Clinical Neuropharmacology最新文献

Background: Treatment of soft tissue sarcoma frequently involves extensive surgery, loss of mobility, and complex rehabilitation programs. Poorer patient-reported outcomes are reported in comparison to those from patients with other cancer types. Understanding patient experience is therefore important to support patients and improve care.

Objective: The aim of this study was an in-depth exploration of patients' experience of being diagnosed with soft tissue sarcoma.

Methods: Semistructured interviews and focus groups were conducted with 68 patients with soft tissue sarcoma (59% female; aged 23-82 years). These were analyzed using adapted framework analysis.

Results: Two overarching themes explained the factors influencing patients' experiences: individual and social factors to manage the impact of soft tissue sarcoma; and context and processes of care. Access to professionals with sarcoma expertise and services in specialist hospitals had an impact on patients' well-being. Lack of access to specialist services and coordinated care were associated with worse experiences. These were influenced by age and support from family/friends/other patients and were crucial in patients' adaptation to living with and beyond a sarcoma diagnosis.

Conclusion: We describe factors that both negatively and positively influenced the experience of patients with soft tissue sarcoma. Access to specialist soft tissue sarcoma and rehabilitation services and support tailored to patients' age and disease trajectory are needed to improve these experiences.

Implication for practice: Nurses are important for helping patients manage the long-term effects and directing them to supportive care services. Rehabilitation services need to be available and easily accessible.

Objectives: Lasmiditan holds important potential in treating migraine, but its ideal dose remains elusive. This meta-analysis is conducted based on aggregate data and aims to compare the efficacy of lasmiditan 200 mg versus 100 mg for acute treatment of migraine attack.

Methods: PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases were systematically searched, and we included the randomized controlled trials comparing the efficacy of lasmiditan 200 mg versus 100 mg for migraine patients. This meta-analysis was conducted using the random-effect model or fixed-effect model based on the heterogeneity. The primary outcome was pain free at 2 hours. Secondary outcomes included pain relief at 2 hours, pain free at 24 hours, most bothersome symptom free at 2 hours, and adverse events.

Results: Seven randomized controlled trials and 6515 patients were included in this meta-analysis. Compared with lasmiditan 100 mg for migraine patients, lasmiditan 200 mg was able to significantly improve pain free at 2 hours (odd ratio [OR], 1.28; 95% confidence interval [CI], 1.14-1.44; P < 0.0001) and pain free at 24 hours (OR, 1.35; 95% CI, 1.14-1.60; P = 0.0005), but showed no effect on pain relief at 2 hours (OR, 1.00; 95% CI, 0.90-1.12; P = 0.98) or most bothersome symptom free at 2 hours (OR, 0.93; 95% CI, 0.83-1.03; P = 0.17). Lasmiditan 200 mg was associated with the increase in adverse events compared with lasmiditan 100 mg (OR, 1.28; 95% CI, 1.15-1.43; P < 0.0001).

Conclusions: Lasmiditan 200 mg is more effective to improve pain free at 2 hours and 24 hours than lasmiditan 100 mg for the acute treatment of migraine patients.

Objective: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE.

Methods: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated.

Results: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use.

Conclusions: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

Background: The purpose of this study was to investigate the relationship between anticholinergic burden (ACB), and cognitive and functional alterations in patients with dementia of Lewy bodies (DLB) during a 1-year follow-up period.

Methods: This cohort study included patients diagnosed with DLB admitted to a tertiary geriatric outpatient clinic. Cognition, functional performance, and nutritional status were assessed at baseline, 6 months, and 12 months during the follow-up period. The ACB was evaluated, and participants were grouped as ACB ≥1 and ACB=0.

Results: A total of 112 patients with DLB (mean age, 79.3 ± 6.8 years; 50.9% female) were included. The mean number of medications was 5.1 ± 4, 56.9% of participants had polypharmacy, and 55.2% had an anticholinergic drug burden. Individuals with ACB ≥1 had lower instrumental activities of daily living (IADL) scores at baseline than those with ACB=0 (P=0.014). The Barthel index and Lawton-Brody IADL scores significantly decreased in the ACB ≥1 group on repetitive measurements over time, whereas only the Lawton-Brody IADL scores worsened in the ACB=0 group (all P<0.001). There were no significant differences in cognitive scores and Mini-Mental State Examination subdomains between the groups. The dependent variable repetitive test revealed a significant deterioration in the orientation subdomain in the ACB ≥1 group over time (P=0.001). Multivariable regression models showed no significant effect of ACB score on cognitive and functional impairment.

Conclusion: Our study provides evidence that the use of anticholinergic drugs in this vulnerable population may potentially increase the morbidity by adversely affecting functional status and cognitive orientation.

Background: Partners of men diagnosed with prostate cancer face their own emotional struggles as they navigate additional caregiver responsibilities while concurrently adjusting to the diagnosis and coping with greater illness uncertainty for their loved one.

Objective: This qualitative systematic review examined the unmet supportive care needs of partners affected by prostate cancer.

Interventions/methods: A meta-aggregation was conducted. Four electronic databases were searched using key words. The methodology followed the Joanna Briggs Institute for qualitative evidence synthesis. The review process followed a registered priori review protocol and was reported using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. Data extraction and quality assessment were conducted in parallel.

Results: Twenty-one publications were included. A total of 239 findings and 32 categories were synthesized into 7 domains of unmet needs as experienced by partners. The domains of needs expressed by the participants included interpersonal/intimacy, physical/daily living, healthcare service, family-related, psychological/emotional needs, and spiritual and social needs.

Conclusions: There are gaps in clinical service support, despite routine clinical consultation with healthcare professionals. Partners may diminish their social networks to protect their husband at the cost to their own self-preservation and well-being.

Implications for practice: Cancer organizations, policy makers, healthcare care professionals, and researchers are slowly making progress to acknowledge the unique support needs of partners affected by cancer. Healthcare professionals should encourage partners to be included in models of prehabilitation to access timely support to address informational, intimacy, spiritual, and daily living needs support.

Objectives: The aim of the study is to report a case with heat intolerance, complex motor fluctuations, and parkinsonism.

Materials and methods: A male with onset of heat intolerance at the age of 46 years developed left upper limb tremor at the age of 58 years. He was diagnosed with Parkinson disease at the age of 62 years and presented to Movement Disorders Clinic Saskatchewan at the age of 65 years. He reported motor response fluctuations, including WO and dyskinesias. There was no history of dizziness on standing, bladder, or sexual dysfunction. We recorded an asymptomatic drop of orthostatic blood pressure. He reported loss of smell sensation for 5 years and REM behavior disorder characterized by talking in his sleep. He was assessed at the age of 65 years over the course of a day with 4 video recordings of his evolving findings and symptoms with his informed consent.

Results: Initial assessment after levodopa was withheld more than 14 hours revealed him to be 'off' with severe dystonic neck flexion and with bradykinesia and rigidity in the limbs. He was anhidrotic, felt hot, and needed a wet towel over his neck. Over the course of 4 hours, he turns "on" with improvement in heat intolerance, neck hypertonicity, and parkinsonian findings and develops evolving dyskinetic movements before turning "off" again. His overall clinical picture was most consistent with multiple system atrophy.

Conclusions: Heat intolerance can precede onset of motor symptoms of parkinsonism by several years and supports a diagnosis of multiple system atrophy. To our knowledge, this is the first documented case of improvement in heat intolerance with levodopa.

Objectives: Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms.

Methods: Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method.

Results: The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40-9.89]; EM, 9.79 [8.23-10.62]; Control, 10.16 [8.60-17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls ( P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety ( r = -0.318, P = 0.002), HADS-Depression ( r = -0.368, P < 0.001), Pittsburgh Sleep Quality Index ( r = -0.303, P = 0.004), and Leeds Dependence Questionnaire ( r = -0.312, P = 0.003).

Conclusions: This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.

Objectives: Rimegepant may have some potential in treating migraine, and this meta-analysis aims to study the efficacy and safety of rimegepant for migraine patients.

Methods: We have searched several databases including PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases and selected the randomized controlled trials comparing the efficacy of rimegepant versus placebo for migraine patients. This meta-analysis was conducted using the random- or fixed-effect model based on the heterogeneity.

Results: Three randomized controlled trials were included in this meta-analysis. Compared with placebo in migraine patients, rimegepant treatment was associated with substantially improved freedom from pain at 2 hours (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.69-2.59; P < 0.00001), pain relief at 2 hours (OR, 1.93; 95% CI, 1.65 to 2.25; P < 0.00001), freedom from the most bothersome symptom at 2 hours (OR, 1.61; 95% CI, 1.35-1.91; P < 0.00001), ability to function normally at 2 hours (OR, 1.69; 95% CI, 1.42-2.01; P < 0.00001), sustained freedom from pain at 24 hours (OR, 2.88; 95% CI, 1.74-4.78; P < 0.0001), sustained pain relief at 24 hours (OR, 2.31; 95% CI, 1.96-2.72; P < 0.00001), and no rescue medication (OR, 2.42; 95% CI, 2.02-2.90; P < 0.00001) but showed no obvious impact on adverse events (OR, 1.27; 95% CI, 1.01-1.60; P = 0.04).

Conclusions: Rimegepant may be effective and safe for the treatment of migraine patients.

Objective: Neuroleptic malignant syndrome (NMS) is a rare life-threatening condition that providers should be cognizant of when prescribing dopamine-receptor antagonists. Atypical antipsychotic agents were initially considered to have a lower risk of inducing the development of NMS compared with conventional antipsychotic. Considerable evidence, however, has suggested that atypical antipsychotics are associated with NMS, including the partial dopamine agonist, aripiprazole. There is growing evidence that other psychotropics, including lithium, cause this condition. Here, the authors present a case of a patient who developed NMS from lithium and aripiprazole and provide a literature review of reported NMS cases with either psychotropic.

Method and results: The authors report the case of 60-year-old male patient who developed NMS over a hospital course during which both aripiprazole and lithium were prescribed. In addition, a literature review was performed and a summary of cases of NMS induced by either lithium and/or aripiprazole is provided.

Conclusions: This case adds to the growing body of literature of aripiprazole and lithium-induced NMS. Only 2 other cases are reported where concomitant aripiprazole and lithium use lead to NMS. Interestingly, our patient did develop lithium toxicity during hospitalization, but the NMS diagnosis occurred after lithium toxicity resolved. This varies from the other 2 cases where NMS developed despite lithium levels always being therapeutic. Unfortunately, there are more questions than answers surrounding this rare complication involving these 2 psychotropics and clinical vigilance is warranted when using these psychotropics especially in cases where aripiprazole and lithium are used in combination.

Objective: Converging evidence supports the role of the glutamate, an excitatory amino acid neurotransmitter, in the pathophysiology of obsessive-compulsive disorder (OCD). Ketamine and esketamine, both noncompetitive N -methyl- d -aspartate antagonists, have emerged as a promising medication for this psychiatric disorder, given its possible efficacy with faster onset and good tolerability. The purpose of this retrospective chart review is to evaluate whether unbiased clinical documentation supports formal clinical trials of esketamine for an OCD indication.

Methods: A retrospective chart review of patients with treatment-resistant OCD receiving a single dose of esketamine (0.5mg/kg) added to standard therapy was conducted. The Yale-Brown Obsessive-Compulsive Scale and the Montgomery-Åsberg Depression Rating Scale were used to evaluate OCD and depressive symptoms respectively at baseline, 24 hours, and 7 days after esketamine administration. Descriptive statistics were used to analyze the data.

Results: Eight subjects were identified in this retrospective chart review: esketamine was administered subcutaneously in 7 and intravenously in 1. One week after infusion, 25% of the sample met criteria for treatment response and 50% for partial response. Major depressive disorder was a comorbid diagnosis in 75% of the sample and 2 of these subjects showed a positive antidepressant response.

Conclusions: Our findings provide preliminary evidence that esketamine may reduce obsessive-compulsive symptoms in a subset of treatment-resistant OCD patients.