ABSTRACT
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.
ABSTRACT
BACKGROUND: Total knee arthroplasty (TKA) in patients with skeletal dysplasias is particularly challenging as a result of the anatomic variances and substantial bony deformities. Little has been written regarding technical considerations that should be made when performing TKA in skeletal dysplasia. QUESTIONS/PURPOSES: We describe special operative considerations that must be made when performing TKA on patients with skeletal dysplasia, including implant selection and ligamentous balancing. PATIENTS AND METHODS: We retrospectively reviewed 12 TKAs in eight patients with varying degrees of deformity (ranging from 30° of varus to 45° of valgus) secondary to three types of skeletal dysplasias: multiple hereditary exostosis, achondroplasia, and osteogenesis imperfecta. Clinical notes, operative records, and radiographic data were reviewed. Minimum followup was 1 year (average, 4 years; range, 1-10 years). RESULTS: We used customized implants in three of the 12 knees. Constrained tibial inserts were used in five knees. All 12 knees underwent releases (soft tissue or epicondylar osteotomy) to address gap balancing or patellar tracking. Average Knee Society scores improved from 35.9 preoperatively to 82.9 postoperatively and average function scores improved from 47.9 preoperatively to 96.7 postoperatively. Complications included two transient peroneal nerve palsies. CONCLUSIONS: Special considerations must be made with regard to implant selection and ligamentous balancing as a result of the unusual anatomy and deformities that accompany skeletal dysplasia, but the short-term clinical results reveal consistent improvements in pain and function. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
