Evaluation of editors' abilities to predict the citation potential of research manuscripts submitted to The BMJ: a cohort study.

OBJECTIVE: To evaluate the ability of The BMJ editors to predict the number of times submitted research manuscripts will be cited. DESIGN: Cohort study. SETTING: Manuscripts submitted to The BMJ, reviewed, and subsequently scheduled for discussion at a prepublication meeting between 27 August 2015 and 29 December 2016. PARTICIPANTS: 10 BMJ research team editors. MAIN OUTCOME MEASURES: Reviewed manuscripts were rated independently by attending editors for citation potential in the year of first publication plus the next year: no citations, below average (<10 citations), average (10-17 citations), or high (>17 citations). Predicted citations were subsequently compared with actual citations extracted from Web of Science (WOS). RESULTS: Of 534 manuscripts reviewed, 505 were published as full length articles (219 in The BMJ) by end of 2019 and indexed in WOS, 22 were unpublished, and one abstract was withdrawn. Among the 505 manuscripts, the median (IQR [range]) number of citations in the year of publication plus the following year was 9 (4-17 [0-150]); 277 (55%) manuscripts were cited <10 times, 105 (21%) were cited 10-17 times, and 123 (24%) cited >17 times. Manuscripts accepted by The BMJ were cited more highly (median 12 (IQR 7-24) citations) than those rejected (median 7 (3-12) citations). For all 10 editors, predicted ratings tended to increase in line with actual citations, but with considerable variation within categories; nine failed to identify the correct citation category for >50% (range 31%-52%) of manuscripts, and κ ranged between 0.01 to 0.19 for agreement between predicted and actual categories. Editors more often rated papers that achieved high actual citation counts as having low citation potential than the reverse. Collectively, the mean percentage of editors predicting the correct citation category was 43%, and for 160 (32%) manuscripts at least 50% of editors predicted the right category. CONCLUSIONS: Editors weren't good at estimating the citation potential of manuscripts individually or as a group; there is no wisdom of the crowd when it comes to BMJ editors.

The cross-sectional area of the vagus nerve is not reduced in Parkinson's disease patients.

Background: Recent studies have revealed the importance of the gut brain axis in the development of Parkinson's disease (PD). It has also been suggested that the cross-sectional area (CSA) of the vagus nerve can be used in the diagnosis of PD. Here, we hypothesize that the CSA of the vagus nerve is decreased in PD patients compared to control participants. Methods: In this study we measured the CSA of the vagus nerve on both sides in 31 patients with PD and 51 healthy controls at the level of the common carotid artery using high-resolution ultrasound. Results: The mean CSA of the left vagus nerve in the PD and the control group was respectively 2.10 and 1.90 and of the right respectively 2.54 and 2.24 mm2. There is no difference in CSA of the vagus nerve in PD patients compared to controls (p = .079). The mean CSA of the right vagus nerve was significantly larger than the left (p < .001). Age, sex and autonomic symptoms were no significant predictors of the CSA of the vagus nerve. Conclusion: These findings show that the CSA of the vagus nerve using ultrasonography is not a reliable diagnostic tool in the diagnosis of PD.

Transcranial sonography findings related to depression in parkinsonian disorders: cross-sectional study in 126 patients.

Background. Transcranial sonography (TCS) has emerged as a potential diagnostic tool for Parkinson's disease. Recent research has suggested that abnormal echogenicity of substantia nigra, raphe nuclei and third ventricle is associated with increased risk of depression among these patients. We sought to reproduce these findings in an ongoing larger study of patients with parkinsonian syndromes. Methods. A total of 126 patients with parkinsonian symptoms underwent the Hamilton Depression Scale, and TCS of the substantia nigra (SN) (n = 126), the raphe nuclei (RN) (n = 80) and the third ventricle (n = 57). We then calculated the correlation between depression and hyper-echogenic SN, hypo-echogenic RN and a wider third ventricle. Results. In patients with PD we found no significant difference of the SN between non-depressed and depressed patients (46% vs. 22%; p = 0.18). Non-depressed patients with other parkinsonisms more often had hyperechogenicity of the SN than depressed patients (51% vs. 0%; p = 0.01). We found no relation between depression and the echogenicity of the RN or the width of the third ventricle. Conclusions. In patients with parkinsonian syndromes, we found no association between depression and hyper-echogenic SN, hypo-echogenic RN or a wider third ventricle, as determined by transcranial sonography.

Abnormal Echogenicity of the Substantia Nigra, Raphe Nuclei, and Third-Ventricle Width as Markers of Cognitive Impairment in Parkinsonian Disorders: A Cross-Sectional Study.

Background. Patients with Parkinson's disease (PD) have a high risk of cognitive problems. Objective. This study assesses whether abnormal echogenicity of the substantia nigra (SN) and raphe nuclei (RN) and the diameter of third ventricle are markers of cognitive impairment in patients with PD and other forms of parkinsonism. Methods. 126 outpatients with early signs of parkinsonism underwent transcranial sonography (TCS). The scales for the outcome of Parkinson's disease cognition (SCOPA-COG) were used as cognitive measure. Definite neurological diagnosis was established after two-year follow-up. Results. One-third of the patients with PD and half of those with APS had signs of cognitive impairment. The echogenicity of the SN was not related to cognitive impairment. The diameter of the third ventricle was significantly larger in PD patients with cognitive impairment compared to those without. In patients with APS we found a significantly higher frequency of hypoechogenic RN in patients with cognitive problems. Conclusions. Cognitive impairment is already present in a substantial proportion of patients with PD and APS at first referral. In patients with APS the frequency of hypoechogenic RN points to the direction of other pathophysiology with more emphasis on deficits in the serotonergic neurotransmitter system. The larger diameter of the third ventricle in PD patients with cognitive impairment may reflect Alzheimer like brain atrophy, as has been reported in earlier studies.

Diffuse large B-cell lymphoma of the cauda equina.

Primary central nervous system (CNS) lymphoma is a rare form of non-Hodgkin's lymphoma. The clinical presentation is variable, depending on its localisation within the nervous system. Only 1% of primary CNS lymphoma emerges in the spinal cord, and the prevalence of primary lymphoma of the cauda equina is unknown, but probably even rarer. Diagnosing primary lymphoma of the cauda equina is difficult, since it can mimic other more common disorders such as a herniated disc, especially in its early stages. Here we present two cases of primary cauda equina lymphoma in which diagnostic work up took a long time, as the final diagnosis was only reached after a nerve root biopsy.

Risk of fracture in patients with Charcot-Marie-Tooth disease.

INTRODUCTION: In this study we evaluated fracture risk in patients with Charcot-Marie-Tooth (CMT) disease. METHODS: We conducted a retrospective cohort study using the UK Clinical Practice Research Datalink (1987-2012). Each patient with CMT disease was matched with up to 6 patients without a history of CMT disease. The outcome measure was fractures. RESULTS: The risk of non-osteoporotic fracture was statistically significantly increased [adjusted hazard ratio (AHR) 1.47, 95% confidence interval (CI) 1.01-2.14], whereas risk of any and osteoporotic fracture did not reach statistical significance compared with control patients [AHR 1.31 (95% CI 0.98-1.74) and AHR 1.10 (95% CI 0.69-1.74), respectively]. CONCLUSIONS: CMT patients have a 1.5-fold increased risk for non-osteoporotic fracture. Studies with larger numbers of CMT patients and with additional data on CMT subtype, bone mineral density, and functional status should be performed to confirm a true association between CMT and an increased risk of fracture.

Five-year fracture risk estimation in patients with Parkinson's disease.

BACKGROUND: Previous studies have shown that patients with Parkinson's disease (PD) are at increased risk of fractures. However, no specific prediction model for fracture estimation among PD patients is currently available. Therefore, the aim of this study was to develop a simple score for estimating the 5-year osteoporotic and hip fracture risks among patients with PD. METHODS: The U.K. Clinical Practice Research Datalink (1987-2011) was used to identify incident PD patients. Cox proportional-hazards models were used to calculate the 5-year risks of osteoporotic and hip fracture among PD patients. The regression model was fitted with various risk factors for fracture and the final Cox model was converted into integer risk scores. RESULTS: We identified 4411 incident PD patients without a history of osteoporotic treatment. The 5-year risks of osteoporotic and hip fracture were plotted in relation to the risk score. Risk scores increased with age, female gender, history of renal disease and history of dementia. The C-statistic, which is a parameter to test the internal validity of the model, was reasonable for the prediction of osteoporotic fracture (0.69) and hip fracture (0.73). CONCLUSION: In this study, we developed a simple model to estimate 5-year fracture risk among incident PD patients. It may be useful in daily practice after external validation.

Motor outcomes during hospitalization in Parkinson's disease patients: a prospective study.

BACKGROUND: Retrospective studies suggest that many Parkinson's disease patients have a worsening of their motor status during hospitalization. We aimed to quantify this prospectively, and study possible contributing factors. METHODS: Over one year we included all consecutive Parkinson's disease patients, newly admitted to a Dutch teaching hospital. We analyzed complications, interventions, and medication distribution. At inclusion and at discharge we assessed the motor status with the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). RESULTS: 48% of 46 admitted patients had complications, mainly confusion/delirium (24%) and infections (15%). At discharge 28% of the patients had a worse motor function with a mean increase of more than 5 points on the UPDRS-III. Medication errors occurred in 39%. This is the most important risk factor (p < 0.000) for motor function deterioration, followed by infections during hospitalization, and not being in control of own Parkinson's disease medication. 24% of patients were allowed to take control of their own Parkinson's disease medication, none of these patients did deteriorate. CONCLUSIONS: This prospective study shows that a substantial part of hospitalized PD patients has a significant worse motor function at discharge mainly due to medication errors and infections. Quality of care could be improved by addressing preventable errors and allow patients to take control of their own Parkinson's disease medication.

Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson's disease: prospective cohort study in 196 patients.

OBJECTIVE: Numerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated. DESIGN: Prospective cohort study for diagnostic accuracy. SETTING: Neurology outpatient clinics of two teaching hospitals in the Netherlands. PATIENTS: 196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a (123)I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176). OUTCOME MEASURES: After 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study. RESULTS: Temporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84. CONCLUSIONS: The diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use. CLINICALTRIALS.GOV IDENTIFIER: NCT0036819.

Neurologists' diagnostic accuracy of depression and cognitive problems in patients with parkinsonism.

BACKGROUND: Depression and cognitive impairment (CI) are important non-motor symptoms in Parkinson's Disease (PD) and related syndromes, but it is not clear how well they are recognised in daily practice. We have studied the diagnostic performance of experienced neurologists on the topics depression and cognitive impairment during a routine encounter with a patient with recent-onset parkinsonian symptoms. METHODS: Two experienced neurologists took the history and examined 104 patients with a recent-onset parkinsonian disorder, and assessed the presence of depression and cognitive impairment. On the same day, all patients underwent a Hamilton Depression Rating Scale test, and a Scales for Outcomes in Parkinson's Disease-Cognition-test (SCOPA-COG). RESULTS: The sensitivity of the neurologists for the topic depression was poor: 33.3%. However, the specificity varied from 90.8 to 94.7%. The patients' sensitivity was higher, although the specificity was lower. On the topic CI, the sensitivity of the neurologists was again low, in a range from 30.4 up to 34.8%: however the specificity was high, with 92.9%. The patients' sensitivity and specificity were both lower, compared to the number of the neurologists. CONCLUSIONS: Neurologists' intuition and clinical judgment alone are not accurate for detection of depression or cognitive impairment in patients with recent-onset parkinsonian symptoms because of low sensitivity despite of high specificity. TRIAL REGISTRATION: (ITRSCC)NCT0036819.

Deterioration of Parkinson's disease during hospitalization: survey of 684 patients.

BACKGROUND: A substantial fraction of Parkinson's disease patients deteriorate during hospitalisation, but the precise proportion and the reasons why have not been studied systematically and the focus has been on surgical wards and on Accident & Emergency departments. We assessed the prevalence and risk factors of deterioration of Parkinson's disease symptoms during hospitalization, including all wards. METHODS: We invited Parkinson's disease patients from three neurology departments in The Netherlands to answer a standardised questionnaire on general, disease and hospital related issues. Patients who had been hospitalized in the previous year were included and analysed. Possible risk factors for Parkinson's disease deterioration were identified. Proportions were analysed using the Chi-Square test and a logistic regression analysis was performed. RESULTS: Eighteen percent of 684 Parkinson's disease patients had been hospitalized at least once in the last year. Twenty-one percent experienced deterioration of motor symptoms, 33% did have one or more complications and 26% had received incorrect anti-Parkinson's medication. There were no statistically significant differences for these variables between admissions on neurologic or non-neurologic wards and between having surgery or not. Incorrect medication during hospitalization was significantly associated with higher risk (OR 5.8, CI 2.5-13.7) of deterioration, as were having infections (OR 6.7 CI 1.8-24.7). A higher levodopa equivalent dose per day was a significant risk factor for deterioration. When adjusting for different variables, wrong medication distribution was the most important risk factor for deterioration. CONCLUSIONS: Incorrect medication and infections are the important risk factors for deterioration of Parkinson's disease patients both for admissions with and without surgery and both for admissions on neurologic and non-neurologic wards. Measures should be taken to improve care and incorporated in guidelines.

Prevalence of pain in Parkinson's disease: a systematic review using the modified QUADAS tool.

Pain has been studied more intensely as a symptom of Parkinson's disease (PD) in recent years. However, studies on the characteristics and prevalence of pain in PD have yielded conflicting results, prompting us to do a systematic review of the literature. A systematic review of the literature was conducted, using different databases. The last inclusion date was March 15, 2011. The modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used, which is especially designed for judging prevalence studies on their methodological quality. Only articles that met the predefined criteria were used in this review. We found 18 articles, of which only 8 met the methodological criteria. Prevalence frequency ranges from 40% to 85% with a mean of 67.6%. Pain is most frequently located in the lower limbs, with almost one-half of all PD patients complaining about musculoskeletal pain (46.4%). The pain fluctuates with on-off periods. Surprisingly, only 52.4% of PD patients with pain used analgesics, most often nonopioids. PD patients seem to be predisposed to develop pain and physicians should be aware of pain as a common feature of PD. As many as one-half of PD patients with pain may be missing out on a potentially useful treatment, and proper treatment could increase quality of life in PD patients.

Clinical problems in the hospitalized Parkinson's disease patient: systematic review.

The problems Parkinson's disease (PD) patients encounter when admitted to a hospital, are known to be numerous and serious. These problems have been inventoried through a systematic review of literature on reasons for emergency and hospital admissions in PD patients, problems encountered during hospitalization, and possible solutions for the encountered problems using the Pubmed database. PD patients are hospitalized in frequencies ranging from 7 to 28% per year. PD/parkinsonism patients are approximately one and a half times more frequently and generally 2 to 14 days longer hospitalized than non-PD patients. Acute events occurring during hospitalization were mainly urinary infection, confusion, and pressure ulcers. Medication errors were also frequent adverse events. During and after surgery PD patients had an increased incidence of infections, confusion, falls, and decubitus, and 31% of patients was dissatisfied in the way their PD was managed. There are only two studies on medication continuation during surgery and one analyzing the effect of an early postoperative neurologic consultation, and numerous case reports, and opinionated views and reviews including other substitutes for dopaminergic medication intraoperatively. In conclusion, most studies were retrospective on small numbers of patients. The major clinical problems are injuries, infections, poor control of PD, and complications of PD treatment. There are many (un-researched) proposals for improvement. A substantial number of PD patients' admissions might be prevented. There should be guidelines concerning the hospitalized PD patients, with accent on early neurological consultation and team work between different specialities, and incorporating nonoral dopaminergic replacement therapy when necessary.

Neuroanatomical correlates of apathy in Parkinson's disease: A magnetic resonance imaging study using voxel-based morphometry.

Apathy is generally defined as a disorder of motivation and is considered one of the most common neuropsychiatric disturbances in Parkinson's disease (PD). Only few studies addressed the neuroanatomical correlates of apathy in PD. The aim of this article was to determine the structural correlates of apathy in PD patients. Fifty-five PD patients underwent a neuropsychiatric and neuropsychological examination, and a 3 T magnetic resonance imaging scan was acquired. A voxel-based multiple regression analysis was used to calculate correlation between gray matter density and severity measures of apathy. Apathy correlates with decreased cognitive functioning and more depressive symptoms but not with more severe motor symptoms. High apathy scores were correlated with low gray matter density values in a number of cortical brain areas: the bilateral precentral gyrus (BA 4, 6), the bilateral inferior parietal gyrus (BA 40), the bilateral inferior frontal gyrus (BA 44, 47), the bilateral insula (BA 13), the right (posterior) cingulate gyrus (BA 24, 30, 31), and the right precuneus (BA 31). Apathy in PD correlates with reduced gray matter density in a number of brain regions. The involvement of the cingulate gyrus and inferior frontal gyrus is in line with the results of earlier studies addressing apathy in patients with Alzheimer's disease or depressive disorder. Further studies addressing the pathogenesis of apathy are needed.

Transcranial duplex in the differential diagnosis of parkinsonian syndromes: a systematic review.

BACKGROUND: Transcranial duplex scanning (TCD) of the substantia nigra (SN) is increasingly used to diagnose Idiopathic Parkinson's Disease (IPD). Up until now 70 diagnostic studies have been published, not only on investigation of the SN, but also of the lenticular nucleus (LN) and the Raphe nuclei (RN). METHOD: We systematically reviewed all diagnostic TCD studies in parkinsonian patients up to June 2008. RESULTS: We found 35 eligible studies. Of the 1534 IPD patients investigated in the 35 studies 200 (13%) had an inconclusive SN-TCD. An increased echo-intensity of the SN was seen in 1167 (87%) of the 1334 IPD patients, 276 (12%) of the 2340 healthy controls and in 41 (30%) of the 138 patients with an atypical parkinsonian syndrome (APS). On the contrary, a pathological LNTCD was found more often in APS patients (79%) than in IPD patients (23%) and healthy controls (6%). A decreased echo-intensity of the RN was found more often in depressed (46%) than in non-depressed IPD patients (16%). CONCLUSIONS: SN-TCD accurately differentiates between patients with IPD and healthy controls, but not between patients with IPD and APS. LN-TCD is only moderate accurate to delineate IPD from APS, but combinations of SN- and LN-TCD may be more promising. RN-TCD has only marginal diagnostic accuracy in diagnosing depression in IPD and non-IPD patients. Before TCD can be implicated, more research is needed to standardize the TCD technique, to investigate the TCD in non-research settings and to determine the additional value of TCD compared with currently used clinical techniques like SPECT imaging.

Multivariable adjustments counteract spectrum and test review bias in accuracy studies.

OBJECTIVES: The STAndards for Reporting studies of Diagnostic accuracy (STARD) for investigators and editors and the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) for reviewers and readers offer guidelines for the quality and reporting of test accuracy studies. These guidelines address and propose some solutions to two major threats to validity: spectrum bias and test review bias. STUDY DESIGN AND SETTING: Using a clinical example, we demonstrate that these solutions fail and propose an alternative solution that concomitantly addresses both sources of bias. We also derive formulas that prove the generality of our arguments. RESULTS: A logical extension of our ideas is to extend STARD item 23 by adding a requirement for multivariable statistical adjustment using information collected in QUADAS items 1, 2, and 12 and STARD items 3-5, 11, 15, and 18. CONCLUSION: We recommend reporting not only variation of diagnostic accuracy across subgroups (STARD item 23) but also the effects of the multivariable adjustments on test performance. We also suggest that the QUADAS be supplemented by an item addressing the appropriateness of statistical methods, in particular whether multivariable adjustments have been included in the analysis.