Changes in Prescribing Practices of Dopaminergic Medications in Individuals with Parkinson's Disease by Expert Care Centers from 2010 to 2017: The Parkinson's Foundation Quality Improvement Initiative.

BACKGROUND: During the past decade, there has been increasing awareness of the side effects of dopamine agonists (DAs), including impulse control disorders. We hypothesized that there may be a shift toward more conservative use of DAs. OBJECTIVE: To explore the change in prescribing practices for dopaminergic medications in Parkinson's disease between 2010 and 2017. METHODS: Data were collected from the Parkinson's Foundation Quality Improvement Initiative registry. Baseline characteristics were compared between the 2010 and 2017 cohorts using chi-squared tests for discrete and t tests for continuous variables. Logistic regressions were conducted for each class of medications to assess the effect of time points (2010 vs. 2017) and prespecified covariates on the probability of prescribing. RESULTS: A total of 2,717 participants from 2010 and 2,900 participants from 2017 were included in the analysis. Mean (standard deviation) age was 67.4 (10) and 68.7 (9.3) for the 2010 and 2017 cohorts, respectively (P < 0.0001). After controlling for baseline characteristics, DA use was unchanged (P = 0.1172). The odds of using monoamine oxidase B inhibitors was 52% higher in 2017 than in 2010 (P < 0.0001), 38% lower for catechol-O-methyltransferase inhibitors (P < 0.0001), 25% lower for amantadine (P < 0.0001), and 31% lower for anticholinergics (P = 0.0153). There was no difference in the utilization of levodopa in the 2 cohorts (86.1% vs. 86.2%; P = 0.5783). CONCLUSIONS: Despite increasing awareness of impulse control disorders, there has been no reduction in the use of DAs during the past decade. Overall, there is less utilization of adjunctive classes of drugs except for an increase in the use of monoamine oxidase B inhibitors.

Advance care planning in Parkinson's disease: ethical challenges and future directions.

Recent discoveries support the principle that palliative care may improve the quality of life of patients with Parkinson's disease and those who care for them. Advance care planning, a component of palliative care, provides a vehicle through which patients, families, and clinicians can collaborate to identify values, goals, and preferences early, as well as throughout the disease trajectory, to facilitate care concordant with patient wishes. While research on this topic is abundant in other life-limiting disorders, particularly in oncology, there is a paucity of data in Parkinson's disease and related neurological disorders. We review and critically evaluate current practices on advance care planning through the analyses of three bioethical challenges pertinent to Parkinson's disease and propose recommendations for each.

The impact of direct vertebral body derotation on the lumbar prominence in Lenke Type 5C curves.

OBJECT: The thoracic rib hump, caused by axial rotation of the spine, is one of the most dissatisfying cosmetic features associated with adolescent idiopathic scoliosis (AIS). However, advances in instrumentation and surgical techniques, such as direct vertebral body derotation (DVBD), have allowed improved correction in the axial plane and the rib hump. In cases of thoracolumbar/lumbar curves (Lenke Type 5), the lumbar prominence can be equally disfiguring and is often associated with waist asymmetry, another cosmetic concern. Although DVBD has been evaluated in the thoracic spine, little is known about its impact on the lumbar spine. The authors investigated the outcomes of DVBD on the lumbar prominence. METHODS: A prospectively collected multicenter database was queried for pediatric patients with AIS and Lenke Type 5 curves. All patients who underwent thoracoplasty procedures were excluded. A total of 34 patients underwent surgical correction via a posterior-only approach using pedicle screw constructs. Nineteen patients underwent concurrent DVBD, and the remaining 15 patients served as a control group and did not undergo DVBD. All patients had a minimum of 2 years of follow-up. RESULTS: The mean age of the entire cohort was 14.9 ± 2.3 years, and the majority of patients were female (88%). All patients had Lenke Type 5C curves with a mean major curve of 46.0° ± 8.7°, which corrected to 13.7° ± 7.2° (70% correction). A mean of 10.7 ± 3.0 levels were fused. Only thoracic kyphosis was significantly different between the groups preoperatively. Similarly, postoperative radiographic parameters were comparable between the groups, with equivalent percentages of correction. Although improvement in the thoracic rib hump was comparable between the groups, the DVBD group had 56.2% correction of the lumbar prominence, and the control group had 76% improvement (p = 0.05). CONCLUSIONS: Although DVBD has been a valuable tool in the management of AIS, the authors' results suggest that its application for thoracolumbar curves may be limited. Further analysis with a larger cohort is required to better ascertain the impact of DVBD on thoracolumbar curves.

The -258A/G (SNP rs12885300) polymorphism of the human type 2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH.

OBJECTIVE: Type 2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The -258A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of -258A/G polymorphism on intrathyroidal thyroxine (T(4)) to triiodothyronine (T(3)) conversion and thyroid hormone (TH) secretion pattern, we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland. DESIGN: Retrospective analysis. METHODS: The TH secretion in response to 500  µg i.v. TRH injection was studied in 45 healthy volunteers. RESULTS: Twenty-six subjects (16 females and ten males, 32.8 ± 10.4 years) were homozygous for the ancestral (-258A/A) allele and 19 (11 females and eight males, 31.1 ± 10.9 years) were carriers of the (-258G/x) variant. While no differences in the peak TSH and T(3) levels were observed, carriers of the -258G/x allele showed a blunted rise in free T(4) (FT(4); P<0.01). The -258G/x92Thr/Thr haplotype, compared with the other groups, had lower TSH values at 60  min (P<0.03). No differences were observed between genotypes in baseline TH levels. CONCLUSIONS: The -258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated FT(4) secretion with a normal T(3) release from the thyroid gland consistent with a shift in the reaction equilibrium toward the product. These data indicate that the -258G DIO2 polymorphism causes changes in the pattern of hormone secretion. These findings are a proof of concept that common polymorphisms in DIO2 can subtly affect the circulating levels of TH and might modulate the TH homeostasis.

The Thr92Ala 5' type 2 deiodinase gene polymorphism is associated with a delayed triiodothyronine secretion in response to the thyrotropin-releasing hormone-stimulation test: a pharmacogenomic study.

BACKGROUND: The common Thr92Ala D2 polymorphism has been associated with changes in pituitary-thyroid axis homeostasis, but published results are conflicting. To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion, we designed prospective pharmacogenomic intervention aimed to detect differences in T3 levels after thyrotropin (TSH)-releasing hormone (TRH)-mediated TSH stimulation of the thyroid gland. METHODS: Eighty-three healthy volunteers were screened and genotyped for the Thr92Ala polymorphism. Fifteen volunteers of each genotype (Thr/Thr, Thr/Ala, and Ala/Ala) underwent a 500 mcg intravenous TRH stimulation test with serial measurements of serum total T3 (TT3), free T4, and TSH over 180 minutes. RESULTS: No differences in baseline thyroid hormone levels were seen among the study groups. Compared to the Thr/Thr group, the Ala/Ala group showed a significantly lower TRH-stimulated increase in serum TT3 at 60 minutes (12.07 ± 2.67 vs. 21.07 ± 2.86 ng/dL, p = 0.029). Thr/Ala subjects showed an intermediate response. Compared to Thr/Thr subjects, the Ala/Ala group showed a blunted rate of rise in serum TT3 as measured by mean time to 50% maximum delta serum TT3 (88.42 ± 6.84 vs. 69.56 ± 6.06 minutes, p = 0.028). Subjects attained similar maximal (180 minutes) TRH-stimulated TT3 levels. TRH-stimulated TSH and free T4 levels were not significantly different among the three genotype groups. CONCLUSIONS: The commonly occurring Thr92Ala D2 variant is associated with a decreased rate of acute TSH-stimulated T3 release from the thyroid consistent with a decrease in intrathyroidal deiodination. These data provide a proof of concept that the Thr92Ala polymorphism is associated with subtle changes in thyroid hormone homeostasis.