Blair Ford

There is increasing need for peer reviewers as the scientific literature grows. Formal education in biostatistics and research methodology during residency training is lacking. In this pilot study, we addressed these issues by evaluating a novel method of teaching residents about biostatistics and research methodology using peer review of standardized manuscripts. We hypothesized that mentored peer review would improve resident knowledge and perception of these concepts more than non-mentored peer review, while improving review quality. A partially blinded, randomized, controlled multi-center study was performed. Seventy-eight neurology residents from nine US neurology programs were randomized to receive mentoring from a local faculty member or not. Within a year, residents reviewed a baseline manuscript and four subsequent manuscripts, all with introduced errors designed to teach fundamental review concepts. In the mentored group, mentors discussed completed reviews with residents. Primary outcome measure was change in knowledge score between pre- and post-tests, measuring epidemiology and biostatistics knowledge. Secondary outcome measures included level of confidence in the use and interpretation of statistical concepts before and after intervention, and RQI score for baseline and final manuscripts. Sixty-four residents (82%) completed initial review with gradual decline in completion on subsequent reviews. Change in primary outcome, the difference between pre- and post-test knowledge scores, did not differ between mentored (−8.5%) and non-mentored (−13.9%) residents (p = 0.48). Significant differences in secondary outcomes (using 5-point Likert scale, 5 = strongly agree) included mentored residents reporting enhanced understanding of research methodology (3.69 vs 2.61; p = 0.001), understanding of manuscripts (3.73 vs 2.87; p = 0.006), and application of study results to clinical practice (3.65 vs 2.78; p = 0.005) compared to non-mentored residents. There was no difference between groups in level of interest in peer review (3.00 vs 3.09; p = 0.72) or the quality of manuscript review assessed by the Review Quality Instrument (RQI) (3.25 vs 3.06; p = 0.50). We used mentored peer review of standardized manuscripts to teach biostatistics and research methodology and introduce the peer review process to residents. Though knowledge level did not change, mentored residents had enhanced perception in their abilities to understand research methodology and manuscripts and apply study results to clinical practice.

Background: To date, nine Parkinson disease (PD) genome-wide association studies in North American, European and Asian populations have been published. The majority of studies have confirmed the association of the previously identified genetic risk factors,SNCAandMAPT, and two studies have identified three new PD susceptibility loci/genes (PARK16, BST1andHLA-DRB5). In a recent meta-analysis of datasets from five of the published PD GWAS an additional 6 novel candidate genes (SYT11, ACMSD, STK39, MCCC1/LAMP3, GAKandCCDC62/HIP1R) were identified. Collectively the associations identified in these GWAS account for only a small proportion of the estimated total heritability of PD suggesting that an 'unknown' component of the genetic architecture of PD remains to be identified.Methods: We applied a GWAS approach to a relatively homogeneous Ashkenazi Jewish (AJ) population from New York to search for both 'rare' and 'common' genetic variants that confer risk of PD by examining any SNPs with allele frequencies exceeding 2%. We have focused on a genetic isolate, the AJ population, as a discovery dataset since this cohort has a higher sharing of genetic background and historically experienced a significant bottleneck. We also conducted a replication study using two publicly available datasets from dbGaP. The joint analysis dataset had a combined sample size of 2,050 cases and 1,836 controls.Results: We identified the top 57 SNPs showing the strongest evidence of association in the AJ dataset (p < 9.9 × 10^-5). Six SNPs located within gene regions had positive signals in at least one other independent dbGaP dataset:LOC100505836(Chr3p24),LOC153328/SLC25A48(Chr5q31.1),UNC13B(9p13.3),SLCO3A1(15q26.1),WNT3(17q21.3) andNSF(17q21.3). We also replicated published associations for the gene regionsSNCA(Chr4q21; rs3775442, p = 0.037),PARK16(Chr1q32.1; rs823114 (NUCKS1), p = 6.12 × 10^-4),BST1(Chr4p15; rs12502586, p = 0.027),STK39(Chr2q24.3; rs3754775, p = 0.005), andLAMP3(Chr3; rs12493050, p = 0.005) in addition to the two most common PD susceptibility genes in the AJ populationLRRK2(Chr12q12; rs34637584, p = 1.56 × 10^-4) andGBA(Chr1q21; rs2990245, p = 0.015).Conclusions: We have demonstrated the utility of the AJ dataset in PD candidate gene and SNP discovery both by replication in dbGaP datasets with a larger sample size and by replicating association of previously identified PD susceptibility genes. Our GWAS study has identified candidate gene regions for PD that are implicated in neuronal signalling and the dopamine pathway.

Parkinson's disease is characterized primarily as a neurodegenerative disorder that leads to disabling motor and cognitive impairment. PD is less widely appreciated as a disease causing a substantial variety of pain syndromes, although the prevalence of pain in PD is approximately 40%. In a minority of patients, pain is so severe and intractable that it overshadows the motor symptoms of the disorder. In recent years, descriptive surveys of non‐motor symptoms in PD have led to a classification of painful sensations into one or more of several categories: musculoskeletal pain, radicular or neuropathic pain, dystonia‐related pain, akathitic discomfort, and primary, central parkinsonian pain. A framework for diagnosing and treating painful PD is described in this review, together with recent insignts into the neurophysiological mechanisms and substrates of pain in PD. © 2010 Movement Disorder Society

Objective: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson’s disease. Design: Open label follow up using blinded ratings of videotaped neurological examinations. Patients: 30 patients with advanced Parkinson’s disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias. Main outcome measures: Unified Parkinson’s disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire. Results: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (pConclusions: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity.