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Clinical and Translational Science May 2024Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal...
Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non-invasive and user-friendly alternative. This two-part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2 mg oromucosal apomorphine (4% weight/volume) and 2 mg subcutaneous apomorphine in a randomized order, followed by 4 and 8 mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7 mg oromucosal apomorphine (7% weight/volume) and 30 mg sublingual apomorphine in a randomized order, followed by 14 mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2 days. Safety, tolerability, and PK were assessed pre- and post-dose. Both study parts showed that oromucosal apomorphine was generally well-tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14 mg oromucosal apomorphine was 753.0 (298.6) ng*min/mL (area under the plasma concentration-time curve from zero to infinity) and 8.0 (3.3) ng/mL (maximum plasma concentration). This was comparable to exposure reached after 2 mg subcutaneous apomorphine and approximately half of the exposure observed with 30 mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues.
Topics: Aged; Female; Humans; Male; Middle Aged; Administration, Oral; Administration, Sublingual; Antiparkinson Agents; Apomorphine; Biological Availability; Cross-Over Studies; Dose-Response Relationship, Drug; Injections, Subcutaneous; Parkinson Disease; Adult; Aged, 80 and over
PubMed: 38712716
DOI: 10.1111/cts.13796 -
European Heart Journal Open May 2024The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the...
AIMS
The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation.
METHODS AND RESULTS
We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing ( < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors.
CONCLUSION
Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.
PubMed: 38708290
DOI: 10.1093/ehjopen/oeae030 -
Journal of Parkinson's Disease 2024Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Autonomic dysfunction precedes endothelial dysfunction in Parkinson's disease (PD) and causes blood pressure and circulation abnormalities that are highly disruptive to one's quality of life. While exercise interventions have proven helpful for motor symptoms of PD, improving associated non-motor symptoms is limited. Low-intensity resistance training with blood flow restriction (LIRT-BFR) improves autonomic dysfunction in non-PD patients and high-intensity resistance training (HIRT) is recommended for motor symptom improvements for people with PD (PwPD).
OBJECTIVE
To determine the effects of LIRT-BFR and HIRT on homocysteine and autonomic and endothelial function in PwPD and to determine the hemodynamic loads during LIRT-BFR and HIRT in PwPD using a novel exercise protocol.
METHODS
Thirty-eight PwPD were assigned LIRT-BFR, HIRT or to a control (CNTRL) group. The LIRT-BFR and HIRT groups exercised three days per week for four weeks. The LIRT-BFR protocol used 60% limb occlusion pressure (LOP) and performed three sets of 20 repetitions at 20% of the one-repetition maximum (1RM). The HIRT group performed three sets of eight repetitions at 80% 1RM. The CNTRL group was asked to continue their normal daily routines.
RESULTS
LIRT-BFR significantly improved orthostatic hypotension (p = 0.026), homocysteine levels (p < 0.001), peripheral circulation (p = 0.003), supine blood pressure (p = 0.028) and heart rate variability (p = 0.041); LIRT-BFR improved homocysteine levels (p < 0.018), peripheral circulation (p = 0.005), supine blood pressure (p = 0.007) and heart rate variability (p = 0.047) more than HIRT; and hemodynamic loads for LIRT-BFR and HIRT were similar.
CONCLUSIONS
LIRT-BFR may be more effective than HIRT for autonomic and endothelial function improvements in PwPD and hemodynamic loads may be lessened in LIRT-BFR protocols using single-joint exercises with intermittent blood flow restriction. Further research is needed to determine if non-motor symptoms improve over time and if results are sustainable.
Topics: Humans; Resistance Training; Parkinson Disease; Male; Female; Aged; Middle Aged; Endothelium, Vascular; Autonomic Nervous System; Blood Flow Restriction Therapy; Homocysteine; Heart Rate; Blood Pressure
PubMed: 38701159
DOI: 10.3233/JPD-230259 -
Movement Disorders Clinical Practice Jun 2024Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic...
BACKGROUND
Blood pressure control in Parkinson's disease (PD) under subthalamic deep brain stimulation (STN-DBS) is influenced by several intertwined aspects, including autonomic failure and levodopa treatment.
OBJECTIVE
To evaluate the effect of chronic STN-DBS, levodopa, and their combination on cardiovascular autonomic functions in PD.
METHODS
We performed cardiovascular reflex tests (CRTs) before and 6-months after STN-DBS surgery in 20 PD patients (pre-DBS vs. post-DBS). CRTs were executed without and with medication (med-OFF vs. med-ON).
RESULTS
CRT results and occurrence of neurogenic orthostatic hypotension (OH) did not differ between pre- and post-DBS studies in med-OFF condition. After levodopa intake, the BP decrease during HUTT was significantly greater compared to med-OFF, both at pre-DBS and post-DBS evaluation. Levodopa-induced OH was documented in 25% and 5% of patients in pre-DBS/med-ON and post-DBS/med-ON study.
CONCLUSION
Chronic stimulation did not influence cardiovascular responses, while levodopa exerts a relevant hypotensive effect. The proportion of patients presenting levodopa-induced OH decreases after STN-DBS surgery.
Topics: Humans; Parkinson Disease; Deep Brain Stimulation; Male; Female; Middle Aged; Aged; Levodopa; Autonomic Nervous System; Antiparkinson Agents; Blood Pressure; Subthalamic Nucleus; Hypotension, Orthostatic
PubMed: 38698586
DOI: 10.1002/mdc3.14060 -
Kardiochirurgia I Torakochirurgia... Mar 2024Although primary spontaneous pneumothorax is a common disease in young adults, each thoracic surgery department performs different procedures for its management.
INTRODUCTION
Although primary spontaneous pneumothorax is a common disease in young adults, each thoracic surgery department performs different procedures for its management.
AIM
The optimal time of postoperative mobilization is not yet standardized in lung surgery.
MATERIAL AND METHODS
This study included male patients with a primary spontaneous pneumothorax who underwent wedge resection of the upper lobe of the lungs via uniportal video-assisted thoracoscopic surgery. Patients were encouraged to stand up within the first postoperative hour. Mobilization was defined as standing and walking at least 100 m from the bed. If orthostatic hypotension occurred, mobilization was postponed for 30 min. Immediately after surgery, intravenous fluids were discontinued, and patients were instructed to drink water. The analgesic treatment needs, length of hospitalization, drainage, and discharge times were recorded.
RESULTS
A total of 43 patients were operated on by the same surgeon. All operations were ended with uniportal video-assisted thoracoscopic surgery. Wedge resection is most commonly indicated for recurrent ipsilateral pneumothorax. Patients walked 345 (range: 150-510) m on the department corridor following bed rest. Paracetamol (2 g) and dexketoprofen (100 mg) were intravenously administered as postoperative analgesia to 76.7% of patients. Narcotic drugs were not needed.
CONCLUSIONS
Mobilization was recommended in the first hour following uniportal video-assisted thoracoscopic surgery for primary spontaneous pneumothorax.
PubMed: 38693989
DOI: 10.5114/kitp.2024.138497 -
Cureus Mar 2024Syncope is the transient loss of consciousness due to cerebral hypoperfusion. A significant number of individuals experience a syncopal attack at one stage of their...
Syncope is the transient loss of consciousness due to cerebral hypoperfusion. A significant number of individuals experience a syncopal attack at one stage of their lives. The common causes of syncope include vasovagal syncope, orthostatic hypotension, and cardiac causes. Drugs are also associated with causing syncope. The drugs involved are mostly those that depress the central nervous system, and concomitant use of more than one of such drugs increases the risk of syncope even further. Tizanidine and alcohol individually can cause hypotension and combining both drugs is not advised due to heightened central nervous system depression and profound hypotension. We present a case of a 53-year-old female with alcohol use disorder who presented with a first-time syncopal attack due to postural hypotension after ingesting both tizanidine and alcohol concurrently. Co-administration of tizanidine and alcohol is not advised, however, cases of syncope have been rarely reported with concomitant use. This case will enlighten physicians to counsel patients about the need to abstain from alcohol consumption when taking tizanidine.
PubMed: 38686239
DOI: 10.7759/cureus.57249 -
Frontiers in Cardiovascular Medicine 2024The long-term prognosis of patients with stable coronary artery disease (CAD) combined with orthostatic hypotension (OH) has rarely been reported. This research was...
BACKGROUND
The long-term prognosis of patients with stable coronary artery disease (CAD) combined with orthostatic hypotension (OH) has rarely been reported. This research was designed to examine whether OH increases the risk of all-cause mortality and cardiovascular death among patients with stable CAD.
METHODS
We retrospectively analyzed retired military personnel over 65 years of age who were hospitalized at the General Hospital of Southern Theater Command of the Chinese People's Liberation Army between March and July 2010. A total of 924 patients with stable CAD were included, among whom 263 had OH. The risk of all-cause mortality and cardiovascular death in OH and non-OH groups were analyzed with the Cox proportional hazards models, and restricted cubic spline plots were utilized for subgroup analyses. Furthermore, competing risk models were applied for sensitivity analyses.
RESULTS
The median age of the patients was 82.00 (80.00-85.00) years. Over 159 months of follow-up, the loss to follow-up rate was 2.27%, and all-cause mortality was observed in 574 (63.57%) patients, including 184 with OH. Moreover, cardiovascular death occurred in 127 patients (13.73%), with 58 cases associated with OH. Although the relationship between OH and all-cause mortality was non-significant [body mass index (BMI) < 25 group, adjusted hazard ratio (HR) = 1.10 with a 95% confidence interval (CI): 0.82-1.40; BMI ≥ 25 group, adjusted HR = 1.30, 95% CI: 0.98-1.70], it was independently related to a growing risk of cardiovascular death (adjusted HR = 1.80, 95% CI: 1.20-2.60). This finding was further validated by using a competing risk model (subdistribution HR = 1.74, 95% CI: 1.22-2.49). Moreover, age, low-density lipoprotein cholesterol, and frequency of hospital admissions were identified as risk factors of cardiovascular death among patients with OH ( < 0.05).
CONCLUSION
Our study, based on retired military personnel with stable CAD, found that OH led to a significantly higher risk of cardiovascular death, but it was not noticeably associated with all-cause mortality on long-term prognosis.
PubMed: 38682102
DOI: 10.3389/fcvm.2024.1342379 -
Journal of Personalized Medicine Apr 2024Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic... (Review)
Review
Orthostatic intolerance is a broad term that represents a spectrum of dysautonomic disorders, including postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH), as manifestations of severe autonomic failure. While the etiology of orthostatic intolerance has not yet fully been uncovered, it has been associated with multiple underlying pathological processes, including peripheral neuropathy, altered renin-aldosterone levels, hypovolemia, and autoimmune processes. Studies have implicated adrenergic, cholinergic, and angiotensin II type I autoantibodies in the pathogenesis of orthostatic intolerance. Several case series have demonstrated that immunomodulation therapy resulted in favorable outcomes, improving autonomic symptoms in POTS and OH. In this review, we highlight the contemporary literature detailing the association of autoimmunity with POTS and OH.
PubMed: 38673062
DOI: 10.3390/jpm14040435 -
Cancers Apr 2024Orthostatic hypotension (OH) is associated with a higher risk of mortality in the general population; however, it has not been studied in the cancer population. This...
BACKGROUND
Orthostatic hypotension (OH) is associated with a higher risk of mortality in the general population; however, it has not been studied in the cancer population. This study aimed to assess the prevalence of OH in cancer patients compared to that in the noncancer population.
METHODS
A total of 411 patients (mean age 63.5 ± 10.6 years) were recruited: patients with active cancer ( = 223) and patients hospitalised for other reasons, but without a cancer diagnosis ( = 188). Medical histories were collected and an orthostatic challenge test was performed. OH was defined as a blood pressure (BP) decrease upon standing of ≥20 mmHg for the systolic or ≥10 mmHg for the diastolic BP after 1 or 3 min; or a systolic BP decrease <90 mmHg.
RESULTS
The prevalence of OH in the subjects with cancer was significantly higher than in the subjects without cancer (28.7% vs. 16.5%, respectively, = 0.003). OH was the most common in the lung cancer patients (57.5%). In a single-variable analysis, the predictors of OH were cancer presence, age ≥ 65 years, and body mass index (BMI) ≥ 30 kg/m. In the multivariable model, the strongest independent predictor of OH was cancer status, which doubled the risk of OH, and BMI ≥ 30 kg/m and diabetes.
CONCLUSIONS
Cancer patients are characterised by a high prevalence of OH. In this population, the recommendation of routine orthostatic challenge tests should be considered.
PubMed: 38672623
DOI: 10.3390/cancers16081541 -
Brain Sciences Mar 2024(1) Background: The differential diagnosis of essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD) can be challenging. Only a few studies have...
(1) Background: The differential diagnosis of essential tremor (ET) and tremor-dominant Parkinson's disease (TDPD) can be challenging. Only a few studies have investigated the autonomic nervous system (ANS) in ET. However, some of these suggested that heart rate variability (HRV) might be useful in the differential diagnosis. (2) Methods: Demographic and clinical data, including medications and comorbidities, were collected from 15 TDPD patients, 19 ET patients, and 20 healthy controls. Assessment with the SCOPA-AUT questionnaire, 5 min HRV analysis in time and frequency domains, and evaluation of orthostatic hypotension (OH) with tilt test were performed. (3) Results: There were no significant differences between all groups on the SCOPA-AUT questionnaire. PD patients had OH more frequently and a larger drop in systolic blood pressure (SBP) during the tilt test than ET patients and controls. HRV was affected in PD, but not in ET and controls. Power in the low frequency band, the standard deviation of all normal RR intervals and SBP drop were potentially useful in differential diagnosis with AUCs of 0.83, 0.78, and 0.83, respectively. (4) Conclusions: Cardiovascular ANS dysfunction was present in TDPD, but not in ET and controls. HRV analysis and assessment of SBP drop may be potentially useful in the differential diagnosis of ET and TDPD.
PubMed: 38671965
DOI: 10.3390/brainsci14040313