbon and fossil fuels markets have multifractal characteristics. We find crude oil to be the most efficient market (lowest multifractal), while coal is the least efficient (highest multifractal). Only coal shows persistent, whereas the other markets exhibit antipersistent behavior. Interestingly, the coal and EU ETS pair demonstrates a higher degree of multifractal patterns. In contrast, the pair of natural gas and EU ETS exhibits the lowest multifractal characteristics among the energy markets. Only the crude oil market shows persistent cross-correlations in the multifractality. These findings have important academic and managerial implications for investors and policymakers.

Management of Neurogenic Orthostatic Hypotension in Neurodegenerative Disorders: A Collaboration Between Cardiology and Neurology.

Treatment of patients with α-synucleinopathies (e.g., Parkinson disease, multiple system atrophy, diffuse Lewy body disease) may require clinicians to manage both neurologic and cardiovascular issues due to autonomic dysfunction. In addition to the underlying neurodegenerative condition, patients often experience blood pressure dysregulation, such as neurogenic orthostatic hypotension (nOH) and/or supine hypertension. This commentary details the collaborative care between a cardiologist and neurologist to effectively manage medically complex patients with nOH by illustrating the case of a 76-year-old man with a history of multiple system atrophy who experienced recurrent syncope when standing or sitting and falls with loss of consciousness. The patient could walk only a few steps before experiencing a substantial drop in systolic blood pressure (100 mmHg). He also had features of profound parkinsonism (e.g., tremor, facial masking) that required treatment with levodopa, but orthostatic symptoms related to the blood pressure drop needed improvement first. The neurologist and cardiologist collaborated to diagnose nOH and initiate droxidopa treatment, which led to resolution of syncope, control of orthostatic symptoms, and improvement of orthostatic blood pressure. Considerations in the collaborative care of patients with nOH are outlined, including screening protocols, treatment goals and options, mitigation of supine hypertension risk (a condition that frequently coexists with nOH), and management of other comorbidities. In conclusion, collaboration between neurologists and cardiologists is an efficient method to improve outcomes for patients with nOH because this care model allows specialist providers to leverage their areas of expertise to manage the wide spectrum of clinical features associated with nOH. Further, communication and cooperation of the patient care team can lead to reduced patient morbidity, optimal relief of nOH symptoms, improvements in activities of daily living and quality of life, and decreased caregiver burden. Management of Neurogenic Orthostatic Hypotension in Neurodegenerative Disorders: A Collaboration Between Cardiology and Neurology (MP4 73511 kb).

People with nervous system disorders such as Parkinson disease, multiple system atrophy, or diffuse Lewy body dementia often experience neurogenic orthostatic hypotension (nOH). nOH occurs when blood pressure becomes too low when a person stands up after lying down or sitting, which can cause weakness, loss of consciousness, and falls. Other common symptoms of nOH include lightheadedness, fainting/feeling faint, trouble thinking clearly, pain in the neck and shoulders ("coat hanger" pain), and feeling tired. People with nOH are at risk of incurring injuries from a fall. A neurologist or cardiologist can identify if a person has nOH by asking about symptoms and measuring the person's blood pressure when lying down and after standing. They may also ask the patient to keep a diary of blood pressure measurements taken at home. When a patient's neurologist and cardiologist work together as a team, they can ensure that nOH is treated safely and effectively, and patients may find their nOH symptoms are better managed. nOH can be treated with lifestyle changes such as drinking more water, eating more salty food, or gentle exercises. If needed, healthcare providers can prescribe medications to treat nOH.

Droxidopa Persistence in Neurogenic Orthostatic Hypotension May Be Affected by Titration Approach.

Droxidopa is approved for the treatment of neurogenic orthostatic hypotension (nOH) symptoms and requires patients to be titrated to individualized effective doses (100-600 mg, three times daily) based on symptomatic response. As per the product label, droxidopa should be titrated every 24-48 hours to an optimum maintenance dose (maximum daily dosage 1,800 mg). In an examination of patients with nOH treated in clinical practice settings (n=4,506) using data from the central Northera specialty-pharmacy hub, titration schedules, daily titration dosage (ie, dosage during first dispensation, the assumed titration period), and daily maintenance dosage (dosage during subsequent dispensations) were characterized. It was found that customized titration schedules (ie, different from the product-label recommendation) had been used in 53% of patients, and these patients had had an average daily titration dosage of 567 mg. In contrast, patients who were titrated as per the label schedule (48 hours, 37%; 24 hours, 10%) had daily titration dosages of 1,500-1,650 mg. A relationship between treatment persistence (measured by number of refills) and maintenance dosage was identified. Average daily maintenance doses in patients who received 2, 3-6, 7-24, and >25 dispensations were 938, 969, 1,069, and 1,167 mg, respectively (P<0.0001). In summary, our data suggest that more than half the patients treated with droxidopa in clinical practice settings are not titrated using the schedule recommended on the product label (ie, not 24-48 hours), and as a result receive lower daily dosages of droxidopa than those treated using the recommended titration schedules. Lower daily maintenance dosages of droxidopa were associated with shorter treatment persistence (ie, fewer dispensations). Reasons for discontinuation could not be examined in this study, but further investigation of these persistence data is warranted.

QTc Interval Prolongation with Therapies Used to Treat Patients with Parkinson's Disease Psychosis: A Narrative Review.

In addition to the classic motor symptoms of Parkinson's disease (PD), people with PD frequently experience nonmotor symptoms that can include autonomic dysfunction and neuropsychiatric symptoms such as PD psychosis (PDP). Common patient characteristics, including older age, use of multiple medications, and arrhythmias, are associated with increased risk of corrected QT interval (QTc) prolongation, and treatments for PDP (antipsychotics, dementia medications) may further increase this risk. This review evaluates how medications used to treat PDP affect QTc interval from literature indexed in the PubMed and Embase databases. Although not indicated for the treatment of psychosis, dementia therapies such as donepezil, rivastigmine, memantine, and galantamine are often used with or without antipsychotics and have minimal effects on QTc interval. Among the antipsychotics, data suggesting clinically meaningful QTc interval prolongation are limited. However, many antipsychotics have other safety concerns. Aripiprazole, olanzapine, and risperidone negatively affect motor function and are not recommended for PDP. Quetiapine is often sedating, can exacerbate underlying neurogenic orthostatic hypotension, and may prolong the QTc interval. Pimavanserin was approved by the US Food and Drug Administration (FDA) in 2016 and remains the only FDA-approved medication available to treat hallucinations and delusions associated with PDP. However, pimavanserin can increase QTc interval by approximately 5-8 ms. The potential for QTc prolongation should be considered in patients with symptomatic cardiac arrhythmias and those receiving QT-prolonging medications. In choosing a medication to treat PDP, expected efficacy must be balanced with potential safety concerns for individual patients.

Current Practices for Outpatient Initiation of Levodopa-Carbidopa Intestinal Gel for Management of Advanced Parkinson's Disease in the United States.

In 2015, the US Food and Drug Administration approved levodopa-carbidopa intestinal gel (LCIG; also known as carbidopa-levodopa enteral suspension in the US) for the treatment of motor fluctuations in patients with advanced Parkinson's disease. LCIG provides a continuous infusion of levodopa and carbidopa by means of a portable pump and percutaneous endoscopic gastrojejunostomy tube. The delivery system has a two-fold pharmacokinetic advantage over orally administered carbidopa/levodopa. First, levodopa is delivered in a continuous rather than intermittent, pulsatile fashion. Second, delivery to levodopa's site of absorption in the jejunum bypasses the stomach, thereby avoiding issues with erratic gastric emptying. In blinded prospective clinical trials and observational studies, LCIG has been shown to significantly decrease "off" time, increase "on" time without troublesome dyskinesia, and reduce dyskinesia. Consistent with procedures in previous studies, LCIG initiation and titration in the pivotal US clinical trial were performed in the inpatient setting and followed a standardized protocol. In clinical practice, however, initiation and titration of LCIG have a great degree of flexibility and, in the US, almost always take place in the outpatient setting. Nonetheless, there remains a significant amount of clinician uncertainty regarding titration in outpatient clinical practice. This review aims to shed light on and provide guidance as to the current methods of titration in the outpatient setting, as informed by the medical literature and the authors' experiences. FUNDING: AbbVie, Inc. Plain language summary available for this article.

Results from recent studies have shown that continuous infusion of levodopa-carbidopa intestinal gel (LCIG) into the jejunum (a part of the small intestine) effectively manages the motor and nonmotor complications (e.g., tremor, extreme stiffness in arms and legs, difficulty walking, and impaired balance) experienced by patients with advanced Parkinson's disease (PD). LCIG is administered by a portable pump directly into the patient's jejunum by a permanent tube that is inserted surgically. LCIG therapy is beneficial to advanced PD patients over orally administered carbidopa/levodopa for two reasons. First, oral carbidopa/levodopa moves from the stomach to the small intestine where it is intermittently absorbed into the blood stream. LCIG is administered continuously and offers better symptom control for longer. Results from clinical trials and observational studies have shown that LCIG significantly decreases "off" time (poor motor control) and increases "on" time (good motor control) in advanced PD patients without troublesome dyskinesia, which results from the higher doses of oral levodopa required to treat the symptoms. Second, LCIG is absorbed in the jejunum, thereby bypassing the stomach where problems can occur because of inconsistent stomach emptying. In the US, titration of LCIG is performed mostly in an outpatient setting. Some clinicians may view titration of LCIG to be too complex and variable, so they avoid using LCIG therapy for their PD patients. Fortunately, emerging data and clinicians' expanding experience with LCIG have shown that titration can be easily managed in an outpatient setting, allowing for more customized therapeutic regimens for patients.

Interferon-tau inhibits the development of diabetes in NOD mice.

Interferon-alpha (IFN-alpha) inhibits the development of diabetes in animal models of autoimmune diabetes. However, the mechanism of the action is not fully understood and drug toxicity could limit its potential clinical utility. Interferon-tau (IFN-tau) is another type 1 interferon, which has less toxicity but may have different biologic activity than IFN-alpha. This study explores the effect of IFN-tau on the diabetic process in non-obese diabetic (NOD) mice. IFN-tau by intraperitoneal, subcutaneous, or oral routes of administration decreased the development of spontaneous diabetes in NOD mice. Islet inflammation was decreased 50%. IFN-tau administration to recipient mice prevented the development of passively transferred and cyclophosphamide accelerated diabetes. IFN-tau treatment also decreased anti-islet effector activity of NOD splenic cells. Immunoregulatory activity of splenic cells was augmented by IFN-tau administration as was the number of splenic CD25+CD4+ cells. Concanavalin A (Con A)-induced release of IFN-gamma was decreased in spleen cells from IFN-tau treated mice. In conclusion, IFN-tau inhibits spontaneous autoimmune diabetes and passively transferred diabetes in the NOD mouse. This diabetes sparing activity may be due to an induction of regulatory cells, possibly CD25+CD4+ T cells, which in turn inhibit anti-islet effector cell activity and the development of insulitis and diabetes. Due to the lower drug toxicity, IFN-tau could be a better drug candidate than IFN-alpha for experimental clinical trials.