Do Parkinson's disease patients disclose their adverse events spontaneously?

PubMed

Perez-Lloret, Santiago; Rey, María Verónica; Fabre, Nelly; Ory, Fabienne; Spampinato, Umberto; Montastruc, Jean-Louis; Rascol, Olivier

2012-05-01

Underreporting of adverse drug reactions is common but has been rarely studied in Parkinson's disease (PD). To compare the prevalence of adverse events (AEs) in relation to antiparkinsonian drugs in PD patients using two different data collection methods: patient's spontaneous reporting versus a predefined investigator-driven structured interview. Secondary objectives were to assess factors related to spontaneous reporting and to compare the rate of AE reporting in PD patients with that of a group of non-parkinsonian post-stroke patients. Cross-sectional study. Ambulatory, cognitively intact PD or post-stroke outpatients. None. Patients were first asked by means of an an open question to disclose any unpleasant effects in connection with their current medications that had occurred during the previous week. Afterwards, a predefined questionnaire listing the most common AEs known to be related to antiparkinsonian drugs was used to question the same patients in a systematic manner about the presence of any AE during the same week. Chronological and semiological criteria were used to classify the reported AEs as "unrelated" or "possibly/plausibly related" to the antiparkinsonian treatment. A total of 203 PD and 52 post-stroke patients of comparable age and sex were recruited. Eighty-five PD and five post-stroke patients reported spontaneously at least one AE (42 vs. 10%, p < 0.01), while 203 PD and 47 post-stroke patients reported at least one AE following the structured questionnaire (100 vs. 90%, p < 0.001). In PD patients, there were a total of 112 spontaneously reported AEs as compared with 1,574 according to the structured questionnaire (7%). Spontaneous disclosure of AEs was associated with experiencing >2 AEs [OR = 1.2 (1.1-3.2)], logistic regression). Seventy-four percent of PD patients had ≥1 AE possibly/plausibly related to antiparkinsonian drugs. Results showed that only 7% of AEs were reported spontaneously by patients, thus underscoring the importance of systematically asking about AEs in PD patients.

Impaired frontal lobe functions in patients with Parkinson's disease and psychosis.

PubMed

Thota, Naveen; Lenka, Abhishek; George, Lija; Hegde, Shantala; Arumugham, Shyam Sundar; Prasad, Shweta; Stezin, Albert; Kamble, Nitish; Yadav, Ravi; Pal, Pramod Kumar

2017-12-01

Patients with Parkinson's disease (PD) may develop several non-motor symptoms (NMS). Psychosis is one of the debilitating NMS of PD. The neurobiology of psychosis is not fully understood. This study aims to compare the frontal lobe functions of PD patients with and without psychosis using the Frontal Assessment Battery (FAB). This study included 69 patients with PD; 34 with psychosis (PD-P) and 35 without psychosis (PD-NP). Mini Mental Status Examination (MMSE) was used to screen for cognitive impairment. Unified Parkinson's disease Rating scale part-III (UPDRS-III) was used to measure the severity and Hoehn and Yahr score (H&Y) was used to measure the stage of PD. Frontal lobe functions were assessed by FAB. The PD-P and PD-NP groups were comparable for age (58.7±8.4 vs 55.7±8.2, p=0.14), age at onset of symptoms (51.4±8.1 vs 50.0±8.8, p=0.48), gender distribution (men: 88%vs 80%, p=0.51), MMSE (28.2±1.9 vs 28.7±1.2 p=0.12), levodopa equivalent dose/day (736.0±376.3 vs 625.2±332.2, p=0.19), UPDRS-III OFF-score (36.7±8.8 vs 35.4±13.2, p=0.64), UPDRS-III ON-score (13.2±5.4 vs 12.4±6.6, p=0.44) and H&Y stage (2.3±0.3 vs 2.3±0.3, p=0.07). PD-P group had lower total FAB score compared to PD-NP group (13.9±2.2 vs 16.5±1.8, p<0.01). On the FAB, PD-P group had lower scores compared to PD-NP in lexical fluency (FAB-2), programming (FAB-3), sensitivity to interference (FAB-4) and inhibitory control (FAB-5). Patients with PD-P had significant frontal lobe dysfunction compared to PD-NP. FAB may be a simple and useful bedside tool to assess frontal dysfunction in patients with PD in a busy neurological set up. Copyright © 2017 Elsevier B.V. All rights reserved.

Risk factors of periodontal disease in maintenance hemodialysis patients

PubMed Central

Hou, Yue; Wang, Xin; Zhang, Cong-Xiao; Wei, Yu-Dan; Jiang, Li-Li; Zhu, Xiao-Yu; Du, Yu-Jun

2017-01-01

Abstract To explore the characteristics and relevant risk factors of periodontal disease (PD) among hemodialysis patients. Uremic patients on maintenance hemodialysis from November 2015 to March 2016 were retrospectively reviewed. Patients were divided into a PD group and a non-PD group. Demographic and laboratory data were collected and analyzed. In all, 136 uremic patients (79 males and 57 females, aged 50.8 ± 15.3 years) on maintenance hemodialysis were included in this study. The incidence of PD increased with age. Hemodialysis patients most likely developed PD if they were male, smokers, or diabetic (P = .009, <.001, and <.001, respectively). Patients brushing their teeth twice daily had significantly less chance of developing PD as compared with those only brushing once daily (P < .001). Hemodialysis patients in the PD group had significantly higher levels of total cholesterol, high-sensitivity C-reactive protein, fasting blood glucose, and peripheral white blood cell counts, compared with the non-PD group (all P < .001). Logistic regression analysis revealed that diabetes, total cholesterol, high-sensitivity C-reactive protein, and peripheral white blood cell count were independent risk factors for developing PD, whereas teeth brushing twice daily and serum calcium were favorable factors for maintenance hemodialysis patients against PD. Identification of risk factors provides a theoretical basis for prevention and improvement of PD among maintenance hemodialysis patients. PMID:28858105

Decreased NURR1 gene expression in patients with Parkinson’s disease

PubMed Central

Le, Weidong; Pan, Tianhong; Huang, Maosheng; Xu, Pingyi; Xie, Wenjie; Zhu, Wen; Zhang, Xiong; Deng, Hao; Jankovic, Joseph

2008-01-01

NURR1 is a transcription factor essential for the development, survival, and functional maintenance of midbrain dopaminergic (DAergic) neurons and NURR1 is a potential susceptibility gene for Parkinson’s disease (PD). To determine whether NURR1 gene expression is altered in patients with PD we measured its expression in human peripheral blood lymphocytes (PBL) in 278 patients with PD, 166 healthy controls (HC), and 256 neurological disease controls (NDC) by quantitative real-time PCR. NURR1 gene expression was significantly decreased in patients with PD (particularly those with family history of PD) as compared with HC (p < 0.01) and also as compared with NDC (p < 0.05). There was no significant difference in NURR1 gene expression among PD patients with or without anti-PD medications. When adjusted for gender, age, and ethnicity, lower levels of NURR1 gene expression were associated with significantly increased risk for PD in women, in patients 60 years old or older, and in patients of Caucasian origin. The observed reduction in PBL NURR1 gene expression indicates possible systemic involvement in PD, and the finding may help identify individuals with PD and other disorders associated with impaired central DAergic system. PMID:18684475

Qualitative Characteristics of Depression in Parkinson's Patients and Controls.

PubMed

Kritzinger, Cleo; Vollstedt, Eva-Juliane; Hückelheim, Katja; Lorwin, Anne; Graf, Julia; Tunc, Sinem; Klein, Christine; Kasten, Meike

2015-01-01

Depression is common in Parkinson's disease (PD); in light of typical PD pathology it may differ phenomenologically from depression in the general population. To assess depressive symptoms in PD patients and control groups and compare symptom profiles. After postal screening of 10,000 citizens of Lübeck, 642 participants were examined and the Beck Depression Inventory (BDI) was sufficiently answered by 477 subjects. Based on motor examinations, we distinguished PD patients, Healthy Controls (HC, no motor impairment), and Disease Controls (DC, motor impairment other than PD). The sample comprised 331 men and 311 women, aged 65 ± 8 years. Out of the overall sample, 198 (41.5%) had a BDI score ≥9. BDI results above 9 points occurred in 34.5% of HC, 50.3% of DC, and 42.4% of PD patients. Compared to the control groups (HC, DC) the PD patients endorsed more "dissatisfaction" and "loss of appetite" but less "feelings of guilt," "self-hate," and "loss of libido." Depressive symptoms are more frequent in PD patients compared to HC but not DC. Interestingly, the distribution of individual symptoms of the BDI differs between groups with an emphasis on loss of pleasure/enjoyment in the PD group, a symptom typically considered to be dopaminergically transmitted.

Antidepressant Studies in Parkinson’s Disease

PubMed Central

Weintraub, Daniel; Morales, Knashawn H.; Moberg, Paul J.; Bilker, Warren B.; Balderston, Catherine; Duda, John E.; Katz, Ira R.; Stern, Matthew B.

2007-01-01

The objective of this study was to determine effect sizes for both antidepressant treatment and placebo for depression in Parkinson’s disease (PD), and to compare the findings with those reported in elderly depressed patients without PD. Recent reviews have concluded that there is little empiric evidence to support the use of antidepressants in PD; however, available data has not been analyzed to determine the effect size for antidepressant treatment in PD depression. A literature review identified antidepressant studies in PD. Suitable studies were analyzed using meta-analytic techniques, and effect sizes were compared with those from antidepressant studies in elderly patients without PD. Large effect sizes were found for both active treatment and placebo in PD, but there was no difference between the two groups. In contrast, active treatment was superior to placebo in depressed elderly patients without PD. In PD, increasing age and a diagnosis of major depression were associated with better treatment response. Results also suggest that newer antidepressants are well tolerated in PD. Despite the high prevalence of depression and antidepressant use in PD, controlled treatment research has been almost non-existent. Meta-analysis results suggest a large but nonspecific effect for depression treatment in PD. In addition, PD patients may benefit less from antidepressant treatment, particularly selective serotonin reuptake inhibitors, than do elderly patients without PD. PMID:15954137

How to address barriers to peritoneal dialysis in the elderly.

PubMed

Brown, Edwina A

2011-03-01

Older patients on dialysis have unique needs and characteristics and their outcomes vary from that of their younger counterparts. Comparatively fewer will start or be maintained on peritoneal dialysis (PD) compared to younger patients, despite the fact that hemodialysis is often poorly tolerated. Barriers to PD for older patients include poor vision, frailty, cognitive dysfunction, accommodation issues, and a bias from renal teams that older patients cannot do PD. The development of assisted PD can overcome many of these barriers. The ability of older patients to use PD as their dialysis modality should not be determined by whether they live in an area where the nephrologist is a PD enthusiast. All patients should be given nonbiased information so they can choose the dialysis modality that gives them the best quality of life and suits their and their family's lifestyle.

Hemodialysis and peritoneal dialysis are associated with similar outcomes for end-stage renal disease treatment in Canada.

PubMed

Yeates, Karen; Zhu, Naisu; Vonesh, Edward; Trpeski, Lilyanna; Blake, Peter; Fenton, Stanley

2012-09-01

There were 35 265 patients receiving renal replacement therapy in Canada at the end of 2007 with 11.0% of patients on peritoneal dialysis (PD) and 48.9% on hemodialysis (HD) and a remaining 40.1% living with a functioning kidney transplant. There are no contemporary studies examining PD survival relative to HD in Canada. The objective was to compare survival outcomes for incident patients starting on PD as compared to HD in Canada. Using data from the Canadian Organ Replacement Register, the Cox proportional hazards (PH) model was employed to study survival outcomes for patients initiating PD as compared to HD in Canada from 1991 to 2004 with follow-up to 31 December 2007. Comparisons of outcomes were made between three successive calendar periods: 1991-95, 1996-2000 and 2001-04 with the relative risk of death of incident patients calculated using an intent-to-treat (ITT) analysis with proportional and non-PH models using a piecewise exponential survival model to compare adjusted mortality rates. In the ITT analysis, overall survival for the entire study period favored PD in the first 18 months and HD after 36 months. However, for the 2001-04 cohort, survival favored PD for the first 2 years and thereafter PD and HD were similar. Among female patients > 65 years with diabetes, PD had a 27% higher mortality rate. Overall, HD and PD are associated with similar outcomes for end-stage renal disease treatment in Canada.

Parkinson's disease psychosis: symptoms, management, and economic burden.

PubMed

Hermanowicz, Neal; Edwards, Kari

2015-08-01

Parkinson’s disease psychosis (PDP) is a costly,debilitating condition that generally develops several years after diagnosis of Parkinson’s disease (PD).PD is the second-most common neurodegenerative disease, and it imposes a significant burden on the healthcare system. Non-motor symptoms commonly manifest in PD, contributing to the severity of a patient’s disability. The neuropsychiatric symptoms that are common in PD can be a significant source of distress to patients and caregivers. Recent studies have shown that more than 50% of patients with PD will develop psychosis at some time over the course of the disease. The responsibility for caring for a person with PDP frequently falls on family members. Caregiver distress is frequently predicted when patients with PD have symptoms of psychosis.Hallucinations and delusions are independent predictors of nursing home placement for patients with PDP. The authors sought to examine total healthcare expenditures among patients with PDP compared with patients with PD without psychosis.All costs were higher for patients with PDP than for those with PD without psychosis and all-Medicare cohorts, with the highest cost differentials found in long-term care costs ($31,178 for PDP vs $14,461 forPD without psychosis), skilled nursing facility costs($6601 for PDP vs $2067 for PD without psychosis),and inpatient costs ($10,125 for PDP vs $6024 for PD without psychosis). Patients with PDP spent an average of 179 days in long-term care, compared with 83 days for patients with PD without psychosis. As expected, long-term care utilization and expenditures were significantly higher for patients with PDP than for patients with PD without psychosis. Reducing long-term care utilization by patients with PDP may significantly lower the overall economic burden associated with PDP.

Gut microbiota in patients with Parkinson's disease in southern China.

PubMed

Lin, Aiqun; Zheng, Wenxia; He, Yan; Tang, Wenli; Wei, Xiaobo; He, Rongni; Huang, Wei; Su, Yuying; Huang, Yaowei; Zhou, Hongwei; Xie, Huifang

2018-05-16

Accumulating evidence has revealed alterations in the communication between the gut and brain in patients with Parkinson's disease (PD), and previous studies have confirmed that alterations in the gut microbiome play an important role in the pathogenesis of numerous diseases, including PD. The aim of this study was to determine whether the faecal microbiome of PD patients in southern China differs from that of control subjects and whether the gut microbiome composition alters among different PD motor phenotypes. We compared the gut microbiota composition of 75 patients with PD and 45 age-matched controls using 16S rRNA next-generation-sequencing. We observed significant increases in the abundance of four bacterial families and significant decreases in the abundance of seventeen bacterial families in patients with PD compared to those of the controls. In particular, the abundance of Lachnospiraceae was reduced by 42.9% in patients with PD, whereas Bifidobacteriaceae was enriched in patients with PD. We did not identify a significant difference in the overall microbial composition among different PD motor phenotypes, but we identified the association between specific taxas and different PD motor phenotypes. PD is accompanied by alterations in the abundance of specific gut microbes. The abundance of certain gut microbes was altered depending on clinical motor phenotypes. Based on our findings, the gut microbiome may be a potential PD biomarker. Copyright © 2018 Elsevier Ltd. All rights reserved.

To rise and to fall: functional connectivity in cognitively normal and cognitively impaired patients with Parkinson's disease.

PubMed

Gorges, Martin; Müller, Hans-Peter; Lulé, Dorothée; Pinkhardt, Elmar H; Ludolph, Albert C; Kassubek, Jan

2015-04-01

Cognitive decline is a burdensome extra-motor symptom associated with Parkinson's disease (PD). This study aimed at investigating intrinsic functional connectivity (iFC) of the brain in cognitively unimpaired (PD-CU) and impaired PD patients (PD-CI) compared with age-matched healthy controls. "Resting-state" functional magnetic resonance imaging was acquired in 53 subjects, that is, 14 PD-CU patients, 17 PD-CI patients, and 22 control subjects. Cognition and cognitive status for patient classification were assessed using detailed neuropsychological testing. In PD-CU patients versus controls, we demonstrated significantly increased iFC (hyperconnectivity) presenting as network expansions in cortical, limbic, and basal ganglia-thalamic areas. Significantly, decreased iFC in PD-CI patients compared with control subjects was observed, predominantly between major nodes of the default mode network. In conclusion, the increased iFC might be the initial manifestation of altered brain function preceding cognitive deficits. Hyperconnectivity could be an adaptive (compensatory) mechanism by recruiting additional resources to maintain normal cognitive performance. As PD-related pathology progresses, functional disruptions within the default mode networks seem to be considerably associated with cognitive decline. Copyright © 2015 Elsevier Inc. All rights reserved.

The pedunculopontine nucleus is related to visual hallucinations in Parkinson's disease: preliminary results of a voxel-based morphometry study.

PubMed

Janzen, J; van 't Ent, D; Lemstra, A W; Berendse, H W; Barkhof, F; Foncke, E M J

2012-01-01

Visual hallucinations (VH) are common in Parkinson's disease (PD) and lead to a poor quality of life. For a long time, dopaminergic therapy was considered to be the most important risk factor for the development of VH in PD. Recently, the cholinergic system, including the pedunculopontine nucleus (PPN), has been implicated in the pathophysiology of VH. The aim of the present study was to investigate grey matter density of the PPN region and one of its projection areas, the thalamus. Thirteen non-demented PD patients with VH were compared to 16 non-demented PD patients without VH, 13 demented PD patients (PDD) with VH and 11 patients with dementia with Lewy bodies (DLB). Isotropic 3-D T1-weighted MRI images (3T) were analysed using voxel-based morphometry (VBM) with the PPN region and thalamus as ROIs. PD and PDD patients with VH showed grey matter reductions of the PPN region and the thalamus compared to PD patients without VH. VH in PD(D) patients are associated with atrophy of the PPN region and its thalamic target area, suggesting that a cholinergic deficit may be involved in the development of VH in PD(D).

Morphologic changes in the mesolimbic pathway in Parkinson's disease motor subtypes.

PubMed

Nyberg, Eric M; Tanabe, Jody; Honce, Justin M; Krmpotich, Theodore; Shelton, Erika; Hedeman, Jessica; Berman, Brian D

2015-05-01

Parkinson's disease (PD) is a common neurodegenerative disorder associated with gray matter atrophy. Cortical atrophy patterns may further help distinguish between PD motor subtypes. Comparable differences in subcortical volumes have not been found. Twenty-one cognitively intact and treated PD patients, including 12 tremor dominant (TD) subtype, Nine postural instability gait dominant (PIGD) subtype, and 20 matched healthy control subjects underwent 3.0 T high-resolution structural MRI scanning. Subcortical volumetric analysis was performed using FreeSurfer and shape analysis was performed with FIRST to assess for differences between PD patients and controls and between PD subtypes. No significant differences in subcortical volumes were found between motor PD subtypes, but comparing grouped PD patients with controls revealed a significant increase in hippocampal volume in PD patients (p = 0.03). A significant shape difference was detected in the right nucleus accumbens (NAcc) between PD and controls and between motor subtypes. Shape differences were driven by positive deviations in the TD subtype. Correlation analysis revealed a trend between hippocampal volume and decreasing MDS-UPDRS (p = 0.06). While no significant differences in subcortical volumes between PD motor subtypes were found, increased hippocampal volumes were observed in PD patients compared to controls. Right NAcc shape differences in PD patients were driven by changes in the TD subtype. These unexpected findings may be related to the effects of chronic dopaminergic replacement on the mesolimbic pathway. Further studies are needed to replicate and determine the clinical significance of such morphologic changes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pain Correlates with Sleep Disturbances in Parkinson's Disease Patients.

PubMed

Fu, Yun-Ting; Mao, Cheng-Jie; Ma, Li-Jing; Zhang, Hui-Jun; Wang, Yi; Li, Jie; Huang, Jun-Ying; Liu, Jun-Yi; Liu, Chun-Feng

2018-01-01

Both sleep disorders and pain decrease quality of life in patients with Parkinson's disease (PD). However, little is known about the relationship between objective sleep disturbances and pain in patients with PD. This study aimed to (1) examine the clinical characteristics of pain in PD patients and (2) explore the correlation between pain and sleep disturbances in PD patients. Parkinson's disease patients (N = 144) underwent extensive clinical evaluations of motor and nonmotor symptoms and characteristics of pain. Overnight video-polysomnography was also conducted. Clinical characteristics and sleep parameters were compared between PD patients with or without pain. Pain was reported by 75 patients (52.1%), with 49 (65.3%) reporting pain of at least moderate severity. PD patients with pain were older and had longer disease duration, more severe PD symptoms as assessed by Hoehn and Yahr stage and the Unified Parkinson's Disease Rating Scale, and higher L-dopa equivalent daily dose compared with PD patients without pain. PD patients with pain also showed significantly decreased sleep efficiency (57.06% ± 15.84% vs. 73.80% ± 12.00%, P < 0.001), increased nonrapid eye movement stage 1 (N1) sleep (33.38% ± 19.32% vs. 17.84% ± 8.48%, P < 0.001), and decreased rapid eye movement sleep (12.76% ± 8.24% vs. 16.06% ± 6.53%, P = 0.009). Binary logistic regression analysis revealed that poorer activities of daily living, depressed mood, higher percentage of N1 sleep, and lower sleep efficiency were independent predictors of pain in patients with PD. Musculoskeletal pain is the most common type of pain in patients with PD. Disrupted sleep continuity, altered sleep architecture, depressed mood, and compromised activities of daily living may be associated with pain in patients with PD. © 2017 World Institute of Pain.

Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients

PubMed Central

Politis, Marios; Wu, Kit; Loane, Clare; Brooks, David J.; Kiferle, Lorenzo; Turkheimer, Federico E.; Bain, Peter; Molloy, Sophie; Piccini, Paola

2014-01-01

Levodopa-induced dyskinesias (LIDs) are the most common and disabling adverse motor effect of therapy in Parkinson’s disease (PD) patients. In this study, we investigated serotonergic mechanisms in LIDs development in PD patients using 11C-DASB PET to evaluate serotonin terminal function and 11C-raclopride PET to evaluate dopamine release. PD patients with LIDs showed relative preservation of serotonergic terminals throughout their disease. Identical levodopa doses induced markedly higher striatal synaptic dopamine concentrations in PD patients with LIDs compared with PD patients with stable responses to levodopa. Oral administration of the serotonin receptor type 1A agonist buspirone prior to levodopa reduced levodopa-evoked striatal synaptic dopamine increases and attenuated LIDs. PD patients with LIDs that exhibited greater decreases in synaptic dopamine after buspirone pretreatment had higher levels of serotonergic terminal functional integrity. Buspirone-associated modulation of dopamine levels was greater in PD patients with mild LIDs compared with those with more severe LIDs. These findings indicate that striatal serotonergic terminals contribute to LIDs pathophysiology via aberrant processing of exogenous levodopa and release of dopamine as false neurotransmitter in the denervated striatum of PD patients with LIDs. Our results also support the development of selective serotonin receptor type 1A agonists for use as antidyskinetic agents in PD. PMID:24531549

Elevated Serum Pesticide Levels and Risk of Parkinson Disease

PubMed Central

Richardson, Jason R.; Shalat, Stuart L.; Buckley, Brian; Winnik, Bozena; O’Suilleabhain, Padraig; Diaz-Arrastia, Ramon; Reisch, Joan; German, Dwight C.

2012-01-01

Background Exposure to pesticides has been reported to increase the risk of Parkinson disease (PD), but identification of the specific pesticides is lacking. Three studies have found elevated levels of organochlorine pesticides in postmortem PD brains. Objective To determine whether elevated levels of organochlorine pesticides are present in the serum of patients with PD. Design Case-control study. Setting An academic medical center. Participants Fifty patients with PD, 43 controls, and 20 patients with Alzheimer disease. Main Outcome Measures Levels of 16 organochlorine pesticides in serum samples. Results β-Hexachlorocyclohexane (β-HCH) was more often detectable in patients with PD (76%) compared with controls (40%) and patients with Alzheimer disease (30%). The median level of β-HCH was higher in patients with PD compared with controls and patients with Alzheimer disease. There were no marked differences in detection between controls and patients with PD concerning any of the other 15 organochlorine pesticides. Finally, we observed a significant odds ratio for the presence of β-HCH in serum to predict a diagnosis of PD vs control (odds ratio, 4.39; 95% confidence interval, 1.67–11.6) and PD vs Alzheimer disease (odds ratio, 5.20), which provides further evidence for the apparent association between serum β-HCH and PD. Conclusions These data suggest that β-HCH is associated with a diagnosis of PD. Further research is warranted regarding the potential role of β-HCH as a etiologic agent for some cases of PD. PMID:19597089

Personality Traits in Panic Disorder Patients With and Without Comorbidities.

PubMed

Zugliani, Morena M; Martin-Santos, Rocio; Nardi, Antonio Egidio; Freire, Rafael Christophe

2017-11-01

Panic disorder (PD) is often correlated with high neuroticism and low extraversion. This study aims to ascertain whether PD patients differ from healthy controls in regard to personality traits and determine if these traits are correlated with comorbid disorders, anxiety, and depression symptoms. Personality traits of 69 PD patients and 42 controls were compared using the Maudsley Personality Inventory. In PD patients, comorbidities, anxiety, and depression symptoms were also evaluated. PD patients showed higher neuroticism and lower extraversion compared with healthy controls. Patients without comorbidities presented similar results to controls, whereas those with comorbidities presented higher neuroticism and lower extraversion scores. PD per se may be unrelated to deviant personality traits, although comorbidities with major depressive disorder and agoraphobia are probably associated with high neuroticism and low extraversion. These traits show a strong correlation with the accumulation and severity of these disorders.

Association of Thiazolidinedione with a Lower Risk of Parkinson's Disease in a Population with Newly-Diagnosed Diabetes Mellitus.

PubMed

Lin, Hsiu-Li; Lin, Hsiu-Chen; Tseng, Yuan-Fu; Chao, Jane Chen-Jui; Hsu, Chien-Yeh

2018-06-11

We investigated the association of thiazolidinedione and its dose effect with the risk of Parkinson's disease (PD) in patients with diabetes mellitus (DM). This study enrolled 38,521 patients with newly-diagnosed DM between 2001 and 2013 and compared them to matched subjects without DM. The hazard ratios (HRs) for PD were compared between the thiazolidinedione-treated and non-thiazolidinedione-treated groups of the study cohort, and between subgroups who received different cumulative dosages of thiazolidinedione. We observed 544 (1.4%) patients with PD during the follow up of median duration of 6.2 years in patients with newly-diagnosed DM who had a higher risk for PD than patients without DM (HR = 1.150). In the study cohort, the risk of PD was significantly lower in the thiazolidinedione-treated group (HR = 0.399) compared to the non-thiazolidinedione-treated group. Thiazolidinedione reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.613 to 0.081 with defined daily doses of 0-90 to > 720, respectively. Thiazolidinedione use was associated with a significantly reduced risk of PD in patients with newly-diagnosed DM. Further studies to elucidate the common mechanism of PD and DM may provide novel therapies for these two diseases.

Decreased PD-1 expression on circulating CD4+T cell and PD-L1 expression on myeloid dendritic cell correlate with clinical manifestations in systemic juvenile idiopathic arthritis.

PubMed

Cai, Li; Zhang, Chenxing; Wu, Jing; Zhou, Wei; Chen, Tongxin

2018-03-30

Programmed cell death-1 (PD-1) and its ligand (PD-L1) mediate negative signal in autoimmune diseases. While little is known about its role in juvenile idiopathic arthritis (JIA). The study aimed to reveal the circulating cell profile and the relative PD-1/PD-L1 expression of JIA subsets, elucidating their underlying immunomodulatory mechanisms. We detected the circulating cells and the relative PD-1/PD-L1 signaling in 101 JIA patients and 50 controls by flow cytometry and analyzed their association with disease activity and clinical manifestations. Different from other JIA types, active systemic JIA (sJIA) patients had lower percentage and count of CD4 + T cells and lower PD-1 expression on them compared with healthy controls (P<0.05), active polyarthritis (P<0.05) and enthesitis-related arthritis (ERA) patients (P<0.05). Also, they had higher percentage and count of myeloid dendritic cell (mDC) and lower PD-L1 expression on mDC compared with healthy controls (P<0.05). Both PD-1 on CD4 + T cell and PD-L1 on mDC were negatively correlated with JADAS-27 in sJIA patients (P<0.05). In addition, PD-1 expression on CD4 + T cell was negatively associated with the number of involved joints (P<0.05) and PD-L1 on mDC was lower in patients with fever (P<0.01), which could further divide patients into two groups of different manifestations. Our finding displayed decreased CD4 + T cell, increased mDC and reduced PD-1/PD-L1 signal in sJIA PBMC comparing with other JIA subsets, which might be helpful in JIA differential diagnosis and responsible for distinct clinical manifestations via different mechanisms. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Erectile function profiles in men with Peyronie's disease.

PubMed

Deveci, Serkan; Palese, Michael; Parker, Marilyn; Guhring, Patricia; Mulhall, John P

2006-05-01

In this study we investigated the erectile function status of men presenting with Peyronie's disease. Demographics of patients regarding age, duration of PD, nature of deformity and comorbidities were compared between the patients with PD, with and without erectile dysfunction. Patients with erectile dysfunction underwent dynamic infusion cavernosometry/cavernosography. The hemodynamic profile of patients presenting with combined PD and ED were analyzed and compared between those with onset of ED before and after diagnosis of PD. Of the 222 patients 78 had ED (35%) by self-report at presentation. The mean age of patients with PD and ED was 52 +/- 22 years old. Hypertension (71.5%), hyperlipidemia (60.4%) and smoking (49.2%) were the leading comorbidities in the entire group. Statistically significant differences were found between the groups with and without ED for hypertension (p = 0.02) and cigarette smoking (p = 0.009). Of 222 patients 45 (20%) had ED that predated PD onset (group 1) and 33 (15%) had ED that postdated the onset of PD (group 2). DICC showed normal hemodynamics in 14 of 78 patients (18%), arteriogenic insufficiency in 50 (64%) and corporoveno-occlusive dysfunction in 16 (20%). CVOD was evenly distributed between groups 1 and 2, whereas arteriogenic ED was significantly higher in group 1 (82%). Site specific leak was seen in 4 of 33 (12%), all group 2 patients. Patients in whom ED postdates the onset of PD are more likely to have normal erectile hemodynamics. Site specific leak is an uncommon contributor to PD and is seen only in the patients with PD in whom ED postdated PD onset. The leading vascular etiology of ED in PD is arteriogenic in older patients and those with greater associated comorbidities.

Clinical characteristics of sleep disorders in patients with Parkinson's disease.

PubMed

Mao, Zhi-Juan; Liu, Chan-Chan; Ji, Su-Qiong; Yang, Qing-Mei; Ye, Hong-Xiang; Han, Hai-Yan; Xue, Zheng

2017-02-01

In order to investigate the sleep quality and influencing factors in patients with Parkinson's disease (PD), 201 PD patients were enrolled and underwent extensive clinical evaluations. Subjective sleep evaluation was assessed using the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). It was found that poor sleep quality (77.11%) and excessive daytime sleepiness (32.34%) were commonly seen in PD patients and positively correlated with disease severity. Then 70 out of the 201 PD patients and 70 age- and sex-matched controls underwent a polysomnographic recording. The parameters were compared between PD group and control group and the influencing factors of sleep in PD patients were analyzed. The results showed that sleep efficiency (SE) was significantly decreased (P<0.01), and sleep latency (SL) and the arousal index (AI) were increased (P<0.05) in the PD group as compared with those in the control group. SE and total sleep time (TST) were positively correlated with the Hoehn and Yahr (H&Y) stage. There was significant difference in the extent of hypopnea and hypoxemia between the PD group and the control group (P<0.05). Our results indicate that PD patients have an overall poor sleep quality and a high prevalence of sleep disorder, which may be correlated with the disease severity. Respiratory function and oxygen supply are also affected to a certain degree in PD patients.

Quality of Life and Physical Function in Older Patients on Dialysis: A Comparison of Assisted Peritoneal Dialysis with Hemodialysis

PubMed Central

Iyasere, Osasuyi U.; Johansson, Lina; Huson, Les; Smee, Joanna; Maxwell, Alexander P.; Farrington, Ken; Davenport, Andrew

2016-01-01

Background and objectives In-center hemodialysis (HD) is often the default dialysis modality for older patients. Few centers use assisted peritoneal dialysis (PD), which enables treatment at home. This observational study compared quality of life (QoL) and physical function between older patients on assisted PD and HD. Design, setting, participants, & measurements Patients on assisted PD who were >60 years old and on dialysis for >3 months were recruited and matched to patients on HD (needing hospital transport) by age, sex, diabetes, dialysis vintage, ethnicity, and index of deprivation. Frailty was assessed using the Clinical Frailty Scale. QoL assessments included Hospital Anxiety and Depression Scale (HADS), Short Form-12, Palliative Outcomes Symptom Scale (renal), Illness Intrusiveness Rating Scale, and Renal Treatment Satisfaction Questionnaire (RTSQ). Physical function was evaluated by Barthel Score and timed up and go test. Results In total, 251 patients (129 PD and 122 HD) were recruited. In unadjusted analysis, patients on assisted PD had a higher prevalence of possible depression (HADS>8; PD=38.8%; HD=23.8%; P=0.05) and higher HADS depression score (median: PD=6; HD=5; P=0.05) but higher RTSQ scores (median: PD=55; HD=51; P<0.01). In a generalized linear regression model adjusting for age, sex, comorbidity, dialysis vintage, and frailty, assisted PD continued to be associated with higher RTSQ scores (P=0.04) but not with other QoL measures. Conclusions There are no differences in measures of QoL and physical function between older patients on assisted PD and comparable patients on HD, except for treatment satisfaction, which is higher in patients on PD. Assisted PD should be considered as an alternative to HD for older patients, allowing them to make their preferred choices. PMID:26712808

PATIENT-REPORTED OUTCOMES OF QUALITY OF LIFE, FUNCTIONING, AND DEPRESSIVE SYMPTOM SEVERITY IN MAJOR DEPRESSIVE DISORDER COMORBID WITH PANIC DISORDER BEFORE AND AFTER SSRI TREATMENT IN THE STAR*D TRIAL

PubMed Central

IsHak, Waguih William; Mirocha, James; Christensen, Scott; Wu, Fan; Kwock, Richard; Behjat, Joseph; Pi, Sarah; Akopyan, A.; Peselow, Eric D.; Cohen, Robert M.; Elashoff, David

2014-01-01

Background Panic disorder (PD) is highly comorbid with major depressive disorder (MDD) with potential impact on patient-reported outcomes of quality of life (QOL), functioning, and depressive symptom severity Methods Using data from the sequenced treatment alternatives to relieve depression (STAR*D) trial, we compared entry and post-SSRI-treatment QOL, functioning, and depressive symptom severity scores in MDD patients with comorbid PD (MDD+PD) to MDD patients without PD (MDDnoPD). We also compared pre- and posttreatment proportions of patients with severe impairments in quality of life and functioning. Results MDD+PD patients experienced significantly lower QOL and functioning and more severe depressive symptoms than MDDnoPD patients at entry. Following treatment with citalopram, both groups showed significant improvements, however, nearly 30–60% of patients still suffered from severe quality of life and functioning impairments. MDD+PD patients exited with lower QOL and functioning than MDDnoPD patients, a difference that became statistically insignificant after adjusting for baseline measures of depressive symptom severity, functioning, and QOL, comorbid anxiety disorders (PTSD, GAD, social, and specific phobias), age, and college education. Conclusions Functional outcomes using QOL and functioning measures should be utilized in treating and researching MDD so that shortfalls in traditional treatment can be identified and additional interventions can be designed to address severe baseline QOL and functioning deficits in MDD comorbid with PD. PMID:23861180

Agoraphobia With and Without Panic Disorder: A 20-Year Follow-up of Integrated Exposure and Psychodynamic Therapy.

PubMed

Hoffart, Asle; Hedley, Liv M; Svanøe, Karol; Langkaas, Tomas Formo; Sexton, Harold

2016-02-01

The aim of the current study was to compare the 20-year outcome in panic disorder with agoraphobia (PD with AG) and agoraphobia without panic disorder (AG without PD) patients after inpatient psychological treatment. Of 53 eligible patients having completed a medication-free integrated exposure and psychodynamic treatment, 38 (71.7%)-25 PD with AG and 13 AG without PD patients-attended 20-year follow-up. AG without PD patients improved less than PD with AG patients did on primary outcome measures. In the PD with AG group, there were large uncontrolled effect sizes (<-2.30). More of the AG without PD patients had avoidant personality disorder at pretreatment, but the presence of this disorder did not predict outcome. The follow-up results support that PD with AG and AG without PD are two different disorders. The results also suggest that the very long-term outcome in PD with AG patients is excellent for this integrated treatment.

Avoidant personality disorder versus social phobia: the significance of childhood neglect.

PubMed

Eikenaes, Ingeborg; Egeland, Jens; Hummelen, Benjamin; Wilberg, Theresa

2015-01-01

Avoidant personality disorder (AvPD) and social phobia (SP) are common disorders both in the community and in clinical settings. Whether the two disorders represent different severity levels of social anxiety disorder is currently in dispute. The relationship between AvPD and SP is probably more complex than previously assumed. Several environmental, temperamental, and constitutional factors may play a role in the etiology of AvPD and SP. Better knowledge about childhood experiences may shed light on similarities and differences between the two disorders. The aim of this study was to compare self-reported childhood experiences in AvPD and SP patients. This is a cross-sectional multi-site study of 91 adult patients with AvPD and/ or SP. We compared patients with AvPD with and without SP (AvPD group) to patients with SP without AvPD (SP group). The patients were examined using structured diagnostic interviews and self-report measures, including Child Trauma Questionnaire, Parental Bonding Instrument, and Adult Temperament Questionnaire. Both AvPD and SP were associated with negative childhood experiences. AvPD patients reported more severe childhood neglect than patients with SP, most pronounced for physical neglect. The difference between the disorders in neglect remained significant after controlling for temperamental factors and concurrent abuse. The study indicates that childhood neglect is a risk factor for AvPD and may be one contributing factor to phenomenological differences between AvPD and SP.

Evaluating the benefits of home-based peritoneal dialysis

PubMed Central

François, Karlien; Bargman, Joanne M

2014-01-01

Peritoneal dialysis (PD) is an effective renal replacement strategy for patients suffering from end-stage renal disease. PD offers patient survival comparable to or better than in-center hemodialysis while preserving residual kidney function, empowering patient autonomy, and reducing financial burden to payors. The majority of patients suffering from kidney failure are eligible for PD. In patients with cardiorenal syndrome and uncontrolled fluid status, PD is of particular benefit, decreasing hospitalization rates and duration. This review discusses the benefits of chronic PD, performed by the patient or a caregiver at home. Recognition of the benefits of PD is a cornerstone in stimulating the use of this treatment strategy. PMID:25506238

[MRI for brain structure and function in patients with first-episode panic disorder].

PubMed

Zhang, Yan; Duan, Lian; Liao, Mei; Yang, Fan; Liu, Jun; Shan, Baoci; Li, Lingjiang

2011-12-01

To determine the brain function and structure in patinets with first-episode panic disorder (PD). All subjects (24 PD patients and 24 healthy subjects) received MRI scan and emotional counting Stroop task during the functional magnetic resonance imaging. Blood oxygenation level dependent functional magnetic resonance imaging and voxel-based morphometric technology were used to detect the gray matter volume. Compared with the healthy controls, left thalamus, left medial frontal gyrus, left anterior cingulate gyrus, left inferior frontal gyrus, left insula (panic-related words vs. neutral words) lacked activation in PD patients, but the over-activation were found in right brain stem, right occipital lobe/lingual gyrus in PD patients. Compared with the healthy controls, the gray matter volume in the PD patients significantly decreased in the left superior temporal gyrus, right medial frontal gyrus, left medial occipital gyrus, dorsomedial nucleus of left thalamus and right anterior cingulate gyrus. There was no significantly increased gray matter volume in any brain area in PD patients. PD patients have selective attentional bias in processing threatening information due to the depression and weakening of the frontal cingulated gyrus.

Walking economy in people with Parkinson's disease.

PubMed

Christiansen, Cory L; Schenkman, Margaret L; McFann, Kim; Wolfe, Pamela; Kohrt, Wendy M

2009-07-30

Gait dysfunction is an early problem identified by patients with Parkinson's disease (PD). Alterations in gait may result in an increase in the energy cost of walking (i.e., walking economy). The purpose of this study was to determine whether walking economy is atypical in patients with PD when compared with healthy controls. A secondary purpose was to evaluate the associations of age, sex, and level of disease severity with walking economy in patients with PD. The rate of oxygen consumption (VO(2)) and other responses to treadmill walking were compared in 90 patients (64.4 +/- 10.3 years) and 44 controls (64.6 +/- 7.3 years) at several walking speeds. Pearson correlation coefficients (r) were calculated to determine relationships of age, sex, and disease state with walking economy in PD patients. Walking economy was significantly worse in PD patients than in controls at all speeds above 1.0 mph. Across all speeds, VO(2) was 6 to 10% higher in PD patients. Heart rate, minute ventilation, respiratory exchange ratio, and rating of perceived exertion were correspondingly elevated. No significant relationship of age, sex, or UPDRS score with VO(2) was found for patients with PD. The findings suggest that the physiologic stress of daily physical activities is increased in patients with early to mid-stage PD, and this may contribute to the elevated level of fatigue that is characteristic of PD. Copyright 2009 Movement Disorder Society.

Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation.

PubMed

Williams, Amy E; Arzola, Gladys Marina; Strutt, Adriana M; Simpson, Richard; Jankovic, Joseph; York, Michele K

2011-06-01

Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson's disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25-30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery. Copyright © 2011 Elsevier Ltd. All rights reserved.

Persian version of frontal assessment battery: Correlations with formal measures of executive functioning and providing normative data for Persian population.

PubMed

Asaadi, Sina; Ashrafi, Farzad; Omidbeigi, Mahmoud; Nasiri, Zahra; Pakdaman, Hossein; Amini-Harandi, Ali

2016-01-05

Cognitive impairment in patients with Parkinson's disease (PD) mainly involves executive function (EF). The frontal assessment battery (FAB) is an efficient tool for the assessment of EFs. The aims of this study were to determine the validity and reliability of the psychometric properties of the Persian version of FAB and assess its correlation with formal measures of EFs to provide normative data for the Persian version of FAB in patients with PD. The study recruited 149 healthy participants and 49 patients with idiopathic PD. In PD patients, FAB results were compared to their performance on EF tests. Reliability analysis involved test-retest reliability and internal consistency, whereas validity analysis involved convergent validity approach. FAB scores compared in normal controls and in PD patients matched for age, education, and Mini-Mental State Examination (MMSE) score. In PD patients, FAB scores were significantly decreased compared to normal controls, and correlated with Stroop test and Wisconsin Card Sorting Test (WCST). In healthy subjects, FAB scores varied according to the age, education, and MMSE. In the FAB subtest analysis, the performances of PD patients were worse than the healthy participants on similarities, fluency tasks, and Luria's motor series. Persian version of FAB could be used as a reliable scale for the assessment of frontal lobe functions in Iranian patients with PD. Furthermore, normative data provided for the Persian version of this test improve the accuracy and confidence in the clinical application of the FAB.

Effect of Dopamine Therapy on Nonverbal Affect Burst Recognition in Parkinson's Disease

PubMed Central

Péron, Julie; Grandjean, Didier; Drapier, Sophie; Vérin, Marc

2014-01-01

Background Parkinson's disease (PD) provides a model for investigating the involvement of the basal ganglia and mesolimbic dopaminergic system in the recognition of emotions from voices (i.e., emotional prosody). Although previous studies of emotional prosody recognition in PD have reported evidence of impairment, none of them compared PD patients at different stages of the disease, or ON and OFF dopamine replacement therapy, making it difficult to determine whether their impairment was due to general cognitive deterioration or to a more specific dopaminergic deficit. Methods We explored the involvement of the dopaminergic pathways in the recognition of nonverbal affect bursts (onomatopoeias) in 15 newly diagnosed PD patients in the early stages of the disease, 15 PD patients in the advanced stages of the disease and 15 healthy controls. The early PD group was studied in two conditions: ON and OFF dopaminergic therapy. Results Results showed that the early PD patients performed more poorly in the ON condition than in the OFF one, for overall emotion recognition, as well as for the recognition of anger, disgust and fear. Additionally, for anger, the early PD ON patients performed more poorly than controls. For overall emotion recognition, both advanced PD patients and early PD ON patients performed more poorly than controls. Analysis of continuous ratings on target and nontarget visual analog scales confirmed these patterns of results, showing a systematic emotional bias in both the advanced PD and early PD ON (but not OFF) patients compared with controls. Conclusions These results i) confirm the involvement of the dopaminergic pathways and basal ganglia in emotional prosody recognition, and ii) suggest a possibly deleterious effect of dopatherapy on affective abilities in the early stages of PD. PMID:24651759

Effects of training and weight support on muscle activation in Parkinson's disease.

PubMed

Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

2013-12-01

The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical Manifestation of Parkinson's Disease in Association with Rapid Eye Movement Sleep Behavior Disorder Onset.

PubMed

Zhang, Hui; Gu, Zhuqin; Sun, Liang; Cao, Ming; Li, Dawei; Ma, Jinghong; Chan, Piu

2016-01-01

To confirm whether the presence and/or timing of rapid eye movement sleep behavior disorder (RBD) onset were associated with differences in clinical features of Parkinson's disease (PD), clinical characteristics of PD patients with RBD occurring before and after PD diagnosis were investigated. Consecutive PD patients were enrolled between July 2011 and February 2012. RBD questionnaire Hong Kong and clinical interviews were used to identify RBD symptoms and onsets. All patients underwent evaluations to collect clinical and treatment information. Of all 79 PD patients, 21 (26.6%) and 22 (27.8%) patients had RBD prior to (RBD-PD) and after PD diagnosis (PD-RBD), respectively. Thirty-six (45.6%) PD patients reported no RBD at the time of study (PD-NRBD). PD-RBD had similar clinical features as PD-NRBD did except that Epworth sleepiness scale score was significantly higher in PD-RBD (p = 0.04). Compared to PD-RBD and PD-NRBD, RBD-PD had a higher frequency of reporting excessive daytime sleepiness (p = 0.019, p = 0.008, respectively) and constipation (p = 0.046, p = 0.032, respectively). Our preliminary results suggest that RBD-PD might be clinically different from PD-RBD, which appears to share similar characteristics with PD-NRBD, regarding only non-motor functions. © 2016 S. Karger AG, Basel.

Cost comparison of peritoneal dialysis versus hemodialysis in end-stage renal disease.

PubMed

Berger, Ariel; Edelsberg, John; Inglese, Gary W; Bhattacharyya, Samir K; Oster, Gerry

2009-08-01

To compare healthcare utilization and costs in patients with end-stage renal disease (ESRD) beginning peritoneal dialysis (PD) or hemodialysis (HD). Retrospective cohort study. Using a US health insurance database, we identified all patients with ESRD who began dialysis between January 1, 2004, and December 31, 2006. Patients were designated as PD patients or as HD patients based on first-noted treatment. Patients with less than 6 months of pretreatment data and those with less than 12 months of data following initiation of dialysis ("pretreatment" and "follow-up," respectively) were dropped from the study sample. The PD patients were matched to HD patients using propensity scoring to control for differences in pretreatment characteristics. Healthcare utilization and costs were then compared over 12 months between propensity-matched PD patients and HD patients using paired t tests and Wilcoxon signed rank tests for continuous variables and using Bowker and McNemar tests for categorical variables, as appropriate. A total of 463 patients met all study entrance criteria; 56 (12%) began treatment with PD, and 407 (88%) began treatment with HD. Fifty PD patients could be propensity matched to an equal number of HD patients. The HD patients were more than twice as likely as matched PD patients to be hospitalized over the subsequent 12 months (hazard ratio, 2.17; 95% confidence interval, 1.34-3.51; P <.01). Their median healthcare costs over the 12-month follow-up period were $43,510 higher ($173,507 vs $129,997 for PD patients, P = .03). Among patients with ESRD, PD patients are less likely than HD patients to be hospitalized in the year following initiation of dialysis. They also have significantly lower total healthcare costs.

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients.

PubMed

Li, Zhenguang; Yu, Zhancai; Zhang, Jinbiao; Wang, Jing; Sun, Chao; Wang, Pengfei; Zhang, Jiangshan

2015-01-01

The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients. © 2015 S. Karger AG, Basel.

Increased percentages of PD-1 on CD4+ T cells is associated with higher INF-γ production and altered IL-17 production in patients with systemic lupus erythematosus.

PubMed

Dolff, S; Quandt, D; Feldkamp, T; Jun, C; Mitchell, A; Hua, F; Specker, C; Kribben, A; Witzke, O; Wilde, B

2014-01-01

Programmed death (PD)-1 is a cell death receptor that, upon stimulation, leads to apoptosis. Previous studies have shown alteration of PD-1 expression on T cells and PD-1 genes in patients with systemic lupus erythematosus (SLE). The aim of this study was to assess the expression of this receptor on effector T cells in patients with SLE. In this study we enrolled 32 SLE patients and 31 healthy controls. T cells from peripheral blood were analysed by flow cytometry for the expression of PD-1. Interferon (IFN)-γ and interleukin (IL)-17-producing cells were investigated for the expression of this co-stimulatory marker. Percentages of CD4(+) T cells expressing PD-1 were significantly increased in patients with SLE compared to healthy controls. The percentage of PD-1 expression was correlated with the production of INF-γ (r = 0.83, p < 0.0001). We also investigated the production of IL-17 by PD-1(+) CD3(+) T cells. Inactive patients (3.2 ± 1.2% vs. 5.9 ± 3.5%, p = 0.002) and patients without lupus nephritis (LN) (3.2 ± 1.5% vs. 5.9 ± 3.5%, p = 0.005) showed lower levels of IL-17 compared to healthy controls. We have demonstrated increased expression of PD-1 on CD4(+) T cells in SLE patients and an association between PD-1 expression on CD4(+) T cells and IFN-γ expression on CD3(+) T cells. We have also shown that there is an altered subset of PD-1(+) T cells in inactive patients and patients without LN producing lower amounts of IL-17.

Glucose dysregulation in Parkinson's disease: Too much glucose or not enough insulin?

PubMed

Marques, Ana; Dutheil, Frédéric; Durand, Elodie; Rieu, Isabelle; Mulliez, Aurélien; Fantini, Maria Livia; Boirie, Yves; Durif, Franck

2018-05-31

To detect changes in glucose regulation in moderate to advanced Parkinson's disease (PD) patients in response to oral glucose intake. Blood glucose and insulin kinetics during a 75-g Oral Glucose Tolerance Test (OGTT) were compared between 50 PD patients and 50 healthy controls (CT) matched for body mass index (BMI), age and sex. Potential relationships between changes in glucose kinetics and clinical parameters were analyzed including Parkinson's disease severity and autonomic function using SCOPA-AUT (Scales for Outcomes in Parkinson's disease, Autonomic dysfunction). Blood glucose was significantly higher at T90 (p = 0.04) and T150 (p = 0.01) in PD patients compared to healthy matched controls. Moreover, the total area under time curve (AUC) for the blood glucose levels was significantly higher in PD patients compared to healthy controls (1187 ± 229 vs 1101 ± 201 mmol min.l -1 ; p = 0.05). Simultaneously, no significant increase of insulin levels was observed in PD patients compared to controls. Higher blood glucose levels were associated with higher BMI (p < 0.001), female gender (p < 0.033), longer duration of PD (p = 0.001), lower dose of dopaminergic treatment (p = 0.023), and higher score of dysautonomia (p = 0.017). Glucose control is impaired in moderate to advanced non-diabetic PD patients, due to impaired adaptive insulin response which may be a novel non-motor consequence of PD associated dysautonomia. Copyright © 2018 Elsevier Ltd. All rights reserved.

Safety and Tolerability of PD-1/PD-L1 Inhibitors Compared with Chemotherapy in Patients with Advanced Cancer: A Meta-Analysis.

PubMed

Nishijima, Tomohiro F; Shachar, Shlomit S; Nyrop, Kirsten A; Muss, Hyman B

2017-04-01

Compared with chemotherapy, significant improvement in survival outcomes with the programmed death receptor-1 (PD-1) inhibitors nivolumab and pembrolizumab and the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab has been shown in several types of advanced solid tumors. We conducted a systematic review and meta-analysis to compare safety and tolerability between PD-1/PD-L1 inhibitors and chemotherapy. PubMed and American Society of Clinical Oncology (ASCO) databases were searched 1966 to September 2016. Eligible studies included randomized controlled trials (RCTs) comparing single-agent U.S. Food and Drug Administration-approved PD-1/PD-L1 inhibitors (nivolumab, pembrolizumab, or atezolizumab) with chemotherapy in cancer patients reporting any all-grade (1-4) or high-grade (3-4) adverse events (AEs), all- or high-grade treatment-related symptoms, hematologic toxicities and immune-related AEs, treatment discontinuation due to toxicities, or treatment-related deaths. The summary incidence, relative risk, and 95% confidence intervals were calculated. A total of 3,450 patients from 7 RCTs were included in the meta-analysis: 4 nivolumab, 2 pembrolizumab, and 1 atezolizumab trials. The underlying malignancies included were non-small cell lung cancer (4 trials) and melanoma (3 trials). Compared with chemotherapy, the PD-1/PD-L1 inhibitors had a significantly lower risk of all- and high-grade fatigue, sensory neuropathy, diarrhea and hematologic toxicities, all-grade anorexia, nausea, and constipation, any all- and high-grade AEs, and treatment discontinuation. There was an increased risk of all-grade rash, pruritus, colitis, aminotransferase elevations, hypothyroidism, and hyperthyroidism, and all- and high-grade pneumonitis with PD1/PD-L1 inhibitors. PD-1/PD-L1 inhibitors are overall better tolerated than chemotherapy. Our results provide further evidence supporting the favorable risk/benefit ratio for PD-1/PD-L1 inhibitors. The Oncologist 2017;22:470-479 IMPLICATIONS FOR PRACTICE: We conducted a systematic review and meta-analysis to compare summary toxicity endpoints and clinically relevant adverse events between programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors and chemotherapy. PD1/PD-L1 inhibitors were associated with a lower risk of treatment-related symptoms (fatigue, anorexia, nausea, diarrhea, constipation, and sensory neuropathy) but a higher risk of immune-related adverse events (AEs). Summary toxicity endpoints favor PD1/PD-L1 inhibitors (any all- and high-grade AEs and treatment discontinuation). PD1/PD-L1 inhibitors are overall better tolerated than chemotherapy. In addition to efficacy data from trials, our findings provide useful information for clinicians for well-balanced discussions with their patients on the risks and benefits of treatment options for advanced cancer. © AlphaMed Press 2017.

CSF lamp2 concentrations are decreased in female Parkinson's disease patients with LRRK2 mutations.

PubMed

Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; Loeffler, David A

2018-03-15

Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2 mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD) patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27). We also examined lamp2's correlations with age, oxidative stress, PD progression, and PD duration. Median lamp2 concentrations (pg/mL) were LRRK2 PD = 127, sPD = 333, CTL = 436, and LRRK2 CTL = 412. Log-transformed lamp2 concentrations, adjusting for gender effects (and excluding male LRRK2 PD patients because of low number), were lower in female LRRK2 PD patients than in LRRK2 CTL (p = 0.002) and CTL (p = 0.005) subjects (p = 0.06 for lamp2 comparison between female LRRK2 PD patients and sPD patients). Lamp2 did not appear to be associated with age, PD progression, or PD duration; however, three of four Spearman rho values for correlations between lamp2 and oxidative stress markers in PD subjects were ≥0.30. These findings suggest that CSF lamp2 concentrations may be decreased in female LRRK2 PD patients compared to healthy individuals with or without LRRK2 mutations. Copyright © 2018 Elsevier B.V. All rights reserved.

Barriers to Increasing Use of Peritoneal Dialysis in Bangladesh: A Survey of Patients and Providers.

PubMed

Savla, Dipal; Ahmed, Sweety; Yeates, Karen; Matthew, Anna; Anand, Shuchi

2017-01-01

Despite a lower requirement for technology and equipment than hemodialysis (HD), peritoneal dialysis (PD) is an underutilized modality in low- and middle-income countries (LMICs). Bangladesh has the lowest use of PD in the world (fewer than 2% of prevalent patients). We evaluated nephrologists' attitudes toward PD and examined differences between patients on HD and PD in Dhaka. We asked nephrologists to fill out an English-language questionnaire. Using convenience sampling but targeting both public and private hospitals in Dhaka, we asked trained nurses to administer a Bangla-language questionnaire to patients on HD ( n = 116) and PD ( n = 41). We validated the questionnaires on a sub-sample ( n = 10 for each group). Of the 43 nephrologists surveyed, 27 (63%) had patients on PD. When compared with nephrologists without patients on PD, those with patients on PD were less likely to believe that survival and quality of life on PD was worse than on HD (odds ratio [OR] = 0.21, 95% confidence interval [CI] 0.05 - 0.83 and OR = 0.11, 95% CI 0.02 - 0.67 respectively) but were not more likely to have received training for PD. Nephrologists named cost of PD as the predominant barrier to increasing use of PD, followed by concerns about patient hygiene and lack of trained nurses. Fifty-two HD patients (45%) did not know about a home-based modality. When compared with patients on HD, patients on PD were more likely to have been educated by non-nephrologists about dialysis, to be "forewarned" about the need for dialysis, to be paying fully, and to be living in a permanent home with a non-communal water source. Some barriers to increasing access to PD-i.e., patient living conditions and cost-are unique to LMICs. Our study also highlights that issues encountered in high-income countries-i.e., nephrologists' subjective preference and lack of patient knowledge about an alternate modality to HD-may play a role as well. Copyright © 2017 International Society for Peritoneal Dialysis.

Altered neural responses to heat pain in drug-naive patients with Parkinson disease.

PubMed

Forkmann, Katarina; Grashorn, Wiebke; Schmidt, Katharina; Fründt, Odette; Buhmann, Carsten; Bingel, Ulrike

2017-08-01

Pain is a frequent but still neglected nonmotor symptom of Parkinson disease (PD). However, neural mechanisms underlying pain in PD are poorly understood. Here, we explored whether the high prevalence of pain in PD might be related to dysfunctional descending pain control. Using functional magnetic resonance imaging we explored neural responses during the anticipation and processing of heat pain in 21 PD patients (Hoehn and Yahr I-III) and 23 healthy controls (HC). Parkinson disease patients were naive to dopaminergic medication to avoid confounding drug effects. Fifteen heat pain stimuli were applied to the participants' forearm. Intensity and unpleasantness ratings were provided for each stimulus. Subjective pain perception was comparable for PD patients and HC. Neural processing, however, differed between groups: PD patients showed lower activity in several descending pain modulation regions (dorsal anterior cingulate cortex [dACC], subgenual anterior cingulate cortex, and dorsolateral prefrontal cortex [DLPFC]) and lower functional connectivity between dACC and DLPFC during pain anticipation. Parkinson disease symptom severity was negatively correlated with dACC-DLPFC connectivity indicating impaired functional coupling of pain modulatory regions with disease progression. During pain perception PD patients showed higher midcingulate cortex activity compared with HC, which also scaled with PD severity. Interestingly, dACC-DLPFC connectivity during pain anticipation was negatively associated with midcingulate cortex activity during the receipt of pain in PD patients. This study indicates altered neural processing during the anticipation and receipt of experimental pain in drug-naive PD patients. It provides first evidence for a progressive decline in descending pain modulation in PD, which might be related to the high prevalence of pain in later stages of PD.

Color Discrimination in Patients with Gaucher Disease and Parkinson Disease.

PubMed

Simon-Tov, Shlomi; Dinur, Tama; Giladi, Nir; Bar-Shira, Anat; Zelis, Mayaan; Zimran, Ari; Elstein, Deborah

2015-01-01

Poor color discrimination among patients with Parkinson disease (PD) has long been recognized. It has been shown that carrying one or two mutations in the β-glucocerebrosidase gene (GBA) for the autosomal disease Gaucher disease (GD), as based initially on clinical evidence, is a genetic risk factor for early-onset PD. The purpose of this study was to assess color discrimination in patients with one or two GBA mutations relative to healthy controls to ascertain whether this function is affected when persons with GD or even one GBA mutation develop PD. The Farnsworth-Munsell 100 hue test (FMHT) was evaluated among patients with GD+PD compared to patients with GD only, obligate GBA carriers with and without PD, patients with PD only, and healthy controls. FMHT outcome include computer-generated TES (Total Error Score) and values recommended by Vingrys & King-Smith. Six groups of 10 persons were tested. Significant differences were seen for male GD+PD and for age in PD. The highest mean TES was in the PD only group, the lowest in the GD only group. There was a significant difference because of PD in groups with GD and GBA carriers. GD+PD means were between GD only and PD only mean scores. These findings confirm that PD impacts color discrimination, more in males with GD+PD but nonetheless, GD+PD patients (but not GBA carriers) had better scores than PD only patients.

Computing the variations in the self-similar properties of the various gait intervals in Parkinson disease patients.

PubMed

Manjeri Keloth, Sana; Arjunan, Sridhar P; Kumar, Dinesh

2017-07-01

This study has investigated the stride, swing, stance and double support intervals of gait for Parkinson's disease (PD) patients with different levels of severity. Self-similar properties of the gait signal were analyzed to investigate the changes in the gait pattern of the healthy and PD patients. To understand the self-similar property, detrended fluctuation analysis was performed. The analysis shows that the PD patients have less defined gait when compared to healthy. The study also shows that among the stance and swing phase of stride interval, the self-similarity is less for swing interval when compared to the stance interval of gait and decreases with the severity of gait. Also, PD patients show decreased self-similar patterns in double support interval of gait. This suggest that there are less rhythmic gait intervals and a sense of urgency to remain in support phase of gait by the PD patients.

Risk and Prognosis of Bacteremia and Fungemia Among Peritoneal Dialysis Patients: A Population-Based Cohort Study.

PubMed

Dalgaard, Lars Skov; Nørgaard, Mette; Povlsen, Johan Vestergaard; Jespersen, Bente; Jensen-Fangel, Søren; Ellermann-Eriksen, Svend; Østergaard, Lars; Schønheyder, Henrik Carl; Søgaard, Ole Schmeltz

♦ BACKGROUND: The incidence of bacteremia and fungemia (BAF) is largely unknown in end-stage renal disease (ESRD) patients initiating peritoneal dialysis (PD). ♦ OBJECTIVE: The main objective was to estimate and compare incidence rates of first episodes of BAF in incident PD patients and a comparison cohort. A secondary objective was to compare causative agents and 30-day post-BAF mortality between PD patients and the comparison cohort. ♦ METHODS: Design: Observational cohort study. Central and North Denmark regions. patients who initiated PD during 1995 - 2010. For each patient we sampled up to 10 controls from the general population matched on age, sex, and municipality. ♦ MAIN OUTCOME: Data on positive blood cultures were retrieved from electronic microbiology databases covering the 2 regions. We calculated incidence rates (IRs) of first-time BAF for PD patients and population controls. Incidence-rate ratios (IRRs) were calculated to compare these rates. Thirty-day mortality was estimated by Kaplan-Meier analysis. ♦ RESULTS: Among 1,024 PD patients and 10,215 population controls, we identified 75 and 282 episodes of BAF, respectively. Incidence rates of BAF were 4.7 (95% confidence interval [CI], 3.8 - 5.9) per 100 person-years of follow-up (PYFU) in PD patients and 0.5 (95% CI, 0.4 - 0.5) per 100 PYFU in population controls (IRR = 10.4; 95% CI, 8.1 - 13.5). In PD patients, the most frequent microorganisms were Escherichia coli (18.7%) and Staphylococcus aureus (13.3%). Escherichia coli (27.3%) also ranked first among population controls. Thirty-day mortality following BAF was 20.8% (95% CI, 12.6 - 31.0) and 20.7% (95% CI, 16.3 - 25.9) among PD patients and population controls, respectively. ♦ CONCLUSIONS: Peritoneal dialysis patients are at markedly higher risk of BAF than population controls. Causative agents and the 30-day post-BAF mortality were similar in the 2 cohorts. Copyright © 2016 International Society for Peritoneal Dialysis.

Mini-extracorporeal circulation technology, conventional bypass and prime displacement in isolated coronary and aortic valve surgery: a propensity-matched in-hospital and survival analysis.

PubMed

Ariyaratnam, Priyadharshanan; Mclean, Lindsay A; Cale, Alexander; Chaudhry, Mubarak A; Vijayan, Ajith; Richards, Neil; Jarvis, Martin A; Haqzad, Yama; Ngaage, Dumbor; Cowen, Michael E; Loubani, Mahmoud

2018-02-14

Conventional cardiopulmonary bypass is the most commonly used means of artificial circulation in cardiac surgery. However, it suffers from the effects of haemodilution and activation of inflammatory/coagulation cascades. Prime displacement (PD) can offset haemodilution and Mini-Extracorporeal Technology (MIECT) can offset both. So far, no study has compared all of these modalities together; hence, we compared the outcomes of these 3 modalities at our institution. This was a retrospective analysis of our cardiac surgical database. A total of 9626 patients underwent conventional bypass (CB), 3125 patients underwent a modification of CB, called PD, and 904 underwent MIECT. A 1:1 propensity-matching algorithm was employed using IBM SPSS 24 to match (i) 813 MIECT patients with 813 CB patients and (ii) 717 MIECT patients with 717 PD patients. The patients included coronary artery bypass grafting and valve surgery. MIECT had significantly (P < 0.05) longer bypass and cross-clamp times compared to CB and PD. MIECT had significantly higher rates of postoperative atrial fibrillation associated with it compared to CB. The mean red cell blood transfusion was significantly lower in the MIECT group compared to the CB group as was the mean platelet transfusion and fresh frozen plasma transfusion. The overall 5-year survival was higher in the MIECT group compared to the CB group (log-rank, P = 0.018). Between the MIECT and the PD groups, we found the incidence of renal failure and gastrointestinal complications to be significantly higher in the PD group compared to the MIECT group. MIECT has short-term advantages over CB and PD. However, due to the retrospective limitations of the study, including calendar time bias, a multicentre randomized controlled trial comparing all 3 modalities will be beneficial for the larger cardiac community. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Alterations of erythrocyte rheology and cellular susceptibility in end stage renal disease: Effects of peritoneal dialysis.

PubMed

Ertan, Nesrin Zeynep; Bozfakioglu, Semra; Ugurel, Elif; Sinan, Mukaddes; Yalcin, Ozlem

2017-01-01

In this study, we investigated the effects of peritoneal dialysis on hemorheological and hematological parameters and their relations with oxidant and antioxidant status of uremic patients. Hemorheological parameters (erythrocyte deformability, erythrocyte aggregation, osmotic deformability, blood and plasma viscosity) were measured in patients with renal insufficiency undergoing peritoneal dialysis (PD) and volunteers. Erythrocyte deformability, osmotic deformability and aggregation in both autologous plasma and 3% dextran 70 were measured by laser diffraction ektacytometry. Enzyme activities of glutathione peroxidase, superoxide dismutase and catalase were studied in erythrocytes; lipid peroxidation was studied by measuring the amount of malondialdehyde in both erythrocytes and plasma samples. Blood viscosity at native hematocrit was significantly lower in PD patients at all measured shear rates compared to controls, but it was high in PD patients at corrected (45%) hematocrit. Erythrocyte deformability did not show any difference between the two groups. Osmotic deformability was significantly lower in PD patients compared to controls. Aggregation index values were significantly high in PD patients in plasma Catalase and glutathione peroxidase activities in erythrocytes were decreased in PD patients whereas superoxide dismutase activity was increased compared to controls. Malondialdehyde was significantly increased in erythrocytes and plasma samples of PD patients which also shows correlations with aggregation parameters. It has been concluded that erythrocytes in PD patients are more prone to aggregation and this tendency could be influenced by lipid peroxidation activity in patient's plasma. These results imply that uremic conditions, loss of plasma proteins and an increased risk of oxidative stress because of decreasing levels of antioxidant enzymes affect erythrocyte rheology during peritoneal dialysis. This level of distortion may have crucial effects, impairing the blood flow dynamics and causing inadequate microcirculatory perfusion.

Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis

PubMed Central

2014-01-01

Introduction A major pathophysiologic mechanism in sepsis is impaired host immunity which results in failure to eradicate invading pathogens and increased susceptibility to secondary infections. Although many immunosuppressive mechanisms exist, increased expression of the inhibitory receptor programmed cell death 1 (PD-1) and its ligand (PD-L1) are thought to play key roles. The newly recognized phenomenon of T cell exhaustion is mediated in part by PD-1 effects on T cells. This study tested the ability of anti-PD-1 and anti-PD-L1 antibodies to prevent apoptosis and improve lymphocyte function in septic patients. Methods Blood was obtained from 43 septic and 15 non-septic critically-ill patients. Effects of anti-PD-1, anti-PD-L1, or isotype-control antibody on lymphocyte apoptosis and interferon gamma (IFN-γ) and interleukin-2 (IL-2) production were quantitated by flow cytometry. Results Lymphocytes from septic patients produced decreased IFN-γ and IL-2 and had increased CD8 T cell expression of PD-1 and decreased PD-L1 expression compared to non-septic patients (P<0.05). Monocytes from septic patients had increased PD-L1 and decreased HLA-DR expression compared to non-septic patients (P<0.01). CD8 T cell expression of PD-1 increased over time in ICU as PD-L1, IFN-γ, and IL2 decreased. In addition, donors with the highest CD8 PD-1 expression together with the lowest CD8 PD-L1 expression also had lower levels of HLA-DR expression in monocytes, and an increased rate of secondary infections, suggestive of a more immune exhausted phenotype. Treatment of cells from septic patients with anti-PD-1 or anti-PD-L1 antibody decreased apoptosis and increased IFN-γ and IL-2 production in septic patients; (P<0.01). The percentage of CD4 T cells that were PD-1 positive correlated with the degree of cellular apoptosis (P<0.01). Conclusions In vitro blockade of the PD-1:PD-L1 pathway decreases apoptosis and improves immune cell function in septic patients. The current results together with multiple positive studies of anti-PD-1 and anti-PD-L1 in animal models of bacterial and fungal infections and the relative safety profile of anti-PD-1/anti-PD-L1 in human oncology trials to date strongly support the initiation of clinical trials testing these antibodies in sepsis, a disorder with a high mortality. PMID:24387680

Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis.

PubMed

Campos, Michael A; Runken, Michael C; Davis, Angela M; Johnson, Michael P; Stone, Glenda A; Buikema, Ami R

2018-04-01

Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct ® ; PD). This study compared clinical and economic outcomes between patients with and without PD program participation. This retrospective study included commercial and Medicare Advantage health insurance plan members with ≥ 1 claim with diagnosis codes for COPD and ≥ 1 medical or pharmacy claim including A1PI (on index date). Outcomes were compared between patients receiving only Prolastin ® or Prolastin ® -C (PD cohort) and patients who received a different brand without PD (Comparator cohort). Demographic and clinical characteristics were captured during 6 months pre-index. Post-index exacerbation episodes and healthcare utilization and costs were compared between cohorts. The study sample comprised 445 patients (n = 213 in PD cohort; n = 232 in Comparator cohort), with a mean age 55.5 years, 50.8% male, and 78.9% commercially insured. The average follow-up was 822 days (2.25 years), and the average time on A1PI was 747 days (2.04 years). Few differences were observed in demographic or clinical characteristics. Adjusting for differences in patient characteristics, the rate of severe exacerbation episodes was reduced by 36.1% in the PD cohort. Adjusted total annual all-cause costs were 11.4% lower, and adjusted mean respiratory-related costs were 10.6% lower in the PD cohort than the Comparator cohort. Annual savings in all-cause total costs in the PD cohort relative to the Comparator cohort was US$25,529 per patient, largely due to significantly fewer and shorter hospitalizations. These results suggest that comprehensive health management services may improve both clinical and economic outcomes among patients with COPD and AATD who receive augmentation therapy. Grifols Shared Services of North America, Inc.

A Comparison of Treatment-Seeking Behavioral Addiction Patients with and without Parkinson's Disease.

PubMed

Sauvaget, Anne; Jiménez-Murcia, Susana; Fernández-Aranda, Fernando; Granero, Roser; Grall-Bronnec, Marie; Victorri-Vigneau, Caroline; Bulteau, Samuel; Derkinderen, Pascal; Vanelle, Jean M; Hakansson, Anders; Mestre-Bach, Gemma; Steward, Trevor; Menchón, José M

2017-01-01

The administration of dopaminergic medication to treat the symptoms of Parkinson's disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N  = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions.

A Comparison of Treatment-Seeking Behavioral Addiction Patients with and without Parkinson’s Disease

PubMed Central

Sauvaget, Anne; Jiménez-Murcia, Susana; Fernández-Aranda, Fernando; Granero, Roser; Grall-Bronnec, Marie; Victorri-Vigneau, Caroline; Bulteau, Samuel; Derkinderen, Pascal; Vanelle, Jean M.; Hakansson, Anders; Mestre-Bach, Gemma; Steward, Trevor; Menchón, José M.

2017-01-01

The administration of dopaminergic medication to treat the symptoms of Parkinson’s disease (PD) is associated with addictive behaviors and impulse control disorders. Little is known, however, on how PD patients differ from other patients seeking treatments for behavioral addictions. The aim of this study was to compare the characteristics of behavioral addiction patients with and without PD. N = 2,460 treatment-seeking men diagnosed with a behavioral addiction were recruited from a university hospital. Sociodemographic, impulsivity [Barratt Impulsiveness Scale (BIS-11)], and personality [Temperament and Character Inventory-Revised (TCI-R)] measures were taken upon admission to outpatient treatment. Patients in the PD group were older and had a higher prevalence of mood disorders than patients without PD. In terms of personality characteristics and impulsivity traits, PD patients appeared to present a more functional profile than PD-free patients with a behavioral addiction. Our results suggest that PD patients with a behavioral addiction could be more difficult to detect than their PD-free counterparts in behavioral addiction clinical setting due to their reduced levels of impulsivity and more standard personality traits. As a whole, this suggests that PD patients with a behavioral addiction may have different needs from PD-free behavioral addiction patients and that they could potentially benefit from targeted interventions. PMID:29163234

Ghrelin and lipid levels in panic disorder before and after treatment and their relationship with agoraphobia.

PubMed

Gul, Isil Gogcegoz; Cumurcu, Birgul Elbozan; Karlidag, Rifat; Turkoz, Yusuf

2015-09-01

We aimed to evaluate serum ghrelin (GHR) levels and lipid profile in panic disorder (PD), with and without agoraphobia, and to compare these parameters before and after treatment. The GHR and lipid profiles were measured in blood samples taken from 31 PD patients with agoraphobia, 22 PD patients without agoraphobia, and 53 control group subjects. 23 of the 53 patients who were prescribed 20 to 40 mg/day paroxetine had continued treatment. The 23 patients who had continued treatment were measured again at the end of twelve weeks. The GHR and triglyceride (TRG), total cholesterol (Total-C), low-density lipoproteins (LDL-C), and very low-density lipoproteins (VLDL-C) levels were higher in the PD with agoraphobia group than the PD without agoraphobia and control groups. The 23 patients that had continued their treatment were re-evaluated, and the serum GHR, Total-C levels, and BMI after treatment were significantly decreased, compared to the values before treatment. There may be a pathophysiological relationship between the GHR and lipid profiles that interact with each other in PD. In fact, this relationship was more marked in PD with agoraphobia than in PD without agoraphobia.

Validation of a novel Montreal Cognitive Assessment scoring algorithm in non-demented Parkinson's disease patients.

PubMed

Sulzer, Patricia; Becker, Sara; Maetzler, Walter; Kalbe, Elke; van Nueten, Luc; Timmers, Maarten; Machetanz, Gerrit; Streffer, Johannes; Salvadore, Giacomo; Scholz, Erich; Tkaczynska, Zuzanna; Brockmann, Kathrin; Berg, Daniela; Liepelt-Scarfone, Inga

2018-06-23

The early diagnosis of mild cognitive impairment (PD-MCI) in Parkinson's disease (PD) is essential as it increases the future risk for PD dementia (PDD). Recently, a novel weighting algorithm for the Montreal Cognitive Assessment (MoCA) subtests has been reported, to best discriminate between those with and without cognitive impairment in PD. The aim of our study was to validate this scoring algorithm in a large sample of non-demented PD patients, hypothesizing that the weighted MoCA would have a higher diagnostic accuracy for PD-MCI than the original MoCA. In 202 non-demented PD patients, we evaluated cognitive status, clinical and demographic data, as well as the MoCA with a weighted and unweighted score. Receiver operating characteristic (ROC) curve analysis was used to evaluate discriminative ability of the MoCA. Group comparisons and ROC analysis were performed for PD-MCI classifications with a cut-off ≤ 1, 1.5, and 2 standard deviation (SD) below appropriate norms. PD-MCI patients scored lower on the weighted than the original MoCA version (p < 0.001) compared to PD patients with normal cognitive function. Areas under the curve only differed significantly for the 2 SD cut-off, leading to an increased sensitivity of the weighted MoCA score (72.9% vs. 70.5%) and specificity compared to the original version (79.0% vs. 65.4%). Our results indicate better discriminant power for the weighted MoCA compared to the original for more advanced stages of PD-MCI (2 SD cut-off). Future studies are needed to evaluate the predictive value of the weighted MoCA for PDD.

Assessment of Oropharyngeal Dysphagia in Patients With Parkinson Disease: Use of Ultrasonography.

PubMed

Oh, Eun Hyun; Seo, Jin Seok; Kang, Hyo Jung

2016-04-01

To compare tongue thickness, the shortest hyoid-thyroid approximation (distance between the hyoid bone and thyroid cartilage), and the time interval between the initiation of tongue movement and the time of the shortest hyoid-thyroid approximation, by using ultrasonography in healthy controls and patients with Parkinson disease (PD). Healthy controls and PD patients with dysphagia were compared. Ultrasonography was performed 3 times for the evaluation of tongue thickness, the shortest hyoid-thyroid approximation, and the time between the initiation of tongue movement and the shortest hyoid-thyroid approximation. A total of 24 healthy controls and 24 PD patients with dysphagia were enrolled. No significant differences were demonstrated between the two groups for the shortest hyoid-thyroid approximation (controls, 1.19±0.34 cm; PD patients, 1.37±0.5 cm; p=0.15) and tongue thickness (controls, 4.42±0.46 cm; PD patients, 4.27±0.51 cm; p=0.3). In contrast, the time to the shortest hyoid-thyroid approximation was significantly different between the two groups (controls, 1.53±0.87 ms; PD patients, 2.4±1.4 ms, p=0.048). Ultrasonography can be useful in evaluating dysphagia in patients with PD by direct visualization and measurement of the hyoid bone. Moreover, ultrasonography might contribute to a greater understanding of the pathophysiology of dysphagia in PD.

Lifetime costs for peritoneal dialysis and hemodialysis in patients in Taiwan.

PubMed

Kao, Tze-Wah; Chang, Yu-Yin; Chen, Pau-Chung; Hsu, Chih-Cheng; Chang, Yu-Kang; Chang, Yu-Hung; Lee, Lukas Jyuhn-Hsiarn; Wu, Kwan-Dun; Tsai, Tun-Jun; Wang, Jung-Der

2013-01-01

This study compared the lifetime costs for peritoneal dialysis (PD) and hemodialysis (HD) patients in Taiwan. Using the National Health Insurance (NHI) database of all end-stage renal disease patients on maintenance dialysis registered from July 1997 to December 2005, we matched eligible PD patients with eligible HD patients on age, sex, and diabetes status. The matched patients were followed until 31 December 2006. Patients were excluded if they were less than 18 years of age, had been diagnosed with cancer before dialysis, or had been dialyzed at centers or clinics other than hospitals. Outcomes-including life expectancy, total lifetime costs, and costs per life-year paid by the NHI-were estimated and compared. The 3136 pairs of matched PD and HD patients had a mean age of 53.2 ± 15.4 years. The total lifetime cost for PD patients (US$139 360 ± US$8 336) was significantly lower than that for HD patients (US$185 235 ± US$9 623, p < 0.001). Except for patients with diabetes (who had a short life expectancy), the total lifetime cost was significantly lower for PD patients than for HD patients regardless of sex and age (p < 0.01). In Taiwan, the total lifetime costs paid by the NHI were lower for PD than for HD patients.

Salience Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease

PubMed Central

Christopher, Leigh; Duff-Canning, Sarah; Koshimori, Yuko; Segura, Barbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

2016-01-01

Objective Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n=9), PD with nonamnestic MCI (n=10), PD without MCI (n=11), and healthy controls (n=14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction. PMID:25448687

Malignant Mesothelioma Effusions Are Infiltrated by CD3+ T Cells Highly Expressing PD-L1 and the PD-L1+ Tumor Cells within These Effusions Are Susceptible to ADCC by the Anti-PD-L1 Antibody Avelumab.

PubMed

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-11-01

The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry, and its prognostic significance was examined. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1-positive and PD-L1-positive infiltrating lymphocytes and their role in inducing PD-L1 expression in tumor cells. Antibody-dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized immunoglobulin G1 anti PD-L1 antibody against primary mesothelioma cell lines, was evaluated in presence of autologous and allogeneic natural killer cells. Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1-positive, which was associated with slightly inferior overall survival compared to patients with PD-L1-negative tumors (median 23.0 versus 33.3 months, p = 0.35). The frequency of PD-L1 expression was similar in patients with pleural and peritoneal mesothelioma, with 62% and 64% of samples testing positive, respectively. In nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12% to 83%. In seven patients with paired malignant effusion and peripheral blood mononuclear cell (PBMC) samples, PD-L1 expression was significantly higher on CD3-positive T cells present in malignant effusions as compared with PBMCs (p = 0.016). In addition, the numbers of CD14-positive PD-1-positive cells were increased in malignant effusions compared with PBMCs (p = 0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced interferon-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab-mediated ADCC in the presence of autologous natural killer cells. Most pleural as well as peritoneal mesotheliomas express PD-L1. Malignant effusions in this disease are characterized by the presence of tumor cells and CD3-positive T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by the anti-PD-L1 antibody avelumab. Published by Elsevier Inc.

Malignant mesothelioma effusions are infiltrated by CD3+ T cells highly expressing PD-L1 and the PD-L1+ tumor cells within these effusions are susceptible to ADCC by the anti-PD-L1 antibody avelumab

PubMed Central

Khanna, Swati; Thomas, Anish; Abate-Daga, Daniel; Zhang, Jingli; Morrow, Betsy; Steinberg, Seth M.; Orlandi, Augusto; Ferroni, Patrizia; Schlom, Jeffrey; Guadagni, Fiorella; Hassan, Raffit

2016-01-01

INTRODUCTION The functional aspects of programmed death 1 (PD-1) and PD ligand 1 (PD-L1) immune checkpoints in malignant mesothelioma have not been studied. METHODS Tumor samples from 65 patients with mesothelioma were evaluated for PD-L1 expression by immunohistochemistry and its prognostic significance. Malignant effusions from patients with pleural and peritoneal mesothelioma were evaluated for PD-1+ and PD-L1+ infiltrating lymphocytes and their role in inducing tumor cell PD-L1 expression. Antibody dependent cellular cytotoxicity (ADCC) of avelumab, a fully humanized IgG1 anti PD-L1 antibody towards primary mesothelioma cell lines was evaluated in presence of autologous and allogeneic NK cells. RESULTS Of 65 pleural and peritoneal mesothelioma tumors examined, 41 (63%) were PD-L1 positive, which was associated with slightly inferior overall survival compared to patients with PD-L1 negative tumors (median 23.0 vs. 33.3 months; p=0.35). The frequency of PD-L1 expression was similar in pleural and peritoneal mesothelioma patients with 62% and 64% of samples positive, respectively. Of nine mesothelioma effusion samples evaluated, the fraction of cells expressing PD-L1 ranged from 12 to 83%. Of 7 patients with paired malignant effusion and peripheral blood mononuclear cells (PBMC) samples, PD-L1 expression was significantly higher on CD3+ T cells present in malignant effusions as compared with PBMC (p=0.016). In addition, CD14+PD-1+ cells were elevated in malignant effusions compared with PBMC (p=0.031). The lymphocytes present in malignant effusions recognized autologous tumor cells and induced IFN-γ-mediated PD-L1 expression on the tumor cell surface. Of the three primary mesothelioma cell lines tested, two were susceptible to avelumab mediated ADCC in presence of autologous NK cells. CONCLUSION The majority of pleural as well as peritoneal mesothelioma express PD-L1. Malignant effusions in this disease are characterized by presence of tumor cells and CD3+ T cells that highly express PD-L1. In addition, mesothelioma tumor cells are susceptible to ADCC by anti-PD-L1 antibody avelumab. PMID:27544053

Dreaming furiously? A sleep laboratory study on the dream content of people with Parkinson's disease and with or without rapid eye movement sleep behavior disorder.

PubMed

Valli, Katja; Frauscher, Birgit; Peltomaa, Taina; Gschliesser, Viola; Revonsuo, Antti; Högl, Birgit

2015-03-01

Rapid eye movement (REM) sleep behavior disorder (RBD) has been related to altered, action-filled, vivid, and aggressive dream content, but research comparing the possible differences in dreams of Parkinson's disease (PD) patients with and without RBD is scarce. The dream content of PD patients with and without RBD was analyzed with specific focus on action-filledness, vividness, emotional valence, and threats. A total of 69 REM and NREM dream reports were collected in the sleep laboratory, 37 from nine PD patients with RBD and 32 from six PD patients without RBD. A content analysis of (1) action-filledness (actions and environmental events); (2) vividness (emotions and cognitive activity); (3) intensity of actions, events and emotions; (4) emotional valence, and (5) threatening events was performed on the transcripts. Altogether 563 dream elements expressing action-filledness and vividness were found. There were no significant between-group differences in the number or distribution of elements reflecting action-filledness or vividness, emotional valence or threats. In within-group analyses, PD patients with RBD had significantly more negative compared to positive dreams (p = 0.012) and compared to PD patients without RBD, a tendency to have more intense actions in their dreams (p = 0.066). Based on the results of this study, there are no major between-group differences in the action-filledness, vividness, or threat content of dreams of PD patients with and without RBD. However, within-group analyses revealed that dreams were more often negatively than positively toned in PD patients with RBD. Copyright © 2014 Elsevier B.V. All rights reserved.

Socioeconomic status in relation to Parkinson's disease risk and mortality: A population-based prospective study.

PubMed

Yang, Fei; Johansson, Anna L V; Pedersen, Nancy L; Fang, Fang; Gatz, Margaret; Wirdefeldt, Karin

2016-07-01

Little is known about the role of socioeconomic status in relation to Parkinson's disease (PD) risk, and no study has investigated whether the impact of socioeconomic status on all-cause mortality differs between individuals with and without PD.In this population-based prospective study, over 4.6 million Swedish inhabitants who participated in the Swedish census in 1980 were followed from 1981 to 2010. The incidence rate of PD and incidence rate ratio were estimated for the association between socioeconomic status and PD risk. Age-standardized mortality rate and hazard ratio (HR) were estimated for the association between socioeconomic status and all-cause mortality for individuals with and without PD.During follow-up, 66,332 incident PD cases at a mean age of 76.0 years were recorded. Compared to individuals with the highest socioeconomic status (high nonmanual workers), all other socioeconomic groups (manual or nonmanual and self-employed workers) had a lower PD risk. All-cause mortality rates were higher in individuals with lower socioeconomic status compared with high nonmanual workers, but relative risks for all-cause mortality were lower in PD patients than in non-PD individuals (e.g., for low manual workers, HR: 1.12, 95% confidence interval [CI]: 1.09-1.15 for PD patients; HR: 1.36, 95% CI: 1.35-1.36 for non-PD individuals).Individuals with lower socioeconomic status had a lower PD incidence compared to the highest socioeconomic group. Lower socioeconomic status was associated with higher all-cause mortality among individuals with and without PD, but such impact was weaker among PD patients.

Abnormal sexuality in Parkinson's disease: fact or fancy?

PubMed

Ferrucci, Roberta; Panzeri, Marta; Ronconi, Lucia; Ardolino, Gianluca; Cogiamanian, Filippo; Barbieri, Sergio; Barone, Paolo; Bertolasi, Laura; Padovani, Alessandro; Priori, Alberto

2016-10-15

Patients with Parkinson's disease (PD) variably report sexual dysfunctions. We assessed sexuality in PD by comparing sexual function between a large group of patients with idiopathic PD and a group of subjects without PD. We recruited 121 patients with mild-to-moderate PD (aged 40-80years) from four Italian Movement Disorder Clinics and 123 non-Parkinsonian controls (NPC) (aged 40-80years). Sexual function was assessed with four scales: the Brief Index of Sexual Functioning (BISF-M for men; BISF-W for women), the International Index of Erectile Function (IIEF), and the Female Sexual Function Index (FSFI). Both groups also underwent assessment with the Beck Depression Inventory (BDI) and the Mini Mental State Examination (MMSE), and patients were assessed with the Parkinson's Disease Questionnaire-8 (PDQ-8). No differences in total score were found between PD and NPC for any sexual function scale (BISF-M, BISF-W, IIEF, FSFI: p>0.05). However, the Orgasm/Pleasure Domain (BISF, D5) was significantly lower in male patients than in controls. Our findings fail to confirm previous findings that PD is associated with a significant sexual impairment. NPC and patients with PD have comparable sexual function in both sexes. Thus, rather than dismissing sexual dysfunction as a normal parkinsonian symptom, physicians should refer patients to sexual medicine specialists who can investigate and discuss problems fully, diagnose possible comorbidities, and suggest appropriate treatments. Copyright © 2016. Published by Elsevier B.V.

Dialysis Modality and Readmission Following Hospital Discharge: A Population-Based Cohort Study.

PubMed

Perl, Jeffrey; McArthur, Eric; Bell, Chaim; Garg, Amit X; Bargman, Joanne M; Chan, Christopher T; Harel, Shai; Li, Lihua; Jain, Arsh K; Nash, Danielle M; Harel, Ziv

2017-07-01

Readmissions following hospital discharge among maintenance dialysis patients are common, potentially modifiable, and costly. Compared with patients receiving in-center hemodialysis (HD), patients receiving peritoneal dialysis (PD) have fewer routine dialysis clinic encounters and as a result may be more susceptible to a hospital readmission following discharge. Population-based retrospective-cohort observational study. Patients treated with maintenance dialysis who were discharged following an acute-care hospitalization during January 1, 2003, to December 31, 2013, across 164 acute-care hospitals in Ontario, Canada. For those with multiple hospitalizations, we randomly selected a single hospitalization as the index hospitalization. Dialysis modality PD or in-center HD. Propensity scores were used to match each patient on PD therapy to 2 patients on in-center HD therapy to ensure that baseline indicators of health were similar between the 2 groups. All-cause 30-day readmission following the index hospital discharge. 28,026 dialysis patients were included in the study. 4,013 PD patients were matched to 8,026 in-center HD patients. Among the matched cohort, 30-day readmission rates were 7.1 (95% CI, 6.6-7.6) per 1,000 person-days for patients on PD therapy and 6.0 (95% CI, 5.7-6.3) per 1,000 person-days for patients on in-center HD therapy. The risk for a 30-day readmission among patients on PD therapy was higher compared with those on in-center HD therapy (adjusted HR, 1.19; 95% CI, 1.08-1.31). The primary results were consistent across several key prespecified subgroups. Lack of information for the frequency of nephrology physician encounters following discharge from the hospital in both the PD and in-center HD cohorts. Limited validation of International Classification of Diseases, Tenth Revision codes. The risk for 30-day readmission is higher for patients on home-based PD compared to in-center HD therapy. Interventions to improve transitions in care between the inpatient and outpatient settings are needed, particularly for patients on PD therapy. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Peritoneal dialysis in rural Australia.

PubMed

Gray, Nicholas A; Grace, Blair S; McDonald, Stephen P

2013-12-20

Australians living in rural areas have lower incidence rates of renal replacement therapy and poorer dialysis survival compared with urban dwellers. This study compares peritoneal dialysis (PD) patient characteristics and outcomes in rural and urban Australia. Non-indigenous Australian adults who commenced chronic dialysis between 1 January 2000 and 31 December 2010 according to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were investigated. Each patient's residence was classified according to the Australian Bureau of Statistics remote area index as major city (MC), inner regional (IR), outer regional (OR), or remote/very remote (REM). A total of 7657 patients underwent PD treatment during the study period. Patient distribution was 69.0% MC, 19.6% IR, 9.5% OR, and 1.8% REM. PD uptake increased with increasing remoteness. Compared with MC, sub-hazard ratios [95% confidence intervals] for commencing PD were 1.70 [1.61-1.79] IR, 2.01 [1.87-2.16] OR, and 2.60 [2.21-3.06] REM. During the first 6 months of PD, technique failure was less likely outside MC (sub-hazard ratio 0.47 [95% CI: 0.35-0.62], P < 0.001), but no difference was seen after 6 months (sub-hazard ratio 1.05 [95% CI: 0.84-1.32], P = 0.6). Technique failure due to technical (sub-hazard ratio 0.57 [95% CI: 0.38-0.84], P = 0.005) and non-medical causes (sub-hazard ratio 0.52 [95% CI: 0.31-0.87], P = 0.01) was less likely outside MC. Time to first peritonitis episode was not associated with remoteness (P = 0.8). Patient survival while on PD or within 90 days of stopping PD did not differ by region (P = 0.2). PD uptake increases with increasing remoteness. In rural areas, PD technique failure is less likely during the first 6 months and time to first peritonitis is comparable to urban areas. Mortality while on PD does not differ by region. PD is therefore a good dialysis modality choice for rural patients in Australia.

Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

PubMed

Shea, Yat Fung; Lam, Man-Fai; Lee, Mi Suen Connie; Mok, Ming Yee Maggie; Lui, Sing-Leung; Yip, Terence P S; Lo, Wai Kei; Chu, Leung Wing; Chan, Tak-Mao

2016-02-01

Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45% were female. The prevalence of CI was 13.9% using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p < 0.001), lower CMMSE (p < 0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p < 0.001). Compared with self-care PD patients, assisted PD patients did not have higher rates exit site infection (p = 0.30) but had a trend of higher PD peritonitis (p = 0.07). CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

CSF biomarkers associated with disease heterogeneity in early Parkinson’s disease: the Parkinson’s Progression Markers Initiative study

PubMed Central

Kang, Ju-Hee; Mollenhauer, Brit; Coffey, Christopher S.; Toledo, Jon B.; Weintraub, Daniel; Galasko, Douglas R.; Irwin, David J.; Van Deerlin, Vivianna; Chen-Plotkin, Alice S.; Caspell-Garcia, Chelsea; Waligórska, Teresa; Taylor, Peggy; Shah, Nirali; Pan, Sarah; Zero, Pawel; Frasier, Mark; Marek, Kenneth; Kieburtz, Karl; Jennings, Danna; Tanner, Caroline M.; Simuni, Tanya; Singleton, Andrew; Toga, Arthur W.; Chowdhury, Sohini; Trojanowski, John Q.; Shaw, Leslie M.

2016-01-01

The development of biomarkers to predict the progression of Parkinson’s disease (PD) from its earliest stage through its heterogeneous course is critical for research and therapeutic development. The Parkinson’s Progression Markers Initiative (PPMI) study is an ongoing international multicenter, prospective study to validate biomarkers in drug-naïve PD patients and matched healthy controls (HC). We quantified cerebrospinal fluid (CSF) alpha-synuclein (α-syn), amyloid-beta1–42 (Aβ1–42), total tau (t-tau), and tau phosphorylated at Thr181 (p-tau) in 660 PPMI subjects at baseline, and correlated these data with measures of the clinical features of these subjects. We found that CSF α-syn, t-tau and p-tau levels, but not Aβ1–42, were significantly lower in PD compared with HC, while the diagnostic value of the individual CSF biomarkers for PD diagnosis was limited due to large overlap. The level of α-syn, but not other biomarkers, was significantly lower in PD patients with non-tremor-dominant phenotype compared with tremor-dominant phenotype. In addition, in PD patients the lowest Aβ1–42, or highest t-tau/Aβ1–42 and t-tau/α-syn quintile in PD patients were associated with more severe non-motor dysfunction compared with the highest or lowest quintiles, respectively. In a multivariate regression model, lower α-syn was significantly associated with worse cognitive test performance. APOE ε4 genotype was associated with lower levels of Aβ1–42, but neither with PD diagnosis nor cognition. Our data suggest that the measurement of CSF biomarkers in early-stage PD patients may relate to disease heterogeneity seen in PD. Longitudinal observations in PPMI subjects are needed to define their prognostic performance. PMID:27021906

Satisfaction with care in peritoneal dialysis patients.

PubMed

Kirchgessner, J; Perera-Chang, M; Klinkner, G; Soley, I; Marcelli, D; Arkossy, O; Stopper, A; Kimmel, P L

2006-10-01

Patient satisfaction is an important aspect of dialysis care, only recently evaluated in clinical studies. We developed a tool to assess peritoneal dialysis (PD) customer satisfaction, and sought to evaluate and validate the Customer Satisfaction Questionnaire (CSQ), quantifying PD patient satisfaction. The CSQ included questions regarding administrative issues, Delivery Service, PD Training, Handling Requests, and transportation. The study was performed using interviews in all Hungarian Fresenius Medical Care dialysis centers offering PD. CSQ results were compared with psychosocial measures to identify if patient satisfaction was associated with perception of social support and illness burden, or depression. We assessed CSQ internal consistency and validity. Factor analysis explored potential underlying dimensions of the CSQ. One hundred and thirty-three patients treated with PD for end-stage renal disease for more than 3 months were interviewed. The CSQ had high internal consistency. There was high patient satisfaction with customer service. PD patient satisfaction scores correlated with quality of life (QOL) and social support measures, but not with medical or demographic factors, or depressive affect. The CSQ is a reliable tool to assess PD customer satisfaction. PD patient satisfaction is associated with perception of QOL. Efforts to improve customer satisfaction may improve PD patients' quantity as well as QOL.

Differential performance on tasks of affective processing and decision-making in patients with Panic Disorder and Panic Disorder with comorbid Major Depressive Disorder.

PubMed

Kaplan, Johanna S; Erickson, Kristine; Luckenbaugh, David A; Weiland-Fiedler, Petra; Geraci, Marilla; Sahakian, Barbara J; Charney, Dennis; Drevets, Wayne C; Neumeister, Alexander

2006-10-01

Neuropsychological studies have provided evidence for deficits in psychiatric disorders, such as schizophrenia and mood disorders. However, neuropsychological function in Panic Disorder (PD) or PD with a comorbid diagnosis of Major Depressive Disorder (MDD) has not been comprehensively studied. The present study investigated neuropsychological functioning in patients with PD and PD + MDD by focusing on tasks that assess attention, psychomotor speed, executive function, decision-making, and affective processing. Twenty-two unmedicated patients with PD, eleven of whom had a secondary diagnosis of MDD, were compared to twenty-two healthy controls, matched for gender, age, and intelligence on tasks of attention, memory, psychomotor speed, executive function, decision-making, and affective processing from the Cambridge Neuropsychological Test Automated Battery (CANTAB), Cambridge Gamble Task, and Affective Go/No-go Task. Relative to matched healthy controls, patients with PD + MDD displayed an attentional bias toward negatively-valenced verbal stimuli (Affective Go/No-go Task) and longer decision-making latencies (Cambridge Gamble Task). Furthermore, the PD + MDD group committed more errors on a task of memory and visual discrimination compared to their controls. In contrast, no group differences were found for PD patients relative to matched control subjects. The sample size was limited, however, all patients were drug-free at the time of testing. The PD + MDD patients demonstrated deficits on a task involving visual discrimination and working memory, and an attentional bias towards negatively-valenced stimuli. In addition, patients with comorbid depression provided qualitatively different responses in the areas of affective and decision-making processes.

Comparison between hyperventilation and breath-holding in panic disorder: patients responsive and non-responsive to both tests.

PubMed

Nardi, Antonio E; Valença, Alexandre M; Mezzasalma, Marco A; Levy, Sandra P; Lopes, Fabiana L; Nascimento, Isabella; Freire, Rafael C; Veras, Andre B; Zin, Walter A

2006-06-15

Our aim was to compare the demographic and psychopathological features of panic disorder (PD) patients who underwent hyperventilation and breath-holding challenge tests, and to describe the features of patients who had a panic attack after both tests versus those patients who did not experience panic after either test. Eighty-five PD patients were induced to hyperventilate (30 breaths/min) for 4 min, and a week later to hold their breath for as long as possible four times with a 2-min interval in between. Anxiety scales were applied before and after the tests. Patients who responded with a panic attack to both tests (BPA, n = 25) were compared with patients who experienced spontaneous panic attacks but did not panic in response to the two tests (NPA, n = 16). The BPA group had a significantly higher presence of respiratory symptoms during a panic attack. The criteria for the respiratory PD subtype were fulfilled in 18 (72.0%) BPA patients and in 6 (37.5%) NPA patients. The BPA patients had a later onset of panic disorder and a higher familial prevalence of PD. Our data suggest that there is a distinction between PD patients who were sensitive to both hyperventilation and breath-holding tests and PD patients who were not affected by the challenge tests. The panic attack may be a final common pathway for different types of stimuli, and respiratory tests may characterize different PD subgroups.

Power Doppler Ultrasound Evaluation of Peripheral Joint, Entheses, Tendon, and Bursa Abnormalities in Psoriatic Patients: A Clinical Study.

PubMed

Tang, Yuanjiao; Yang, Yujia; Xiang, Xi; Wang, Liyun; Zhang, Lingyan; Qiu, Li

2018-06-01

To evaluate the prevalence rates of peripheral joint, enthesis, tendon, and bursa abnormalities by power Doppler (PD) ultrasonic examination in patients with psoriatic arthritis (PsA), psoriatic patients without clinical signs of arthritis (non-PsA psoriasis group), and healthy individuals, to detect subclinical PsA. A total of 253 healthy volunteers, 242 non-PsA psoriatic patients, and 86 patients with PsA were assessed by 2-dimensional and power Doppler (PD) ultrasound. Peripheral joint, enthesis, tendon, and bursa abnormalities were observed, characterizing abnormal PD. The affected patients and sites with abnormalities in various ages were compared among groups; PD signal grades for the abnormalities were also compared. In the PsA group, significantly higher percentages of sites showing joint effusion/synovitis, enthesitis, and tenosynovitis in all age groups, and markedly higher rates of sites with bursitis were found in young and middle age groups, compared with the non-PsA and control groups (all p < 0.01). Meanwhile, the non-PsA group showed significantly higher rates of joint effusion/synovitis and enthesitis sites, and elevated PD signal grades of synovitis, enthesitis, and tenosynovitis in comparison with the control group, both in young and middle age groups (all p < 0.01). Patients with PsA have high percentages and PD signal grades of peripheral joint, tendon, enthesis, and bursa involvement. Young and middle-aged non-PsA patients have high synovitis and enthesitis percentages, and elevated PD signal grades of synovitis, enthesitis, and tenosynovitis.

Hyposalivation and xerostomia among Parkinson's disease patients and its impact on quality of life.

PubMed

Barbe, A G; Heinzler, A; Derman, Shm; Hellmich, M; Timmermann, L; Noack, M J

2017-05-01

Parkinson's disease (PD) adversely affects oral health (OH). However, the informative value of xerostomia compared to objective parameters and its impact on quality of life (QoL) are still unclear. This study aimed to explore whether xerostomia correlates with hyposalivation and to define its impact on OH-related QoL. Whole stimulated saliva (WSS) was collected from 30 patients with PD and 30 matched healthy controls. Objective parameters (community periodontal index of treatment needs, plaque/gingivitis index, mucosa situation and cheilitis angularis) and questionnaires (German Oral Health Impact Profile [OHIPG]-14, visual analogue scale [VAS], xerostomia [yes/no] and the Unified Parkinson's Disease Rating Scale-II) were assessed. Eighty-seven per cent of patients with PD showed hyposalivation vs 50% of controls (P = 0.001); 50% of patients with PD reported xerostomia, and none of controls (P < 0.001). The OHIPG-14 was impaired in patients with PD compared to controls (P < 0.001), PD patients with xerostomia reported mean VAS values of 4.1 (s.d.: 2.2). WSS did not correlate with VAS values. Half of the patients with PD reported xerostomia and underestimated their xerostomic status, with higher probability than healthy controls. WSS did not reflect the grade of xerostomia. Patients with PD suffered from impaired OH-related QoL. Dental teams should not overlook these oral health risks. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Permanent cardiac pacing in patients with end-stage renal disease undergoing dialysis.

PubMed

Wang, I-Kuan; Lin, Kuo-Hung; Lin, Shih-Yi; Lin, Cheng-Li; Chang, Chiz-Tzung; Yen, Tzung-Hai; Sung, Fung-Chang

2016-12-01

Studies investigating the risk of cardiac dysrhythmia warranting permanent pacemaker therapy for end-stage renal disease (ESRD) patients are limited. This study investigated the incidence rate of permanent cardiac pacing in dialysis patients. Using the Taiwan National Health Insurance Database, we identified 28 471 newly diagnosed ESRD patients in 2000-2010 [9700 on peritoneal dialysis (PD) and 18 771 on hemodialysis (HD)] and 113 769 randomly selected controls without kidney disease, frequency-matched by sex, age and diagnosis date. We also established propensity score-matched HD and PD cohorts with 9700 patients each. Incidence rates and hazard ratios (HRs) of implantation were evaluated by the end of 2011. Complications were also evaluated among patients with implantation. The incidence rates of permanent pacemaker implantation were 5.93- and 3.50-fold greater in HD and PD patients than in controls (1.44 and 0.85 versus 0.24 per 1000 person-years, respectively). The adjusted HRs (aHRs) of implantation were 3.26 [95% confidence interval (CI) = 2.41-4.42] and 2.36 (95% CI = 1.56-3.58) for HD and PD patients, respectively, compared with controls. The pacemaker implantation rate was 0.33 per 1000 person-years greater in the propensity score-matched HD cohort than in the PD cohort, with an aHR of 1.30 (95% CI = 0.82-2.05) for the HD cohort compared with the PD cohort. Dialysis patients are at an increased risk of dysrhythmia requiring pacemaker implantation compared with the general population. The risks are not significantly different between HD and PD patients. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.

PubMed

Abrahams, Alferso C; Habib, Sayed M; Dendooven, Amélie; Riser, Bruce L; van der Veer, Jan Willem; Toorop, Raechel J; Betjes, Michiel G H; Verhaar, Marianne C; Watson, Christopher J E; Nguyen, Tri Q; Boer, Walther H

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFβ1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

PubMed Central

Abrahams, Alferso C.; Habib, Sayed M.; Dendooven, Amélie; Riser, Bruce L.; van der Veer, Jan Willem; Toorop, Raechel J.; Betjes, Michiel G. H.; Verhaar, Marianne C.; Watson, Christopher J. E.; Nguyen, Tri Q.; Boer, Walther H.

2014-01-01

Introduction Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study. PMID:25384022

Protein Carbamylation in Peritoneal Dialysis and the Effect of Low Glucose Plus Amino Acid Solutions.

PubMed

Trottier, Caitlin; Perl, Jeffrey; Freeman, Megan; Thadhani, Ravi; Berg, Anders; Kalim, Sahir

2018-01-01

Protein carbamylation is a post-translational urea-driven protein modification associated with mortality. Free amino acids (AAs) competitively inhibit protein carbamylation and parenteral AA therapy reduces carbamylation in hemodialysis (HD) patients. Peritoneal dialysis (PD) yields differences in urea clearance and AA balance compared with HD, but the influence of PD and intraperitoneal AA solutions on carbamylation is unclear. Thus, we first measured carbamylated albumin (C-Alb; a marker of carbamylation load) in 100 diabetic HD patients frequency-matched by age, sex, and race to 98 diabetic PD subjects from the IMPENDIA trial, which originally compared the metabolic effects of low-glucose PD solutions (incorporating icodextrin and AAs) to a control group (dextrose-only solutions). We then determined the effects of the AA-enriched PD solutions by measuring the 6-month change in C-Alb within the IMPENDIA cohort by treatment allocation (48 treated vs 50 controls). Peritoneal dialysis patients, when compared with HD patients, had higher baseline urea and higher C-Alb. Among IMPENDIA participants, there was no difference in C-Alb change in either arm, but treated subjects showed a trend towards increased carbamylation. Treated subjects also demonstrated an increase in urea, possibly explaining the carbamylation trend. In summary, carbamylation levels in PD patients appeared higher than in matched HD patients. A regimen of AA and low-glucose PD solutions did not reduce C-Alb in IMPENDIA subjects. Copyright © 2018 International Society for Peritoneal Dialysis.

Propofol Requirement for Induction of Unconsciousness Is Reduced in Patients with Parkinson's Disease: A Case Control Study

PubMed Central

Xu, Xiao-ping; Yu, Xi-ya; Wu, Xi; Hu, Xiao-wu; Chen, Jian-chun; Li, Jin-bao; Deng, Xiao-ming

2015-01-01

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, but whether the neurodegenerative process influences the pharmacodynamics of propofol remains unclear. We aimed to evaluate the effect of PD on pharmacodynamics of propofol. A total of 31 PD patients undergoing surgical treatment (PD group) and 31 pair-controlled non-PD patients undergoing intracranial surgery (NPD group) were recruited to investigate the propofol requirement for unconsciousness induction. Unconsciousness was induced in all patients with target-controlled infusion of propofol. The propofol concentration at which unconsciousness was induced was compared between the two groups. EC50 and EC95 were calculated as well. Demographic data, bispectral index, and hemodynamic values were comparable between PD and NPD groups. The mean target concentration of propofol when unconsciousness was achieved was 2.32 ± 0.38 μg/mL in PD group, which was significantly lower than that in NPD group (2.90 ± 0.35 μg/mL). The EC50 was 2.05 μg/mL (95% CI: 1.85–2.19 μg/mL) in PD group, much lower than the 2.72 μg/mL (95% CI: 2.53–2.88 μg/mL) in NPD group. In conclusion, the effective propofol concentration needed for induction of unconsciousness in 50% of patients is reduced in PD patients. (This trial is registered with NCT01998204.) PMID:26495319

Comparison of peritoneal dialysis and hemodialysis after kidney transplant failure.

PubMed

Kang, G W; Jang, M H; Hwang, E A; Park, S B; Han, S Y

2013-10-01

Patients with a failed kidney transplant represent a unique chronic kidney disease population that is increasing in number and is at high risk of morbidity and mortality. Among transplant-naïve patients, those treated with peritoneal dialysis (PD) show an early survival advantage compared with those treated with hemodialysis (HD). But any advantage of PD after allograft failure is unknown. The aim of this study was to investigate the clinical outcomes of patients with failed allografts according to the type of dialysis modality. We reviewed medical records of patients who initiated dialysis after kidney transplant failure from November 1982 to May 2011. Demographics features, clinical data, and survival outcomes were compared between PD and HD patients who had experienced allograft failure. The 182 patients with failed allografts showed the most common cause to be chronic rejection. The median duration of function before allograft failure was 74.0 months. After allograft failure, 145 (79.7%) patients returned to HD and 37 (20.3%) to PD. Twenty-three patients (12.6%) died over the median 69.1 months duration of follow-up. During the observation period, 16 HD (11%) and 7 PD (8.9%) patients died. The survival rates of PD patients at 1 year were 91.2% and 84.4%, respectively, at 1 and 3 years, and those of HD patients 94.8% and 88.9%. There was no significant difference in the survivals of the 2 groups. The study suggests that the outcome of patients starting PD after kidney transplant failure was similar to those starting HD. Therefore, PD can be regarded to be a good treatment option for patients returning to dialysis after kidney transplant failure. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Economic evaluation of policy options for dialysis in end-stage renal disease patients under the universal health coverage in Indonesia.

PubMed

Afiatin; Khoe, Levina Chandra; Kristin, Erna; Masytoh, Lusiana Siti; Herlinawaty, Eva; Werayingyong, Pitsaphun; Nadjib, Mardiati; Sastroasmoro, Sudigdo; Teerawattananon, Yot

2017-01-01

This study aims to assess the value for money and budget impact of offering hemodialysis (HD) as a first-line treatment, or the HD-first policy, and the peritoneal dialysis (PD) first policy compared to a supportive care option in patients with end-stage renal disease (ESRD) in Indonesia. A Markov model-based economic evaluation was performed using local and international data to quantify the potential costs and health-related outcomes in terms of life years (LYs) and quality-adjusted life years (QALYs). Three policy options were compared, i.e., the PD-first policy, HD-first policy, and supportive care. The PD-first policy for ESRD patients resulted in 5.93 life years, equal to the HD-first policy, with a slightly higher QALY gained (4.40 vs 4.34). The total lifetime cost for a patient under the PD-first policy is around 700 million IDR, which is lower than the cost under the HD-first policy, i.e. 735 million IDR per patient. Compared to supportive care, the incremental cost-effectiveness ratio of the PD-first policy is 193 million IDR per QALY, while the HD-first policy resulted in 207 million IDR per QALY. Budget impact analysis indicated that the required budget for the PD-first policy is 43 trillion IDR for 53% coverage and 75 trillion IDR for 100% coverage in five years, which is less than the HD-first policy, i.e. 88 trillion IDR and 166 trillion IDR. The PD-first policy was found to be more cost-effective compared to the HD-first policy. Budget impact analysis provided evidence on the enormous financial burden for the country if the current practice, where HD dominates PD, continues for the next five years.

Effectiveness of anti-PD-1/PD-L1 antibodies in urothelial carcinoma patients with different PD-L1 expression levels: a meta-analysis.

PubMed

Liu, Junqi; Zhang, Chuanfeng; Hu, Jiegang; Tian, Qing; Wang, Xin; Gu, Hao; Zhang, Song; Zhao, Di; Fan, Ruitai

2018-02-23

Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD-1)/programmed death-ligand1 (PD-L1) inhibitors. We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD-1/PD-L1 antibodies in patients with different PD-L1 expression levels. We divided patients into three groups according to the percentages of PD-L1-positive cells, namely the low- PD-L1 (PD-L1 < 1%), the medium-PD-L1 (PD-L1 ≥ 1 and < 5%) and the high-PD-L1 (PD-L1 ≥ 5%) groups. We found that the high-PD-L1 group responded significantly better than other groups (P = 0.0003, ORs = 0.45, 95%CI: 0.29-071; P = 0.0009, ORs = 0.43, 95%CI: 0.25-0.73, for low-PD-L1 and medium-PD-L1 groups, respectively), while the latter two groups responded similarly (P = 0.90, ORs = 1.06, 95%CI: 0.62-1.83) to both PD-1 and PD-L1 inhibitors. Furthermore, we found that the medium-PD-L1 and high-PD-L1 groups responded similarly to PD-1/ PD-L1 inhibitors (P = 0.65, ORs = 1.11, 95%CI: 0.69-1.77), while the low-PD-L1 group responded better to PD-1 inhibitors than PD-L1 inhibitors (P = 0.046, ORs = 1.92, 95%CI: 0.98-3.89). Our results suggest that PD-L1 positive patients should be defined as those with ≥ 5% or greaterPD-L1-positive cells. PD-1 antibodies performed better only in the low-group patients, likely because they could block the interactions of PD-1 with both PD-L1 and PD-L2.

Increased risk of hydrocephalus in long-term dialysis patients.

PubMed

Wang, I-Kuan; Lin, Cheng-Li; Cheng, Yu-Kai; Chou, Che-Yi; Liang, Chih-Chia; Yen, Tzung-Hai; Sung, Fung-Chang

2016-05-01

The risk of hydrocephalus in end-stage renal disease (ESRD) patients on dialysis has not been studied in depth. Using Taiwan National Health Insurance claims data, we identified 29 684 incident ESRD patients from 2000 to 2010, including 10 030 peritoneal dialysis (PD) patients and 19 654 hemodialysis (HD) patients. The control cohort consisted of 118 736 people randomly selected from those without kidney disease, frequency matched with ESRD patients by age, sex and index year. We also established propensity score-matched cohorts with 10 014 PD and 10 014 HD patients. The incidence rates and hazard ratios (HRs) of hydrocephalus were calculated until the end of 2011. Incidence rates of hydrocephalus were greater in HD and PD patients than in controls (8.44 and 11.0 versus 4.11 per 10 000 person-years, respectively), with an adjusted HR of 1.86 [95% confidence interval (CI) 1.43-2.41] for all ESRD patients compared with controls. A higher proportion of hydrocephalus patients underwent surgical bypass to relieve hydrocephalus in ESRD patients than controls, 40.7% (46/113) versus 24.5% (67/273), with an adjusted odds ratio of 2.11 (95% CI 1.33-3.36). Compared with controls, the adjusted HRs of communicating hydrocephalus for HD and PD patients were 1.77 (95% CI 1.22-2.55) and 2.51 (95% CI 1.61-3.89), respectively. The propensity score-matched analysis showed an HR of 0.72 (95% CI 0.42-1.23) for hydrocephalus in HD patients compared with PD patients. Patients with ESRD are at an increased risk of hydrocephalus. The risk difference between HD and PD patients is not significant. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

"Biocompatible" Neutral pH Low-GDP Peritoneal Dialysis Solutions: Much Ado About Nothing?

PubMed

Misra, Paraish S; Nessim, Sharon J; Perl, Jeffrey

2017-03-01

Adverse outcomes in peritoneal dialysis (PD), including PD related infections, the loss of residual kidney function (RKF), and longitudinal, deleterious changes in peritoneal membrane function continue to limit the long-term success of PD therapy. The observation that these deleterious changes occur upon exposure to conventional glucose-based PD solutions fuels the search for a more biocompatible PD solution. The development of a novel PD solution with a neutral pH, and lower in glucose degradation products (GDPs) compared to its conventional predecessors has been labeled a "biocompatible" solution. While considerable evidence in support of these novel solutions' biocompatibility has emerged from cell culture and animal studies, the clinical benefits as compared to conventional PD solutions are less clear. Neutral pH low GDP (NpHLGDP) PD solutions appear to be effective in reducing infusion pain, but their effects on other clinical endpoints including peritoneal membrane function, preservation of RKF, PD-related infections, and technique and patient survival are less clear. The literature is limited by studies characterized by relatively few patients, short follow-up time, heterogeneity with regards to the novel PD solution type under study, and the different patient populations under study. Nonetheless, the search for a more biocompatible PD solution continues with emerging data on promising non glucose-based solutions. © 2017 Wiley Periodicals, Inc.

Patients with Parkinson's disease display a dopamine therapy related negative bias and an enlarged range in emotional responses to facial emotional stimuli.

PubMed

Lundqvist, Daniel; Svärd, Joakim; Michelgård Palmquist, Åsa; Fischer, Håkan; Svenningsson, Per

2017-09-01

The literature on emotional processing in Parkinson's disease (PD) patients shows mixed results. This may be because of various methodological and/or patient-related differences, such as failing to adjust for cognitive functioning, depression, and/or mood. In the current study, we tested PD patients and healthy controls (HCs) using emotional stimuli across a variety of tasks, including visual search, short-term memory (STM), categorical perception, and emotional stimulus rating. The PD and HC groups were matched on cognitive ability, depression, and mood. We also explored possible relationships between task results and antiparkinsonian treatment effects, as measured by levodopa equivalent dosages (LED), in the PD group. The results show that PD patients use a larger emotional range compared with HCs when reporting their impression of emotional faces on rated emotional valence, arousal, and potency. The results also show that dopaminergic therapy was correlated with stimulus rating results such that PD patients with higher LED scores rated negative faces as less arousing, less negative, and less powerful. Finally, results also show that PD patients display a general slowing effect in the visual search tasks compared with HCs, indicating overall slowed responses. There were no group differences observed in the STM or categorical perception tasks. Our results indicate a relationship between emotional responses, PD, and dopaminergic therapy, in which PD per se is associated with stronger emotional responses, whereas LED levels are negatively correlated with the strength of emotional responses. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Multiscale entropy analysis of electroencephalography during sleep in patients with Parkinson disease.

PubMed

Chung, Chen-Chih; Kang, Jiunn-Horng; Yuan, Rey-Yue; Wu, Dean; Chen, Chih-Chung; Chi, Nai-Fang; Chen, Po-Chih; Hu, Chaur-Jong

2013-07-01

Sleep disorders are frequently seen in patients with Parkinson disease (PD), including rapid eye movement (REM) behavior disorder and periodic limb movement disorder. However, knowledge about changes in non-REM sleep in patients with PD is limited. This study explored the characteristics of electroencephalography (EEG) during sleep in patients with PD and non-PD controls. We further conducted multiscale entropy (MSE) analysis to evaluate and compare the complexity of sleep EEG for the 2 groups. There were 9 patients with PD (Hoehn-Yahr stage 1 or 2) and 11 non-PD controls. All participants underwent standard whole-night polysomnography (PSG), which included 23 channels, 6 of which were for EEG. The raw data of the EEG were extracted and subjected to MSE analysis. Patients with PD had a longer sleep onset time and a higher spontaneous EEG arousal index. Sleep stage-specific increased MSE was observed in patients with PD during non-REM sleep. The difference was more marked and significant at higher time scale factors (TSFs). In conclusion, increased biosignal complexity, as revealed by MSE analysis, was found in patients with PD during non-REM sleep at high TSFs. This finding might reflect a compensatory mechanism for early defects in neuronal network control machinery in PD.

Early Corneal Innervation and Trigeminal Alterations in Parkinson Disease: A Pilot Study.

PubMed

Arrigo, Alessandro; Rania, Laura; Calamuneri, Alessandro; Postorino, Elisa Imelde; Mormina, Enricomaria; Gaeta, Michele; Marino, Silvia; Di Lorenzo, Giuseppe; Quartarone, Angelo; Anastasi, Giuseppe; Puzzolo, Domenico; Aragona, Pasquale

2018-04-01

To describe corneal innervation and trigeminal alterations in drug-naive patients with Parkinson disease (PD). A case series study was conducted by recruiting 3 early drug-naive patients with PD, 2 men and 1 woman (age: 72, 68, and 66, respectively). Ophthalmologic assessment included Ocular Surface Disease Index questionnaire, visual acuity by the logarithm of the minimum angle of resolution score, pupillary light reflexes, extrinsic ocular movements, corneal sensitivity, and slit-lamp examination. Corneal innervation parameter changes were evaluated in vivo using the Confoscan 4 confocal microscope, and they were compared with a control data set. The Heidelberg Retina Tomograph 3 (HRT3) has been used to assess retinal alterations in our patients, if compared with normal range values provided by the HRT3. Moreover, 3T magnetic resonance imaging (MRI) analysis of water diffusion property changes of trigeminal nerves was performed. All data were analyzed and compared with 2 control data sets made by 14 age-matched controls. Patients with PD showed profound alterations of corneal innervation and of trigeminal diffusion MRI parameters, compared with controls. Strong differences (PD vs. controls) were found for deep nerve tortuosity (Kallinikos mean 19.94 vs. 2.13) and the number of beadings (mean 34.2 vs. 15.5). HRT3 retinal evaluation revealed less structural changes compared with the normal range. Diffusion MRI showed profound changes of white matter diffusion properties (PD vs. controls), with fractional anisotropy decrement (mean 0.3029 vs. 0.3329) and mean diffusivity increment (mean 0.00127 vs. 0.00106). Corneal innervation changes might occur earlier in patients with PD than in retinal ones. Confocal corneal innervation analysis might provide possible early biomarkers for a better PD evaluation and for its earlier diagnosis.

Is Dialysis Modality a Factor in the Survival of Patients Initiating Dialysis After Kidney Transplant Failure?

PubMed Central

Perl, Jeffrey; Dong, James; Rose, Caren; Jassal, Sarbjit Vanita; Gill, John S.

2013-01-01

♦ Background: Kidney transplant failure (TF) is among the leading causes of dialysis initiation. Whether survival is similar for patients treated with peritoneal dialysis (PD) and with hemodialysis (HD) after TF is unclear and may inform decisions concerning dialysis modality selection. ♦ Methods: Between 1995 and 2007, 16 113 adult dialysis patients identified from the US Renal Data System initiated dialysis after TF. A multivariable Cox proportional hazards model was used to evaluate the impact of initial dialysis modality (1 865 PD, 14 248 HD) on early (1-year) and overall mortality in an intention-to-treat approach. ♦ Results: Compared with HD patients, PD patients were younger (46.1 years vs 49.4 years, p < 0.0001) with fewer comorbidities such as diabetes mellitus (23.1% vs 25.7%, p < 0.0001). After adjustment, survival among PD patients was greater within the first year after dialysis initiation [adjusted hazard ratio (AHR): 0.85; 95% confidence interval (CI): 0.74 to 0.97], but lower after 2 years (AHR: 1.15; 95% CI: 1.02 to 1.29). During the entire period of observation, survival in both groups was similar (AHR for PD compared with HD: 1.09; 95% CI: 1.0 to 1.20). In a sensitivity analysis restricted to a cohort of 1865 propensity-matched pairs of HD and PD patients, results were similar (AHR: 1.03; 95% CI: 0.93 to 1.14). Subgroups of patients with a body mass index exceeding 30 kg/m2 [AHR: 1.26; 95% CI: 1.05 to 1.52) and with a baseline estimated glomerular filtration rate (eGFR) less than 5 mL/min/1.73 m2 (AHR: 1.45; 95% CI: 1.05 to 1.98) experienced inferior overall survival when treated with PD. ♦ Conclusions: Compared with HD, PD is associated with an early survival advantage, inferior late survival, and similar overall survival in patients initiating dialysis after TF. Those data suggest that increased initial use of PD among patients returning to dialysis after TF may be associated with improved outcomes, except among patients with a higher BMI and those who initiate dialysis at lower levels of eGFR. The reasons behind the inferior late survival seen in PD patients are unclear and require further study. PMID:24084843

PSP as distinguished from CBD, MSA-P and PD by clinical and imaging differences at an early stage.

PubMed

Kurata, Tomoko; Kametaka, Satsuki; Ohta, Yasuyuki; Morimoto, Nobutoshi; Deguchi, Shoko; Deguchi, Kentaro; Ikeda, Yoshio; Takao, Yoshiki; Ohta, Taisei; Manabe, Yasuhiro; Sato, Shuhei; Abe, Koji

2011-01-01

Because it is often difficult to precisely diagnose and distinguish progressive supranuclear palsy (PSP) from corticobasal degeneration (CBD), multiple system atrophy-parkinsonism (MSA-P) and Parkinson's disease (PD) at the onset of the disease, we compared the patients and clarified the features of these diseases. We compared 77 PSP, 26 CBD, 26 MSA-P and 166 PD patients from clinical and imaging points of view including cerebral blood flow (CBF) in the frontal eye field. The clinical characteristics of PSP were supranuclear gaze disturbance, optokinetic nystagmus (OKN) impairment and falls at the first visit. On head MRI, midbrain tegmentum atrophy was much more frequently detected in PSP than in all of the other groups. Heart-to-mediastinum average count ratio (H/M) in iodine-123 meta-iodobenzyl guanidine ((123)I-MIBG) myocardial scintigraphy was not decreased in PSP, CBD, MSA-P and PD-Yahr 1 (-1), but patients of PD-2, 3, 4 and 5 showed a significant decrease compared with the PSP group. The CBF in the left frontal eye field of PD-3 group and that in right frontal eye field of PD-3 and PD-4 groups were lower than that of PSP group, although other groups showed a tendency without a significant decrease compared with PSP group. PSP is distinguishable from CBD, MSA-P and PD even at the early stage with extra-ocular movement (EOM) disturbance, falls, atrophy of the midbrain tegmentum, and H/M in (123)I-MIBG myocardial scintigraphy, and the reduction of CBF in area 8 could serve as a supplemental diagnostic method for distinguishing PSP from PD-3 or PD-4.

Neonatal indirect hyperbilirubinemia and glucose-6-phosphate dehydrogenase deficiency.

PubMed

Isa, Hasan M; Mohamed, Masooma S; Mohamed, Afaf M; Abdulla, Adel; Abdulla, Fuad

2017-04-01

This study aimed to determine the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among infants with neonatal indirect hyperbilirubinemia (NIH); compare G6PD-deficient and G6PD-normal patients regarding hyperbilirubinemia and need for exchange transfusions (ET); and assess risk factors for ET and kernicterus. This is a case-control retrospective study. Medical records of NIH patients admitted to the Pediatric Department, Salmaniya Medical Complex, Bahrain, between January 2007 and June 2010 were reviewed. Data on sex, age at presentation, hospitalization duration, need for ET, hemoglobin (Hb) level, reticulocyte count, direct Coombs test, serum total and indirect bilirubin levels, thyroid function, blood and urine cultures, G6PD status, and blood groups were collected and compared between the G6PD-deficent and G6PD-normal patients. Of 1,159 NIH patients admitted, 1,129 were included, of whom 646 (57%) were male. Among 1,046 patients tested, 442 (42%) were G6PD deficient, 49 (4%) needed ET, and 11 (1%) had suspected Kernicterus. The G6PD-deficient patients were mainly male ( P <0.0001), and had lower Hb levels ( P <0.0001) and higher maximum bilirubin levels ( P =0.001). More G6PD-deficient patients needed ET ( P <0.0001). G6PD deficiency ( P =0.006), lower Hb level ( P =0.002), lower hematocrit count ( P =0.02), higher bilirubin level ( P <0.0001), higher maximal bilirubin level ( P <0.0001), and positive blood culture result ( P <0.0001) were significant risk factors for ET. Maximal bilirubin level was a significant risk factor for kernicterus ( P =0.021) and independently related to ET ( P =0.03). G6PD deficiency is an important risk factor for severe NIH. In G6PD-deficent neonates, management of NIH should be hastened to avoid irreversible neurological complications.

Separating the effect of reward from corrective feedback during learning in patients with Parkinson's disease.

PubMed

Freedberg, Michael; Schacherer, Jonathan; Chen, Kuan-Hua; Uc, Ergun Y; Narayanan, Nandakumar S; Hazeltine, Eliot

2017-06-01

Parkinson's disease (PD) is associated with procedural learning deficits. Nonetheless, studies have demonstrated that reward-related learning is comparable between patients with PD and controls (Bódi et al., Brain, 132(9), 2385-2395, 2009; Frank, Seeberger, & O'Reilly, Science, 306(5703), 1940-1943, 2004; Palminteri et al., Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19179-19184, 2009). However, because these studies do not separate the effect of reward from the effect of practice, it is difficult to determine whether the effect of reward on learning is distinct from the effect of corrective feedback on learning. Thus, it is unknown whether these group differences in learning are due to reward processing or learning in general. Here, we compared the performance of medicated PD patients to demographically matched healthy controls (HCs) on a task where the effect of reward can be examined separately from the effect of practice. We found that patients with PD showed significantly less reward-related learning improvements compared to HCs. In addition, stronger learning of rewarded associations over unrewarded associations was significantly correlated with smaller skin-conductance responses for HCs but not PD patients. These results demonstrate that when separating the effect of reward from the effect of corrective feedback, PD patients do not benefit from reward.

Peritoneal dialysis in rural Australia

PubMed Central

2013-01-01

Background Australians living in rural areas have lower incidence rates of renal replacement therapy and poorer dialysis survival compared with urban dwellers. This study compares peritoneal dialysis (PD) patient characteristics and outcomes in rural and urban Australia. Methods Non-indigenous Australian adults who commenced chronic dialysis between 1 January 2000 and 31 December 2010 according to the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) were investigated. Each patient’s residence was classified according to the Australian Bureau of Statistics remote area index as major city (MC), inner regional (IR), outer regional (OR), or remote/very remote (REM). Results A total of 7657 patients underwent PD treatment during the study period. Patient distribution was 69.0% MC, 19.6% IR, 9.5% OR, and 1.8% REM. PD uptake increased with increasing remoteness. Compared with MC, sub-hazard ratios [95% confidence intervals] for commencing PD were 1.70 [1.61-1.79] IR, 2.01 [1.87-2.16] OR, and 2.60 [2.21-3.06] REM. During the first 6 months of PD, technique failure was less likely outside MC (sub-hazard ratio 0.47 [95% CI: 0.35-0.62], P < 0.001), but no difference was seen after 6 months (sub-hazard ratio 1.05 [95% CI: 0.84-1.32], P = 0.6). Technique failure due to technical (sub-hazard ratio 0.57 [95% CI: 0.38-0.84], P = 0.005) and non-medical causes (sub-hazard ratio 0.52 [95% CI: 0.31-0.87], P = 0.01) was less likely outside MC. Time to first peritonitis episode was not associated with remoteness (P = 0.8). Patient survival while on PD or within 90 days of stopping PD did not differ by region (P = 0.2). Conclusions PD uptake increases with increasing remoteness. In rural areas, PD technique failure is less likely during the first 6 months and time to first peritonitis is comparable to urban areas. Mortality while on PD does not differ by region. PD is therefore a good dialysis modality choice for rural patients in Australia. PMID:24359341

Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials.

PubMed

Khunger, Monica; Rakshit, Sagar; Pasupuleti, Vinay; Hernandez, Adrian V; Mazzone, Peter; Stevenson, James; Pennell, Nathan A; Velcheti, Vamsidhar

2017-08-01

Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use. MEDLINE, Embase, and Scopus databases were searched up to November 2016. Rates of pneumonitis of any grade and grade ≥ 3 from all clinical trials investigating nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab as single agents in NSCLC were collected. The incidence of pneumonitis across trials was calculated using DerSimonian-Laird random effects models. We compared incidences between PD-1 and PD-L1 inhibitors and between treatment naive and previously treated patients. Nineteen trials (12 with PD-1 inhibitors [n = 3,232] and 7 with PD-L1 inhibitors [n = 1,806]) were identified. PD-1 inhibitors were found to have statistically significant higher incidence of any grade pneumonitis compared with PD-L1 inhibitors (3.6%; 95% CI, 2.4%-4.9% vs 1.3%; 95% CI, 0.8%-1.9%, respectively; P = .001). PD-1 inhibitors were also associated with higher incidence of grade 3 or 4 pneumonitis (1.1%; 95% CI, 0.6%-1.7% vs 0.4%; 95% CI, 0%-0.8%; P = .02). Treatment naive patients had higher incidence of grade 1 through 4 pneumonitis compared with previously treated patients (4.3%; 95% CI, 2.4%-6.3% vs 2.8%; 95% CI, 1.7%- 4%; P = .03). There was a higher incidence of pneumonitis with use of PD-1 inhibitors compared with PD-L1 inhibitors. Higher rate of pneumonitis was more common in treatment naive patients. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

A Cost Evaluation of Peritoneal Dialysis and Hemodialysis in the Treatment of End-Stage Renal Disease in São Paulo, Brazil

PubMed Central

de Abreu, Mirhelen Mendes; Walker, David R.; Sesso, Ricardo C.; Ferraz, Marcos B.

2013-01-01

♦ Objective: Conventional hemodialysis (HD) predominates over peritoneal dialysis (PD) around the world. Prospective and comparative studies comparing the costs of these modalities are scarce. In the present prospective assessment, we describe the resources used and total patient costs for both HD and PD. ♦ Methodology: We assessed 249 patients on HD and 228 on PD. All patients were 18 years of age or older and on stable dialysis. The information was collected at three points over 1 year, using standard questionnaires. The sources for costs were the Brazilian public and private health care systems. Societal perspective was considered. ♦ Statistical Analysis: Core trends and dispersions were measured. Regression models assessed the impact of modality on the average total cost per patient per year. ♦ Results: Of the 249 HD patients and 228 PD dialysis patients, 189 (74%) and 160 (70%) respectively completed follow-up. The mean age for women was 55.8 years; for men, it was 59.8 years (p = 0.001). The average total cost per patient-year was US$28 570 for HD and US$27 158 for PD. By category, the costs consisted of direct medical-hospital costs (82.3% for HD, 86.5% for PD), direct nonmedical costs (5.3% for HD, 3.7% for PD), and indirect costs (12.4% for HD, 9.8% for PD). Overall costs were less for PD patients than for their HD counterparts (p = 0.025). ♦ Conclusions: Maintenance dialysis represented the most important source of costs for both modalities; loss of productivity incurred significant costs. Future studies should contemplate the social consequences arising from each modality. PMID:23209041

Protein intake, nitrogen balance and nutritional status in patients with Parkinson's disease; time for a change?

PubMed

Zilli Canedo Silva, Maryanne; Carol Fritzen, Natali; de Oliveira, Marlon; Paes da Silva, Michel; Rasmussen Petterle, Ricardo; Teive, Hélio Afonso; de Mesquita Barros Almeida Leite, Christiane; Rabito, Estela Iraci; Madalozzo Schieferdecker, Maria Eliana; Carvalho, Mauricio

2015-06-01

To evaluate protein intake, nitrogen balance and nutritional status of clinically stable patients with Parkinson's disease (PD). A cross-sectional study of PD patients Hoehn-Yahr scale stage 1-3 and subjects with no neurologic disease (controls) matched for age and gender. All participants underwent a diet history interview, anthropometric measurements, bioelectrical impedance and food record over three non-consecutive days, including a weekend. A 24-hour urine collection and fasting venous blood sampling were collected from the participants for evaluation of creatinine clearance, creatinine height index and the nitrogen balance. The mean age of PD patients was 58.9 ± 12.8 year compared to 54.7 ± 12.6 year of the controls, P = 0.34. One third of PD group had symptoms of dysphagia and ingested less water and fibers when compared to controls. Calf circumference was small in PD group (35.5 ± 2.8 vs. 38.4 ± 3.5 cm, P = 0.012). Intake of nitrogen was significantly lower and nitrogen balance was negative in PD patients (-1.8 ± 3.9 vs. 1.1 ± 4.2 controls, P = 0.06). The antioxidants folate and vitamin E were consumed in small amounts in both groups, although significantly less in PD patients (P = 0.04 and 0.03, respectively). Daily intakes of protein of approximately 1.1 g/kg by clinically stable PD patients may not be enough to ensure a neutral calorie-nitrogen balance and muscle tissue conservation. Larger studies are necessary to provide a more comprehensive picture of PD patients' metabolic status. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Ultrasound-detected subclinical inflammation was better reflected by the disease activity score (DAS-28) in patients with suspicion of inflammatory arthritis compared to established rheumatoid arthritis.

PubMed

Ciurtin, Coziana; Wyszynski, Karol; Clarke, Robert; Mouyis, Maria; Manson, Jessica; Marra, Giampiero

2016-10-01

Limited data are available about the ultrasound (US)-detected inflammatory features in patients with suspicion of inflammatory arthritis (S-IA) vs. established rheumatoid arthritis (RA). Our study aimed to assess if the presence of power Doppler (PD) can be predicted by a combination of clinical, laboratory and US parameters. We conducted a real-life, retrospective cohort study comparing clinical, laboratory and US parameters of 108 patients with established RA and 93 patients with S-IA. We propose a PD signal prediction model based on a beta-binomial distribution for PD variable using a mix of outcome measures. Patients with RA in clinical remission had significantly more active inflammation and erosions on US when compared with patients with S-IA with similar disease scores (p = 0.03 and p = 0.01, respectively); however, RA patients with different disease activity score (DAS-28) scores had similar PD scores (p = 0.058). The PD scores did not correlate with erosions (p = 0.38) or DAS-28 scores (p = 0.28) in RA patients, but they correlated with high disease activity in S-IA patients (p = 0.048). Subclinical inflammation is more common in patients with RA in clinical remission or with low disease activity than in patients with S-IA; therefore, US was more useful in assessing for true remission in RA rather than diagnosing IA in patients with low disease activity scores. This is the first study to propose a PD prediction model integrating several outcome measures in the two different groups of patients. Further research into validating this model can minimise the risk of underdiagnosing subclinical inflammation.

Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

PubMed

Danti, S; Toschi, N; Diciotti, S; Tessa, C; Poletti, M; Del Dotto, P; Lucetti, C

2015-12-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. © 2015 EAN.

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Risk of immune-related colitis with PD-1/PD-L1 inhibitors vs chemotherapy in solid tumors: systems assessment.

PubMed

Su, Qiang; Zhang, Xiaochen; Shen, Xinhua; Hou, Yanli; Sun, Zhigang; Gao, Zu Hua

2018-01-01

Background: We performed a meta-analysis to evaluate the risk of immune-related colitis associated with PD1/PD-L1 inhibitors as compared to chemotherapy in solid tumor patients. Methods: Eligible studies were identified through a comprehensive search of multiple databases and included solid tumor patients in randomized controlled trials (RCTs) with PD-1/PD-L1 inhibitors. The data was analyzed by Stata version 12.0 software. Results: After exclusion of ineligible studies, 11 clinical trials were considered eligible for the meta-analysis, including 5751 patients. Compared with chemotherapy, the risk ratios (RRs) of all-grade colitis were significant for the PD-1 inhibitor subgroup (RR 2.69, 95% confidence interval (CI): 1.15-6.29, p=0.023), and for pembrolizumab subgroup (RR 3.17, 95% CI: 1.08-9.37, p=0.037), but not for nivolumab treatment and PD-L1 inhibitor (atezolizumab) treatment (RR 2.05, 95% CI: 0.52-8.13, p=0.305; RR 4.75,95% CI: 0.56-40.50, p=0.154, respectively). The RR of all-grade colitis was significant for PD-1/PD-L1 inhibitor in NSCLC (RR 4.34, 95% CI: 1.37-13.82, p=0.013), and not significant in melanoma (RR 2.11, 95% CI: 0.54-8.34, p=0.285). Moreover, the RRs of all-grade diarrhea were significant for the PD-1 inhibitor subgroup (RR 0.61, 95% CI: 0.44-0.83, p=0.002), for the nivolumab subgroup (RR 0.54, 95% CI: 0.34-0.87, p=0.012), and for atezolizumab subgroup (RR 0.48, 95% CI: 0.25-0.89, p=0.021). The RR of high-grade diarrhea was significant for atezolizumab subgroup (RR 0.34, 95% CI: 0.12-0.94, p=0.037). Conclusions: Our meta-analysis demonstrates that compared with chemotherapy, pembrolizumab may result in a higher risk of all-grade immune-mediated colitis. PD-1/PD-L1 inhibitor treatment in NSCLC patients, but not in melanoma patients, increases the risk of all-grade colitis incidence.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

PubMed

Luo, ChunYan; Song, Wei; Chen, Qin; Yang, Jing; Gong, QiYong; Shang, Hui-Fang

2017-07-01

Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

Fragmented sleep: an unrevealed problem in peritoneal dialysis patients.

PubMed

Yngman-Uhlin, Pia; Johansson, Anna; Fernström, Anders; Börjeson, Sussanne; Edéll-Gustafsson, Ulla

2011-04-01

The aim of this study was to describe the sleep-wake cycle, sleep quality, fatigue and Health Related Quality of Life (HRQoL) measured with questionnaires, actigraphy and a sleep diary during a one-week period in patients undergoing peritoneal dialysis (PD) treatment at home. A further aim was to explore differences compared with patients with coronary artery disease (CAD) and individuals from the general population. In this study one-week actigraphy registration, four questionnaires (Uppsala Sleep Inventory, SF-36, FACIT-fatigue, International Restless Legs Study Groups' form) and a sleep diary were used. Data from 68 participants and 470 nights were collected. PD patients (n = 28) had more fragmented sleep (p < 0.001) and worse sleep efficiency (SE%) (p < 0.0001) than the CAD (n = 22) and the population (n = 18) groups. Pruritus (57%), restless legs (46%) and fatigue (89%) were prevalent in PD patients. Pruritus correlated with fragmented sleep (r = -0.45, p = 0.01) and SE (r = -0.49, p = 0.01). In HRQoL, the physical component score was decreased in the PD and CAD groups (p < 0.01) compared to the population group. To the authors' knowledge this study is the first to demonstrate that PD patients have deteriorated sleep, with serious fragmentation measured by a one-week actigraphy registration. Further, PD patients exhibit worse sleep quality than CAD patients and individuals in the population. Evaluation of sleep in clinical practice is highly recommended since PD patients are vulnerable individuals with extended self-care responsibilities and at risk for comorbidity secondary to insufficient sleep. Future research on whether PD patients' sleep problems and fatigue can be improved by an individual non-pharmacological intervention programme is required.

Effects of Personality Disorders on Functioning and Well-Being in Major Depressive Disorder

PubMed Central

SKODOL, ANDREW E.; GRILO, CARLOS M.; PAGANO, MARIA E.; BENDER, DONNA S.; GUNDERSON, JOHN G.; SHEA, M. TRACIE; YEN, SHIRLEY; ZANARINI, MARY C.; MCGLASHAN, THOMAS H.

2008-01-01

Background Patients with depressive disorders have limitations in physical and emotional functioning comparable to patients with chronic medical conditions. Personality disorders (PDs) are also known to be associated with functional impairment. Aims To determine the effects of PDs on the functioning and well-being of patients with major depressive disorder (MDD). Method In the Collaborative Longitudinal Personality Disorders Study, 668 patients who met criteria for schizotypal, borderline, avoidant, or obsessive-compulsive PDs or for MDD and no PD were assessed with semi-structured interviews at baseline, 6, 12, 24, and 36 months. In this study, 151 patients who met criteria for current MDD at the 36-month follow-up were compared on the basis of the presence (n = 118) or absence (n = 33) of persistent PD. Physical and social/emotional functioning and well-being were assessed using the Medical Outcomes Study (MOS) Short-Form Health Survey (SF-36). These results were compared with those of a sample of patients with MDD seen in the mental health specialty sector who were followed in the Medical Outcomes Study. Results Patients with MDD and co-occurring PD had significantly more impairment on scales measuring role limitations due to emotional problems, social functioning, and general health perceptions than patients with MDD and no PD. Although patients with MDD and no PD were found to have levels of functioning and well-being that were lower in several domains than those previously reported in depressed patients recruited from mental health settings, patients with MDD and co-occurring PD were found to have much lower levels of functioning in all areas than reported samples. Conclusions Co-occurring PDs contribute significantly to impairment in social and emotional functioning and reduced well-being in patients with MDD. PMID:16304504

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists.

PubMed

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off.

Transdermal Patch of Rotigotine Attenuates Freezing of Gait in Patients with Parkinson's Disease: An Open-Label Comparative Study of Three Non-Ergot Dopamine Receptor Agonists

PubMed Central

Ikeda, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kawabe, Kiyokazu; Iwasaki, Yasuo

2016-01-01

Objective Parkinson's disease (PD) is characterized by the progressive degeneration of the nigrostriatal dopaminergic neurons. Rotigotine is a non-ergot dopamine receptor agonist (DA). Its transdermal patch maintains the effective concentrations for 24 hours. Freezing of gait (FOG) is a common and devastating symptom in PD patients. Little is known about therapeutic effects of rotigotine on FOG in PD patients. Herein we compared how three non-ergot DAs of rotigotine, pramipexole LA and ropinirole CR influence FOG, besides classical motor deficits in PD patients. Methods Rotigotine (maintenance doses of 9-27 mg/day) was administered in 51 patients, 36 patients received pramipexole LA (1.5-4.5 mg/day) and 35 patients received ropinirole CR (8-16 mg/day). The Unified PD Rating Scale (UPDRS) parts I-IV, FOG questionnaire (16 items) and wearing off time were examined from baseline to 7 months after DA administration. UPDRS parts I-IV were evaluated during on time and FOG was recorded during off time if patients experienced wearing off. Results A total of 111 patients completed the study. UPDRS parts II-III scores and wearing off time were significantly reduced after each DA treatment compared to baseline. FOG was found in 54 patients (49%). Most patients developed FOG during off time only. FOG scores were significantly decreased at 2 months after rotigotine treatment whereas pramipexole LA and ropinirole treatment did not alter FOG scores. Conclusion The present study indicates that transdermal patch of rotigotine attenuated the FOG off time. The similar binding affinities to dopamine receptors between rotigotine and dopamine, and 24 hours steady hemodynamics could contribute to the therapeutic mechanism of rotigotine on FOG in PD patients with wearing off. PMID:27725534

Spontaneous T-cell responses against the immune check point programmed-death-ligand 1 (PD-L1) in patients with chronic myeloproliferative neoplasms correlate with disease stage and clinical response.

PubMed

Holmström, Morten Orebo; Riley, Caroline Hasselbalch; Skov, Vibe; Svane, Inge Marie; Hasselbalch, Hans Carl; Andersen, Mads Hald

2018-01-01

The Chronic Myeloproliferative Neoplasms (MPN) are cancers characterized by hyperinflammation and immune deregulation. Concurrently, the expression of the immune check point programmed death ligand 1 (PD-L1) is induced by inflammation. In this study we report on the occurrence of spontaneous T cell responses against a PD-L1 derived epitope in patients with MPN. We show that 71% of patients display a significant immune response against PD-L1, and patients with advanced MPN have significantly fewer and weaker PD-L1 specific immune responses compared to patients with non-advanced MPN. The PD-L1 specific T cell responses are CD4 + T cell responses, and by gene expression analysis we show that expression of PD-L1 is enhanced in patients with MPN. This could imply that the tumor specific immune response in MPN could be enhanced by vaccination with PD-L1 derived epitopes by boosting the anti-regulatory immune response hereby allowing tumor specific T cell to exert anti-tumor immunity.

Psychogenic and neural visual-cue response in PD dopamine dysregulation syndrome.

PubMed

Loane, Clare; Wu, Kit; O'Sullivan, Sean S; Lawrence, Andrew D; Woodhead, Zoe; Lees, Andrew J; Piccini, Paola; Politis, Marios

2015-11-01

Dopamine dysregulation syndrome (DDS) in Parkinson's disease (PD) patients refers to the compulsive use of dopaminergic replacement therapy and has serious psycho-social consequences. Mechanisms underlying DDS are not clear although has been linked to dysfunctional brain reward networks. With fMRI, we investigate behavioral and neural response to drug-cues in six PD DDS patients and 12 PD control patients in both the ON and OFF medication state. Behavioral measures of liking, wanting and subjectively 'feeling ON medication' were also collected. Behaviorally, PD DDS patients feel less ON and want their drugs more at baseline compared to PD controls. Following drug-cue exposure, PD DDS patients feel significantly more ON medication, which correlates with significant increases in reward related regions. The results demonstrate that exposure to drug-cues increases the subjective feeling of being 'ON' medication which corresponds to dysfunctional activation in reward related regions in PD DDS patients. These findings should be extended in future studies. Visual stimuli being sufficient to elicit behavioral response through neuroadaptations could have direct implications to the management of addictive behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

PubMed

Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

2017-01-01

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

Evaluation of autonomic functions of patients with multiple system atrophy and Parkinson's disease by head-up tilt test.

PubMed

Watano, Chikako; Shiota, Yuri; Onoda, Keiichi; Sheikh, Abdullah Md; Mishima, Seiji; Nitta, Eri; Yano, Shozo; Yamaguchi, Shuhei; Nagai, Atsushi

2018-02-01

The aim of this study was to evaluate the autonomic neural function in Parkinson's disease (PD) and multiple system atrophy (MSA) with head-up tilt test and spectral analysis of cardiovascular parameters. This study included 15 patients with MSA, 15 patients with PD, and 29 healthy control (HC) subjects. High frequency power of the RR interval (RR-HF), the ratio of low frequency power of RR interval to RR-HF (RR-LF/HF) and LF power of systolic BP were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively. Both patients with PD and MSA showed orthostatic hypotension and lower parasympathetic function (RR-HF) at tilt position as compared to HC subjects. Cardiac sympathetic function (RR-LF/HF) was significantly high in patients with PD than MSA at supine position. RR-LF/HF tended to increase in MSA and HC, but decreased in PD by tilting. Consequently, the change of the ratio due to tilting (ΔRR-LF/HF) was significantly lower in patients with PD than in HC subjects. Further analysis showed that compared to mild stage of PD, RR-LF/HF at the supine position was significantly higher in advanced stage. By tilting, it was increased in mild stage and decreased in the advanced stage of PD, causing ΔRR-LF/HF to decrease significantly in the advanced stage. Thus, we demonstrated that spectral analysis of cardiovascular parameters is useful to identify sympathetic and parasympathetic disorders in MSA and PD. High cardiac sympathetic function at the supine position, and its reduction by tilting might be a characteristic feature of PD, especially in the advanced stage.

UK Renal Registry 15th annual report: Chapter 8 UK multisite peritoneal dialysis access catheter audit for first PD catheters 2011.

PubMed

Briggs, Victoria; Pitcher, David; Braddon, Fiona; Fogarty, Damian; Wilkie, Martin

2013-01-01

The central paradigm of effective peritoneal dialysis (PD) is an appropriate standard of PD catheter function. The aim of the project was to develop an effective national PD access audit which would identify an 'appropriate standard' of PD catheter function. The UK Renal Registry collected centre specific information on various PD access outcome measures including catheter functionality and post-insertion complications. The first PD access audit covering England, Northern Ireland and Wales was conducted during April to June 2012 looking at incident dialysis patients in 2011. Forty three data collection spreadsheets were returned from a total of 65 centres describing 917 PD catheter placements. The median age of PD patients was 61 years and 61.5% were male. The proportion of patients initiated on PD in comparison to HD was lower in socially deprived areas. There was a relationship between the timing of nephrology referral and the likelihood of surgical assessment regarding PD catheter placement. Patients with diabetes did not have higher rates of PD catheter failure or of early peritonitis. A comparative PD catheter audit has the potential to provide valuable information on an important patient related outcome measure and lead to an improvement in patient experience. There was wide variation between centres of PD catheter use for late presenting patients. Overall patients were more likely to get a PD catheter if they had been known to the service for more than 1 year. The percutaneous insertion technique was associated with a higher early (less than 2 week) peritonitis rate and more catheter flow problems. Copyright © 2013 S. Karger AG, Basel.

Mitochondrial dysfunction of immortalized human adipose tissue-derived mesenchymal stromal cells from patients with Parkinson's disease.

PubMed

Moon, Hyo Eun; Yoon, Seung Hee; Hur, Yong Suk; Park, Hyung Woo; Ha, Ji Young; Kim, Kyung-Hee; Shim, Jung Hee; Yoo, Seung Hyun; Son, Jin H; Paek, Seung Leal; Kim, In Keyoung; Hwang, Jae Ha; Kim, Dong Gyu; Kim, Han-Joon; Jeon, Beom Seok; Park, Sung Sup; Paek, Sun Ha

2013-12-01

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson's Disease

PubMed Central

Moon, Hyo Eun; Yoon, Seung Hee; Hur, Yong Suk; Park, Hyung Woo; Ha, Ji Young; Kim, Kyung-Hee; Shim, Jung Hee; Yoo, Seung Hyun; Son, Jin H.; Paek, Seung Leal; Kim, In Keyoung; Hwang, Jae Ha; Kim, Dong Gyu; Kim, Han-Joon; Jeon, Beom Seok; Park, Sung Sup

2013-01-01

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD. PMID:24465144

Incidence and mortality trends of aspiration pneumonia in Parkinson's disease in the United States, 1979-2010.

PubMed

Akbar, Umer; Dham, Bhavpreet; He, Ying; Hack, Nawaz; Wu, Samuel; Troche, Michelle; Tighe, Patrick; Nelson, Eugene; Friedman, Joseph H; Okun, Michael S

2015-09-01

Careful examination of long-term analyses and trends is essential in understanding the medico-economic burden of this common complication. We sought to describe the long-term (32-year) trends of incidence and mortality in PD patients hospitalized with aspiration pneumonia (AsPNA). Incidence and mortality of AsPNA in hospitalized PD versus non-PD patients was assessed by logistic regression analysis applied to a national database between the years 1979 and 2010. Covariates such as age-decennium, gender, year AsPNA occurred, and the interactions with PD diagnosis were investigated. Rate of AsPNA and mortality over the 32-years was trended and compared. AsPNA occurred in 3.6% of PD patients and 1.0% of non-PD patients. The average mortality for PD patients was less (17% vs. 22%). Long-term (32-year) trends revealed a nearly 10-fold increase in incidence of AsPNA in PD (0.4% in 1979, 4.9% in 2010), decreasing mortality overtime, higher likelihood in males, and increasing average age of AsPNA patients (steeper increase in PD). All p-values<0.05. In regression analysis, each successive year had a slight increase in odds of AsPNA (OR 1.03 in PD, OR1.06 in non-PD). Trends over 32 years revealed a 10-fold increase in AsPNA among PD and non-PD patients, and an associated decrease in mortality. Our data suggest that PD patients are living longer, have slightly more AsPNA, but a lower mortality than was seen in past decades. Further research should investigate the causes of AsPNA in PD, and also potential interventions to decrease its occurrence. Copyright © 2015 Elsevier Ltd. All rights reserved.

The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease

PubMed Central

Gan-Or, Ziv; Ozelius, Laurie J.; Bar-Shira, Anat; Saunders-Pullman, Rachel; Mirelman, Anat; Kornreich, Ruth; Gana-Weisz, Mali; Raymond, Deborah; Rozenkrantz, Liron; Deik, Andres; Gurevich, Tanya; Gross, Susan J.; Schreiber-Agus, Nicole; Giladi, Nir; Bressman, Susan B.

2013-01-01

Objective: To study the possible association of founder mutations in the lysosomal storage disorder genes HEXA, SMPD1, and MCOLN1 (causing Tay-Sachs, Niemann-Pick A, and mucolipidosis type IV diseases, respectively) with Parkinson disease (PD). Methods: Two PD patient cohorts of Ashkenazi Jewish (AJ) ancestry, that included a total of 938 patients, were studied: a cohort of 654 patients from Tel Aviv, and a replication cohort of 284 patients from New York. Eight AJ founder mutations in the HEXA, SMPD1, and MCOLN1 genes were analyzed. The frequencies of these mutations were compared to AJ control groups that included large published groups undergoing prenatal screening and 282 individuals matched for age and sex. Results: Mutation frequencies were similar in the 2 groups of patients with PD. The SMPD1 p.L302P was strongly associated with a highly increased risk for PD (odds ratio 9.4, 95% confidence interval 3.9–22.8, p < 0.0001), as 9/938 patients with PD were carriers of this mutation compared to only 11/10,709 controls. Conclusions: The SMPD1 p.L302P mutation is a novel risk factor for PD. Although it is rare on a population level, the identification of this mutation as a strong risk factor for PD may further elucidate PD pathogenesis and the role of lysosomal pathways in disease development. PMID:23535491

Iowa Gambling Task Performance in Parkinson Disease Patients with Impulse Control Disorders.

PubMed

Biars, Julia W; Johnson, Nicole L; Nespeca, Michelle; Busch, Robyn M; Kubu, Cynthia S; Floden, Darlene P

2018-04-27

A subgroup of patients with Parkinson disease (PD) develops impulse control disorders (ICD) associated with their dopamine replacement therapy. Patients and their families may be reluctant to report ICD symptoms or unaware these symptoms are related to PD medication, which can make detecting an ICD difficult for clinicians. Ideally, a behavioral measure that is sensitive to ICD could be employed to ensure that patients with these behaviors are identified and treated. The Iowa Gambling Task (IGT), a standardized decision-making task, has proven sensitive in other populations with impulse control problems. We hypothesized that the IGT would differentiate between PD patients with and without ICD. We compared IGT performance and disease variables in 24 PD patients with ICD and 24 PD patients without ICD. Patient groups were matched in terms of age, sex, and duration of PD. There were no significant differences in IGT scores between PD groups. IGT performance declined with increasing age, but the majority of patients performed within normal limits based on published age- and education-corrected normative data. The IGT did not distinguish between PD patients with and without ICD. Increasing age negatively impacted performance in both groups. Other studies have found that IGT performance may decline in normal aging. Our results suggest that the IGT lacks the sensitivity and specificity needed to differentiate between age-related deficits and disruption in frontal-subcortical circuits underlying ICD associated with PD medications. Therefore, the IGT is not an appropriate behavioral measure for ICD in PD patients.

Parkinson's patients' executive profile and goals they set for improvement: Why is cognitive rehabilitation not common practice?

PubMed

Vlagsma, T T; Koerts, J; Fasotti, L; Tucha, O; van Laar, T; Dijkstra, H; Spikman, J M

2016-01-01

Impairments in executive functions (EF) are the core cognitive impairment in patients with Parkinson's disease (PD). Surprisingly, cognitive rehabilitation is not routinely offered to patients with PD. However, in patients with acquired brain injury (ABI), cognitive rehabilitation, in particular strategic executive training, is common practice and has been shown to be effective. In this study, we determined whether PD patients have different needs and aims with regard to strategic executive training than ABI patients, and whether possible differences might be a reason for not offering this kind of cognitive rehabilitation programme to patients with PD. Patients' needs and aims were operationalised by individually set goals, which were classified into domains of EF and daily life. In addition, patients with PD and ABI were compared on their cognitive, in particular EF, profile. Overall, PD patients' goals and cognitive profile were similar to those of patients with ABI. Therefore, based on the findings of this study, there is no reason to assume that strategic executive training cannot be part of standard therapy in PD. However, when strategic executive training is applied in clinical practice, disease-specific characteristics need to be taken into account.

Alternating verbal fluency performance following bilateral subthalamic nucleus deep brain stimulation for Parkinson's disease.

PubMed

Marshall, D F; Strutt, A M; Williams, A E; Simpson, R K; Jankovic, J; York, M K

2012-12-01

Despite common occurrences of verbal fluency declines following bilateral subthalamic nucleus deep brain stimulation (STN-DBS) for the treatment of Parkinson's disease (PD), alternating fluency measures using cued and uncued paradigms have not been evaluated. Twenty-three STN-DBS patients were compared with 20 non-surgical PD patients on a comprehensive neuropsychological assessment, including cued and uncued intradimensional (phonemic/phonemic and semantic/semantic) and extradimensional (phonemic/semantic) alternating fluency measures at baseline and 6-month follow-up. STN-DBS patients demonstrated a greater decline on the cued phonemic/phonemic fluency and the uncued phonemic/semantic fluency tasks compared to the PD patients. For STN-DBS patients, verbal learning and information processing speed accounted for a significant proportion of the variance in declines in alternating phonemic/phonemic and phonemic/semantic fluency scores, respectively, whilst only naming was related to uncued phonemic/semantic performance for the PD patients. Both groups were aided by cueing for the extradimensional task at baseline and follow-up, and the PD patients were also aided by cueing for the phonemic/phonemic task on follow-up. These findings suggest that changes in alternating fluency are not related to disease progression alone as STN-DBS patients demonstrated greater declines over time than the PD patients, and this change was related to declines in information processing speed. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Depression and Parkinson disease: prevalence, temporal relationship, and determinants.

PubMed

Yapici Eser, Hale; Bora, Hatice Ayşe; Kuruoğlu, Aslı

2017-04-18

Comorbidity of depression in Parkinson disease (PD) is a major factor that changes patients' quality of life. However, the neurobiological and sociodemographic risk factors for this comorbidity are not well studied. In this study, we aimed to define the prevalence, temporal relationship, and psychosocial and clinical determinants of depression comorbid with PD. Fifty-five PD patients were evaluated with SCID, a data form that assessed sociodemographic and PD-related variables, UPDRS III, HAM-D, HAM-A, MMSE, and the Apathy Evaluation Scale. Depression (lifetime: 45.5%, last month: 25.5%, before PD: 20%) was the most frequent psychiatric diagnosis. The major determinants of depression in the last month and depression before PD were early onset of PD and young age. Patients on pramipexole treatment were less likely to be diagnosed with depression in the last month. Other sociodemographic and PD-related variables were not significantly different for lifetime, last month, and pre-PD depression diagnosis compared to their counterparts. Depression is prevalent both before and after patient gets a PD diagnosis. Depression is not only the result of PD-related life changes but it is also a preceding factor that may decrease the age of PD onset.

Fluid Status in Peritoneal Dialysis Patients: The European Body Composition Monitoring (EuroBCM) Study Cohort

PubMed Central

Van Biesen, Wim; Williams, John D.; Covic, Adrian C.; Fan, Stanley; Claes, Kathleen; Lichodziejewska-Niemierko, Monika; Verger, Christian; Steiger, Jurg; Schoder, Volker; Wabel, Peter; Gauly, Adelheid; Himmele, Rainer

2011-01-01

Background Euvolemia is an important adequacy parameter in peritoneal dialysis (PD) patients. However, accurate tools to evaluate volume status in clinical practice and data on volume status in PD patients as compared to healthy population, and the associated factors, have not been available so far. Methods We used a bio-impedance spectroscopy device, the Body Composition Monitor (BCM) to assess volume status in a cross-sectional cohort of prevalent PD patients in different European countries. The results were compared to an age and gender matched healthy population. Results Only 40% out of 639 patients from 28 centres in 6 countries were normovolemic. Severe fluid overload was present in 25.2%. There was a wide scatter in the relation between blood pressure and volume status. In a multivariate analysis in the subgroup of patients from countries with unrestricted availability of all PD modalities and fluid types, older age, male gender, lower serum albumin, lower BMI, diabetes, higher systolic blood pressure, and use of at least one exchange per day with the highest hypertonic glucose were associated with higher relative tissue hydration. Neither urinary output nor ultrafiltration, PD fluid type or PD modality were retained in the model (total R2 of the model = 0.57). Conclusions The EuroBCM study demonstrates some interesting issues regarding volume status in PD. As in HD patients, hypervolemia is a frequent condition in PD patients and blood pressure can be a misleading clinical tool to evaluate volume status. To monitor fluid balance, not only fluid output but also dietary input should be considered. Close monitoring of volume status, a correct dialysis prescription adapted to the needs of the patient and dietary measures seem to be warranted to avoid hypervolemia. PMID:21390320

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

PubMed Central

Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2014-01-01

AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

White matter integrity and cognition in Parkinson's disease: a cross-sectional study

PubMed Central

Auning, Eirik; Kjærvik, Veslemøy Krohn; Selnes, Per; Aarsland, Dag; Haram, Astrid; Bjørnerud, Atle; Hessen, Erik; Esnaashari, Abdolreza; Fladby, Tormod

2014-01-01

Objective We used diffusion tensor imaging (DTI) to test the following hypotheses: (1) there is decreased white matter (WM) integrity in non-demented Parkinson’s disease (PD), (2) WM integrity is differentially reduced in PD and early Alzheimer’s disease (AD) and (3) DTI changes in non-demented PD are specifically associated with cognitive performance. Methods This study included 18 non-demented patients with PD, 18 patients with mild cognitive impairment due to incipient AD and 19 healthy elderly normal control (NC) participants in a cross-sectional design. The participants underwent DTI, and tract-based spatial statistics was used to analyse and extract radial diffusivity and fractional anisotropy. Correlations between scores from a battery of neuropsychological tests and DTI were performed in the PD group. Results Patients with PD had significant differences in DTI in WM underlying the temporal, parietal and occipital cortex as compared with NC. There were no significant differences between the PD and AD groups in the primary region of interest analyses, but compared with NC there was a tendency for more anterior changes in AD in contrast to more posterior changes in PD. In a secondary whole-brain analysis there were frontoparietal areas with significant differences between AD and PD. In patients with PD, there were significant correlations between DTI parameters in WM underlying the prefrontal cortex and executive and visuospatial abilities. Conclusions In early, non-demented PD we found reduced WM integrity underlying the temporal, parietal and occipital cortices. In addition, WM integrity changes in prefrontal areas were associated with executive and visuospatial ability. These findings support that DTI may be an important biomarker in early PD, and that WM changes are related to cognitive impairment in PD. PMID:24448846

Peritoneal Dialysis in Asia.

PubMed

Kwong, Vickie Wai-Ki; Li, Philip Kam-Tao

2015-12-01

There is a growing demand of dialysis in Asia for end-stage renal failure patients. Diabetes mellitus is the leading cause of end-stage renal failure in many countries in Asia. The growth of peritoneal dialysis (PD) in Asia is significant and seeing a good trend. With the enhanced practices of PD, the quality of care in PD in Asia is also improved. Overall, PD and hemodialysis (HD) are comparable in clinical outcome. There is a global trend in the reduction of peritonitis rates and Asian countries also witness such improvement. The socio-economic benefits of PD for end-stage renal failure patients in both urban and rural areas in the developed and developing regions of Asia are an important consideration. This can help to reduce the financial burden of renal failure in addressing the growing demand of patients on dialysis. Initiatives should be considered to further drive down the cost of PD in Asia. Growing demand for dialysis by an increasing number of end-stage renal failure patients requires the use of a cost-effective quality dialysis modality. PD is found to be comparable to HD in outcome and quality. In most countries in Asia, PD should be more cost-effective than HD. A 'PD-first' or a 'PD as first considered therapy' policy can be an overall strategy in many countries in Asia in managing renal failure patients, taking the examples of Hong Kong and Thailand. (1) PD is cheaper than HD and provides a better quality of life worldwide, but its prevalence is significantly lower than that of HD in all countries, with the exception of Hong Kong. Allowing reimbursement of PD but not HD has permitted to increase the use of PD over HD in many Asian countries like Hong Kong, Vietnam, Taiwan, Thailand, as well as in New Zealand and Australia over the last years. In the Western world, however, HD is still promoted, and the proportion of patients treated with PD decreases. Japan remains an exception in Asia where PD penetration is very low. Lack of adequate education of practitioners and information of patients might as well be reasons for the low penetration of PD in both the East and West. (2) Patient survival of PD varies between and within countries but is globally similar to HD. (3) Peritonitis remains the main cause of morbidity in PD patients. South Asian countries face specific issues such as high tuberculosis and mycobacterial infections, which are rare in developed Asian and Western countries. The infection rate is affected by climatic and socio-economic factors and is higher in hot, humid and rural areas. (4) Nevertheless, the promotion of a PD-first policy might be beneficial particularly for remote populations in emerging countries where the end-stage renal disease rate is increasing dramatically.

The Clinical Findings Useful for Driving Safety Advice for Parkinson's Disease Patients.

PubMed

Ando, Rina; Iwaki, Hirotaka; Tsujii, Tomoaki; Nagai, Masahiro; Nishikawa, Noriko; Yabe, Hayato; Aiba, Ikuko; Hasegawa, Kazuko; Tsuboi, Yoshio; Aoki, Masashi; Nakashima, Kenji; Nomoto, Masahiro

2018-02-28

Objective We conducted a study to obtain information that could be used to provide Parkinson's disease (PD) patients with appropriate advice on safe driving. Methods Consecutive PD patients who visited our office were studied. Among these patients, those who had experienced driving after being diagnosed with PD were interviewed by neurologists and a trained nurse to investigate their previous car accidents, motor function, cognitive function, sleepiness, levodopa equivalent dose (LED), and emotional dysregulation. The rates of major car accidents before and after the onset of PD were compared. Results Fifteen patients had experienced a major car accident resulting in human injury or serious property damage since the onset of PD. When the rates of major car accidents before and after the onset of PD were compared, the ratio was 4.3 (95% CI 1.9-9.7). The incidence of accidents after the onset of PD was correlated with age, disease duration, LED, the cognitive function (MMSE, MoCA-J), but not the motor symptom score (UPDRS part III at the time of the study). The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) score was also higher in patients with major car accidents. Conclusion The severity of symptoms (Hoehn-Yahr classification), cognitive function, and disease duration were expected to be risk factors for car accidents. However, the motor symptom score (UPDRS part III) was not associated with the incidence of major car accidents. In addition to a low cognitive function and the severity of symptoms, the QUIP score might be an independent factor that can be referenced when advising PD patients to refrain from driving.

Space-Based but not Object-Based Inhibition of Return is Impaired in Parkinson's Disease

PubMed Central

Possin, Katherine L.; Filoteo, J. Vincent; Song, David D.; Salmon, David P.

2009-01-01

Impairments in certain aspects of attention have frequently been reported in Parkinson's disease (PD), including reduced inhibition of return (IOR). Recent evidence suggests that IOR can occur when attention is directed at objects or locations, but previous investigations of IOR in PD have not systematically compared these two frames of reference. The present study compared the performance of 18 nondemented patients with PD and 18 normal controls on an IOR task with two conditions. In the “object-present” condition, objects surrounded the cues and targets so that attention was cued to both a spatial location and to a specific object. In the “object-absent” condition, surrounding objects were not presented so that attention was cued only to a spatial location. When participants had to rely on space-based cues, PD patients demonstrated reduced IOR compared to controls. In contrast, when objects were present in the display and participants could use object-based cues, PD patients exhibited normal IOR. These results suggest that PD patients are impaired in inhibitory aspects of space-based attention, but are able to overcome this impairment when their attention can be directed at object-based frames of reference. This dissociation supports the view that space-based and object-based components of attention involve distinct neurocognitive processes. PMID:19397864

Space-based but not object-based inhibition of return is impaired in Parkinson's disease.

PubMed

Possin, Katherine L; Filoteo, J Vincent; Song, David D; Salmon, David P

2009-06-01

Impairments in certain aspects of attention have frequently been reported in Parkinson's disease (PD), including reduced inhibition of return (IOR). Recent evidence suggests that IOR can occur when attention is directed at objects or locations, but previous investigations of IOR in PD have not systematically compared these two frames of reference. The present study compared the performance of 18 nondemented patients with PD and 18 normal controls on an IOR task with two conditions. In the "object-present" condition, objects surrounded the cues and targets so that attention was cued to both a spatial location and to a specific object. In the "object-absent" condition, surrounding objects were not presented so that attention was cued only to a spatial location. When participants had to rely on space-based cues, PD patients demonstrated reduced IOR compared to controls. In contrast, when objects were present in the display and participants could use object-based cues, PD patients exhibited normal IOR. These results suggest that PD patients are impaired in inhibitory aspects of space-based attention, but are able to overcome this impairment when their attention can be directed at object-based frames of reference. This dissociation supports the view that space-based and object-based components of attention involve distinct neurocognitive processes.

Alterations of Brain Structural Network in Parkinson's Disease With and Without Rapid Eye Movement Sleep Behavior Disorder.

PubMed

Guo, Tao; Guan, Xiaojun; Zeng, Qiaoling; Xuan, Min; Gu, Quanquan; Huang, Peiyu; Xu, Xiaojun; Zhang, Minming

2018-01-01

Rapid eye movement sleep behavior disorder (RBD) has a strong association with alpha synucleinpathies such as Parkinson's disease (PD) and PD patients with RBD tend to have a poorer prognosis. However, we still know little about the pathogenesis of RBD in PD. Therefore, we aim to detect the alterations of structural correlation network (SCN) in PD patients with and without RBD. A total of 191 PD patients, including 51 patients with possible RBD (pRBD) and 140 patients with non-possible RBD, and 76 normal controls were included in the present study. Structural brain networks were constructed by thresholding gray matter volume correlation matrices of 116 regions and analyzed using graph theoretical approaches. There was no difference in global properties among the three groups. Significant enhanced regional nodal measures in limbic system, frontal-temporal regions, and occipital regions and decreased nodal measures in cerebellum were found in PD patients with pRBD (PD-pRBD) compared with PD patients without pRBD. Besides, nodes in frontal lobe, temporal lobe, and limbic system were served as hubs in both two PD groups, and PD-pRBD exhibited additionally recruited hubs in limbic regions. Based on the SCN analysis, we found PD-pRBD exhibited a reorganization of nodal properties as well as the remapping of the hub distribution in whole brain especially in limbic system, which may shed light to the pathophysiology of PD with RBD.

Swallowing impairment and pulmonary dysfunction in Parkinson's disease: the silent threats.

PubMed

Monteiro, Larissa; Souza-Machado, Adelmir; Pinho, Patrícia; Sampaio, Marília; Nóbrega, Ana Caline; Melo, Ailton

2014-04-15

Swallowing disorders and respiratory impairment are frequent in Parkinson's disease (PD) patients, and aspiration pneumonia remains the leading cause of death among these subjects. The objective of this study was to investigate whether there is an association between pulmonary impairment and swallowing dysfunction in PD patients. A cross-sectional study with a comparison group was conducted with PD patients. Subjects were submitted to demographic questionnaires and underwent spirometric and videofluorographic assessments. Significance level was considered at 95% (p<0.05). Among 35 PD patients, 40% presented with swallowing complaints. However, 22% of the clinically asymptomatic patients presented airway food penetration when submitted to videofluoroscopy. In 20% of PD patients material entered the airways and there was contact with the vocal folds in 7%. However, there was an efficient cleaning with residue deglutition in almost all patients. No penetration/aspiration was detected among the controls. Respiratory parameters were below the normal predicted values in PD patients when compared to the healthy controls. These data suggest an association between pulmonary dysfunction and swallowing impairment in PD patients; even in patients without swallowing complaints, impaired pulmonary function can be detected. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel three-dimensional dynamic anorectal ultrasonography technique for the assessment of perineal descent, compared with defaecography.

PubMed

Murad-Regadas, S M; dos Santos, D; Soares, G; Regadas, F S P; Rodrigues, L V; Buchen, G; Kenmoti, V T; Surimã, W S; Fernandes, G O da S

2012-06-01

The purpose of the study was to describe a novel three-dimensional dynamic anorectal ultrasonography technique (dynamic 3-DAUS) for assessment of perineal descent (PD) and establishment of normal range values, comparing it with defaecography. Secondarily, the study compares the ability of the two techniques to identify various pelvic floor dysfunctions. A prospective study was undertaken in 29 women (mean age 43 years) with obstructed defecation disorder. All patients underwent defaecography and dynamic 3-DAUS and the results were compared. Lee kappa coefficients (K) were used. On defaecography, PD > 3 cm was detected in 12 patients. On dynamic 3-DAUS, 10 of these patients had PD > 2.5 cm. Seventeen had normal PD on defaecography and PD ≤ 2.5 cm on dynamic 3-DAUS (K 0.85). Normal relaxation was observed in 10 patients and anismus in 14 with both techniques (K 0.65). Both techniques identified five patients without rectocele, two with grade I rectocele (K 0.89 and 1.00, respectively) and 10 with grade II and nine with grade III (K 0.72 and 0.77, respectively). Rectal intussusception was identified in six patients on defaecography. These were confirmed on dynamic 3-DAUS in addition to the identification of another seven cases indicating moderate agreement (K 0.46). Enterocele/sigmoidocele grade III was identified in one patient with both techniques, indicating substantial agreement (K 0.65). Dynamic 3-DAUS was shown to be a reliable technique for the assessment of PD and pelvic floor dysfunctions, identifying all disorders and confirming findings from defaecography. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

Cognitive impairment and PD patients' capacity to consent to research

PubMed Central

Cary, Mark; Moelter, Stephen T.; Siderowf, Andrew; Sullo, Elizabeth; Xie, Sharon; Weintraub, Daniel

2013-01-01

Objective: To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity. Methods: A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale–2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE). Results: Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity. Conclusions: PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity. PMID:23892706

Increased Levels of Pro-Inflammatory and Anti-Inflammatory Cellular Responses in Parkinson's Disease Patients: Search for a Disease Indicator.

PubMed

Yang, Likun; Guo, Changfeng; Zhu, Jie; Feng, Yi; Chen, Weiliang; Feng, Zhizhong; Wang, Dan; Sun, Shibai; Lin, Wei; Wang, Yuhai

2017-06-18

BACKGROUND Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and it arises when most of the dopaminergic neurons of substantia nigra region die. Several mechanisms have been postulated as the causative event in PD pathology, and neuroinflammation is most crucial among them. MATERIAL AND METHODS We analyzed T-helper 17 (Th17) cells and myeloid-derived suppressor cells (MDSCs) from 80 PD patients to assess inflammatory processes and to find a cost-effective means to evaluate PD prognosis. RESULTS We found significantly increased numbers of Th17 cells and MDSCs count in peripheral circulation in PD patients compared with controls (p<0.001). A positive correlation was found between Th17 cells and MDSCs in PD patients (r=0.421, p<0.05). CONCLUSIONS Our results show the effector role of Th17 cells and MDSCs in PD pathology and shows their utility as effective biomarkers for PD diagnosis.

Glucose-6-phosphate dehydrogenase deficiency (G6PD) as a risk factor of male neonatal sepsis.

PubMed

Rostami-Far, Z; Ghadiri, K; Rostami-Far, M; Shaveisi-Zadeh, F; Amiri, A; Rahimian Zarif, B

2016-01-01

Introduction. Neonatal sepsis is a disease process, which represents the systemic response of bacteria entering the bloodstream during the first 28 days of life. The prevalence of sepsis is higher in male infants than in females, but the exact cause is unknown. Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme in the pentose phosphate pathway, which leads to the production of NADPH. NADPH is required for the respiratory burst reaction in white blood cells (WBCs) to destroy microorganisms. The purpose of this study was to evaluate the prevalence of G6PD deficiency in neonates with sepsis. Materials and methods. This study was performed on 76 neonates with sepsis and 1214 normal neonates from February 2012 to November 2014 in the west of Iran. The G6PD deficiency status was determined by fluorescent spot test. WBCs number and neutrophils percentages were measured and compared in patients with and without G6PD deficiency. Results. The prevalence of the G6PD deficiency in neonates with sepsis was significantly higher compared to the control group (p=0.03). WBCs number and neutrophils percentages in G6PD deficient patients compared with patients without G6PD deficiency were decreased, but were not statistically significant (p=0.77 and p=0.86 respectively). Conclusions. G6PD deficiency is a risk factor of neonatal sepsis and also a justification for more male involvement in this disease. Therefore, newborn screening for this disorder is recommended.

The prevalence of personality disorders in psychiatric outpatients with borderline intellectual functioning: Comparison with outpatients from regular mental health care and outpatients with mild intellectual disabilities.

PubMed

Wieland, Jannelien; Van Den Brink, Annemarie; Zitman, Frans G

2015-01-01

There is little research on the subject of personality disorder (PD) in individuals with borderline intellectual functioning (BIF). Unlike in most countries, in the Netherlands, patients with BIF are eligible for specialized mental health care. This offers the unique possibility of examining the rates of PDs in patients, who in other countries are treated relatively invisibly in regular mental health care. To compare, in a naturalistic setting, the frequency of PD diagnoses in outpatients with BIF with outpatients from regular mental health care and outpatients with mild ID. We compared the rates of all DSM-IV-TR axis II PDs in outpatients with BIF (BIF group; n = 235) with rates of the same disorders in outpatients from regular mental health care (RMHC group; n = 1026) and outpatients with mild intellectual disability (ID) (mild ID group; n = 152) in a naturalistic cross-sectional anonymized medical chart review. Over half of the patients with BIF (52.8%) were diagnosed with a PD, compared with one in five in the RMHC group (19.3%) and one in three of the mild ID group (33.6%). All PD diagnoses, except for cluster A PDs and histrionic PDs, were most frequently diagnosed in the BIF group. PD NOS and borderline PD were the most frequently diagnosed PDs in BIF. The majority of PD patients had one or more comorbid axis I disorder. There is a high frequency of PD diagnoses in BIF outpatients in daily clinical practice. In anticipation of further scientific research, results suggest that PDs should not be overlooked in patients with BIF.

Circulating and tumor-infiltrating Tim-3 in patients with colorectal cancer

PubMed Central

Gao, Quanli; Yuan, Peng; Zhao, Peng; Yuan, Huijuan; Fan, Huijie; Li, Tiepeng; Qin, Peng; Han, Lu; Fang, Weijia; Suo, Zhenhe

2015-01-01

T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8+ T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn't show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8+ T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3+PD-1+CD8+ T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3+PD-1+CD8+ T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3+PD-1+CD8+ T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3+PD-1+CD8+ T cells produced significantly less IFN-γ than Tim-3−PD-1−CD8+ T cells, followed by Tim-3+PD-1−CD8+ T cells, and Tim-3−PD-1+CD8+ T cells, indicating a stronger inhibition of IFN-γ production of Tim-3+CD8+ T cells. It is also found in this study that Tim-3+PD-1+CD8+ T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential therapeutic approach for CRC patients. PMID:26008981

Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1.

PubMed

Champiat, Stéphane; Dercle, Laurent; Ammari, Samy; Massard, Christophe; Hollebecque, Antoine; Postel-Vinay, Sophie; Chaput, Nathalie; Eggermont, Alexander; Marabelle, Aurélien; Soria, Jean-Charles; Ferté, Charles

2017-04-15

Purpose: While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs. The prevalence, the natural history, and the predictive factors of HPD in patients with cancer treated by anti-PD-1/PD-L1 remain unknown. Experimental Design: Medical records from all patients ( N = 218) prospectively treated in Gustave Roussy by anti-PD-1/PD-L1 within phase I clinical trials were analyzed. The tumor growth rate (TGR) prior ("REFERENCE"; REF) and upon ("EXPERIMENTAL"; EXP) anti-PD-1/PD-L1 therapy was compared to identify patients with accelerated tumor growth. Associations between TGR, clinicopathologic characteristics, and overall survival (OS) were computed. Results: HPD was defined as a RECIST progression at the first evaluation and as a ≥2-fold increase of the TGR between the REF and the EXP periods. Of 131 evaluable patients, 12 patients (9%) were considered as having HPD. HPD was not associated with higher tumor burden at baseline, nor with any specific tumor type. At progression, patients with HPD had a lower rate of new lesions than patients with disease progression without HPD ( P < 0.05). HPD is associated with a higher age ( P < 0.05) and a worse outcome (overall survival). Interestingly, REF TGR (before treatment) was inversely correlated with response to anti-PD-1/PD-L1 ( P < 0.05) therapy. Conclusions: A novel aggressive pattern of hyperprogression exists in a fraction of patients treated with anti-PD-1/PD-L1. This observation raises some concerns about treating elderly patients (>65 years old) with anti-PD-1/PD-L1 monotherapy and suggests further study of this phenomenon. Clin Cancer Res; 23(8); 1920-8. ©2016 AACR See related commentary by Sharon, p. 1879 . ©2016 American Association for Cancer Research.

Reduction of neuromelanin-positive nigral volume in patients with MSA, PSP and CBD.

PubMed

Kashihara, Kenichi; Shinya, Takayoshi; Higaki, Fumiyo

2011-01-01

Diseases presenting extrapyramidal symptoms are accompanied by nigral cell loss. In the previous study, we demonstrated the reduction of the neuromelanin-positive volume of substantia nigra (SN) pars compacta (SNc) in patients with Parkinson's disease (PD) using 3-Tesla MRI. In the present study we investigated the neuromelanin-positive SNc volume in patients with the other parkinsonian disorders including multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) and compared the results with those with PD, spinocerebellar ataxia (SCA) and controls. Axial T1-weighted (T1W) images were obtained with a 3-Tesla MRI scanner. The border of the neuromelanin-positive region of the SNc was traced manually on these images with a pentablet pointing device and the SNc volume was calculated. The SNc volumes of 28 patients with MSA, 11 patients with PSP and 10 patients with CBD were compared with those of 80 patients with PD, 9 patients with SCA and 54 patients who had suffered mild acute ischemic stroke as controls. The mean volumes for the left and right SN were used for statistical analyses. The volumes of the neuromelanin-positive SNc region in patients with MSA, PSP and CBD, but not SCA were reduced to the same extent as PD patients compared with controls. Reduced volume of the neuromelanin-positive SNc region of patients with MSA, PSP and CBD was detected by neuromelanin MR imaging. Volumetric evaluation of neuromelanin MR imaging may provide a biomarker of nigral degeneration in patients with MSA, PSP and CBD as in patients with PD.

Screening for prodromal Parkinson's disease in the general community: a sleep-based approach.

PubMed

Postuma, Ronald B; Pelletier, Amelie; Berg, Daniela; Gagnon, Jean-Francois; Escudier, Frédérique; Montplaisir, Jacques

2016-05-01

Neuroprotective therapy for Parkinson's disease (PD) is most likely to be effective if provided in its prodromal stages. However, identifying prodromal PD is difficult because PD is relatively uncommon, and most markers are nonspecific. Rapid eye movement (REM) sleep behavior disorder (RBD) is by far the strongest clinical marker of prodromal PD, but most patients do not seek out medical attention. Developing an efficient way of diagnosing RBD from the general community may be the most practical method to detect prodromal PD. We developed a screening strategy that began with a newspaper advertisement containing a single-question screen for RBD. All screen-positive subjects underwent an interview based on the Innsbruck RBD inventory aimed to optimize the positive predictive value. Those who passed both screens underwent confirmatory polysomnography. The proportion of screened RBD patients who met the International Parkinson and Movement Disorder Society (MDS) criteria for prodromal PD was assessed. A broad array of clinical markers of neurodegeneration was compared between newspaper-screened RBD patients and 130 RBD patients clinically referred to the sleep center. Of 111 RBD-screen-positive participants, 40 (36%) passed the secondary screen, and 29 underwent full polysomnography. Of these 29 patients, 19 were ultimately proven to have RBD (PPV = 66%), 12 (63%) of whom met the criteria for prodromal PD. Compared to patients referred to the sleep center, newspaper-screened patients had similar age, sex, olfaction, autonomic function, and color vision. However, motor and cognitive assessments were slightly better in newspaper-screened patients. A multistep screening approach using RBD screening questionnaires and telephone follow-up can efficiently identify prodromal PD in the general community. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuromelanin imaging and midbrain volumetry in progressive supranuclear palsy and Parkinson's disease.

PubMed

Taniguchi, Daisuke; Hatano, Taku; Kamagata, Koji; Okuzumi, Ayami; Oji, Yutaka; Mori, Akio; Hori, Masaaki; Aoki, Shigeki; Hattori, Nobutaka

2018-05-14

Background Nigral degeneration patterns differ between PSP and PD. However, the relationship between nigral degeneration and midbrain atrophy in PSP remains unclear. Objective We analyzed differences and relationships between nigral degeneration and midbrain atrophy in PSP and PD. Methods Neuromelanin-sensitive MRI and midbrain volumetry were performed in 11 PSP patients, 24 PD patients, and 10 controls to measure the neuromelanin-sensitive SNpc area and midbrain volume. Results The neuromelanin-sensitive SNpc area and midbrain volume were significantly smaller in PSP patients compared with PD patients and controls. Motor deficits were inversely correlated with neuromelanin-sensitive SNpc area in PD, but not PSP patients. There was no significant correlation between neuromelanin-sensitive SNpc area and midbrain volume in either disease group. Midbrain volumetry discriminated PSP from PD. Diagnostic accuracy was improved when neuromelanin-sensitive MRI analysis was added. Conclusions Neuromelanin-sensitive MRI and midbrain volumetry may reflect the clinical and pathological characteristics of PSP and PD. Combining neuromelanin-sensitive MRI and midbrain volumetry may be useful for differentiating PSP from PD. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Verbal Fluency Performance in Patients with Non-demented Parkinson's Disease

PubMed Central

Khatoonabadi, Ahmad Reza; Bakhtiyari, Jalal

2013-01-01

Objective While Parkinson's disease (PD) has traditionally been defined by motor symptoms, many researches have indicated that mild cognitive impairment is common in non-demented PD patients. The purpose of this study was to compare verbal fluency performance in non-demented Parkinson's disease patients with healthy controls. Method In this cross-sectional study thirty non-demented Parkinson's disease patients and 30 healthy controls, matched by age, gender and education, were compared on verbal fluency performance. Verbal fluency was studied with a Phonemic Fluency task using the letters F, A, and S, a semantic fluency task using the categories animals and fruits. The independent t-test was used for data analysis. Results Overall, participants generated more words in the semantic fluency task than in the phonemic fluency task. Results revealed significant differences between patients and controls in semantic fluency task (p<.05). In addition, PD patients showed a significant reduction of correctly generated words in letter fluency task. The total number of words produced was also significantly lower in the PD group (p<.05). Conclusion Verbal fluency disruption is implied in non-demented PD patients in association with incipient cognitive impairment. PMID:23682253

A study of the clinical and biochemical profile of peritoneal dialysis fluid low in glucose degradation products.

PubMed

Lai, Kar Neng; Lam, Man Fai; Leung, Joseph C K; Chan, Loretta Y; Lam, Christopher W K; Chan, Iris H S; Chan, Hoi Wong; Li, Chun Sang; Wong, Sunny S H; Ho, Yiu Wing; Cheuk, Au; Tong, Matthew K L; Tang, Sydney C W

2012-01-01

Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

PubMed Central

Lai, Kar Neng; Lam, Man Fai; Leung, Joseph C.K.; Chan, Loretta Y.; Lam, Christopher W.K.; Chan, Iris H.S.; Chan, Hoi Wong; Li, Chun Sang; Wong, Sunny S.H.; Ho, Yiu Wing; Cheuk, Au; Tong, Matthew K.L.; Tang, Sydney C.W.

2012-01-01

♦ Objective: Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. ♦ Methods: We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. ♦ Results: Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. ♦ Conclusions: It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum. PMID:22045098

Anticipatory Postural Adjustment During Self-Initiated, Cued, and Compensatory Stepping in Healthy Older Adults and Patients With Parkinson Disease.

PubMed

Schlenstedt, Christian; Mancini, Martina; Horak, Fay; Peterson, Daniel

2017-07-01

To characterize anticipatory postural adjustments (APAs) across a variety of step initiation tasks in people with Parkinson disease (PD) and healthy subjects. Cross-sectional study. Step initiation was analyzed during self-initiated gait, perceptual cued gait, and compensatory forward stepping after platform perturbation. People with PD were assessed on and off levodopa. University research laboratory. People (N=31) with PD (n=19) and healthy aged-matched subjects (n=12). Not applicable. Mediolateral (ML) size of APAs (calculated from center of pressure recordings), step kinematics, and body alignment. With respect to self-initiated gait, the ML size of APAs was significantly larger during the cued condition and significantly smaller during the compensatory condition (P<.001). Healthy subjects and patients with PD did not differ in body alignment during the stance phase prior to stepping. No significant group effect was found for ML size of APAs between healthy subjects and patients with PD. However, the reduction in APA size from cued to compensatory stepping was significantly less pronounced in PD off medication compared with healthy subjects, as indicated by a significant group by condition interaction effect (P<.01). No significant differences were found comparing patients with PD on and off medications. Specific stepping conditions had a significant effect on the preparation and execution of step initiation. Therefore, APA size should be interpreted with respect to the specific stepping condition. Across-task changes in people with PD were less pronounced compared with healthy subjects. Antiparkinsonian medication did not significantly improve step initiation in this mildly affected PD cohort. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Rise of PD-L1 expression during metastasis of colorectal cancer: Implications for immunotherapy.

PubMed

Wang, Huan Bin; Yao, Han; Li, Chu Shu; Liang, Lun Xi; Zhang, Yao; Chen, Ying Xuan; Fang, Jing-Yuan; Xu, Jie

2017-10-01

Programmed death-ligand 1 (PD-L1) expression in colorectal cancer (CRC) was implicated in predicting anti-PD-1/PD-L1 therapy efficacy. However, therapeutic response has also been found in patients without PD-L1 expression in the primary tumor. In the present study, we aimed to clarify the prevalence of PD-L1 in primary and metastatic CRC. The expression of PD-L1 was determined by immunohistochemistry in matched primary and metastatic CRC. PD-L1 expression was significantly more prevalent in metastatic CRCs than in primary tumors, and the expression of PD-L1 in primary CRC may not represent the tumors that spread to distant organs. Positive expression of PD-L1 was found in 81.8% of metastatic CRC, being significantly more prevalent than in primary CRC (40.9%; P = 0.012, Fisher's exact test). While comparing the primary and metastatic lesions of the same patients, we found that PD-L1 expression frequently increased during the metastatic process. However, PD-L1 expression was rarely decreased in metastatic lesions. Intratumoral heterogeneity expression of PD-L1 was found in both metastatic CRC (22.2%) and primary CRCs (33.3%). PD-L1 was prevalently expressed in metastatic CRC, and increased PD-L1 expression was frequently found in metastatic CRC as compared to primary tumors. PD-L1 expression in metastatic CRC should be considered as an independent factor while evaluating the suitability of patients for immunotherapy. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Functional neurological disorders in Parkinson disease.

PubMed

Wissel, Benjamin D; Dwivedi, Alok K; Merola, Aristide; Chin, Danielle; Jacob, Cara; Duker, Andrew P; Vaughan, Jennifer E; Lovera, Lilia; LaFaver, Kathrin; Levy, Ariel; Lang, Anthony E; Morgante, Francesca; Nirenberg, Melissa Jill; Stephen, Christopher; Sharma, Nutan; Romagnolo, Alberto; Lopiano, Leonardo; Balint, Bettina; Yu, Xin X; Bhatia, Kailash P; Espay, Alberto J

2018-06-01

To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features. A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036). A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

STK39, But Not BST1, HLA-DQB1, and SPPL2B Polymorphism, Is Associated With Han-Chinese Parkinson's Disease in Taiwan

PubMed Central

Chang, Kuo-Hsuan; Wu, Yih-Ru; Chen, Yi-Chun; Fung, Hon-Chung; Lee-Chen, Guey-Jen; Chen, Chiung-Mei

2015-01-01

Abstract Neuroinflammation is emerging as an important pathway involved in Parkinson's disease (PD) pathogenesis. Herein, we investigated the effect of 4 top PD-associated genetic variants in Caucasians listed on the top risk loci identified by meta-analysis of genome wide-association studies in PDGene database (http://www.pdgene.org/top_results), including serine threonine kinase 39 (STK39) rs1955337, bone marrow stromal cell antigen 1 (BST1) rs11724635, major histocompatibility complex, class II, DQ beta 1 (HLA-DQB1) rs9275326, and signal peptide peptidase-like 2B (SPPL2B) rs62120679, by genotyping 596 Han-Chinese patients with PD and 597 age-matched control subjects. Compared with subjects with STK39 rs1955337 GG genotype, those with TT genotype had a 1.64-fold increased risk of PD (95% confidence interval: 1.13–2.39, P = 0.010). The recessive model also demonstrated an increased PD risk in TT genotype (odds ratio: 1.59, 95% confidence interval: 1.12–2.27) compared with the other genotypes (GT + GG). PD patients demonstrate a similar genotypic and allelic frequency in BST1 rs11724635, HLA-DQB1 rs9275326, and SPPL2B rs62120679 compared with controls. These findings suggested that the STK39 rs1955337 TT genotype is a risk factor for Han-Chinese patients with PD in Taiwan. The ethnic discrepancies of the other 3 genetic variants may indicate a distinct genetic background of neuroinflammation between PD patients in Han-Chinese and Caucasians. PMID:26469904

Equivalent Fall Risk in Elderly Patients on Hemodialysis and Peritoneal Dialysis.

PubMed

Farragher, Janine; Rajan, Tasleem; Chiu, Ernest; Ulutas, Ozkan; Tomlinson, George; Cook, Wendy L; Jassal, Sarbjit V

2016-01-01

♦ Accidental falls are common in the hemodialysis (HD) population. The high fall rate has been attributed to a combination of aging, kidney disease-related morbidity, and HD treatment-related hazards. We hypothesized that patients maintained on peritoneal dialysis (PD) would have fewer falls than those on chronic HD. The objective of this study was to compare the falls risk between cohorts of elderly patients maintained on HD and PD, using prospective data from a large academic dialysis facility. ♦ Patients aged 65 years or over on chronic in-hospital HD and PD at the University Health Network were recruited. Patients were followed biweekly, and falls occurring within the first year recorded. Fall risk between the 2 groups was compared using both crude and adjusted Poisson lognormal random effects modeling. ♦ Out of 258 potential patients, 236 were recruited, assessed at baseline, and followed biweekly for falls. Of 74 PD patients, 40 (54%) experienced 86 falls while 76 out of 162 (47%) HD patients experienced a total of 305 falls (crude fall rate 1.25 vs 1.60 respectively, odds ratio [OR] falls in PD patients 0.78, 95% confidence interval [CI] 0.61 - 0.92, p = 0.04). After adjustment for differences in comorbidity, number of medications, and other demographic differences, PD patients were no less likely to experience accidental falls than HD patients (OR 1.63, 95% CI 0.88 - 3.04, p = 0.1). ♦ We conclude that accidental falls are equally common in the PD population and the HD population. These data argue against post-HD hypotension as the sole contributor to the high fall risk in the dialysis population. Copyright © 2016 International Society for Peritoneal Dialysis.

Restless legs syndrome in patients with Parkinson's disease: a comparative study on prevalence, clinical characteristics, quality of life and nutritional status.

PubMed

Fereshtehnejad, S-M; Shafieesabet, M; Shahidi, G A; Delbari, A; Lökk, J

2015-04-01

Restless legs syndrome (RLS) is a common neurological disorder that can coexist with Parkinson's disease (PD). However, the association between these two movement disorders is quite poorly explored and previous findings are controversial in different aspects. To compare prevalence of RLS in Iranian PD population with a matched control group and to investigate the impact of comorbid RLS on quality of life (QoL), nutritional status, and clinical characteristics in PD population. This study was conducted on 108 individuals with idiopathic PD (IPD) and 424 matched controls. RLS was diagnosed using the International Restless Legs Syndrome Study Group (IRLSSG) criteria. Further assessments were performed on clinical characteristics, PD severity scales, psychiatric features, nutritional status, fatigue, and QoL in PD patients with and without RLS. Restless legs syndrome was significantly more common among the patients with IPD (14.8%) compared to the controls (7.5%) [OR = 2.1 (95% CI: 1.1-4.0)]. IPD subjects with RLS had significantly higher anxiety score [10.1 (SD = 5.1) vs 5.9 (SD = 5.0); P = 0.003], worse nutritional status [23.7 (SD = 2.7) vs 25.4 (SD = 3.7); P = 0.008], and poorer QoL [26.9 (SD = 13.1) vs 17.0 (SD = 13.2); P = 0.006]. The number of positive answers to the IRLSSG diagnostic criteria had significant direct correlation with unpredictability of the off periods and the presence of symptomatic orthostasis. Our study demonstrated a higher prevalence of RLS in patients with PD compared to general population. PD patients with RLS suffer from more anxiety, worse nutritional status, and worse QoL. RLS negatively accompanies with psychiatric problems, emotional behaviors, stigma, and cognitive impairment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impairment of work productivity in panic disorder patients.

PubMed

Lee Park, Yu; Kim, Won; Chae, Jeong-Ho; Seo Oh, Kang; Frick, Kevin D; Woo, Jong-Min

2014-03-01

Panic disorder (PD) has a critical impact on productivity at the workplace. This study aimed to identify the lost productivity time (LPT) for patients with PD. It also assessed change in LPT for patients with PD after 12 weeks of treatment with Selective Serotonin Reuptake Inhibitors (SSRIs), compared with healthy controls. Working patients diagnosed with PD without other major medical or psychiatric illness were enrolled at outpatient psychiatric clinics (N=108). Age and sex-matched healthy controls were recruited through advertisement (N=108). Health and productivity, PD symptoms, and depressive symptoms were assessed using the Korean version of the World Health Organization's Health and Work Performance Questionnaire (HPQ), the Panic Disorder Severity Scale (PDSS), and the Hamilton Rating Scales for Depression (HAM-D), respectively at baseline, week 4, and week 12. At baseline, the PD group showed significantly higher LPT compared to the control group (103.02 vs. 47.28h in the past 4 weeks). After 12 weeks of treatment, the PD group displayed significant clinical improvement as well as improved productivity with a marked reduction in LPT. Among the patients who completed the treatment, LPT due to PD was reduced from 104.38 to 55.15h in the past 4 weeks. There may be selection bias due to case-control study design. These data suggest that, after the treatment, there was significant improvement in clinical symptoms, and that productivity loss due to PD was almost entirely recovered to the level of healthy controls after 12 weeks of psychiatric outpatient treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Small fiber neuropathy in Parkinson's disease: A clinical, pathological and corneal confocal microscopy study.

PubMed

Kass-Iliyya, Lewis; Javed, Saad; Gosal, David; Kobylecki, Christopher; Marshall, Andrew; Petropoulos, Ioannis N; Ponirakis, Georgios; Tavakoli, Mitra; Ferdousi, Maryam; Chaudhuri, Kallol Ray; Jeziorska, Maria; Malik, Rayaz A; Silverdale, Monty A

2015-12-01

Autonomic and somatic denervation is well established in Parkinson's disease (PD). (1) To determine whether corneal confocal microscopy (CCM) can non-invasively demonstrate small nerve fiber damage in PD. (2) To identify relationships between corneal nerve parameters, intraepidermal nerve fiber density (IENFD) and clinical features of PD. Twenty-six PD patients and 26 controls underwent CCM of both eyes. 24/26 PD patients and 10/26 controls underwent skin biopsies from the dorsa of both feet. PD patients underwent assessment of parasympathetic function [deep breathing heart rate variability (DB-HRV)], autonomic symptoms [scale for outcomes in Parkinson's disease - autonomic symptoms (SCOPA-AUT)], motor symptoms [UPDRS-III "ON"] and cumulative Levodopa dose. PD patients had significantly reduced corneal nerve fiber density (CNFD) with increased corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) compared to controls. CNBD and CNFL but not CNFD correlated inversely with UPDRS-III and SCOPA-AUT. All CCM parameters correlated strongly with DB-HRV. There was no correlation between CCM parameters and disease duration, cumulative Levodopa dose or pain. IENFD was significantly reduced in PD compared to controls and correlated with CNFD and UPDRS-III. However, unlike CCM measures, IENFD correlated with disease duration and cumulative Levodopa dose but not with autonomic dysfunction. CCM identifies corneal nerve fiber pathology, which correlates with autonomic symptoms, parasympathetic deficits and motor scores in patients with PD. IENFD is also reduced and correlates with CNFD and motor symptoms but not parasympathetic deficits, indicating it detects different aspects of peripheral nerve pathology in PD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Side of symptom onset affects motor dysfunction in Parkinson's disease.

PubMed

Haaxma, C A; Helmich, R C G; Borm, G F; Kappelle, A C; Horstink, M W I M; Bloem, B R

2010-11-10

The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic denervation in Parkinson's disease (PD). Using the pegboard dexterity test, we compared motor performance of both hands between healthy subjects (n=48), PD patients with predominantly right-hemispheric dopamine depletion (PD-RIGHT; n=83) and PD patients with more severe left-hemispheric dopamine depletion (PD-LEFT; n=103). All subjects were right-handed. After adjusting for hand-dominance effects, we found that PD-RIGHT patients exhibited a 55% larger difference between right and left dexterity scores than PD-LEFT patients. This effect could be attributed to greater motor dysfunction of the more-affected hand in PD-RIGHT patients, while the less-affected hand performed similarly in both groups. We conclude that the side of symptom onset affects motor dysfunction in PD, and suggest that the non-dominant right hemisphere may be more susceptible to dopaminergic denervation than the dominant left hemisphere. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer.

PubMed

Okuma, Yusuke; Hosomi, Yukio; Nakahara, Yoshiro; Watanabe, Kageaki; Sagawa, Yukiko; Homma, Sadamu

2017-02-01

Programmed cell death-ligand 1 (PD-L1) expressed in tumor tissues is a key molecule for immune suppression, given its role in immune checkpoints. The significance and implication of soluble PD-L1 (sPD-L1) in the blood of lung cancer patients remain unknown. Blood samples were prospectively collected from patients with advanced lung cancer, and the plasma sPD-L1 concentrations were measured by enzyme-linked immunosorbent assay. The correlations of the plasma sPD-L1 levels with clinico-pathological status, laboratory data, and survival of the patients were analyzed. Ninety-six patients with advanced lung cancer were analyzed, including 73 with adenocarcinoma, 12 with squamous cell carcinoma, and seven with small-cell lung cancer. Sixty-five were naïve to chemotherapy, and 20 had received two or more lines of chemotherapy. The mean plasma sPD-L1 concentration of all the patients was 6.95±2.90ng/ml (range 2.30-20.0ng/ml), and this value is significantly increased compared with that previously reported for normal subjects. No correlation of the plasma sPD-L1 level with histological subtypes, adenocarcinoma genetic status, smoking history, clinical stage or laboratory data was found. However, overall survival was significantly reduced in patients with high (≥7.32ng/ml) compared with low (<7.32ng/ml) plasma sPD-L1 levels (13.0 vs. 20.4 months, p=0.037). Multivariate analysis revealed that high sPD-L1 levels were significantly related to poor prognosis (hazard ratio 1.99, p=0.041). High plasma sPD-L1 levels were associated with poor prognosis in patients with advanced lung cancer, possibly associated with suppression of anti-tumor immunity. Clinical trial register and their clinical registration number: UMIN%000014760. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

White matter microstructure changes in the thalamus in Parkinson disease with depression: A diffusion tensor MR imaging study.

PubMed

Li, W; Liu, J; Skidmore, F; Liu, Y; Tian, J; Li, K

2010-11-01

Depression occurs frequently in PD; however the neural basis of depression in PD remains unclear. The aim of this study was to characterize possible depression-related white matter microstructural changes in the thalamus of patients with DPD compared with those with NDPD. FA and MD maps from DTI were obtained in 14 patients with DPD and 18 patients with NDPD. Region-of-interest-guided VBA was conducted on the FA maps to detect possible microstructural differences in the thalamus between these 2 patient groups. Moreover, mean FA and MD in regions with a detected difference were compared between DPD and NDPD groups, and correlations between diffusion quantities and the severity of depression were analyzed. White matter microstructure differences were found between the patients with DPD and NDPD in the bilateral mediodorsal thalamic regions. In these regions, patients with DPD showed significantly decreased FA values (P < .005) compared with patients with NDPD, and the mean values of FA were negatively correlated with the scores of depression severity (P < .05) for patients with PD. No significant differences of MD were found in the mediodorsal thalamus between these 2 groups. Our results provide preliminary evidence that the mediodorsal thalamus may play an important role in depression in PD and suggest a relationship between FA in the mediodorsal thalamus and the presence of depressive symptoms in patients with DPD. These findings may be helpful for further understanding the potential mechanisms of depression in PD.

Metabolic alterations in patients with Parkinson disease and visual hallucinations.

PubMed

Boecker, Henning; Ceballos-Baumann, Andres O; Volk, Dominik; Conrad, Bastian; Forstl, Hans; Haussermann, Peter

2007-07-01

Visual hallucinations (VHs) occur frequently in advanced stages of Parkinson disease (PD). Which brain regions are affected in PD with VH is not well understood. To characterize the pattern of affected brain regions in PD with VH and to determine whether functional changes in PD with VH occur preferentially in visual association areas, as is suggested by the complex clinical symptomatology. Positron emission tomography measurements using fluorodeoxyglucose F 18. Between-group statistical analysis, accounting for the variance related to disease stage. University hospital. Patients Eight patients with PD and VH and 11 patients with PD without VH were analyzed. The presence of VH during the month before positron emission tomography was rated using the Neuropsychiatric Inventory subscale for VH (PD and VH, 4.63; PD without VH, 0.00; P < .002). Parkinson disease with VH, compared with PD without VH, was characterized by reduction in the regional cerebral metabolic rate for glucose consumption (P < .05, corrected for false discovery rate) in occipitotemporoparietal regions, sparing the occipital pole. No significant increase in regional glucose metabolism was detected in patients with PD and VH. The pattern of resting-state metabolic changes in regions of the dorsal and ventral visual streams, but not in primary visual cortex, in patients with PD and VH, is compatible with the functional roles of visual association areas in higher-order visual processing. These findings may help to further elucidate the functional mechanisms underlying VH in PD.

The effect of speed-accuracy strategy on response interference control in Parkinson's disease.

PubMed

Wylie, S A; van den Wildenberg, W P M; Ridderinkhof, K R; Bashore, T R; Powell, V D; Manning, C A; Wooten, G F

2009-07-01

Studies that used conflict paradigms such as the Eriksen Flanker task show that many individuals with Parkinson's disease (PD) have pronounced difficulty resolving the conflict that arises from the simultaneous activation of mutually exclusive responses. This finding fits well with contemporary views that postulate a key role for the basal ganglia in action selection. The present experiment aims to specify the cognitive processes that underlie action selection deficits among PD patients in the context of variations in speed-accuracy strategy. PD patients (n=28) and healthy controls (n=17) performed an arrow version of the flanker task under task instructions that either emphasized speed or accuracy of responses. Reaction time (RT) and accuracy rates decreased with speed compared to accuracy instructions, although to a lesser extent for the PD group. Differences in flanker interference effects among PD and healthy controls depended on speed-accuracy strategy. Compared to the healthy controls, PD patients showed larger flanker interference effects under speed stress. RT distribution analyses suggested that PD patients have greater difficulty suppressing incorrect response activation when pressing for speed. These initial findings point to an important interaction between strategic and computational aspects of interference control in accounting for cognitive impairments of PD. The results are also compatible with recent brain imaging studies that demonstrate basal ganglia activity to co-vary with speed-accuracy adjustments.

BRCA1/2 and TP53 mutation status associates with PD-1 and PD-L1 expression in ovarian cancer.

PubMed

Wieser, Verena; Gaugg, Inge; Fleischer, Martina; Shivalingaiah, Giridhar; Wenzel, Soeren; Sprung, Susanne; Lax, Sigurd F; Zeimet, Alain G; Fiegl, Heidelinde; Marth, Christian

2018-04-03

Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status. TP53 -mutated OC strongly expressed PD-L1 compared to TP53 wild-type OC ( p = 0.028) and BRCA1/2 -mutated OC increasingly expressed PD-1 ( p = 0.024) and PD-L1 ( p = 0.012) compared to BRCA1/2 wild-type OC. For the first time in human, we noted a strong correlation between tumoral IFNG and PD-1 or PD-L1 mRNA-expression, respectively ( p < 0.001). OC tissue increasingly expressed PD-1 compared to healthy controls (vs. ovaries: p < 0.001; vs. tubes: p = 0.018). PD-1 and PD-L1 mRNA-expression increased with higher tumor grade ( p = 0.008 and p = 0.027, respectively) and younger age (< median age, p = 0.001). Finally, in the major subgroup of our cohort, FIGO stage III/IV HGSOC, high PD-1 and PD-L1 mRNA-expression was associated with reduced progression-free ( p = 0.024) and overall survival ( p = 0.049) but only in the univariate analysis. Our study suggests that in OC PD-1 / PD-L1 mRNA-expression is controlled by IFNγ and affected by TP53 and BRCA1/2 mutations. We suggest that these mutations might serve as potential predictive factors that guide anti- PD1 / PD-L1 immunotherapy.

Parkinson Patients' Initial Trust in Avatars: Theory and Evidence.

PubMed

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson's disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients' interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research.

Prevalence of Cognitive Impairment Among Peritoneal Dialysis Patients, Impact on Peritonitis and Role of Assisted Dialysis.

PubMed

Shea, Yat Fung; Lam, Man Fai; Lee, Mi Suen Connie; Mok, Ming Yee Maggie; Lui, Sing-Leung; Yip, Terence P S; Lo, Wai Kei; Chu, Leung Wing; Chan, Tak-Mao

2016-01-01

♦ Chronic renal failure and aging are suggested as risk factors for cognitive impairment (CI). We studied the prevalence of CI among peritoneal dialysis (PD) patients using Montreal Cognitive Assessment (MoCA), its impact on PD-related peritonitis in the first year, and the potential role of assisted PD. ♦ One hundred fourteen patients were newly started on PD between February 2011 and July 2013. Montreal Cognitive Assessment was performed in the absence of acute illness. Data on patient characteristics including demographics, comorbidities, blood parameters, dialysis adequacy, presence of helpers, medications, and the number PD-related infections were collected. ♦ The age of studied patients was 59±15.0 years, and 47% were female. The prevalence of CI was 28.9%. Patients older than 65 years old (odds ratio [OR] 4.88, confidence interval [CI] 1.79 - 13.28 p = 0.002) and with an education of primary level or below (OR 4.08, CI 1.30 - 12.81, p = 0.016) were independent risk factors for CI in multivariate analysis. Patients with PD-related peritonitis were significantly older (p < 0.001) and more likely to have CI as defined by MoCA (p = 0.035). After adjustment for age, however, CI was not a significant independent risk factor for PD-related peritonitis among self-care PD patients (OR 2.20, CI 0.65 - 7.44, p = 0.20). When we compared patients with MoCA-defined CI receiving self-care and assisted PD, there were no statistically significant differences between the 2 groups in terms of age, MoCA scores, or comorbidities. There were also no statistically significant differences in 1-year outcome of PD-related peritonitis rates or exit-site infections. ♦ Cognitive impairment is common among local PD patients. Even with CI, peritonitis rate in self-care PD with adequate training is similar to CI patients on assisted PD. Copyright © 2016 International Society for Peritoneal Dialysis.

Interference from retrieval cues in Parkinson's disease.

PubMed

Crescentini, Cristiano; Marin, Dario; Del Missier, Fabio; Biasutti, Emanuele; Shallice, Tim

2011-11-01

Existing studies on memory interference in Parkinson's disease (PD) patients have provided mixed results and it is unknown whether PD patients have problems in overcoming interference from retrieval cues. We investigated this issue by using a part-list cuing paradigm. In this paradigm, after the study of a list of items, the presentation of some of these items as retrieval cues hinders the recall of the remaining ones. We tested PD patients' (n = 19) and control participants' (n = 16) episodic memory in the presence and absence of part-list cues, using initial-letter probes, and following either weak or strong serial associative encoding of list items. Both PD patients and control participants showed a comparable and significant part-list cuing effect after weak associative encoding (13% vs. 12% decrease in retrieval in part-list cuing vs. no part-list cuing -control- conditions in PD patients and control participants, respectively), denoting a similar effect of cue-driven interference in the two populations when a serial retrieval strategy is hard to develop. However, only PD patients showed a significant part-list cuing effect after strong associative encoding (20% vs. 5% decrease in retrieval in patients and controls, respectively). When encoding promotes the development of an effective serial retrieval strategy, the presentation of part-list cues has a specifically disruptive effect in PD patients. This indicates problems in strategic retrieval, probably related to PD patients' increased tendency to rely on external cues. Findings in control conditions suggest that less effective encoding may have contributed to PD patients' memory performance.

Risk factors of severe peritoneal sclerosis in chronic peritoneal dialysis patients.

PubMed

Alatab, Sudabeh; Najafi, Iraj; Pourmand, Gholamreza; Hosseini, Mostafa; Shekarchian, Soroosh

2017-11-01

Peritoneal dialysis (PD) offers the healthiest way for starting renal replacement therapy (RRT) in End Stage Renal Disease patients, however exposes long-term PD patients to a dangerous complication named encapsulating peritoneal sclerosis (EPS). In this study, we searched for possible risk factors of EPS. Data were collected from two PD centers covering period 1995-2012 and comprised 464 patients. Control group defined as PD patients stayed on PD >42 month (n = 122), and case group was 12 confirmed EPS patients. Associations were analyzed using linear regression analysis. Prevalence and incidence of EPS were 2.59% and 8.9% with an incidence of 0.7% patient-years, respectively. The age at start of PD in EPS patients (32.75 ± 10.8 year) was significantly lower compared with control group (49.61 ± 16.18 year, p = .0001). The mean duration of PD in EPS and control group were 2494.4 ± 940.9 and 1890.2 ± 598.8 days (p = .002). Control group had 145 episodes of peritonitis during total duration of 7686 patient months (peritonitis rate of 1/53). This was 1/26 with a total 38 episodes of peritonitis during the total duration of 997 patient months (p = .01) for EPS group. In regression analysis, PD duration, age at PD start and duration of Ultrafiltration failure (UFF) were associated with EPS. Longer time being on PD, younger age, and higher UFF duration were the risk factors for EPS development.

Postural control and freezing of gait in Parkinson's disease.

PubMed

Schlenstedt, Christian; Muthuraman, Muthuraman; Witt, Karsten; Weisser, Burkhard; Fasano, Alfonso; Deuschl, Günther

2016-03-01

The relationship between freezing of gait (FOG) and postural instability in Parkinson's disease (PD) is unclear. We analyzed the impact of FOG on postural control. 31 PD patients with FOG (PD+FOG), 27 PD patients without FOG (PD-FOG) and 22 healthy control (HC) were assessed in the ON state. Postural control was measured with the Fullerton Advanced Balance (FAB) scale and with center of pressure (COP) analysis during quiet stance and maximal voluntary forward/backward leaning. The groups were balanced concerning age, disease duration and disease severity. PD+FOG performed significantly worse in the FAB scale (21.8 ± 5.8) compared to PD-FOG (25.6 ± 5.0) and HC (34.9 ± 2.4) (mean ± SD, p < 0.01). PD+FOG had impaired ability to voluntary lean forward, difficulties to stand on foam with eyes closed and reduced limits of stability compared to PD-FOG (p < 0.05). During quiet stance the average anterior-posterior COP position was significantly displaced towards posterior in PD+FOG in comparison to PD-FOG and HC (p < 0.05). The COP position correlated with severity of FOG (p < 0.01). PD+FOG and PD-FOG did not differ in average COP sway excursion, sway velocity, sway regularity and postural control asymmetry. PD+FOG have reduced postural control compared to PD-FOG and HC. Our results show a relationship between the anterior-posterior COP position during quiet stance and FOG. The COP shift towards posterior in PD+FOG leads to a restricted precondition to generate forward progression during gait initiation. This may contribute to the occurrence of FOG or might be a compensatory strategy to avoid forward falls. Copyright © 2015 Elsevier Ltd. All rights reserved.

The risk stratification and prognostic evaluation of soluble programmed death-1 on patients with sepsis in emergency department.

PubMed

Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Fang, Yingying; Shao, Rui

2018-01-01

To evaluate the efficacy of soluble programmed death-1 (sPD-1) for risk stratification and prediction of 28-day mortality in patients with sepsis, we compared serum sPD-1 with procalcitonin (PCT), C-reactive protein (CRP), and the Mortality in Emergency Department Sepsis (MEDS) score. A total of 60 healthy volunteers and 595 emergency department (ED) patients were recruited for this prospective cohort study. According to the severity of their condition on ED arrival, the patients were allocated to the systemic inflammatory response syndrome group (130 cases), sepsis group (276 cases), severe sepsis group (121 cases), and septic shock group (68 cases). In addition, all patients with sepsis were also divided into the survivor group (349 cases) and nonsurvivor group (116 cases) according to the 28-day outcomes. When the severity of sepsis increased, the levels of sPD-1 gradually increased. The levels of sPD-1, PCT, CRP and the MEDS score were also higher in the nonsurvivor group compared to the survivor group. Logistic regression suggested that sPD-1, PCT, and the MEDS score were independent risk factors for 28-day mortality of patients with sepsis. Area under the curve (AUC) of sPD-1, PCT and the MEDS score for 28-day mortality was 0.725, 0.693, and 0.767, respectively, and the AUC was improved when all 3 factors were combined (0.843). Serum sPD-1 is positively correlated with the severity of sepsis, and it is valuable for risk stratification of patients and prediction of 28-day mortality. Combining sPD-1 with PCT and the MEDS score improves the prognostic evaluation. Copyright © 2017 Elsevier Inc. All rights reserved.

Thalamic volume and related visual recognition are associated with freezing of gait in non-demented patients with Parkinson's disease.

PubMed

Sunwoo, Mun Kyung; Cho, Kyoo H; Hong, Jin Yong; Lee, Ji E; Sohn, Young H; Lee, Phil Hyu

2013-12-01

The pathophysiology of freezing of gait (FOG) in non-demented Parkinson's disease (PD) patients remains poorly understood. Recent studies have suggested that neurochemical alterations in the cholinergic systems play a role in the development of FOG. Here, we evaluated the association between subcortical cholinergic structures and FOG in patients with non-demented PD. We recruited 46 non-demented patients with PD, categorized into PD with (n = 16) and without FOG (n = 30) groups. We performed neuropsychological test, region-of-interest-based volumetric analysis of the substantia innominata (SI) and automatic analysis of subcortical brain structures using a computerized segmentation procedure. The comprehensive neuropsychological assessment showed that PD patients with FOG had lower cognitive performance in the frontal executive and visual-related functions compared with those without freezing of gait. The normalized SI volume did not differ significantly between the two groups (1.65 ± 0.18 vs. 1.68 ± 0.31). The automatic analysis of subcortical structures revealed that the thalamic volumes were significantly reduced in PD patients with FOG compared with those without FOG after adjusting for age, sex, disease duration, the Unified PD Rating Scale scores and total intracranial volume (left: 6.71 vs. 7.16 cm3, p = 0.029, right: 6.47 vs. 6.91 cm3, p = 0.026). Multiple linear regression analysis revealed that thalamic volume showed significant positive correlations with visual recognition memory (left: β = 0.441, p = 0.037, right: β = 0.498, p = 0.04). These data suggest that thalamic volume and related visual recognition, rather than the cortical cholinergic system arising from the SI, may be a major contributor to the development of freezing of gait in non-demented patients with PD. Copyright © 2013. Published by Elsevier Ltd.

Cognitive function and advanced kidney disease: longitudinal trends and impact on decision-making.

PubMed

Iyasere, Osasuyi; Okai, David; Brown, Edwina

2017-02-01

Background: Cognitive impairment commonly affects renal patients. But little is known about the influence of dialysis modality on cognitive trends or the influence of cognitive impairment on decision-making in renal patients. This study evaluated cognitive trends amongst chronic kidney disease (CKD), haemodialysis (HD) and peritoneal dialysis (PD) patients. The relationship between cognitive impairment and decision-making capacity (DMC) was also assessed. Methods: Patients were recruited from three outpatient clinics. Cognitive function was assessed 4-monthly for up to 2 years, using the Montreal Cognitive Assessment (MoCA) tool. Cognitive trends were assessed using mixed model analysis. DMC was assessed using the Macarthur Competency Assessment tool (MacCAT-T). MacCAT-T scores were compared between patients with cognitive impairment (MoCA <26) and those without. Results: In total, 102 (41 HD, 25 PD and 36 CKD) patients were recruited into the prospective study. After multivariate analysis, the total MoCA scores declined faster in dialysis compared with CKD patients [coefficient = -0.03, 95% confidence interval (95% CI) = -0.056 to - 0.004; P = 0.025]. The MoCA executive scores declined faster in the HD compared with PD patients (coefficient = -0.12, 95% CI = -0.233 to - 0.007; P = 0.037). DMC was assessed in 10 patients. Those with cognitive impairment had lower MacCAT-T compared with those without [median (interquartile range) 19 (17.9-19.6) versus 17.4 (16.3-18.4); P = 0.049]. Conclusions: Cognition declines faster in dialysis patients compared with CKD patients and in HD patients compared with PD patients. Cognitive impairment affects DMC in patients with advanced kidney disease.

Impact of methicillin-resistant Staphylococcus Aureus (MRSA) infection on patient outcome after pancreatoduodenectomy (PD)--a cause for concern?

PubMed

Sanjay, Pandanaboyana; Fawzi, Ali; Kulli, Christoph; Polignano, Francesco M; Tait, Iain S

2010-11-01

This study evaluated the impact of methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired infection on postoperative complications and patient outcome after pancreatoduodenectomy (PD). Seventy-nine patients who underwent PD were monitored for hospital-acquired MRSA. The patients were grouped as (1) no MRSA infection, (2) skin colonization with MRSA, and (3) systemic MRSA infection. Forty (51%) of the 79 patients were MRSA positive during hospital admission. Fourteen of the 40 patients swabbed for MRSA were found positive (skin colonization), and 26 patients (33%) developed systemic MRSA infection after PD. The sites of MRSA infection included (1) abdominal drain fluid (16/26; 42%), (2) sputum (4/26; 15%), (3) blood cultures (2/26; 8%), and (4) combination of sites (9/26; 35%). The patients with systemic MRSA infection had a longer postoperative stay (31 vs 22 days; P = 0.005) and increased incidence of chest infections compared with MRSA-negative patients (14 vs 4; P = 0.02). Four of the 16 patients with MRSA-positive drain fluid had a postpancreatectomy hemorrhage compared with 3 of the 63 patients with no MRSA infection in drain fluid (P = 0.02). Of the 79 patients admitted for PD, 51% became colonized with MRSA infection. Systemic hospital-acquired MRSA infection in 33% was associated with prolonged postoperative stay, increased wound and chest infections, and increased risk of postoperative hemorrhage.

Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors.

PubMed

Chovanec, Michal; Cierna, Zuzana; Miskovska, Viera; Machalekova, Katarina; Svetlovska, Daniela; Kalavska, Katarina; Rejlekova, Katarina; Spanik, Stanislav; Kajo, Karol; Babal, Pavel; Mardiak, Jozef; Mego, Michal

2017-03-28

Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. PD-L1 positive TILs were found significantly more often in seminomas (95.9% of patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%), choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with high infiltration of PD-L1 positive TILs (HS ≥ 160) had significantly better progression-free survival (HR = 0.17, 95% CI 0.09 - 0.31, p = 0.0006) and overall survival (HR = 0.08, 95% CI 0.04 - 0.16, p = 0.001) opposite to patients with lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in TGCTs. Surgical specimens from 240 patients with primary TGCTs were included into this translational study. The PD-1 and PD-L1 expression on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti-PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted histoscore (HS) method. The prognostic value of PD-L1 expressing TILs in TGCTs was demonstrated for the first time.

Synovial T cell hyporesponsiveness to myeloid dendritic cells is reversed by preventing PD-1/PD-L1 interactions.

PubMed

Moret, Frederique M; van der Wurff-Jacobs, Kim M G; Bijlsma, Johannes W J; Lafeber, Floris P J G; van Roon, Joel A G

2014-11-30

The aim of this study was to investigate PD-1/PD-L1 involvement in the hyporesponsiveness of rheumatoid arthritis (RA) synovial fluid (SF) CD4 T cells upon stimulation by thymic stromal lymphopoietin (TSLP)-primed CD1c myeloid dendritic cells (mDCs). Expression of PD-1 on naïve (Tn), central memory (Tcm) and effector memory (Tem) CD4 T cell subsets was assessed by flow cytometry. PD-L1 expression and its regulation upon TSLP stimulation of mDCs from peripheral blood (PB) and SF of RA patients were investigated by quantitative RT-PCR and flow cytometry. The involvement of PD-1/PD-L1 interactions in SF T cell hyporesponsiveness upon (TSLP-primed) mDC activation was determined by cell culture in the presence of PD-1 blocking antibodies, with or without interleukin 7 (IL-7) as a recognized suppressor of PD-1 expression. PD-1 expression was increased on CD4 T cells derived from SF compared with PB of RA patients. TSLP increased PD-L1 mRNA expression in both PB and SF mDCs. PD-L1 protein expression was increased on SF mDCs compared with PB mDCs and was associated with T cell hyporesponsiveness. Blockade of PD-1, as well as IL-7 stimulation, during cocultures of memory T cells and (TSLP-primed) mDCs from RA patients significantly recovered T cell proliferation. SF T cell hyporesponsiveness upon (TSLP-primed) mDC stimulation in RA joints is partially dependent on PD-1/PD-L1 interactions, as PD-1 and PD-L1 are both highly expressed on SF T cells and mDCs, respectively, and inhibiting PD-1 availability restores T cell proliferation. The potential of IL-7 to robustly reverse this hyporesponsiveness suggests that such proinflammatory cytokines in RA joints strongly contribute to memory T cell activation.

Features of GBA-associated Parkinson's disease at presentation in the UK Tracking Parkinson's study.

PubMed

Malek, Naveed; Weil, Rimona S; Bresner, Catherine; Lawton, Michael A; Grosset, Katherine A; Tan, Manuela; Bajaj, Nin; Barker, Roger A; Burn, David J; Foltynie, Thomas; Hardy, John; Wood, Nicholas W; Ben-Shlomo, Yoav; Williams, Nigel W; Grosset, Donald G; Morris, Huw R

2018-01-29

To examine the influence of the glucocerebrosidase ( GBA ) mutation carrier state on age at onset of Parkinson's disease (PD), the motor phenotype and cognitive function at baseline assessment in a large cohort of UK patients. We also analysed the prevalence of mood and behavioural problems that may confound the assessment of cognitive function. We prospectively recruited patients with PD in the Tracking Parkinson's study. We fully sequenced the GBA gene in all recently diagnosed patients (≤3.5 years). We examined cognitive (Montreal Cognitive Assessment) and motor (Movement Disorder Society Unified Parkinson's Disease Rating Scale part 3) function at a baseline assessment, at an average of 1.3 years after diagnosis. We used logistic regression to determine predictors of PD with mild cognitive impairment and PD with dementia. We studied 1893 patients with PD: 48 (2.5%) were heterozygous carriers for known Gaucher's disease (GD) causing pathogenic mutations; 117 (6.2%) had non-synonymous variants, previously associated with PD, and 28 (1.5%) patients carried variants of unknown significance in the GBA gene. L444P was the most common pathogenic GBA mutation. Patients with pathogenic GBA mutations were on average 5 years younger at disease onset compared with non-carriers (P=0.02). PD patients with GD-causing mutations did not have an increased family risk of PD. Patients with GBA mutations were more likely to present with the postural instability gait difficulty phenotype compared with non-carriers (P=0.02). Patients carrying pathogenic mutations in GBA had more advanced Hoehn and Yahr stage after adjustment for age and disease duration compared with non-carriers (P=0.005). There were no differences in cognitive function between GBA mutation carriers and non-carriers at this early disease stage. Our study confirms the influence of GBA mutations on the age of onset, disease severity and motor phenotype in patients with PD. Cognition did not differ between GBA mutation carriers and non-carriers at baseline, implying that cognitive impairment/dementia, reported in other studies at a later disease stage, is not present in recently diagnosed cases. This offers an important window of opportunity for potential disease-modifying therapy that may protect against the development of dementia in GBA -PD. NCT02881099; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease.

PubMed

Yadav, Santosh K; Kathiresan, Nagarajan; Mohan, Suyash; Vasileiou, Georgia; Singh, Anup; Kaura, Deepak; Melhem, Elias R; Gupta, Rakesh K; Wang, Ena; Marincola, Francesco M; Borthakur, Arijitt; Haris, Mohammad

2016-11-01

Parkinson's disease (PD) is a progressive neurological disorder and appears to have gender-specific symptoms. Studies have observed a higher frequency for development of PD in male than in female. In the current study, we evaluated the gender-based changes in cortical thickness and structural connectivity in PD patients. With informed consent, 64 PD (43 males and 21 females) patients, and 46 (12 males and 34 females) age-matched controls underwent clinical assessment including Mini-Mental State Examination (MMSE) and magnetic resonance imaging on a 1.5 Tesla clinical MR scanner. Whole brain high-resolution T1-weighted images were acquired from all subjects and used to measure cortical thickness and structural network connectivity. No significant difference in MMSE score was observed between male and female both in control and PD subjects. Male PD patients showed significantly reduced cortical thickness in multiple brain regions including frontal, parietal, temporal, and occipital lobes as compared with those in female PD patients. The graph theory-based network analysis depicted lower connection strengths, lower clustering coefficients, and altered network hubs in PD male than in PD female. Male-specific cortical thickness changes and altered connectivity in PD patients may derive from behavioral, physiological, environmental, and genetical differences between male and female, and may have significant implications in diagnosing and treating PD among genders.

Effect of peritoneal dialysis on expression of vascular endothelial growth factor, basic fibroblast growth factor and endostatin of the peritoneum in peritoneal dialysis patients.

PubMed

Gao, Dan; Zhao, Zhan-Zheng; Liang, Xian-Hui; Li, Yan; Cao, Ying; Liu, Zhang-Suo

2011-11-01

The aim of this study is to investigate the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) in human peritoneum and investigate the relationship between them and peritoneum neoangiogensis in the patients with uraemia and peritoneal dialysis (PD). Peritoneal biopsies were obtained from normal subjects (n = 8), uraemic predialysis patients (n = 12) and PD patients (n = 10). The mRNA expression of VEGF, bFGF and ES in peritoneal tissues were measured through real-time polymerase chain reaction. The protein expression of VEGF, bFGF and ES in peritoneal tissues were determined through western blot. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. The mRNA and protein of VEGF, bFGF and ES were expressed in all peritoneal samples. Compared with the normal control group, the mRNA and protein expression of VEGF and bFGF in peritoneal tissues were all significantly upregulated in the uraemic predialysis and PD group (all P < 0.05). Compared with the normal control group, the protein expression of ES were significantly upregulated in the uraemic predialysis and PD group (all (P < 0.05), but the mRNA expression of ES did not have obvious differences in the uraemic predialysis and PD group as compared to the normal control group (P > 0.05). MVD of peritoneal tissue were increased in the uraemic predialysis and PD group compared with the normal group (all P < 0.05). A significant positive correlation was found between VEGF mRNA expression and MVD, bFGF mRNA expression and MVD. The mRNA expression of VEGF and bFGF, the protein expression of VEGF, bFGF, and ES and microvessel density (MVD) are increased both in the uraemic predialysis and PD patients. These results show that uraemia circumstances and non-physiological compatibility of peritoneal dialysis solution might increase VEGF, bFGF and ES expression and MVD, which might participate in the increment of the peritoneum neoangiogensis and ultrafiltration failure in PD patients. © 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.

Cortical hypometabolism and hypoperfusion in Parkinson's disease is extensive: probably even at early disease stages.

PubMed

Borghammer, Per; Chakravarty, Mallar; Jonsdottir, Kristjana Yr; Sato, Noriko; Matsuda, Hiroshi; Ito, Kengo; Arahata, Yutaka; Kato, Takashi; Gjedde, Albert

2010-05-01

Recent cerebral blood flow (CBF) and glucose consumption (CMRglc) studies of Parkinson's disease (PD) revealed conflicting results. Using simulated data, we previously demonstrated that the often-reported subcortical hypermetabolism in PD could be explained as an artifact of biased global mean (GM) normalization, and that low-magnitude, extensive cortical hypometabolism is best detected by alternative data-driven normalization methods. Thus, we hypothesized that PD is characterized by extensive cortical hypometabolism but no concurrent widespread subcortical hypermetabolism and tested it on three independent samples of PD patients. We compared SPECT CBF images of 32 early-stage and 33 late-stage PD patients with that of 60 matched controls. We also compared PET FDG images from 23 late-stage PD patients with that of 13 controls. Three different normalization methods were compared: (1) GM normalization, (2) cerebellum normalization, (3) reference cluster normalization (Yakushev et al.). We employed standard voxel-based statistics (fMRIstat) and principal component analysis (SSM). Additionally, we performed a meta-analysis of all quantitative CBF and CMRglc studies in the literature to investigate whether the global mean (GM) values in PD are decreased. Voxel-based analysis with GM normalization and the SSM method performed similarly, i.e., both detected decreases in small cortical clusters and concomitant increases in extensive subcortical regions. Cerebellum normalization revealed more widespread cortical decreases but no subcortical increase. In all comparisons, the Yakushev method detected nearly identical patterns of very extensive cortical hypometabolism. Lastly, the meta-analyses demonstrated that global CBF and CMRglc values are decreased in PD. Based on the results, we conclude that PD most likely has widespread cortical hypometabolism, even at early disease stages. In contrast, extensive subcortical hypermetabolism is probably not a feature of PD.

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment

PubMed Central

Iwata, Tomoaki; Kondo, Yasuteru; Kimura, Osamu; Morosawa, Tatsuki; Fujisaka, Yasuyuki; Umetsu, Teruyuki; Kogure, Takayuki; Inoue, Jun; Nakagome, Yu; Shimosegawa, Tooru

2016-01-01

Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors. The immune-suppressive functions of MDSCs in hepatocellular carcinoma (HCC) patients have not been clarified. Therefore, we tried to analyze the biological significance of MDSCs in HCC patients. We quantified PD-L1+MDSCs of HCC patients in various conditions by using multi-color flow cytometry analysis. PBMCs from HCC patients contained significantly higher percentages of PD-L1+MDSCs in comparison to those from healthy subjects (p < 0.001). The percentages of PD-L1+MDSCs were reduced by curative treatment for HCC (p < 0.05), and the percentages of PD-L1+MDSCs before treatment were inversely correlated with disease-free survival time. After we cocultivated PBMCs and several liver cancer cell lines in a transwell coculture system, the percentages of PD-L1+MDSCs were significantly increased compared with control (p < 0.05). The expression of M-CSF and VEGFA was higher in the cell lines that strongly induced PD-L1+MDSCs. Peripheral blood from HCC patients had significantly higher percentages of PD-L1+MDSCs in comparison to those of healthy subjects, and the percentages of PD-L1+MDSCs were reduced by HCC treatment, suggesting that we might use PD-L1+MDSCs as a new biomarker of HCC. PMID:27966626

PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment.

PubMed

Iwata, Tomoaki; Kondo, Yasuteru; Kimura, Osamu; Morosawa, Tatsuki; Fujisaka, Yasuyuki; Umetsu, Teruyuki; Kogure, Takayuki; Inoue, Jun; Nakagome, Yu; Shimosegawa, Tooru

2016-12-14

Myeloid-derived suppressor cells (MDSCs) could have important roles in immune regulation, and MDSCs can be induced in patients with various malignant tumors. The immune-suppressive functions of MDSCs in hepatocellular carcinoma (HCC) patients have not been clarified. Therefore, we tried to analyze the biological significance of MDSCs in HCC patients. We quantified PD-L1 + MDSCs of HCC patients in various conditions by using multi-color flow cytometry analysis. PBMCs from HCC patients contained significantly higher percentages of PD-L1 + MDSCs in comparison to those from healthy subjects (p < 0.001). The percentages of PD-L1 + MDSCs were reduced by curative treatment for HCC (p < 0.05), and the percentages of PD-L1 + MDSCs before treatment were inversely correlated with disease-free survival time. After we cocultivated PBMCs and several liver cancer cell lines in a transwell coculture system, the percentages of PD-L1 + MDSCs were significantly increased compared with control (p < 0.05). The expression of M-CSF and VEGFA was higher in the cell lines that strongly induced PD-L1 + MDSCs. Peripheral blood from HCC patients had significantly higher percentages of PD-L1 + MDSCs in comparison to those of healthy subjects, and the percentages of PD-L1 + MDSCs were reduced by HCC treatment, suggesting that we might use PD-L1 + MDSCs as a new biomarker of HCC.

Quality of life in chronic renal patients on hemodialysis or peritoneal dialysis: a comparative study in a referral service of Curitiba - PR.

PubMed

Gonçalves, Fernanda Aguiar; Dalosso, Ingrid Fernandes; Borba, Jéssica Maria Camargo; Bucaneve, Juliana; Valerio, Nayra Maria Prado; Okamoto, Cristina Terumy; Bucharles, Sergio Gardano Elias

2015-01-01

Chronic kidney disease (CKD) compromises the health and routine of the patient. On the fifth stage of CKD, the patient becomes eligible to start renal replacement therapy: hemodialysis (HD), peritoneal dialysis (PD) or kidney transplantation. The type of CKD treatment is essential to improving quality of life of the patient. To compare the quality of life of CKD stage 5 patients who perform HD and home PD. Cross-sectional study with data collection, by convenience, through the application of socioeconomic and KDQOL SF-36 questionnaires in HD and PD patients of the Pro-Renal Foundation and satellite clinics in Curitiba-PR. The sample was 338 patients, 222 HD and 116 PD. Average age: 54.4 years for HD group (± 15.28) and 58.00 for the DP group (± 13.99). The variables: work status (p < 0.05), encouragement by dialysis staff (p < 0.01) and patient satisfaction (p < 0.001) were in favor of DP; while physical functioning (p < 0.05) and emotional function (p < 0.01) were to HD. Objectively, PD was more favorable regarding quality of life, for the large number of items with significant results when compared to HD. However, the two variables of greatest significance found in HD (physical functioning and emotional functioning) ended up having a much greater impact on well-being and daily-life of the patient in the environment external to the clinic than those who were higher in DP, making HD the most favorable for patient quality of life.

Caregivers' and physicians' attitudes to rotigotine transdermal patch versus oral Parkinson's disease medication: an observational study.

PubMed

Sieb, Jörn Peter; Themann, Peter; Warnecke, Tobias; Lauterbach, Thomas; Berkels, Reinhard; Grieger, Frank; Lorenzl, Stefan

2015-05-01

To provide real-world data on caregiver and physician perceptions of the advantages and disadvantages of rotigotine transdermal patch (Neupro * ) versus oral Parkinson's Disease (PD) medication. Cross-sectional, non-interventional study in routine clinical practice in Germany (NCT01330290). Patients had PD with documented need for care, and had received rotigotine transdermal patch as add-on to oral PD treatment for ≥1 month. Caregivers/nurses and physicians assessed rotigotine transdermal patch versus oral PD medications using questionnaires. Specific questions regarding the possible benefits of transdermal application were asked and comprised questions on: swallowing dysfunction, nausea/vomiting, monitoring therapy, once daily application, application independently from meals, application to sleeping patients, caregiving efforts (caregivers only) and clinical aspects (physicians only). Each question was assessed on a 5 point scale ranging from -2 (major disadvantage) to 2 (major advantage) compared with oral treatment. Primary outcomes were mean total scores of all questions for caregivers/nurses and physicians who provided responses for ≥4 questions. As there are no validated tools to assess physician/caregiver preference in the PD setting, there is no reference against which the current findings can be compared; this study serves to pilot the questionnaires. Questionnaire responses from 128 caregivers/nurses and 41 physicians were documented for 147 patients. One hundred (68%) patients had a caregiving family member; 40 (27%) were cared for by a nurse. Mean PD duration was 8.2 (SD 6.3) years; 136 (93%) patients were taking levodopa. Mean total score of caregivers'/nurses' questionnaires was 1.32 (SD 0.67) and of physicians' questionnaires was 1.46 (0.32) indicating a perceived advantage of rotigotine transdermal patch over oral PD therapy. Mean scores for individual questions were in the range 1.03-1.54 for caregivers/nurses and 1.15-1.87 for physicians. When given a choice about rationale to prescribe, physicians cited pharmaceutical form (patch) in 139 (95%) cases and active agent (rotigotine) in 89 (61%) cases. Caregivers/nurses and physicians perceived advantages with rotigotine transdermal patch compared to an oral PD medication as add-on therapy in patients with PD; advantages were observed in aspects of medical treatment as well as in everyday situations of caregiving of PD patients.

Glucose-6-phosphate dehydrogenase a novel hope on a blood-based diagnosis of Alzheimer's disease.

PubMed

Evlice, Ahmet; Ulusu, Nuriye Nuray

2017-03-01

Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder that numerous factors have key properties in the development of this proteopathy. Glucose-6-phosphate dehydrogenase (G6PD) is the most common form of enzymopathy. We have examined G6PD enzyme activity levels in the serum of newly diagnosed AD patients compared with control subjects without dementia from the both sexes. Serum G6PD levels were found to be significantly higher (approximately two times) in AD patients compared to control geriatric subjects in both sexes. We have concluded that G6PD seems to play an integral role in the progress and/or prevention of AD.

Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated, advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials

PubMed Central

Zhuansun, Yongxun; Huang, Fengting; Du, Yumo; Lin, Lin

2017-01-01

Background The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. Methods PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients. Only randomized controlled trials (RCTs) comparing anti-PD-1/PD-L1 antibody with conventional chemotherapy in NSCLC were included. Overall survival (OS) in the intention-to-treat population was the primary outcome. The secondary outcomes were: progression-free survival (PFS) in the intention-to-treat population, objective response rate (ORR), the incidence of adverse events, OS and PFS in different PD-L1 expression subgroups. Results Four trials with a total of 2,174 patients were included. Anti-PD-1/PD-L1 antibody showed a significant benefit to OS in the intention-to-treat population [combined hazard ratio (HR) 0.67; 95% CI: 0.61–0.75, P<0.00001], a 33% reduction in the relative risk of death. PFS also favored anti-PD-1/PD-L1 antibody (HR 0.81, 95% CI: 0.70–0.95, P=0.009). The ORR was significantly higher with anti-PD-1/PD-L1 antibody than those with chemotherapy (RR of nonresponse, 0.92; 95% CI: 0.89–0.95, P<0.00001). Anti-PD-1/PD-L1 antibody was associated with greater efficacy than chemotherapy across the end points of OS and PFS when tumor PD-L1 expression scored ≥1%, ≥5%, and ≥50%, except for tumor PD-L1 expression scored <1%. The group receiving anti-PD-1/PD-L1 antibody had lower rates of treatment-related adverse events of any grade (RR 0.77; 95% CI: 0.73–0.81, P<0.00001) and treatment-related adverse events of grade 3–5 (RR 0.24; 95% CI: 0.14–0.41, P<0.00001). Conclusions Anti-PD-1/PD-L1 antibody significantly improved survival compared with chemotherapy in previously-treated, progressive NSCLC patients. Besides, it also had a better safety profile. PMID:28449473

Anti-PD-1/PD-L1 antibody versus conventional chemotherapy for previously-treated, advanced non-small-cell lung cancer: a meta-analysis of randomized controlled trials.

PubMed

Zhuansun, Yongxun; Huang, Fengting; Du, Yumo; Lin, Lin; Chen, Rui; Li, Jianguo

2017-03-01

The anti-PD-1/PD-L1 monoclonal antibody has showed promising results in various cancers via enhancing T cell functions. However, many questions remain in the role and safety in previously-treated, advanced non-small-cell lung cancer (NSCLC). Thus, we conducted a meta-analysis incorporating all available evidences to evaluate the efficacy and safety of anti-PD-1/PD-L1 antibody compared with chemotherapy. PubMed, Web of Science and the Cochrane Library database were searched for the studies about the efficacy and safety of anti-PD-1/PD-L1 antibody in previously-treated, progressive NSCLC patients. Only randomized controlled trials (RCTs) comparing anti-PD-1/PD-L1 antibody with conventional chemotherapy in NSCLC were included. Overall survival (OS) in the intention-to-treat population was the primary outcome. The secondary outcomes were: progression-free survival (PFS) in the intention-to-treat population, objective response rate (ORR), the incidence of adverse events, OS and PFS in different PD-L1 expression subgroups. Four trials with a total of 2,174 patients were included. Anti-PD-1/PD-L1 antibody showed a significant benefit to OS in the intention-to-treat population [combined hazard ratio (HR) 0.67; 95% CI: 0.61-0.75, P<0.00001], a 33% reduction in the relative risk of death. PFS also favored anti-PD-1/PD-L1 antibody (HR 0.81, 95% CI: 0.70-0.95, P=0.009). The ORR was significantly higher with anti-PD-1/PD-L1 antibody than those with chemotherapy (RR of nonresponse, 0.92; 95% CI: 0.89-0.95, P<0.00001). Anti-PD-1/PD-L1 antibody was associated with greater efficacy than chemotherapy across the end points of OS and PFS when tumor PD-L1 expression scored ≥1%, ≥5%, and ≥50%, except for tumor PD-L1 expression scored <1%. The group receiving anti-PD-1/PD-L1 antibody had lower rates of treatment-related adverse events of any grade (RR 0.77; 95% CI: 0.73-0.81, P<0.00001) and treatment-related adverse events of grade 3-5 (RR 0.24; 95% CI: 0.14-0.41, P<0.00001). Anti-PD-1/PD-L1 antibody significantly improved survival compared with chemotherapy in previously-treated, progressive NSCLC patients. Besides, it also had a better safety profile.

Retinal nerve fiber layer thinning: a window into rapid eye movement sleep behavior disorders in Parkinson's disease.

PubMed

Yang, Zi-Jiao; Wei, Jing; Mao, Cheng-Jie; Zhang, Jin-Ru; Chen, Jing; Ji, Xiao-Yan; Liu, Jun-Yi; Shen, Yun; Xiong, Kang-Ping; Huang, Jun-Ying; Yang, Ya-Ping; Liu, Chun-Feng

2016-12-01

Retinal nerve fiber layer (RNFL) thinning occurs in Parkinson's disease (PD) and other neurodegenerative diseases. Idiopathic RBD (iRBD) is a well-established prodromal hallmark of synucleinopathies and occurs secondary to many neurodegenerative diseases, including PD. The aim of this study is to determine whether or not retinal structures are altered with the onset of rapid eye movement (REM) sleep behavior disorders (RBD). In all, a total of 63 patients with PD, 14 patients with idiopathic RBD, and 26 sex- and age-matched healthy controls were enrolled and underwent optical coherence tomography measurements (HD-OCT (Zeiss) ) for the average and every quadrant of RNFL thickness. The REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) was used to classify PD patients with clinically probable RBD (PD + pRBD) or without probable RBD (PD - pRBD). Patients with iRBD were identified by polysomnography. For patients with RBD (idiopathic or secondary to PD), we found a significant decrease in RNFL thickness compared with groups without RBD (PD - pRBD and healthy controls) (all p < 0.05). Average RNFL thickness in patients with iRBD is significantly thinner than in healthy controls (p < 0.05). In PD, the average RNFL thickness was dramatically thinner in the PD + pRBD group than the PD - pRBD group (p < 0.005). Compared with healthy controls, RNFL thickness was slightly thinner in the drug-naive PD group but not the PD group with drug treatment. Multiple linear regression analysis showed that RBDSQ score was negatively associated with average and inferior RNFL variation in PD (all p < 0.005). The findings show that RNFL was slightly but significantly thinner in idiopathic RBD. In PD, RNFL thickness may vary depending on the presence of RBD.

The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia.

PubMed

Petrowski, Katja; Wintermann, Gloria; Smolka, Michael N; Huebner, Thomas; Donix, Markus

2014-01-01

Panic disorder with agoraphobia (PD-A) has been associated with abnormal neural activity for threat-related stimuli (faces, places). Recent findings suggest a disturbed neural processing of emotionally neutral stimuli at a more general level. Using functional magnetic resonance imaging (fMRI) we investigated the neural processing of emotionally neutral faces and places in PD-A. Fifteen patients with PD-A and fifteen healthy subjects participated in the study. When they perceived neutral faces and places, the patients with PD-A showed significantly less brain activity in the fusiform gyrus, the inferior occipital gyrus, the calcarine gyrus, the cerebellum, and the cuneus compared with the healthy controls. However, the patients with PD-A showed significantly more brain activity in the precuneus compared with controls subjects. It was not possible to distinguish the agoraphobia-associated effects from possible contributions due to general anxiety induced by fMRI. For future investigations, an additional clinical control group with patients suffering from panic disorder without agoraphobia would be of interest. In addition, the psychopathology concerning the agoraphobic symptoms needs to be investigated in more detail. The findings suggest altered neural processing of emotionally neutral faces and places in patients with PD-A. Reduced neural activity in different brain regions may indicate difficulties in recognizing the emotional content in face and place stimuli due to anxiety-related hyper-arousal. © 2013 Published by Elsevier B.V.

Anti-PD1 following ipilimumab for mucosal melanoma: durable tumor response associated with severe hypothyroidism and rhabdomyolysis.

PubMed

Min, Le; Hodi, F Stephen

2014-01-01

Treatment with fully human monoclonal antibodies against programmed death 1 (PD1) receptor has shown great promise for a number of advanced malignancies. Although inflammatory adverse events have been well described with anti-CTL antigen 4 (CTLA4) therapy, experience with the range of adverse effects of anti-PD1 remains comparatively limited. Here, we report on a patient with advanced mucosal melanoma who received four doses of MK-3475, a fully human monoclonal antibody against PD1, and experienced a durable near-complete response but developed severe hypothyroidism, rhabdomyolysis, and acute kidney injury. To our knowledge, this is the first case reported of a patient with advanced mucosal melanoma who responded to anti-PD1 therapy. With the promising antitumor effects of anti-PD1 in a wide array of tumors, we expect an increasing number of patients to be exposed to anti-PD1 therapies. Recognition of infrequent presentations of adverse events such as elevated creatine kinase levels and thyroid disorders in patients who receive anti-PD1 therapy is important. ©2014 AACR.

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

PubMed Central

Lee, Kyong Ok; Park, Se Jin; Kim, Ji Hong; Lee, Jae Seung; Kim, Pyung Kil

2013-01-01

Purpose Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. Materials and Methods We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. Results We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). Conclusion Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD. PMID:23709435

Parkinson disease and musculoskeletal pain: an 8-year population-based cohort study.

PubMed

Lien, Wei-Hung; Lien, Wei-Chih; Kuan, Ta-Shen; Wu, Shang-Te; Chen, Yi-Ting; Chiu, Ching-Ju

2017-07-01

The aim of this study was to evaluate the incidence and clinical features of musculoskeletal pain (MSP) in patients with Parkinson disease (PD) compared with a control group without the disease. The retrospective cohort study used a subset of the Taiwan National Health Insurance Research Database (NHIRD) comprising information on 1 million beneficiaries randomly sampled from the entire population of Taiwan. A total of 490 patients aged 50 and above with newly diagnosed Parkinson disease were identified during a period from 2000 to 2005. Among them, 199 developed MSP after PD. The control group consisted of 1960 participants without PD over the study period randomly selected by matching PD cases according to the date of PD incidence, age, and sex. The study groups were then followed to the end of 2007. Musculoskeletal pain was the end point. The incidence rate ratios of MSP were higher in the PD group than in the control group, representing an adjusted hazard ratio of 1.31 (95% confidence interval 1.09 to 1.58). PD was associated with a significantly elevated risk of MSP in all sex and age stratifications, with the highest hazard ratio noted for middle-aged male patients with PD, followed by older male patients with PD. This study showed that the PD may significantly increase the risk of developing MSP. The risk of developing MSP seems to be greatest for middle-aged male patients with PD. Clinicians should be more alert for MSP in patients with PD, and early intervention should be considered.

Emotion processing in Parkinson's disease: an EEG spectral power study.

PubMed

Yuvaraj, R; Murugappan, M; Omar, Mohd Iqbal; Ibrahim, Norlinah Mohamed; Sundaraj, Kenneth; Mohamad, Khairiyah; Satiyan, M

2014-07-01

Although an emotional deficit is a common finding in Parkinson's disease (PD), its neurobiological mechanism on emotion recognition is still unknown. This study examined the emotion processing deficits in PD patients using electroencephalogram (EEG) signals in response to multimodal stimuli. EEG signals were investigated on both positive and negative emotions in 14 PD patients and 14 aged-matched normal controls (NCs). The relative power (i.e., ratio of EEG signal power in each frequency band compared to the total EEG power) was computed over three brain regions: the anterior (AF3, F7, F3, F4, F8 and AF4), central (FC5 and FC6) and posterior (T7, P7, O1, O2, P8 and T8) regions for theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-60 Hz) frequency sub-bands, respectively. Behaviorally, PD patients showed decreased performance in classifying emotional stimuli as measured by subjective ratings. EEG power at theta, alpha, beta, and gamma bands in all regions were significantly different between the NC and PD groups during both the emotional tasks, with p-values less than 0.05. Furthermore, an increase of relative spectral powers in the theta and gamma bands and a decrease of relative powers in the alpha and beta bands were observed for PD patients compared with NCs during emotional information processing. The results suggest the possibility of the existence of a distinctive neurobiological substrate of PD patients during emotional information processing. Also, these distributed spectral powers in different frequency bands might provide meaningful information about emotional processing in PD patients.

Correlation of PD-1/PD-L1 polymorphisms and expressions with clinicopathologic features and prognosis of ovarian cancer.

PubMed

Tan, Dan; Sheng, Li; Yi, Qing-Hua

2018-02-06

To explore the correlation of PD-1/PD-L1 polymorphisms and their expressions with clinicopathologic features and prognosis of ovarian cancer. A total of 164 patients with ovarian cancer were enrolled as case group and 170 healthy women as control group. We conducted quantitative reverse transcription-PCR (qRT-PCR) to determine PD-1/PD-L1 expressions in peripheral blood mononuclear cells (PBMCs). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific amplification were used to detect PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk for ovarian cancer. PD-1 rs2227982 C>T was associated with FIGO stage and differentiation grade, while PD-L1 rs4143815 C>G was correlated with histological type and differentiation grade. Besides, PD-1/PD-L1 expressions were positively correlated in PBMCs of patients with ovarian cancer to be associated with differentiation grade. Compared with wild homozygous patients, PD-1/PD-L1 expressions were significantly decreased in PBMCs of ovarian cancer patients carried with the mutant genotypes of rs2227982 C>T and rs4143815 C>G. The PFS and OS in ovarian cancer patients with wild homozygous genotype of rs2227982 C>T and rs4143815 C>G were significantly higher than those with mutant genotypes, which were significantly lower in patients with low expressions of PD-1/PD-L1 than those with high expressions. Univariate COX regression analysis identified FIGO staging, differentiation grade, rs2227982 C>T, rs4143815 C>G and expressions of PD-1/PD-L1 as the prognostic factors, and multivariate COX regression analysis demonstrated that high FIGO stage and low expressions of PD-1/PD-L1 were independent risk factors for the prognosis of ovarian cancer. PD-1 rs2227982 C>T and PD-L1 rs4143815 C>G polymorphisms increased the risk of ovarian cancer, leading to a poor prognosis, associated with low expressions of PD-1 and PD-L1. While high PD-1 and PD-L1 expressions are indicators of a favorable prognosis in ovarian cancer.

A survey of subjective constipation in Parkinson's disease patients in shanghai and literature review.

PubMed

Gan, Jing; Wan, Ying; Shi, Junjie; Zhou, Mingzhu; Lou, Zhiyin; Liu, Zhenguo

2018-03-15

Constipation is one of the most frequent non-motor symptoms (NMS) in Parkinson's disease (PD) and the prevalence of constipation in PD patients varies among different studies. We designed this study to survey the prevalence and clinical characteristics of subjective constipation and the appearance chronology between the emergence of constipation and onset of motor symptoms in PD patients from Shanghai, China. 268 PD patients were continuously recruited into this study. Parkinson's related clinical information of the participants was collected. A spectrum of motor and nonmotor features was assessed with scales and questionnaires. Subjective constipation was defined by ROME III criteria. 54.10% PD patients suffer from constipation. Among them, there was 47.59% having constipation before onset of motor symptoms. Compared with patients without constipation, patients with constipation reported lower daily water intake and less exercise, and were dominated by bradykinetic-rigid motor phenotype at onset and were prone to have anxiety, depression and insomnia. The time span between constipation and the onset of motor symptoms was (6.62 ± 9.32) years. Constipation occurred more frequently between 2 and 10 years before onset of motor symptoms. Patients suffering with constipation were then divided into two groups according to the time sequence of constipation and motor onset: 'constipation pre-motor sign' group and 'constipation post-motor sign' group. Total timespan from earliest initial symptoms to present was similar. Compared with 'constipation post-motor sign' group, the patients in 'constipation pre-motor sign' group experienced an older motor symptoms onset age, less serious motor symptoms, more serious constipation and less daily levodopa dosage. Our results supported that constipation could be a pre-motor symptom of PD. Different clinical characteristics were found in different constipation-loading time relative to motor symptoms. Research of constipation may be useful to better understand the early stages of PD and assessment of constipation with validated criteria may have utility as a risk factor for predicting PD in the prodromal phase.

Gray matter atrophy associated with mild cognitive impairment in Parkinson's disease.

PubMed

Chen, Fu-Xiang; Kang, De-Zhi; Chen, Fu-Yong; Liu, Ying; Wu, Gang; Li, Xun; Yu, Liang-Hong; Lin, Yuan-Xiang; Lin, Zhang-Ya

2016-03-23

The underlying pathology of brain leading to cognitive impairment in Parkinson's disease (PD) remains poorly understood. The aim of our study was to test the hypothesis that mild cognitive impairment (MCI) in PD may be related to atrophy of special gray matter regions. High-resolution T1-weighted magnetic resonance images of the brains and comprehensive cognitive function tests were acquired in 37 PD patients and 21 healthy controls (HC) from September 2013 to October 2014. Patients were divided into two groups: PD with MCI (PD-MCI, n=18) and PD with normal cognition (PDNC, n=19). Gray matter density differences were analyzed using voxel-based morphometry (VBM). VBM and cognitive results, UPDRS scores and Hoehn-Yahr stages were compared between PD-MCI, PDCN and HC group, and correlation analyses were performed between those brain areas and cognition scores, UPDRS scores and disease duration, which showed significant group differences. The demographic data and motor severity among three groups were similar. However, comprehensive cognitive function results were more severe in PD-MCI than the other two groups. Compared to the HC group, the PDNC group showed reductions in gray matter density in frontal, temporal, parietal, bilateral insula lobes and many other regions of brain. Besides above changes, the PD-MCI group also revealed gray matter concentration decrease in left hippocampus and thalamus, and these changes still remained when compared with the PDNC group. The HC group did not show any more areas of atrophy in gray matter than others. Gray matter loss in PD represented significant correlations with global cognitive scores, motor severity or disease duration in some of these atrophic regions. The initial stages of cognitive function decline in patients with PD is closely associated with gray matter atrophy in left hippocampus and thalamus. These two regions may serve as potential imaging biomarkers for PD-MCI. Copyright © 2016. Published by Elsevier Ireland Ltd.

Do the outcomes of living donor renal allograft recipients differ with peritoneal dialysis and hemodialysis as a bridge renal replacement therapy?

PubMed

Prasad, Narayan; Vardhan, Harsh; Baburaj, Vinod P; Bhadauria, Dharmendra; Gupta, Amit; Sharma, Raj K; Kaul, Anupama

2014-11-01

This study was undertaken to compare the outcomes of living donor renal transplant recipients using peritoneal dialysis (PD) and hemodialysis (HD) as a bridge modality for renal replacement therapy till renal transplantation. The demographic profiles of the recipients and donors, the patients' native kidney disease (diabetic versus non-diabetic), duration on dialysis, requirement of anti-hypertensive drugs, number of blood transfusions, human leukocyte antigen (HLA) mismatch status, pre- and post-transplant infectious complications, and post-transplant outcomes of patients were compared between the two groups. The demographic features of the study patients were similar in the two groups. The duration of dialysis prior to transplant was significantly longer in the PD group than in the HD group of patients. The anti-hypertensive drug requirement was lower and the hemoglobin level and residual urine volume at the time of transplant were relatively better in the PD patients compared to the HD patients. The number of acute rejection episodes, delayed graft function, surgical complications, glomerular filtration rate at one month and at the last follow-up, were also similar in both groups. The short-term and long-term graft survival was similar in both groups of patients. The one-, two-, five-, and eight-year death-censored graft survival rates of the PD patients were 98, 95, 85, and 73%, respectively, and in the HD group of patients, they were 100, 93, 84, and 79%, respectively. The one-, two-, five-, and eight-year patient survival rates in the PD group were 97, 92, 77, and 66%, respectively, and in the HD group, they were 97, 92, 79, and 69%, respectively. Our study suggests that the outcomes of the living donor renal allograft recipients did not differ between the groups of patients who used PD or HD as renal replacement therapy prior to renal transplantation.

Different aspects of emotional intelligence of borderline personality disorder.

PubMed

Peter, Mathell; Arntz, Arnoud R; Klimstra, Theo; Vingerhoets, Ad J J M

2018-01-01

The present study investigated deficiencies in different components of emotional intelligence in borderline personality disorder (BPD). The Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Emotional Quotient Inventory (EQ-i) were used to assess EI dimensions. BPD patients (N = 85; 69 women; M = 33.6 years) were compared with Cluster C personality disorder (PD) patients (N = 39; 23 women; M = 36.6 years) and nonpatients (N = 69; 44 women; M = 35.6 years). Compared to the Cluster C PD patients and the nonpatient group, BPD patients displayed only deficits in their ability to understand emotions as measured with the Mayer-Salovey-Caruso Emotional Intelligence Test. The Emotional Quotient Inventory only revealed deficits in stress management in BPD patients compared to Cluster C PD patients. Our findings suggest that BPD patients have the ability to regulate emotions effectively, but they subjectively experience deficits in emotion regulation and therefore may not use this ability when they need it. Copyright © 2017 John Wiley & Sons, Ltd.

A Network Meta-analysis Comparing the Efficacy and Safety of Anti-PD-1 with Anti-PD-L1 in Non-small Cell Lung Cancer.

PubMed

You, Wei; Liu, Mei; Miao, Ji-Dong; Liao, Yu-Qian; Song, Yi-Bing; Cai, Dian-Kun; Gao, Yang; Peng, Hao

2018-01-01

Background : This network meta-analysis aimed at comparing anti-programmed death 1 (anti-PD-1) with anti-programmed death ligand 1(anti-PD-L1) immunotherapy in patients with metastatic, previously treated non-small cell lung cancer (NSCLC) who failed first-line treatment. Methods : We searched electronic databases to identify all eligible clinical trials. End-points included overall survival (OS), progression-free survival (PFS) and objective response. Hazard ratios (HRs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted. Network meta-analysis was performed using the frequentist approach for multiple treatment comparisons. Results : In total, 3024 patients were randomly assigned: 1117 received anti-PD-1 therapy (nivolumab + pembrolizumab), 569 received anti-PD-L1 (atezolizumab) and 1338 received docetaxel. Anti-PD-1 (HR, 0.56; 95% CI, 0.48-0.66) and anti-PD-L1 (HR, 0.64; 95% CI, 0.51-0.79) achieved better OS than docetaxel, and anti-PD-1 was superior to docetaxel in terms of PFS (HR, 0.75; 95% CI, 0.62-0.89). Moreover, anti-PD-1 achieved the highest effect on OS and PFS, with a P-score of 91.2% and 95.5%, respectively. With regard to tumor response, anti-PD-1 group had a higher rate of responders than that in anti-PD-L1 (HR, 0.35; 95% CI, 0.19-0.65) and docetaxel (HR, 0.36; 95% CI, 0.25-0.52) groups. Undoubtedly, anti-PD-1 and anti-PD-L1 obtained less toxicity profile than docetaxel, and no significant difference was observed between anti-PD-1 and anti-PD-L1 groups. Conclusions : Anti-PD-1 may be a better choice for patients with metastatic and previously treated NSCLC who failed first-line treatment in terms of the treatment ranking.

Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy.

PubMed

Nagaya, Tadanobu; Tanaka, Naoki; Kimura, Takefumi; Kitabatake, Hiroyuki; Fujimori, Naoyuki; Komatsu, Michiharu; Horiuchi, Akira; Yamaura, Takahiro; Umemura, Takeji; Sano, Kenji; Gonzalez, Frank J; Aoyama, Toshifumi; Tanaka, Eiji

2015-06-01

It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD. The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients. The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase α, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) γ compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation. Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPARγ, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD. These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.

Objective Assessment of Bradykinesia Estimated from the Wrist Extension in Older Adults and Patients with Parkinson's Disease.

PubMed

Rabelo, Amanda Gomes; Neves, Lucio Pereira; Paixão, Ana Paula S; Oliveira, Fábio Henrique Monteiro; de Souza, Luciane Aparecida Pascucci Sande; Vieira, Marcus Fraga; Pereira, Adriano A; Andrade, Adriano O

2017-11-01

Parkinson's disease (PD) presents several motor signs, including tremor and bradykinesia. However, these signs can also be found in other motor disorders and in neurologically healthy older adults. The incidence of bradykinesia in PD is relatively high in all stages of the disorder, even when compared to tremor. Thus, this research proposes an objective assessment of bradykinesia in patients with PD (G PD : 15 older adults with Parkinson's disease, 65.3 ± 9.1 years) and older adults (G HV : 12 healthy older adults, 60.1 ± 6.1 years). The severity of bradykinesia in the participants of G PD was assessed using the Unified Parkinson's Disease Rating Scale. Movement and muscular activity were detected by means of inertial (accelerometer, gyroscope, magnetometer) and electromyographic sensors while the participants performed wrist extension against gravity with the forearm on pronation. Mean and standard error of inertial and electromyographic signal parameters could discriminate PD patients from healthy older adults (p value <0.05). In discriminating patients with PD from healthy older adults, the mean sensitivity and specificity were respectively 86.67 and 83.33%. The discrimination between the groups, based on the objective evaluation of bradykinesia, may contribute to the accurate diagnosis of PD and to the monitoring of therapies to control parkinsonian bradykinesia, and opens the possibility for further comparative studies considering individuals suffering from other motor disorders.

Treadmill training improves overground walking economy in Parkinson's disease: a randomized, controlled pilot study.

PubMed

Fernández-Del-Olmo, Miguel Angel; Sanchez, Jose Andres; Bello, Olalla; Lopez-Alonso, Virginia; Márquez, Gonzalo; Morenilla, Luis; Castro, Xabier; Giraldez, Manolo; Santos-García, Diego

2014-01-01

Gait disturbances are one of the principal and most incapacitating symptoms of Parkinson's disease (PD). In addition, walking economy is impaired in PD patients and could contribute to excess fatigue in this population. An important number of studies have shown that treadmill training can improve kinematic parameters in PD patients. However, the effects of treadmill and overground walking on the walking economy remain unknown. The goal of this study was to explore the walking economy changes in response to a treadmill and an overground training program, as well as the differences in the walking economy during treadmill and overground walking. Twenty-two mild PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). We evaluated the energy expenditure of overground walking, before and after each of the training programs. The energy expenditure of treadmill walking (before the program) was also evaluated. The treadmill, but not the overground training program, lead to an improvement in the walking economy (the rate of oxygen consumed per distance during overground walking at a preferred speed) in PD patients. In addition, walking on a treadmill required more energy expenditure compared with overground walking at the same speed. This study provides evidence that in mild PD patients, treadmill training is more beneficial compared with that of walking overground, leading to a greater improvement in the walking economy. This finding is of clinical importance for the therapeutic administration of exercise in PD.

Parkinson Patients’ Initial Trust in Avatars: Theory and Evidence

PubMed Central

Javor, Andrija; Ransmayr, Gerhard; Struhal, Walter; Riedl, René

2016-01-01

Parkinson’s disease (PD) is a neurodegenerative disease that affects the motor system and cognitive and behavioral functions. Due to these impairments, PD patients also have problems in using the computer. However, using computers and the Internet could help these patients to overcome social isolation and enhance information search. Specifically, avatars (defined as virtual representations of humans) are increasingly used in online environments to enhance human-computer interaction by simulating face-to-face interaction. Our laboratory experiment investigated how PD patients behave in a trust game played with human and avatar counterparts, and we compared this behavior to the behavior of age, income, education and gender matched healthy controls. The results of our study show that PD patients trust avatar faces significantly more than human faces. Moreover, there was no significant difference between initial trust of PD patients and healthy controls in avatar faces, while PD patients trusted human faces significantly less than healthy controls. Our data suggests that PD patients’ interaction with avatars may constitute an effective way of communication in situations in which trust is required (e.g., a physician recommends intake of medication). We discuss the implications of these results for several areas of human-computer interaction and neurological research. PMID:27820864

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

PubMed

Liao, Jin-Lan; Xiong, Zu-Ying; Yang, Zhi-Kai; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia; Dong, Jie

2017-01-01

Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Profiling the dynamic expression of checkpoint molecules on cytokine-induced killer cells from non-small-cell lung cancer patients.

PubMed

Zhang, Lin; Wang, Jian; Wei, Feng; Wang, Kaiyuan; Sun, Qian; Yang, Fan; Jin, Hao; Zheng, Yu; Zhao, Hua; Wang, Limei; Yu, Wenwen; Zhang, Xiying; An, Yang; Yang, Lili; Zhang, Xinwei; Ren, Xiubao

2016-07-12

Immune checkpoints associate with dysfunctional T cells, which have a reduced ability to clear pathogens or cancer cells. T-cell checkpoint blockade may improve patient survival. However, checkpoint molecules on cytokine-induced killer (CIK) cell, a non-specific adoptive immunotherapy, remain unknown. In present study, we detected the dynamic expression of eight major checkpoint molecules (CTLA-4, PD-1, PD-L1, TIM- 3, CEACAM-1, LAG-3, TIGIT and BTLA) on CIK cells from NSCLC patients. The majority of these molecules, except BTLA, were sharply elevated during the early stage of CIK cell culture. Thereafter, PD-1 and TIGIT expressions decreased gradually towards the initial level (day 0). Moreover, CTLA-4 faded away during the later stage of CIK culture. LAG-3 expression decreased but was still significantly higher than the initial level. Of note, PD-L1 remained stably upregulated during CIK culture compared with PD-1, indicating that PD-L1 might act as an inhibitory molecule on CIK cells instead of PD-1. Furthermore, TIM-3 and CEACAM1 were strongly expressed simultaneously during long-term CIK culture and showed a significant and mutually positive correlation. BTLA displayed a distinct pattern, and its expression gradually decreased throughout the CIK culture. These observations suggested that CIK cells might be partly exhausted before clinical transfusion, characterized by the high expression of PD-L1, LAG-3, TIM- 3, and CEACAM-1 and the low expression of TIGIT, BTLA, PD-1, and CTLA-4 compared with initial culture. Our results imply that implementing combined treatment on CIK cells before transfusion via antibodies targeting PD-L1, LAG-3, TIM-3, and CEACAM-1 might improve the efficiency of CIK therapy for NSCLC patients.

Effluent CA 125 concentration in chronic peritoneal dialysis patients: influence of PD duration, peritoneal transport and PD regimen.

PubMed

Fusshöller, Andreas; Grabensee, Bernd; Plum, Jörg

2003-01-01

In terms of the integrity of the peritoneal membrane in peritoneal dialysis (PD), the peritoneal mesothelial cells play a pivotal role since its monolayer constitutes the first line of the peritoneal membrane. Cancer antigen 125 (CA 125) is released by peritoneal mesothelial cells and correlates with the mesothelial cell mass in PD. Since its effluent concentration is easy to determine in chronic PD patients, CA 125 serves as an in vivo marker of biocompatibility. We performed a cross-sectional study to investigate the relation between PD duration, peritoneal transport and the PD regimen (CAPD/CCPD) on effluent CA 125 concentration in 22 chronic PD patients. We compared long-term (>6 months) with short-term PD treatment, patients with high small solute transport properties (MTAC >11 ml/min, d/p ratio of creatinine >0.72) to patients with low small solute transport and CAPD with APD patients. A peritoneal equilibration test was performed with 1.36% glucose. Dialysate/plasma (D/P) ratio and mass transfer area coefficient (MTAC) of creatinine were calculated and the 4-hour effluent concentration of CA 125 was determined. CA 125 tended to be lower in the long-term PD patients and also in APD patients, but statistical significance was missing. Effluent CA 125 was significantly increased in patients with an MTAC of creatinine >11 ml/min (40.2 +/- 11.2 vs. 20.7 +/- 1.2 U/ml) and in patients with a d/p ratio of creatinine >0.72 (48.2 +/- 11.0 vs. 21.6 +/- 1.6 U/ml). CA 125 and the d/p ratio of creatinine were positively correlated (r = 0.68). The positive correlation of CA 125 with peritoneal small solute transport especially in the early phase of PD treatment indicates an initial correlation of the mesothelial cell mass with the peritoneal surface area. A direct relation between the CA 125 concentration and peritoneal transport is unlikely. In our study the CA 125 effluent concentration tended to be lower in long-term PD patients and also in APD patients, possibly indicating a cell depletory influence of the conventional PD fluid. Copyright 2003 S. Karger AG, Basel

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma

PubMed Central

Kiyasu, Junichi; Miyoshi, Hiroaki; Hirata, Akie; Arakawa, Fumiko; Ichikawa, Ayako; Niino, Daisuke; Sugita, Yasuo; Yufu, Yuji; Choi, Ilseung; Abe, Yasunobu; Uike, Naokuni; Nagafuji, Koji; Okamura, Takashi; Akashi, Koichi; Takayanagi, Ryoichi; Shiratsuchi, Motoaki

2015-01-01

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1+ DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1+ DLBCL. We also defined the criteria for microenvironmental PD-L1+ (mPD-L1+) DLBCL (ie, PD-L1– DLBCL in which PD-L1+ nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1+ tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1+ and mPD-L1+ DLBCL were 11% and 15.3%, respectively. Both PD-L1+ and mPD-L1+ DLBCL were significantly associated with non–germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1+ TILs was significantly higher in GCB-type tumors and lower in mPD-L1– and PD-L1+ DLBCL. Patients with PD-L1+ DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1– DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1+ and mPD-L1– DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1+ DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup. PMID:26239088

Cerebral blood flow changes in hemodialysis and peritoneal dialysis patients: an arterial-spin labeling MR imaging.

PubMed

Jiang, Xiao Lu; Wen, Ji Qiu; Zhang, Long Jiang; Zheng, Gang; Li, Xue; Zhang, Zhe; Liu, Ya; Zheng, Li Juan; Wu, Long; Chen, Hui Juan; Kong, Xiang; Luo, Song; Lu, Guang Ming; Ji, Xue Man; Zhang, Zong Jun

2016-08-01

We used arterial-spin labeling (ASL) MR imaging, a non-invasive technique to evaluate cerebral blood flow (CBF) changes in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) and hemodialysis (HD), and nondialysis ESRD patients compared with healthy cohort. Ninety seven ESRD patients including 32 PD patients (20 male, 12 female; mean age 33 ± 8 years), 33 HD patients (22 male, 11 female; mean age 33 ± 8 years) and 32 nondialysis patients (20 male, 12 female; mean age 35 ± 7 years) and 31 age- and gender-matched healthy controls (20 male, 11 female; mean age 32 ± 8 years) were included in this study. All subjects underwent ASL MR imaging, neuropsychologic tests, and ESRD patients underwent laboratory testing. CBF values were compared among PD, HD, nondialysis patients and control groups. Correlation analysis and multiple regression analysis were performed to investigate the association between CBF values and hemoglobin, neuropsychologic test results, serum creatinine, urea levels, disease duration, and dialysis duration. Elevated CBFs of whole brain region, gray matter, and white matter were found in all ESRD patient groups compared with healthy controls (all P < 0.001). However, compared with non-dialysis ESRD patients, both PD and HD patients had widespread regional CBF decline mainly in bilateral frontal and anterior cingulate cortices. There were no differences for CBF between PD and HD patient groups. Negative correlations were observed between mean CBFs of whole brain region, gray matter, and white matter and the hemoglobin level in all ESRD patients. Multiple linear regression showed elevated CBF of multiple brain areas correlated with some neuropsychological tests in ESRD patients (all P < 0.001, AlphaSim corrected), but the association was not present or shrank after adjusting hemoglobin level. This study found that mean CBF was predominantly increased in patients with ESRD, which correlated with their hemoglobin level and neurocognitive disorders. There were no differences of CBF change and cognitive function between PD and HD ESRD patients with long-term treatment. The degree of anemia may be a predominant risk factor for cognitive impairment in these ESRD patients.

Evaluation of handwriting kinematics and pressure for differential diagnosis of Parkinson's disease.

PubMed

Drotár, Peter; Mekyska, Jiří; Rektorová, Irena; Masarová, Lucia; Smékal, Zdeněk; Faundez-Zanuy, Marcos

2016-02-01

We present the PaHaW Parkinson's disease handwriting database, consisting of handwriting samples from Parkinson's disease (PD) patients and healthy controls. Our goal is to show that kinematic features and pressure features in handwriting can be used for the differential diagnosis of PD. The database contains records from 37 PD patients and 38 healthy controls performing eight different handwriting tasks. The tasks include drawing an Archimedean spiral, repetitively writing orthographically simple syllables and words, and writing of a sentence. In addition to the conventional kinematic features related to the dynamics of handwriting, we investigated new pressure features based on the pressure exerted on the writing surface. To discriminate between PD patients and healthy subjects, three different classifiers were compared: K-nearest neighbors (K-NN), ensemble AdaBoost classifier, and support vector machines (SVM). For predicting PD based on kinematic and pressure features of handwriting, the best performing model was SVM with classification accuracy of Pacc=81.3% (sensitivity Psen=87.4% and specificity of Pspe=80.9%). When evaluated separately, pressure features proved to be relevant for PD diagnosis, yielding Pacc=82.5% compared to Pacc=75.4% using kinematic features. Experimental results showed that an analysis of kinematic and pressure features during handwriting can help assess subtle characteristics of handwriting and discriminate between PD patients and healthy controls. Copyright © 2016 Elsevier B.V. All rights reserved.

Depression in Parkinson's disease: convergence from voxel-based morphometry and functional magnetic resonance imaging in the limbic thalamus.

PubMed

Cardoso, Ellison Fernando; Maia, Fernanda Martins; Fregni, Felipe; Myczkowski, Martin Luis; Melo, Luciano M; Sato, João R; Marcolin, Marco Antonio; Rigonatti, Sergio P; Cruz, Antonio Cesário; Barbosa, Egberto Reis; Amaro, Edson

2009-08-15

Depression is the most frequent psychiatric disorder in Parkinson's disease (PD). Although evidence suggests that depression in PD is related to the degenerative process that underlies the disease, further studies are necessary to better understand the neural basis of depression in this population of patients. In order to investigate neuronal alterations underlying the depression in PD, we studied thirty-six patients with idiopathic PD. Twenty of these patients had the diagnosis of major depression disorder and sixteen did not. The two groups were matched for PD motor severity according to Unified Parkinson Disease Rating Scale (UPDRS). First we conducted a functional magnetic resonance imaging (fMRI) using an event-related parametric emotional perception paradigm with test retest design. Our results showed decreased activation in the left mediodorsal (MD) thalamus and in medial prefrontal cortex in PD patients with depression compared to those without depression. Based upon these results and the increased neuron count in MD thalamus found in previous studies, we conducted a region of interest (ROI) guided voxel-based morphometry (VBM) study comparing the thalamic volume. Our results showed an increased volume in mediodorsal thalamic nuclei bilaterally. Converging morphological changes and functional emotional processing in mediodorsal thalamus highlight the importance of limbic thalamus in PD depression. In addition this data supports the link between neurodegenerative alterations and mood regulation.

Economic impact of disease progression in follicular non-Hodgkin lymphoma

PubMed Central

Beveridge, Roy; Satram-Hoang, Sacha; Sail, Kavita; Darragh, Joseph; Chen, Clara; Forsyth, Michael; Reyes, Carolina

2011-01-01

Using a retrospective claims database, we estimated the economic costs of progression among patients with follicular non-Hodgkin lymphoma (f-NHL) treated in an outpatient community-based setting. Patients with f-NHL who received care between 1 July 2006 and 31 December 2009 were categorized into two cohorts based on whether they experienced progressive disease (PD) or not. Costs per patient per month (PPPM) were compared between patients with PD versus non-PD. Follow-up time was censored at the last entry for disease status or 6 months after the date of remission/stable disease or progression. Of the 1002 patients with f-NHL identified, 268 progressed and 734 did not. The mean overall costs PPPM over the 6-month follow-up period were significantly higher for patients with PD versus non-PD ($3527 vs. $860; difference = $2667; p < 0.001). This cost difference persisted within all resource categories evaluated. Results of this study indicate that therapies which delay progression for patients with f-NHL may result in potential cost savings. PMID:21745172

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Classical eyeblink conditioning in Parkinson's disease.

PubMed

Daum, I; Schugens, M M; Breitenstein, C; Topka, H; Spieker, S

1996-11-01

Patients with Parkinson's disease (PD) show impairments of a range of motor learning tasks, including tracking or serial reaction time task learning. Our study investigated whether such deficits would also be seen on a simple type of motor learning, classic conditioning of the eyeblink response. Medicated and unmediated patients with PD showed intact unconditioned eyeblink responses and significant learning across acquisition; the learning rates did not differ from those of healthy control subjects. The overall frequency of conditioned responses was significantly higher in the medicated patients with PD relative to control subjects, and there was also some evidence of facilitation in the unmedicated patients with PD. Conditioning of electrodermal and electrocortical responses was comparable in all groups. The findings are discussed in terms of enhanced excitability of brainstem pathways in PD and of the involvement of different neuronal circuits in different types of motor learning.

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study

PubMed Central

Vychytil, Andreas; Remón, César; Michel, Catherine; Williams, Paul; Rodríguez-Carmona, Ana; Marrón, Belén; Vonesh, Ed; van der Heyden, Synke; Filho, Jose C. Divino

2008-01-01

Background. Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. Methods. The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal™) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. Results. There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. Conclusion. Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates. PMID:18556747

Deep Brain Stimulation for Parkinson's Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis.

PubMed

Fundament, Tomasz; Eldridge, Paul R; Green, Alexander L; Whone, Alan L; Taylor, Rod S; Williams, Adrian C; Schuepbach, W M Michael

2016-01-01

Parkinson's disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications.

Comparison of glycated albumin and hemoglobin A1c concentrations in diabetic subjects on peritoneal and hemodialysis.

PubMed

Freedman, Barry I; Shenoy, Rajeev N; Planer, Jonathan A; Clay, Kimberly D; Shihabi, Zak K; Burkart, John M; Cardona, Cesar Y; Andries, Lilian; Peacock, Todd P; Sabio, Hernan; Byers, Joyce R; Russell, Gregory B; Bleyer, Anthony J

2010-01-01

Relative to hemoglobin A(1c) (HbA(1c)), percentage of glycated albumin (GA%) more accurately reflects recent glycemic control in diabetic hemodialysis (HD) patients. To determine the accuracy of glycemic assays in a larger sample including patients on peritoneal dialysis (PD), HbA(1c) and GA% were measured in 519 diabetic subjects: 55 on PD, 415 on HD, and 49 non-nephropathy controls. Mean +/- SD serum glucose levels were higher in HD and PD patients relative to non-nephropathy controls (HD 169.7 +/- 62 mg/dL, PD 168.6 +/- 66 mg/dL, controls 146.1 +/- 66 mg/dL; p = 0.03 HD vs controls, p = 0.13 PD vs controls). GA% was also higher in HD and PD patients (HD 20.6% +/- 8.0%, PD 19.0% +/- 5.7%, controls 15.7% +/- 7.7%; p < 0.02 HD vs controls and PD vs controls). HbA(1c) was paradoxically lower in dialysis patients (HD 6.78% +/- 1.6%, PD 6.87% +/- 1.4%, controls 7.3% +/- 1.4%; p = 0.03 HD vs controls, p = 0.12 PD vs controls). The serum glucose/HbA(1c) ratio differed significantly between dialysis patients and controls (p < 0.0001 HD vs controls, p = 0.002 PD vs controls), while serum glucose/GA% ratio was similar across groups (p = 0.96 HD vs controls, p = 0.64 PD vs controls). In best-fit multivariate models with HbA(1c) or GA% as outcome variable, dialysis status was a significant predictor of HbA(1c) but not GA%. The relationship between HbA(1c) and GA% differs in diabetic patients with end-stage renal disease who perform either PD or HD compared to those without nephropathy. HbA(1c) significantly underestimates glycemic control in peritoneal and hemodialysis patients relative to GA%.

Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson's disease and multiple system atrophy--comparison with normal elderly.

PubMed

Wang, Yao; Shao, Wei-bo; Gao, Li; Lu, Jie; Gu, Hao; Sun, Li-hua; Tan, Yan; Zhang, Ying-dong

2014-01-01

There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson's disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration. Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson's disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed. Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients. These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.

Risk for femoral fractures in Parkinson's disease patients with and without severe functional impairment.

PubMed

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Impaired balance is a major problem in patients with idiopathic Parkinson's disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79; 95%-CI: 1.66-1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment.

PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma.

PubMed

Varki, Vinod; Ioffe, Olga B; Bentzen, Soren M; Heath, Jon; Cellini, Ashley; Feliciano, Josephine; Zandberg, Dan P

2018-05-01

To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status. We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%). Of 66 cases, 42 were immunocompetent, 24 immunosuppressed (13 organ transplant, 8 HIV+, 3 other). Defining positive expression at > 5%, 26% of tumors were positive for PD-L1, 85% for B7-H3, 80% had CD8 T cells that expressed PD-1 and 55% had TII that expressed PD-L1. Tum-B7-H3% was significantly higher (median 60 vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, including when factoring in cause of immunosuppression. No significant difference in Tum-PD-L1%, TII-PD-L1%, CD8 density, or CD8-PD-1% was observed. Tumors from HIV+ patients lacked PD-L1 expression, and had lower B7-H3% (median 2.5 vs. 60%, p = 0.007), and higher CD8 density (median 75% vs. 40%, p = 0.04) compared to immunocompetent patients. Higher tumor grade (R s  = 0.34, p = 0.006) and LVI (R s  = 0.61, p < 0.001) were both associated with higher Tum-PD-L1%. cSCC showed expression of PD-L1 on tumor in 26% of cases, and high tumor B7-H3 expression (85%) and PD-1 expression on CD8 TILs (80%). Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.

Retrospective Molecular Epidemiology Study of PD-L1 Expression in Patients with EGFR-Mutant Non-small Cell Lung Cancer.

PubMed

Cho, Jong Ho; Zhou, Wei; Choi, Yoon-La; Sun, Jong-Mu; Choi, Hyejoo; Kim, Tae-Eun; Dolled-Filhart, Marisa; Emancipator, Kenneth; Rutkowski, Mary Anne; Kim, Jhingook

2018-01-01

Data are limited on programmed death ligand 1 (PD-L1) expression in epidermal growth factor receptor ( EGFR )-mutant non-small cell lung cancer (NSCLC). We retrospectively evaluated the relationship between PD-L1 expression and recurrence-free survival (RFS) and overall survival in 319 patients with EGFR -mutant NSCLC who were treated at Samsung Medical Center from 2006 to 2014. Membranous PD-L1 expression on tumor cells was measured using the PD-L1 IHC 22C3 pharmDx antibody and reported as tumor proportion score (TPS). Kaplan-Meier methods, log-rank test, and Cox proportional hazards models were used for survival analysis. All patients had ≥1 EGFR mutation-54% in exon 19 and 39% in exon 21. Overall, 51% of patients had PD-L1-positive tumors. The prevalence of PD-L1 positivity was higher among patients with stages II-IV versus stage I disease (64% vs. 44%) and among patients with other EGFR mutations (75%) than with L858R mutation (39%) or exon 19 deletion (52%). PD-L1 positivity was associated with shorter RFS, with an adjusted hazard ratio of 1.52 (95% confidence interval [CI], 0.81 to 2.84; median, 18 months) for the PD-L1 TPS ≥ 50% group, 1.51 (95% CI, 1.02 to 2.21; median, 31 months) for the PD-L1 TPS 1%-49% group, and 1.51 (95% CI, 1.05 to 2.18) for the combined PD-L1-positive groups (TPS ≥ 1%) compared with the PD-L1-negative group (median, 35 months). PD-L1 expression is associated with disease stage and type of EGFR mutation. PD-L1 positivity might be associated with worse RFS among patients with surgically treated EGFR -mutant NSCLC.

“Nomophobia”: Impact of Cell Phone Use Interfering with Symptoms and Emotions of Individuals with Panic Disorder Compared with a Control Group

PubMed Central

King, Anna Lucia Spear; Valença, Alexandre Martins; Silva, Adriana Cardoso; Sancassiani, Federica; Machado, Sergio; Nardi, Antonio Egidio

2014-01-01

Panic disorder refers to the frequent and recurring acute attacks of anxiety. Objective: This study describes the routine use of mobiles phones (MPs) and investigates the appearance of possible emotional alterations or symptoms related to their use in patients with panic disorder (PD). Background: We compared patients with PD and agoraphobia being treated at the Panic and Respiration Laboratory of The Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil, to a control group of healthy volunteers. Methods: An MP-use questionnaire was administered to a consecutive sample of 50 patients and 70 controls. Results: People with PD showed significant increases in anxiety, tachycardia, respiratory alterations, trembling, perspiration, panic, fear and depression related to the lack of an MP compared to the control group. Conclusions: Both groups exhibited dependence on and were comforted by having an MP; however, people with PD and agoraphobia showed significantly more emotional alterations as well as intense physical and psychological symptoms when they were apart from or unable to use an MP compared to healthy volunteers. PMID:24669231

"Nomophobia": impact of cell phone use interfering with symptoms and emotions of individuals with panic disorder compared with a control group.

PubMed

King, Anna Lucia Spear; Valença, Alexandre Martins; Silva, Adriana Cardoso; Sancassiani, Federica; Machado, Sergio; Nardi, Antonio Egidio

2014-01-01

Panic disorder refers to the frequent and recurring acute attacks of anxiety. This study describes the routine use of mobiles phones (MPs) and investigates the appearance of possible emotional alterations or symptoms related to their use in patients with panic disorder (PD). We compared patients with PD and agoraphobia being treated at the Panic and Respiration Laboratory of The Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil, to a control group of healthy volunteers. An MP-use questionnaire was administered to a consecutive sample of 50 patients and 70 controls. People with PD showed significant increases in anxiety, tachycardia, respiratory alterations, trembling, perspiration, panic, fear and depression related to the lack of an MP compared to the control group. Both groups exhibited dependence on and were comforted by having an MP; however, people with PD and agoraphobia showed significantly more emotional alterations as well as intense physical and psychological symptoms when they were apart from or unable to use an MP compared to healthy volunteers.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

PubMed

Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-02-01

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

PubMed Central

Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

2014-01-01

Objective Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. Methods The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Results Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Conclusions Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications. PMID:23899625

Prevalence of Symptoms of Depression, Anxiety, and Posttraumatic Stress Disorder in Workers With Upper Extremity Complaints.

PubMed

Degen, Ryan M; MacDermid, Joy C; Grewal, Ruby; Drosdowech, Darren S; Faber, Kenneth J; Athwal, George S

2016-07-01

Study Design Cross-sectional cohort study. Background Symptoms of depression, panic disorder (PD), and posttraumatic stress disorder (PTSD) have been associated with musculoskeletal complaints and could represent barriers to recovery in injured workers. Objectives To determine the prevalence of symptoms of depression, PD, and PTSD utilizing the Patient Health Questionnaire (PHQ) in a cohort of patients presenting to an upper extremity injured-worker clinic; secondarily, to identify any relationships between patients screening positive and patient-reported outcome measures. Methods In 2010, 418 patients completed the PHQ during their initial evaluation. Patients with PHQ scores exceeding threshold values for symptoms of depression, PD, or PTSD were compared based on patient-reported outcome scores, including the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). The prevalence of symptoms, and their relationship with presenting complaints and patient-reported outcomes, were calculated. Results Thirty-one percent of patients scored above thresholds for symptoms of at least 1 mental health disorder. Of those who screened positive, 67% screened positive for depression, 44% for PTSD, and 50% for PD, with 43% of patients positive for multiple symptoms. Patients experiencing neck pain had significantly higher screening rates of depressive symptoms (62.5% versus 20.1%, P = .004) and PD (37.5% versus 12.9%, P = .044) compared with other presenting complaints. Similarly, patients with chronic pain had higher rates of depression (54.5% versus 20.1%, P = .006), PD (63.6% versus 12%, P<.001), and PTSD (36.4% versus 14.8%, P = .05) compared with other presenting complaints. Patients endorsing depressive symptoms had significantly lower SF-36 mental component summary scores (26.3 ± 10.7 versus 37.6 ± 9.9, P<.001) and higher shortened-version DASH (72.3 ± 16.7 versus 61.5 ± 11.1, P = .003) and DASH work scores (86.5 ± 19.2 versus 82.1 ± 20.1, P = .007) compared to patients endorsing other items on the PHQ. Conclusion In this prospective cohort study of injured workers, we identified a relatively high prevalence of symptoms of psychological disorders utilizing the PHQ, with one third of injured workers screening positive for symptoms of depression, PD, or PTSD. Further longitudinal follow-up is necessary to determine the impact on treatment outcomes. Level of Evidence Symptom prevalence, level 1b. J Orthop Sports Phys Ther 2016;46(7):590-595. Epub 12 May 2016. doi:10.2519/jospt.2016.6265.

Peritonitis remains the major clinical complication of peritoneal dialysis: the London, UK, peritonitis audit 2002-2003.

PubMed

Davenport, Andrew

2009-01-01

Over the past two decades, the rate of peritonitis in patients treated by peritoneal dialysis (PD) has been significantly reduced. However, peritonitis remains a major complication of PD, accounting for considerable mortality and hospitalization among PD patients. To compare the outcome of peritonitis in a large unselected group of PD patients with that from single-center and selected groups. We audited the outcome of peritonitis in PD patients attending the 12 PD units in the Thames area in 2002 and 2003. There were 538 patients on continuous ambulatory PD (CAPD) and 325 patients on automated PD (APD) and/or continuous cycling PD (CCPD) at the end of 2002, and 635 CAPD and 445 APD/CCPD patients at the end of 2003. There were 1467 episodes of PD peritonitis during the 2-year period, including 129 recurrent episodes, with the average number of months between peritonitis episodes being 14.7 for CAPD and 18.1 for APD/CCPD, p < 0.05. However there was considerable variation between units. Coagulase-negative staphylococcus (CoNS) was the most common cause, accounting for around 30% of all peritonitis episodes, including recurrences, followed by non-pseudomonas gram negatives and Staphylococcus aureus. Cure rates were 77.2% for CoNS, 46.6% for S. aureus, and 7.7% for methicillin-resistant S. aureus. The cure rate for pseudomonas was 21.4%, and other gram negatives 56.7%. In total, there were 351 episodes of culture-negative peritonitis, with an average cure rate of 76.9%. Cure rates were higher for those centers that used a combination of intraperitoneal gentamicin and cephalosporins than those centers that used oral-based regimes. A total of 296 PD catheters were removed as a direct consequence of PD peritonitis: 121 due to gram-positive and 123 due to gram-negative organisms. Only 49 catheters were reinserted and the patients returned to PD. 52 patients died during or subsequent to their episode of PD peritonitis, with an overall mortality rate of 3.5%. This audit showed that, in a large unselected population of PD patients, the incidence of peritonitis was significantly greater than that reported in single-center short-term studies, and varied from unit to unit. Similarly, the success of treating PD peritonitis varied not only with the cause of the infection but also from unit to unit. PD peritonitis remains a major cause of patients discontinuing PD and switching to hemodialysis.

Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders

PubMed Central

Ogaki, Kotaro; Koga, Shunsuke; Heckman, Michael G.; Fiesel, Fabienne C.; Ando, Maya; Labbé, Catherine; Lorenzo-Betancor, Oswaldo; Moussaud-Lamodière, Elisabeth L.; Soto-Ortolaza, Alexandra I.; Walton, Ronald L.; Strongosky, Audrey J.; Uitti, Ryan J.; McCarthy, Allan; Lynch, Timothy; Siuda, Joanna; Opala, Grzegorz; Rudzinska, Monika; Krygowska-Wajs, Anna; Barcikowska, Maria; Czyzewski, Krzysztof; Puschmann, Andreas; Nishioka, Kenya; Funayama, Manabu; Hattori, Nobutaka; Parisi, Joseph E.; Petersen, Ronald C.; Graff-Radford, Neill R.; Boeve, Bradley F.; Springer, Wolfdieter; Wszolek, Zbigniew K.; Dickson, Dennis W.

2015-01-01

Objective: To assess the role of CHCHD2 variants in patients with Parkinson disease (PD) and Lewy body disease (LBD) in Caucasian populations. Methods: All exons of the CHCHD2 gene were sequenced in a US Caucasian patient-control series (878 PD, 610 LBD, and 717 controls). Subsequently, exons 1 and 2 were sequenced in an Irish series (355 PD and 365 controls) and a Polish series (394 PD and 350 controls). Immunohistochemistry and immunofluorescence studies were performed on pathologic LBD cases with rare CHCHD2 variants. Results: We identified 9 rare exonic variants of unknown significance. These variants were more frequent in the combined group of PD and LBD patients compared to controls (0.6% vs 0.1%, p = 0.013). In addition, the presence of any rare variant was more common in patients with LBD (2.5% vs 1.0%, p = 0.050) compared to controls. Eight of these 9 variants were located within the gene's mitochondrial targeting sequence. Conclusions: Although the role of variants of the CHCHD2 gene in PD and LBD remains to be further elucidated, the rare variants in the mitochondrial targeting sequence may be a risk factor for Lewy body disorders, which may link CHCHD2 to other genetic forms of parkinsonism with mitochondrial dysfunction. PMID:26561290

Differential Interactions between Comorbid Anxiety Disorders and Substance Use Disorder in Rapid Cycling Bipolar I or II Disorder

PubMed Central

Gao, Keming; Tolliver, Bryan; Kemp, David E.; Verduin, Marcia L.; Ganocy, Stephen J.; Bilali, Sarah; Brady, Kathleen; Shim, Seong S.; Findling, Robert; Calabrese, Joseph R.

2008-01-01

Objective Anxiety disorders (AD) and substance use disorders (SUD) commonly co-occur with bipolar disorder. This study was undertaken to assess AD-SUD-bipolar subtype interactions. Methods Extensive clinical interview and MINI were used to ascertain DSM-IV diagnoses of rapid cycling bipolar I (RCBPDI) or II (RCBPDII) disorder, SUDs, and ADs including generalized anxiety disorder (GAD), panic disorder (PD), and obsessive-compulsive disorder (OCD). Data at the initial assessment of four studies was used to compare the prevalence differences in ADs between RCBPDI and RCBPDII by using protocol-defined SUD categories, “Never,” “Lifetime, but not recent,” or “Recent.” Results Five-hundred sixty-six of 568 patients (RCBPDI n=320, RCBPDII n=246) were eligible for analyses. In the “Never” group (n=191), patients with RCBPDI and RCBPDII had similar risk for ADs. In the “Lifetime, but not recent” group (n=195), RCBPDI patients had significantly higher risks for GAD (OR=3.29), PD (OR=2.95), but not OCD, compared with their RCBPDII counterparts. Similarly, in the “Recent” group (n=180), RCBPDI patients also had significantly higher risks for GAD (OR=3.6), PD (OR=3.8), but not OCD, compared with their RCBPDII counterparts. Limitations Data were cross-sectional and not all ADs were included. Conclusion In this large cohort of patients with rapid cycling bipolar disorder, risk for having GAD, PD, but not OCD increased significantly in patients with bipolar I disorder compared to their bipolar II counterparts when a history of SUD was present. However, there were no significant differences in the risk for GAD, PD, or OCD between the subtypes among patients without a history of SUD. PMID:18234350

Knowledge of Parkinson's Disease in a Multiethnic Urban Asian Setting.

PubMed

Tan, Ai Huey; Tan, Chong Tin; Marras, Connie; Loh, Kwong Weng; Wye Ho, Niki Wai; Lim, Quan Hziung; Tan, Pei Wen; Lim, Chee Chean; Cheong, Yee Weai; Kong, Sik Thien; Schee, Jie Ping; Tan, Kean Hoong; Soo, Suet Ker; Vanderschaaf, Cheryl; Lai Heong Lew, Sara; Mahamad, Ummi Affah; Goh, Khean Jin; Yong, Hoi Sen; Lim, Shen-Yang

2015-01-01

Public knowledge regarding Parkinson's disease (PD) is important to facilitate good health-seeking behavior, but the literature on this topic is scarce. We aimed to explore the level of public knowledge regarding PD in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller cohort of PD patients and caregivers. A Knowledge of PD Questionnaire (KPDQ) was developed and administered to members of the Malaysian general public, and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and general knowledge regarding PD. 1,258 members of the general public completed the KPDQ. Tremor was the most widely recognized symptom (recognized by 79.0% of respondents); however, 83.7% incorrectly believed that all PD patients experience tremor. Memory problem was the most widely recognized NMS. Overall, motor symptoms were better recognized than NMS. Common misperceptions were that there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female gender, Chinese ethnicity, tertiary education, healthcare-related work, and knowing someone with PD were independently associated with higher KPDQ scores. PD patients (n = 116) and caregivers (n = 135) demonstrated superior knowledge compared with the general public group, but one-third of them believed that PD is currently curable. This is the only study on public knowledge regarding PD in Asia. Important gaps in knowledge were evident, which could present a barrier to early diagnosis and appropriate treatment of PD. This highlights the need for targeted education campaigns and further research in this area.

Barriers to medication adherence and its relationship with outcomes in pediatric dialysis patients.

PubMed

Silverstein, Douglas M; Fletcher, Angela; Moylan, Kathleen

2014-08-01

Medication adherence is a major factor determining outcome in children with chronic disease. Children with end-stage renal disease are challenged with requirements for renal replacement therapy in addition to complicated medication regimens. We assessed barriers to medication adherence in 22 pediatric patients receiving chronic dialysis [63.6 % hemodialysis (HD), 36.4 % peritoneal dialysis (PD); age 15.9 ± 0.7 years, dialysis vintage 31.6 ± 6.5 months]. Adherence was assessed by a 16-question survey with a maximum score (difficulty) of 64. The overall mean adherence score was 30.9 ± 2.4 (range 16-49; median  27.5). There was a trend for lower adherence scores in patients on HD (27.5 ± 2.9) compared to those on PD (36.8 ± 3.7) (p = 0.06). Compared to HD patients, the mean score/question was significantly higher in PD patients (1.7 ± 0.2 vs. 2.4 ± 0.2, respectively; p = 0.006). Of the 16 questions, HD and PD patients gave a mean response of ≤1.2 for five and zero questions, respectively. Neither gender, age nor dialysis vintage was related to adherence scores. There was also a trend for adherence scores to be higher in females (35.6 ± 3.7) than in males (27.5 ± 2.9) (p = 0.1), but this difference did not reach statistical significance. Markers of mineral bone disease were similar in HD and PD patients. Among all targets in HD and PD patients combined, there was no relationship between adherence scores and number of targets reached (r = -0.09, p = 0.7). There are many barriers to medication adherence in pediatric patients receiving dialysis. In our patient group the difficulties were more evident in patients receiving PD than in those receiving HD.

Hemodialysis versus Peritoneal Dialysis: A Comparison of Survival Outcomes in South-East Asian Patients with End-Stage Renal Disease.

PubMed

Yang, Fan; Khin, Lay-Wai; Lau, Titus; Chua, Horng-Ruey; Vathsala, A; Lee, Evan; Luo, Nan

2015-01-01

Studies comparing patient survival of hemodialysis (HD) and peritoneal dialysis (PD) have yielded conflicting results and no such study was from South-East Asia. This study aimed to compare the survival outcomes of patients with end-stage renal disease (ESRD) who started dialysis with HD and PD in Singapore. Survival data for a maximum of 5 years from a single-center cohort of 871 ESRD patients starting dialysis with HD (n = 641) or PD (n = 230) from 2005-2010 was analyzed using the flexible Royston-Parmar (RP) model. The model was also applied to a subsample of 225 propensity-score-matched patient pairs and subgroups defined by age, diabetes mellitus, and cardiovascular disease. After adjusting for the effect of socio-demographic and clinical characteristics, the risk of death was higher in patients initiating dialysis with PD than those initiating dialysis with HD (hazard ratio [HR]: 2.08; 95% confidence interval [CI]: 1.67-2.59; p<0.001), although there was no significant difference in mortality between the two modalities in the first 12 months of treatment. Consistently, in the matched subsample, patients starting PD had a higher risk of death than those starting HD (HR: 1.73, 95% CI: 1.30-2.28, p<0.001). Subgroup analysis showed that PD may be similar to or better than HD in survival outcomes among young patients (≤65 years old) without diabetes or cardiovascular disease. ESRD patients who initiated dialysis with HD experienced better survival outcomes than those who initiated dialysis with PD in Singapore, although survival outcomes may not differ between the two dialysis modalities in young and healthier patients. These findings are potentially confounded by selection bias, as patients were not randomized to the two dialysis modalities in this cohort study.

Risk of hematologic toxicities with programmed cell death-1 inhibitors in cancer patients: a meta-analysis of current studies.

PubMed

Sui, Jiang-Dong; Wang, Ying; Wan, Yue; Wu, Yong-Zhong

2018-01-01

Programmed cell death-1 (PD-1) inhibitor-related hematologic toxicities are a category of rare but clinically serious and potentially life-threatening adverse events; however, little is known about their risks across different treatment regimens and tumor types. The objective of this study was to compare the incidences of PD-1 inhibitor-related hematologic toxicities among different therapeutic regimens and tumor types. Twenty-six original articles on PD-1 inhibitor trials were identified based on a PubMed search completed on September 26, 2017. The incidences of hematologic toxicities were collected. A total of 26 studies containing 5,088 patients were included in the meta-analysis. PD-1 inhibitor monotherapy was associated with an increased risk of all-grade anemia in cancer patients (5%, 95% CI 4%-6%), particularly in patients with renal cell carcinoma (RCC) (8%, 95% CI 6%-12%), compared with all-grade thrombocytopenia (2%, 95% CI 1%-5%), leukopenia (2%, 95% CI 1%-3%), and neutropenia (1%, 95% CI 0-1%). However, low incidences of high-grade hematologic toxicities were observed in cancer patients treated with PD-1 inhibitor monotherapy. The use of PD-1 inhibitors in combination with ipilimumab, peptide vaccines, or chemotherapy had significantly higher risks than PD-1 inhibitor monotherapy for all-grade anemia (13%, 95% CI 5%-31%), thrombocytopenia (6%, 95% CI 2%-18%), leukopenia (5%, 95% CI 1%-35%), neutropenia (4%, 95% CI 1%-26%), and only high-grade thrombocytopenia (4%, 95% CI 1%-15%). In addition, all-grade and high-grade hematologic toxicities in chemotherapy and everolimus treatment arms were more frequent than in PD-1 inhibitor monotherapy arms. The risks of PD-1 inhibitor-related hematologic toxicities were higher in RCC than in other cancers, and during combination therapy. These results may contribute toward enhancing awareness among clinicians about frequent clinical monitoring when managing PD-1 inhibitors.

Cerebral oximetry values in dialyzed surgical patients: a comparison between hemodialysis and peritoneal dialysis.

PubMed

Papadopoulos, Georgios; Dounousi, Evangelia; Papathanasiou, Athanasios; Papathanakos, Georgios; Tzimas, Petros

2013-07-01

Cerebral tissue regional oxygen saturation (rSO2) through near-infrared spectroscopy (NIRS) is a method for non-invasive monitoring of cerebral tissue oxygenation. However, nowadays there is limited information on the level of cerebral tissue oxygenation in dialyzed end-stage renal disease (ESRD) surgical patients. The aim of this observational study was to evaluate the baseline cerebral rSO2 values, to compare values between hemodialysis (HD) and peritoneal dialysis (PD) patients and identify risk factors that could predict cerebral tissue oxygenation in these patients. Thirty-two ESRD patients (≥18 years old), scheduled to undergo elective minor or major surgery, were enrolled. Patients were allocated in two groups according to dialysis modality. Twenty-three patients were treated with HD and nine were treated with PD. Demographic and clinical characteristics, comorbidities and arterial hemoglobin oxygen saturation (SpO2) of the study population were recorded. Patients who were treated with HD had significant lower baseline rSO2 values compared with PD patients [median, 50% (28-63) vs. 63% (45-69), p = 0.002]. Hierarchical linear regression model analysis showed that preoperative Hb and SpO2 were positive predictive variables (B = 0.353, p = 0.01 and B = 0.375, p = 0.009, respectively) for rSO2. Moreover, dialysis modality was independent predictor for baseline rSO2. The modality of dialysis remained an independent predictor for rSO2 after controlling for the other significant variables (B = 0.291, p = 0.032) and PD was associated with higher baseline values of rSO2. In conclusion, ESRD surgical patients undergoing PD treatment appear to have significantly higher baseline cerebral tissue saturation values compared with HD.

Comparison of frequency, risk factors, and time course of postoperative delirium in octogenarians after transcatheter aortic valve implantation versus surgical aortic valve replacement.

PubMed

Eide, Leslie S P; Ranhoff, Anette H; Fridlund, Bengt; Haaverstad, Rune; Hufthammer, Karl Ove; Kuiper, Karel K J; Nordrehaug, Jan Erik; Norekvål, Tone M

2015-03-15

Postoperative delirium (PD) after transcatheter aortic valve implantation (TAVI) remains to be explored. We sought to (1) determine the incidence of PD in octogenarians who underwent TAVI or surgical aortic valve replacement (SAVR), (2) identify its risk factors, and (3) describe possible differences in the onset and course of PD between treatment groups. A prospective cohort study of consecutive patients aged ≥80 years with severe aortic stenosis who underwent elective TAVI or SAVR (N = 143) was conducted. The incidence of PD was assessed for 5 days using the Confusion Assessment Method (CAM). Risk factors for PD were studied with logistic regression. Patients treated with TAVI were older (p ≤0.001), had lower cognitive scores (p = 0.007), and more co-morbidities (p = 0.003). Despite this, significantly fewer (p = 0.013) patients treated with TAVI (44%) experienced PD compared to patients treated with SAVR (66%). Undergoing SAVR (p = 0.02) and having lower cognitive function (p = 0.03) emerged as risk factors for PD, whereas gender, activities of daily living, frailty, atrial fibrillation, and postoperative use of opioids and anxiolytics did not. Patients treated with TAVI and without PD during the first 2 postoperative days were unlikely to experience PD on subsequent days. The onset of PD after SAVR could occur at any time during the postoperative evaluation. In conclusion, SAVR in octogenarian patients with aortic stenosis might be considered as a predisposing factor for PD. Our data also suggest that the onset of PD was more unpredictable after SAVR. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Speed Pressure in Conflict Situations Impedes Inhibitory Action Control in Parkinson’s Disease

PubMed Central

Van Wouwe, N.C.; van den Wildenberg, W.P.M.; Claassen, D.O.; Kanoff, K.; Bashore, T.R.; Wylie, S.A.

2014-01-01

Parkinson’s disease (PD) is a neurodegenerative basal ganglia disease that disrupts cognitive control processes involved in response selection. The current study investigated the effects of PD on the ability to resolve conflicts during response selection when performance emphasized response speed versus response accuracy. Twenty-one (21) PD patients and 21 healthy controls (HC) completed a Simon conflict task, and a subset of 10 participants from each group provided simultaneous movement-related potential (MRP) data to track patterns of motor cortex activation and inhibition associated with the successful resolution of conflicting response tendencies. Both groups adjusted performance strategically to emphasize response speed or accuracy (i.e., speed-accuracy effect). For HC, interference from a conflicting response was reduced when response accuracy rather than speed was prioritized. For PD patients, however, there was a reduction in interference, but it was not statistically significant. The conceptual framework of the Dual-Process Activation-Suppression (DPAS) model revealed that the groups experienced similar susceptibility to making fast impulsive errors in conflict trials irrespective of speed-accuracy instructions, but PD patients were less proficient and delayed compared to HC at suppressing the interference from these incorrect response tendencies, especially under speed pressure. Analysis of MRPs on response conflict trials showed attenuated inhibition of the motor cortex controlling the conflicting impulsive response tendency in PD patients compared to HC. These results further confirm the detrimental effects of PD inhibitory control mechanisms and their exacerbation when patients perform under speed pressure. The results also suggest that a downstream effect of inhibitory dysfunction in PD is diminished inhibition of motor cortex controlling conflicting response tendencies. PMID:25017503

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

PubMed

Fengler, S; Roeske, S; Heber, I; Reetz, K; Schulz, J B; Riedel, O; Wittchen, H U; Storch, A; Linse, K; Baudrexel, S; Hilker, R; Mollenhauer, B; Witt, K; Schmidt, N; Balzer-Geldsetzer, M; Dams, J; Dodel, R; Gräber, S; Pilotto, A; Petrelli, A; Fünkele, S; Kassubek, J; Kalbe, E

2016-08-01

Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

Usefulness of rCBF analysis in diagnosing Parkinson's disease: supplemental role with MIBG myocardial scintigraphy.

PubMed

Nagamachi, Shigeki; Wakamatsu, Hideyuki; Kiyohara, Shogo; Fujita, Seigo; Futami, Shigemi; Tamura, Shozo; Nakazato, Masamitsu; Yamashita, Syuichi; Arita, Hideo; Nishii, Ryuichi; Kawai, Keiichi

2008-08-01

(123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is a useful tool for differentiating idiopathic Parkinson's disease (PD) from parkinsonism (PS) caused by other disorders. However, cardiac MIBG uptake is affected by various causes. Alternatively, hypoperfusion in the occipital lobe of PD is reported recently. The objective is to clarify the correlation between regional cerebral blood flow (rCBF) alteration and cardiac MIBG uptake in PD. In addition, we examined whether additional brain perfusion analysis improved the differential diagnostic ability for PD from PS when compared with MIBG scintigraphy alone. Forty-nine patients with PD (27 mild groups: Hoehn and Yahr stages I, II; 22 severe groups: Hoehn and Yahr stages III, IV) and 28 patients with PS participated. We compared absolute rCBF values between PD and PS. In addition, we determined correlation between MIBG parameters and each rCBF value. Finally, we compared the diagnostic ability for the differentiation of PD from PS between two diagnostic criteria, each MIBG index abnormality alone [heart-to-mediastinum ratio, H/M (E) < 1.9, H/E (D) < 1.7, washout rate > 40%] and each MIBG index abnormality or occipital lobe hypoperfusion (<36 ml/100 g per min). Absolute rCBF value of occipital lobe was significantly lower in severe PD as compared with PS or mild PD. In the correlation analysis, rCBF of occipital lobe correlated positively with MIBG parameters (H/M). Regarding the diagnostic ability, sensitivity improved by accounting for occipital hypoperfusion as compared with MIBG indices alone. In contrast, neither specificity nor accuracy improved by adding occipital lobe analysis. MIBG parameters (H/M) correlated positively with occipital hypoperfusion in PD. In the differential diagnosis between PD and PS, although its usefulness might be limited, analysis of rCBF in the occipital lobe added to (123)I-MIBG myocardial imaging can be recommended.

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease.

PubMed

Zoetmulder, Marielle; Nikolic, Miki; Biernat, Heidi; Korbo, Lise; Friberg, Lars; Jennum, Poul

2016-06-15

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. © 2016 American Academy of Sleep Medicine.

Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

PubMed Central

Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

2016-01-01

Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve the outcomes for pretreated advanced NSCLC patients, with a better safety profile than docetaxel. PMID:27583876

Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease.

PubMed

Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi

2015-06-01

Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55-1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population.

Handwriting Impairments in People With Parkinson's Disease and Freezing of Gait.

PubMed

Heremans, Elke; Nackaerts, Evelien; Broeder, Sanne; Vervoort, Griet; Swinnen, Stephan P; Nieuwboer, Alice

2016-11-01

Recent studies show that patients with Parkinson's disease (PD) and freezing of gait (FOG) experience motor problems outside their gait freezing episodes. Because handwriting is also a sequential movement, it may be affected in PD patients with FOG relative to those without. The current study aimed to assess the quality of writing in PD patients with and without FOG in comparison to healthy controls (CTs) during various writing tasks. Handwriting was assessed by the writing of cursive loops on a touch-sensitive writing tablet and by means of the Systematic Screening of Handwriting Difficulties (SOS) test in 30 PD patients with and without freezing and 15 healthy age-matched CTs. The tablet tests were performed at 2 different sizes, either continuously or alternatingly, as indicated by visual target lines. Patients with freezing showed decreased writing amplitudes and increased variability compared with CTs and patients without freezing on the writing tablet tests. Writing problems were present during both tests but were more pronounced during writing at alternating compared with writing at continuous size. Patients with freezing also had a higher total score on the SOS test than patients without freezing and CTs, reflecting more extensive handwriting problems, particularly with writing fluency. Writing is more severely affected in PD patients with FOG than in those without FOG. These results indicate that deficient movement sequencing and adaptation is a generic problem in patients with FOG. © The Author(s) 2016.

Cortical functional anatomy of voluntary saccades in Parkinson disease.

PubMed

Rieger, Jochem W; Kim, Aleander; Argyelan, Miklos; Farber, Mark; Glazman, Sofya; Liebeskind, Marc; Meyer, Thomas; Bodis-Wollner, Ivan

2008-10-01

In Parkinson Disease (PD) several aspects of saccades are affected. The saccade-generating brainstem neurons are spared, however, the signals they receive may be flawed. In particular voluntary saccades suffer, but the functional anatomy of the impairment of saccade-related cortical control is unknown. We measured blood-oxygenation-level-dependent (BOLD) activation with functional Magnetic Resonance Imaging (fMRI) while healthy participants and patients with PD performed horizontal voluntary saccades between peripheral visual targets or fixated centrally. We compared saccade-related BOLD-activity vs. fixation in patients with PD and in healthy controls and correlated perisaccadic BOLD-activity in PD patients with saccade kinetics (multistep saccades). Saccade related BOLD-activation was found in both PD and healthy participants in the superior parietal cortex (PEF) and the occipital cortex. Our results suggest remarkable hypoactivity of the frontal and supplementary eye fields (FEF and SEF) in PD patients. On the other hand, PD patients showed a statistically more reliable BOLD modulation than healthy participants in the posterior cingulate gyrus, the parahippocampal gyrus, inferior parietal lobule, precuneus and in the middle temporal gyrus. Given abnormal frontal and normal PEF responses, our results suggest that in PD a frontal cortical circuitry, known to be associated with saccade planning, selection, and predicting a metric error of the saccade, is deficient.

Speech rate in Parkinson's disease: A controlled study.

PubMed

Martínez-Sánchez, F; Meilán, J J G; Carro, J; Gómez Íñiguez, C; Millian-Morell, L; Pujante Valverde, I M; López-Alburquerque, T; López, D E

2016-09-01

Speech disturbances will affect most patients with Parkinson's disease (PD) over the course of the disease. The origin and severity of these symptoms are of clinical and diagnostic interest. To evaluate the clinical pattern of speech impairment in PD patients and identify significant differences in speech rate and articulation compared to control subjects. Speech rate and articulation in a reading task were measured using an automatic analytical method. A total of 39 PD patients in the 'on' state and 45 age-and sex-matched asymptomatic controls participated in the study. None of the patients experienced dyskinesias or motor fluctuations during the test. The patients with PD displayed a significant reduction in speech and articulation rates; there were no significant correlations between the studied speech parameters and patient characteristics such as L-dopa dose, duration of the disorder, age, and UPDRS III scores and Hoehn & Yahr scales. Patients with PD show a characteristic pattern of declining speech rate. These results suggest that in PD, disfluencies are the result of the movement disorder affecting the physiology of speech production systems. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Vitamin D increases programmed death receptor-1 expression in Crohn’s disease

PubMed Central

Bendix, Mia; Greisen, Stinne; Dige, Anders; Hvas, Christian L.; Bak, Nina; Jørgensen, Søren P.; Dahlerup, Jens F.; Deleuran, Bent; Agnholt, Jørgen

2017-01-01

Background: Vitamin D modulates inflammation in Crohns disease (CD). Programmed death (PD)-1 receptor contributes to the maintenance of immune tolerance. Vitamin D might modulate PD-1 signalling in CD. Aim: To investigate PD-1 expression on T cell subsets in CD patients treated with vitamin D or placebo. Methods: We included 40 CD patients who received 1200 IU vitamin D3 for 26 weeks or placebo and eight healthy controls. Peripheral blood mononuclear cells (PBMCs) and plasma were isolated at baseline and week 26. The expressions of PD-1, PD-L1, and surface activation markers were analysed by flow cytometry. Soluble PD-1 plasma levels were measured by ELISA. Results: PD-1 expression upon T cell stimulation was increased in CD4+CD25+int T cells in vitamin D treated CD patients from 19% (range 10 39%) to 29% (11 79%)(p = 0.03) compared with placebo-treated patients. Vitamin D treatment, but not placebo, decreased the expression of the T cell activation marker CD69 from 42% (31 62%) to 33% (19 - 54%)(p = 0.01). Soluble PD-1 levels were not influenced by vitamin D treatment. Conclusions: Vitamin D treatment increases CD4+CD25+int T cells ability to up-regulate PD-1 in response to activation and reduces the CD69 expression in CD patients. PMID:28412753

Perspectives on the prevalence and treatment of personality disorder.

PubMed

Winship, G; Hardy, S

2007-04-01

Personality disorder (PD) is the most prevalent psychiatric disorder. A methodical literature search identified that PD is under researched compared with other mental health problems such as depression or schizophrenia. Social and psychotherapeutic approaches emerge as dominant treatment approaches with PD where there is good evidence of efficacy. Collaborative group-based therapeutic approaches appear to offer a therapeutic counterpoise to the anti-social traits often prevalent in PD. A retrospective analysis of formal group therapy on acute inpatient units (treating PD patients among other mental health disorders) reveals only one violent incident in over 40,000 treatment hours of formal group therapy. It is argued that group-based and social therapy should be the recommended treatment approach because these approaches have been shown to create a safe and contained milieu, establishing a good base for therapeutic gain with PD patients. The case for widening the scope of collaborative group and community-based therapies is considered and the merits and shortcomings of a key worker system with PD patients are critiqued.

Identification of Glutathione S-Transferase Pi as a Protein Involved in Parkinson Disease Progression

PubMed Central

Shi, Min; Bradner, Joshua; Bammler, Theo K.; Eaton, David L.; Zhang, JianPeng; Ye, ZuCheng; Wilson, Angela M.; Montine, Thomas J.; Pan, Catherine; Zhang, Jing

2009-01-01

Parkinson disease (PD) typically affects the cortical regions during the later stages of disease, with neuronal loss, gliosis, and formation of diffuse cortical Lewy bodies in a significant portion of patients with dementia. To identify novel proteins involved in PD progression, we prepared synaptosomal fractions from the frontal cortices of pathologically verified PD patients at different stages along with age-matched controls. Protein expression profiles were compared using a robust quantitative proteomic technique. Approximately 100 proteins displayed significant differences in their relative abundances between PD patients at various stages and controls; three of these proteins were validated using independent techniques. One of the confirmed proteins, glutathione S-transferase Pi, was further investigated in cellular models of PD, demonstrating that its level was intimately associated with several critical cellular processes that are directly related to neurodegeneration in PD. These results have, for the first time, suggested that the levels of glutathione S-transferase Pi may play an important role in modulating the progression of PD. PMID:19498008

Deep brain stimulation of the subthalamic nucleus improves temperature sensation in patients with Parkinson's disease.

PubMed

Maruo, Tomoyuki; Saitoh, Youichi; Hosomi, Koichi; Kishima, Haruhiko; Shimokawa, Toshio; Hirata, Masayuki; Goto, Tetsu; Morris, Shayne; Harada, Yu; Yanagisawa, Takufumi; Aly, Mohamed M; Yoshimine, Toshiki

2011-04-01

Patients with Parkinson's disease (PD) reportedly show deficits in sensory processing in addition to motor symptoms. However, little is known about the effects of bilateral deep brain stimulation of the subthalamic nucleus (STN-DBS) on temperature sensation as measured by quantitative sensory testing (QST). This study was designed to quantitatively evaluate the effects of STN-DBS on temperature sensation and pain in PD patients. We conducted a QST study comparing the effects of STN-DBS on cold sense thresholds (CSTs) and warm sense thresholds (WSTs) as well as on cold-induced and heat-induced pain thresholds (CPT and HPT) in 17 PD patients and 14 healthy control subjects. The CSTs and WSTs of patients were significantly smaller during the DBS-on mode when compared with the DBS-off mode (P<.001), whereas the CSTs and WSTs of patients in the DBS-off mode were significantly greater than those of healthy control subjects (P<.02). The CPTs and HPTs in PD patients were significantly larger on the more affected side than on the less affected side (P<.02). Because elevations in thermal sense and pain thresholds of QST are reportedly almost compatible with decreases in sensation, our findings confirm that temperature sensations may be disturbed in PD patients when compared with healthy persons and that STN-DBS can be used to improve temperature sensation in these patients. The mechanisms underlying our findings are not well understood, but improvement in temperature sensation appears to be a sign of modulation of disease-related brain network abnormalities. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Chocolate consumption is increased in Parkinson's disease. Results from a self-questionnaire study.

PubMed

Wolz, Martin; Kaminsky, Alice; Löhle, Matthias; Koch, Rainer; Storch, Alexander; Reichmann, Heinz

2009-03-01

Clinical observations in Parkinson's disease (PD) patients suggested an increased chocolate consumption. Chocolate contains high contents of various biogenic amines potentially influencing brain monoamine metabolism. 498 PD patients and their partners were evaluated by a structured self-questionnaire asking for consumption of chocolate and non-chocolate sweets, changes in chocolate consumption during the disease course, and depressive symptoms. Questionnaires from 274 patients (55 %) and 234 controls were eligible for further analysis. Consumption of chocolate was significantly higher in PD patients compared to controls, while consumption of non-chocolate sweets was similar in both groups. Our study suggests that chocolate consumption is increased in PD independent of concomitant depressive symptoms measured by BDI-1. Although reasons for increased chocolate consumption in PD remain elusive, it may hypothetically be a consequence of the high content of various biogenic amines and/or caffeine analogues with potential antiparkinsonian effects.

Association of postdischarge complications with reoperation and mortality in general surgery.

PubMed

Kazaure, Hadiza S; Roman, Sanziana A; Sosa, Julie A

2012-11-01

To describe procedure-specific types, rates, and risk factors for postdischarge (PD) complications occurring within 30 days after 21 groups of inpatient general surgery procedures. Retrospective cohort study. American College of Surgeons National Surgical Quality Improvement Program 2005 through 2010 Participant Use Data Files. A total of 551,510 adult patients who underwent one of 21 groups of general surgery procedures in the inpatient setting. Postdischarge complications, reoperation, and mortality. Of 551,510 patients (mean age, 54.6 years), 16.7% experienced a complication; 41.5% occurred PD. Of the PD complications, 75.0% occurred within 14 days PD. Proctectomy (14.5%), enteric fistula repair (12.6%), and pancreatic procedures (11.4%) had the highest PD complication rates. Breast, bariatric, and ventral hernia repair procedures had the highest proportions of complications that occurred PD (78.7%, 69.4%, and 62.0%, respectively). For all procedures, surgical site complications, infections, and thromboembolic events were the most common. Occurrence of an inpatient complication increased the likelihood of a PD complication (12.5% vs 6.2% without an inpatient complication; P < .001). Compared with patients without a PD complication, those with a PD complication had higher rates of reoperation (4.6% vs 17.9%, respectively; P < .001) and death (2.0% vs 6.9%, respectively; P < .001) within 30 days after surgery; those whose PD complication was preceded by an inpatient complication had the highest rates of reoperation (33.7%) and death (24.7%) (all P < .001). After adjustment, PD complications were associated with procedure type, American Society of Anesthesiologists class higher than 3, and steroid use. The PD complication rates vary by procedure, are commonly surgical site related, and are associated with mortality. Fastidious, procedure-specific patient triage at discharge as well as expedited patient follow-up could improve PD outcomes.

Assessment of postural asymmetry in mild to moderate Parkinson's disease.

PubMed

Geurts, A C H; Boonstra, T A; Voermans, N C; Diender, M G; Weerdesteyn, V; Bloem, B R

2011-01-01

Asymmetry of symptoms of Parkinson's disease is clinically most evident for appendicular impairments. For axial impairments such as freezing of gait, asymmetry is less obvious. To date, asymmetries in balance control in PD patients have seldom been studied. Therefore, in this study we investigated whether postural control can be asymmetrically affected in mild to moderate PD patients. Seventeen PD patients were instructed to stand as still and symmetrically as possible on a dual force-plate during two trials. Dynamic postural asymmetry was assessed by comparing the centre-of-pressure velocities between both legs. Results showed that four patients (24%) had dynamic postural asymmetry, even after correcting for weight-bearing asymmetry. Hence, this study suggests that postural control can be asymmetrical in early PD. However, future studies should investigate the prevalence of dynamic postural asymmetry, in a larger group of PD patients. It should also be further investigated whether this approach can be used as a tool to support the initial diagnosis or monitor disease progression, or as an outcome measure for interventions aimed at improving balance in PD. Copyright © 2010 Elsevier B.V. All rights reserved.

Neutral Solution Low in Glucose Degradation Products Is Associated with Less Peritoneal Fibrosis and Vascular Sclerosis in Patients Receiving Peritoneal Dialysis

PubMed Central

Kawanishi, Kunio; Honda, Kazuho; Tsukada, Misao; Oda, Hideaki; Nitta, Kosaku

2013-01-01

♦ Background: The effects of novel biocompatible peritoneal dialysis (PD) solutions on human peritoneal membrane pathology have yet to be determined. Quantitative evaluation of human peritoneal biopsy specimens may reveal the effects of the new solutions on peritoneal membrane pathology. ♦ Methods: Peritoneal specimens from 24 PD patients being treated with either acidic solution containing high-glucose degradation products [GDPs (n = 12)] or neutral solution with low GDPs (n = 12) were investigated at the end of PD. As controls, pre-PD peritoneal specimens, obtained from 13 patients at PD catheter insertion, were also investigated. The extent of peritoneal fibrosis, vascular sclerosis, and advanced glycation end-product (AGE) accumulation were evaluated by quantitative or semi-quantitative methods. The average densities of CD31-positive vessels and podoplanin-positive lymphatic vessels were also determined. ♦ Results: Peritoneal membrane fibrosis, vascular sclerosis, and AGE accumulation were significantly suppressed in the neutral group compared with the acidic group. The neutral group also showed lower peritoneal equilibration test scores and preserved ultrafiltration volume. The density of blood capillaries, but not of lymphatic capillaries, was significantly increased in the neutral group compared with the acidic and pre-PD groups. ♦ Conclusions: Neutral solutions with low GDPs are associated with less peritoneal membrane fibrosis and vascular sclerosis through suppression of AGE accumulation. However, contrary to expectation, blood capillary density was increased in the neutral group. The altered contents of the new PD solutions modified peritoneal membrane morphology and function in patients undergoing PD. PMID:23123670

Gambling behavior in Parkinson's Disease: Impulsivity, reward mechanism and cortical brain oscillations.

PubMed

Balconi, Michela; Angioletti, Laura; Siri, Chiara; Meucci, Nicoletta; Pezzoli, Gianni

2018-03-20

Psychopathological components, such as reward sensitivity and impulsivity, and dopaminergic treatment are crucial characteristics related to the development of Pathological Gambling (PG) in Parkinson's Disease (PD). The aim of the present study is to investigate the differences in decision-making in PD patients with or without PG considering both neurophysiological and behavioral aspects. The IOWA Gambling Task (IGT) and electroencephalographic (EEG) activity were considered to elucidate the decision and post-feedback processes in PG. The sample included fifty-two PD patients, divided in three groups: 17 PD patients with active gambling behavior (PD Gamblers, PDG); 15 PD patients who remitted from PG (PD Non-Gamblers, PDNG); and a Control Group (CG) composed by 20 patients with PD only. EEG and IGT performance were recorded during decision and post-feedback phase. Results showed worse performance and an increase of the low frequency bands in the frontal area for the PDG group compared to the other two groups. In addition, higher BAS (Behavioral Activation System) and BIS-11 (Barratt Impulsiveness Scale) personality components were correlated to groups' behavioral response. These results show an anomalous behavioral (IGT) and cortical response of PDG patients related to their inability to use adequate control mechanisms during a decision-making task where reward mechanisms (BAS) and impulsivity (BIS-11) are relevant. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients

PubMed Central

Buhmann, Carsten; Forkmann, Katarina; Diedrich, Sabrina; Wesemann, Katharina; Bingel, Ulrike

2015-01-01

Background Pain is highly prevalent in patients with Parkinson’s disease (PD), but little is known about the underlying pathophysiological mechanisms. The susceptibility to pain is known to depend on ascending and descending pathways. Because parts of the descending pain inhibitory system involve dopaminergic pathways, dysregulations in dopaminergic transmission might contribute to altered pain processing in PD. Deficits in endogenous pain inhibition can be assessed using conditioned pain modulation (CPM) paradigms. Methods Applying such a paradigm, we investigated i) whether CPM responses differ between PD patients and healthy controls, ii) whether they are influenced by dopaminergic medication and iii) whether there are effects of disease-specific factors. 25 patients with idiopathic PD and 30 healthy age- and gender-matched controls underwent an established CPM paradigm combining heat pain test stimuli at the forearm and the cold pressor task on the contralateral foot as the conditioning stimulus. PD patients were tested under dopaminergic medication and after at least 12 hours of medication withdrawal. Results No significant differences between CPM responses of PD patients and healthy controls or between PD patients “on” and “off” medication were found. These findings suggest (i) that CPM is insensitive to dopaminergic modulations and (ii) that PD is not related to general deficits in descending pain inhibition beyond the known age-related decline. However, at a trend level, we found differences between PD subtypes (akinetic-rigid, tremor-dominant, mixed) with the strongest impairment of pain inhibition in the akinetic-rigid subtype. Conclusions There were no significant differences between CPM responses of patients compared to healthy controls or between patients “on” and “off” medication. Differences between PD subtypes at a trend level point towards different pathophysiological mechanisms underlying the three PD subtypes which warrant further investigation and potentially differential therapeutic strategies in the future. PMID:26270817

CXCR4-CXCL12-CXCR7, TLR2-TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients.

PubMed

D'Alterio, Crescenzo; Nasti, Guglielmo; Polimeno, Marianeve; Ottaiano, Alessandro; Conson, Manuel; Circelli, Luisa; Botti, Giovanni; Scognamiglio, Giosuè; Santagata, Sara; De Divitiis, Chiara; Nappi, Anna; Napolitano, Maria; Tatangelo, Fabiana; Pacelli, Roberto; Izzo, Francesco; Vuttariello, Emilia; Botti, Gerardo; Scala, Stefania

2016-01-01

A neoadjuvant clinical trial was previously conducted in patients with resectable colorectal cancer liver metastases (CRLM). At a median follow up of 28 months, 20/33 patients were dead of disease, 8 were alive with disease and 5 were alive with no evidence of disease. To shed further insight into biological features accounting for different outcomes, the expression of CXCR4-CXCL12-CXCR7, TLR2-TLR4, and the programmed death receptor-1 (PD-1)/programmed death-1 ligand (PD-L1) was evaluated in excised liver metastases. Expression profiles were assessed through qPCR in metastatic and unaffected liver tissue of 33 CRLM neoadjuvant-treated patients. CXCR4 and CXCR7, TLR2/TLR4, and PD-1/PD-L1 mRNA were significantly overexpressed in metastatic compared to unaffected liver tissues. CXCR4 protein was negative/low in 10/31, and high in 21/31, CXCR7 was negative/low in 16/31 and high in 15/31, CXCL12 was negative/low in 14/31 and high in 17/31 CRLM. PD-1 was negative in 19/30 and positive in 11/30, PD-L1 was negative/low in 24/30 and high in 6/30 CRLM. Stromal PD-L1 expression, affected the progression-free survival (PFS) in the CRLM population. Patients overexpressing CXCR4 experienced a worse PFS and cancer specific survival (CSS) ( p = 0.001 and p = 0.0008); in these patients, KRAS mutation identified a subgroup with a significantly worse CSS ( p < 0.01). Thus, CXCR4 and PD-L1 expression discriminate patients with the worse PFS within the CRLM evaluated patients. Within the CXCR4 high expressing patients carrying Mut-KRAS in CRLM identifies the worst prognostic group. Thus, CXCR4 targeting plus anti-PD-1 therapy should be explored to improve the prognosis of Mut-KRAS-high CXCR4-CRLMs.

Impaired intracortical transmission in G2019S leucine rich-repeat kinase Parkinson patients.

PubMed

Ponzo, Viviana; Di Lorenzo, Francesco; Brusa, Livia; Schirinzi, Tommaso; Battistini, Stefania; Ricci, Claudia; Sambucci, Manolo; Caltagirone, Carlo; Koch, Giacomo

2017-05-01

A mutation in leucine-rich repeat kinase 2 is the most common cause of hereditary Parkinson's disease (PD), yet the neural mechanisms and the circuitry potentially involved are poorly understood. We used different transcranial magnetic stimulation protocols to explore in the primary motor cortex the activity of intracortical circuits and cortical plasticity (long-term potentiation) in patients with the G2019S leucine-rich repeat kinase 2 gene mutation when compared with idiopathic PD patients and age-matched healthy subjects. Paired pulse transcranial magnetic stimulation was used to investigate short intracortical inhibition and facilitation and short afferent inhibition. Intermittent theta burst stimulation, a form of repetitive transcranial magnetic stimulation, was used to test long-term potentiation-like cortical plasticity. Leucine-rich repeat kinase 2 and idiopathic PD were tested both in ON and in OFF l-dopa therapy. When compared with idiopathic PD and healthy subjects, leucine-rich repeat kinase 2 PD patients showed a remarkable reduction of short intracortical inhibition in both ON and in OFF l-dopa therapy. This reduction was paralleled by an increase of intracortical facilitation in OFF l-dopa therapy. Leucine-rich repeat kinase 2 PD showed abnormal long-term potentiation-like cortical plasticity in ON l-dopa therapy. The motor cortex in leucine-rich repeat kinase 2 mutated PD patients is strongly disinhibited and hyperexcitable. These abnormalities could be a result of an impairment of inhibitory (gamma-Aminobutyric acid) transmission eventually related to altered neurotransmitter release. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Decision-making performance in Parkinson's disease correlates with lateral orbitofrontal volume.

PubMed

Kobayakawa, Mutsutaka; Tsuruya, Natsuko; Kawamura, Mitsuru

2017-01-15

Patients with Parkinson's disease (PD) exhibit poor decision-making, and the underlying neural correlates are unclear. We used voxel-based morphometry with Diffeomorphic Anatomical Registration through Exponentiated Lie algebra to examine this issue. The decision-making abilities of 20 patients with PD and 37 healthy controls (HCs) were measured with a computerized Iowa Gambling Task (IGT). We assessed the local gray matter volumes of the patients and HCs and their correlations with decision-making performance, disease duration, disease severity, and anti-Parkinsonism medication dose. Compared with the HCs, the patients with PD exhibited poor IGT performances. The gray matter volumes in the medial orbitofrontal cortex, left inferior temporal cortex, and right middle frontal gyrus were decreased in the patients. Results in the regression analysis showed that lateral orbitofrontal volume correlated with performance in the IGT in PD. Regions that correlated with disease duration, severity, and medication dose did not overlap with orbitofrontal regions. Our results indicate that the lateral and medial orbitofrontal cortex are related to decision-making in PD patients. Since the medial orbitofrontal cortex is shown to be involved in monitoring reward, reward monitoring seems to be impaired as a whole in PD patients. Meanwhile, the lateral region is related to evaluation of punishment, which is considered to have an influence on individual differences in decision-making performance in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of starting hemodialysis with an arteriovenous fistula or central venous catheter compared with peritoneal dialysis: a retrospective cohort study.

PubMed

Coentrão, Luis; Santos-Araújo, Carla; Dias, Claudia; Neto, Ricardo; Pestana, Manuel

2012-08-23

Although several studies have demonstrated early survival advantages with peritoneal dialysis (PD) over hemodialysis (HD), the reason for the excess mortality observed among incident HD patients remains to be established, to our knowledge. This study explores the relationship between mortality and dialysis modality, focusing on the role of HD vascular access type at the time of dialysis initiation. A retrospective cohort study was performed among local adult chronic kidney disease patients who consecutively initiated PD and HD with a tunneled cuffed venous catheter (HD-TCC) or a functional arteriovenous fistula (HD-AVF) in our institution in the year 2008. A total of 152 patients were included in the final analysis (HD-AVF, n = 59; HD-TCC, n = 51; PD, n = 42). All cause and dialysis access-related morbidity/mortality were evaluated at one year. Univariate and multivariate analysis were used to compare the survival of PD patients with those who initiated HD with an AVF or with a TCC. Compared with PD patients, both HD-AVF and HD-TCC patients were more likely to be older (p<0.001) and to have a higher frequency of diabetes mellitus (p = 0.017) and cardiovascular disease (p = 0.020). Overall, HD-TCC patients were more likely to have clinical visits (p = 0.069), emergency room visits (p<0.001) and hospital admissions (p<0.001). At the end of follow-up, HD-TCC patients had a higher rate of dialysis access-related complications (1.53 vs. 0.93 vs. 0.64, per patient-year; p<0.001) and hospitalizations (0.47 vs. 0.07 vs. 0.14, per patient-year; p = 0.034) than HD-AVF and PD patients, respectively. The survival rates at one year were 96.6%, 74.5% and 97.6% for HD-AVF, HD-TCC and PD groups, respectively (p<0.001). In multivariate analysis, HD-TCC use at the time of dialysis initiation was the important factor associated with death (HR 16.128, 95%CI [1.431-181.778], p = 0.024). Our results suggest that HD vascular access type at the time of renal replacement therapy initiation is an important modifier of the relationship between dialysis modality and survival among incident dialysis patients.

OLFACTORY DYSFUNCTION IN PARKINSON’S DISEASE: POSITIVE EFFECT OF CIGARETTE SMOKING

PubMed Central

Sharer, James D.; Leon-Sarmiento, Fidias E.; Morley, James F.; Weintraub, Daniel; Doty, Richard L.

2014-01-01

Background There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson’s disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal non-motor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population. Methods We evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 Parkinson’s patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, current). Results The patients exhibited much lower UPSIT scores than did the controls (P<0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never- and past-PD smokers (respective Ps=0.0005 & 0.0019). The female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 & 0.06). Age-related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack years, was evident. Conclusions PD patients who currently smoke do not exhibit the smoking-related decline in olfaction observed in non-PD control subjects who currently smoke. The physiologic basis of this phenomenon is yet to be defined. PMID:25545729

Pleiotropic Effects of Variants in Dementia Genes in Parkinson Disease.

PubMed

Ibanez, Laura; Dube, Umber; Davis, Albert A; Fernandez, Maria V; Budde, John; Cooper, Breanna; Diez-Fairen, Monica; Ortega-Cubero, Sara; Pastor, Pau; Perlmutter, Joel S; Cruchaga, Carlos; Benitez, Bruno A

2018-01-01

Background: The prevalence of dementia in Parkinson disease (PD) increases dramatically with advancing age, approaching 80% in patients who survive 20 years with the disease. Increasing evidence suggests clinical, pathological and genetic overlap between Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia with PD. However, the contribution of the dementia-causing genes to PD risk, cognitive impairment and dementia in PD is not fully established. Objective: To assess the contribution of coding variants in Mendelian dementia-causing genes on the risk of developing PD and the effect on cognitive performance of PD patients. Methods: We analyzed the coding regions of the amyloid-beta precursor protein ( APP ), Presenilin 1 and 2 ( PSEN1, PSEN2 ), and Granulin ( GRN ) genes from 1,374 PD cases and 973 controls using pooled-DNA targeted sequence, human exome-chip and whole-exome sequencing (WES) data by single variant and gene base (SKAT-O and burden tests) analyses. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). The effect of coding variants in dementia-causing genes on cognitive performance was tested by multiple regression analysis adjusting for gender, disease duration, age at dementia assessment, study site and APOE carrier status. Results: Known AD pathogenic mutations in the PSEN1 (p.A79V) and PSEN2 (p.V148I) genes were found in 0.3% of all PD patients. There was a significant burden of rare, likely damaging variants in the GRN and PSEN1 genes in PD patients when compared with frequencies in the European population from the ExAC database. Multiple regression analysis revealed that PD patients carrying rare variants in the APP, PSEN1, PSEN2 , and GRN genes exhibit lower cognitive tests scores than non-carrier PD patients ( p = 2.0 × 10 -4 ), independent of age at PD diagnosis, age at evaluation, APOE status or recruitment site. Conclusions: Pathogenic mutations in the Alzheimer disease-causing genes ( PSEN1 and PSEN2) are found in sporadic PD patients. PD patients with cognitive decline carry rare variants in dementia-causing genes. Variants in genes causing Mendelian neurodegenerative diseases exhibit pleiotropic effects.

Risk for Femoral Fractures in Parkinson’s Disease Patients with and without Severe Functional Impairment

PubMed Central

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Background Impaired balance is a major problem in patients with idiopathic Parkinson’s disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Methods Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Results Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28–2.98) than in women (HR = 1.79; 95%-CI: 1.66–1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. Conclusion The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment. PMID:24853110

Competency to consent to medical treatment in cognitively impaired patients with Parkinson's disease.

PubMed

Dymek, M P; Atchison, P; Harrell, L; Marson, D C

2001-01-09

To investigate capacity to consent to medical treatment (competency) in cognitively impaired patients with PD. Although competency has been studied empirically in patients with cortical dementia (AD), no empirical studies have examined competency in patients with PD or other subcortical neurodegenerative disorders. Patients with PD with cognitive impairment (n = 20) and older controls (n = 20) were compared using a standardized competency measure (Capacity to Consent to Treatment Instrument [CCTI]) and neuropsychological test measures. The CCTI tests competency performance and assigns outcomes (capable, marginally capable, incapable) under four different legal standards (LS). Patients with PD performed below controls on the four LS: capacity to evidence a treatment choice (LS1) (p < 0.03), capacity to appreciate consequences of a treatment choice (LS3) (p < 0.03), capacity to provide rational reasons for a treatment choice (LS4) (p < 0.0001), and capacity to understand the treatment situation and choices (LS5) (p < 0.0001). With respect to competency outcomes, patients with PD demonstrated increasing compromise (marginally capable or incapable outcomes) across the four standards: LS1 (25%), LS3 (45%), LS4 (55%), and LS5 (80%). In the PD group, simple measures of executive function (the Executive Interview) and to a lesser extent memory/orientation (Dementia Rating Scale, Memory subscale) were key predictors of competency performance and outcome on the LS. Cognitively impaired patients with PD are likely to have impaired consent capacity, and are at risk of losing competency over the course of their neurodegenerative illness. Patients with PD have particular difficulty meeting more stringent, clinically relevant competency standards that tap reasoning skills and comprehension of treatment information. Executive dysfunction appears to be a primary neurocognitive mechanism for competency loss in PD.

Pathophysiology of Small-Fiber Sensory System in Parkinson's Disease

PubMed Central

Lin, Chin-Hsien; Chao, Chi-Chao; Wu, Shao-Wei; Hsieh, Paul-Chen; Feng, Fang-Ping; Lin, Yea-Huey; Chen, Ya-Mei; Wu, Ruey-Meei; Hsieh, Sung-Tsang

2016-01-01

Abstract Sensory symptoms are frequent nonmotor complaints in patients with Parkinson's disease (PD). However, few investigations integrally explored the physiology and pathology of the thermonociceptive pathway in PD. We aim to investigate the involvement of the thermonociceptive pathway in PD. Twenty-eight PD patients (16 men, with a mean age and standard deviation of 65.6 ± 10.7 years) free of neuropathic symptoms and systemic disorders were recruited for the study and compared to 23 age- and gender-matched control subjects (12 men, with a mean age and standard deviation of 65.1 ± 9.9 years). We performed skin biopsy, contact heat-evoked potential (CHEP), and quantitative sensory tests (QST) to study the involvement of the thermonociceptive pathway in PD. The duration of PD was 7.1 ± 3.2 (range 2–17 years) years and the UPDRS part III score was 25.6 ± 9.7 (range 10–48) during the off period. Compared to control subjects, PD patients had reduced intra-epidermal nerve fiber (IENF) density (2.48 ± 1.65 vs 6.36 ± 3.19 fibers/mm, P < 0.001) and CHEP amplitude (18.02 ± 10.23 vs 33.28 ± 10.48 μV, P < 0.001). Twenty-three patients (82.1%) had abnormal IENF densities and 18 (64.3%) had abnormal CHEP. Nine patients (32.1%) had abnormal thermal thresholds in the feet. In total 27 patients (96.4%) had at least 1 abnormality in IENF, CHEP, or thermal thresholds of the foot, indicating dysfunctions in the small-fiber nerve system. In control subjects, CHEP amplitude linearly correlated with IENF density (P < 0.001). In contrast, this relationship disappeared in PD (P = 0.312) and CHEP amplitude was negatively correlated with motor severity of PD independent of age, gender, and anti-PD medication dose (P = 0.036), suggesting the influences of central components on thermonociceptive systems in addition to peripheral small-fiber nerves in PD. The present study suggested impairment of small-fiber sensory system at both peripheral and central levels is an intrinsic feature of PD, and skin biopsy, CHEP, and QST provided an integral approach for assessing such dysfunctions. PMID:26962835

Immunotherapy in NSCLC: A Promising and Revolutionary Weapon.

PubMed

Rolfo, Christian; Caglevic, Christian; Santarpia, Mariacarmela; Araujo, Antonio; Giovannetti, Elisa; Gallardo, Carolina Diaz; Pauwels, Patrick; Mahave, Mauricio

2017-01-01

Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. Targeted therapies for EGFR and ALK mutant patients have showed better results when compared with chemotherapy, nevertheless most of patients will fail and need to be treated with chemotherapy if they still have a good performance status.Immunotherapy recently has become the most revolutionary treatment in solid tumors patients. First results in unresectable and metastatic melanoma patients treated with an anti CTLA-4 monoclonal antibody showed an unexpected 3-year overall survival of at least 25%.Lung cancer cells have multiple immunosuppressive mechanisms that allow to escape of the immune system and survive, however blocking CTLA-4 pathway with antibodies as monotherapy treatment have not achieved same results than in melanoma patients. PD-1 expression has been demonstrated in different tumor types, suggesting than PD-1 / PD-L1 pathway is a common mechanism used by tumors to avoid immune surveillance and favoring tumor growth. Anti PD-1 and anti PD-L1 antibodies have showed activity in non-small cell lung cancer patients with significant benefit in overall survival, long lasting responses and good safety profile, including naïve and pretreated patients regardless of the histological subtype. Even more, PD-1 negative expression patients achieve similar results in overall survival when compared with patients treated with chemotherapy. In the other side high PD-1 expression patients that undergo immunotherapy treatment achieve better results in terms of survival with lesser toxicity. Combining different immunotherapy treatments, combination of immunotherapy with chemotherapy or with targeted treatment are under research with some promising PRELIMINARY results in non-small cell lung cancer patients.This chapter attempts to summarize the development of immunotherapy treatment in non-small cell lung cancer patients and explain the results that have leaded immunotherapy as a new standard of treatment in selected NSCLC patients.

Anemia in patients with coinherited thalassemia and glucose-6-phosphate dehydrogenase deficiency.

PubMed

Pornprasert, Sakorn; Phanthong, Siratcha

2013-01-01

Thalassemia and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency are genetic disorders that cause hemolytic anemia. In areas with high frequencies of both hematological disorders, coinheritance of G-6-PD deficiency with thalassemia can be found. Whether G-6-PD deficiency, coinherited with thalassemia, enhances severe anemia is still unclear. Hematological parameters between thalassemia carriers with G-6-PD deficiency and those without G-6-PD deficiency were compared. The G-6-PD deficiency was diagnosed in 410 blood samples from thalassemia patients using a fluorescent spot test. The levels of hemoglobin (Hb), packed cell volume (PCV), mean corpuscular volume (MCV) and Hb A2/Hb E [β26(B8)Glu→Lys; HBB: c.79G>A] were measured using an automated blood counter and high performance liquid chromatography (HPLC), respectively. The G-6-PD deficiency was found in 37 samples (9.02%). Mean levels of Hb, PCV, MCV and Hb A2/E were similar between the two groups. Thus, G-6-PD deficiency did not enhance red blood cell pathology or induce more anemic severity in thalassemia patients.

Survival analysis: comparing peritoneal dialysis and hemodialysis in Taiwan.

PubMed

Huang, Chiu-Ching; Cheng, Kuang-Fu; Wu, Hong-Dar Isaac

2008-06-01

Comparisons of survival in patients on peritoneal dialysis (PD) and on hemodialysis (HD) have been conducted in many Western countries, but publications on this subject in Asian populations are scarce. The present study estimated the survival and the relative mortality hazard for HD and PD patients in Taiwan. Incident end-stage renal disease patients reported to the Taiwan Renal Registry during 1995 - 2002 were included in the study. Patients had to be 20 years of age or older and had to have survived for the first 90 days on dialysis. A total of 45,820 incident HD and 2,809 incident PD patients formed the study population. Patients on PD were treated mainly with traditional glucose-based solutions. Using an intent-to-treat analysis, the Cox proportional hazards (CPH) model was applied to identify the factors that predict survival by treatment modality. Subgroup analyses were conducted by stratifying patients according to sex, comorbidity, age, and diabetes status. Kaplan-Meier estimates were used to explore the survival of HD and PD patients. Adjustments were implemented using the CPH model. The overall 1-year, 2-year, 3-year, 5-year and 10-year survival rates for PD patients were 89.8%, 77.6%, 67.6%, 55.5%, and 35% respectively. The equivalent survival rates for HD patients were 87.5%, 76.6%, 68.1%, 54.3%, and 33.8%. The differences were not statistically significant (p = 0.125). The CPH analysis stratified by diabetes status and age revealed that PD patients 55 years of age or younger and nondiabetic had a lower mortality ratio (MR) of 0.94. But the MR increased to 1.31 for nondiabetic patients older than 55. The MR for PD versus HD further increased to 1.72 for diabetic patients 55 years of age or younger, and to 1.99 for diabetic patients older than 55. After adjusting for both demographic and clinical case-mix differences, PD and HD patients were observed to have similar long-term survival. Subgroup analyses revealed that, among diabetic patients and patients older than 55, those on HD experienced better survival than did those on PD.

Implementation of enhanced recovery programme after pancreatoduodenectomy: a single-centre UK pilot study.

PubMed

Abu Hilal, Mohammed; Di Fabio, Francesco; Badran, Abdallah; Alsaati, Hani; Clarke, Hannah; Fecher, Imogen; Armstrong, Thomas H; Johnson, Colin D; Pearce, Neil W

2013-01-01

Data on enhanced recovery programmes after pancreatoduodenectomy (ERP-PD) is limited. The aim of this pilot study was to evaluate the feasibility, safety and clinical outcomes of ERP-PD when implemented at a high-volume UK university referral centre. This was an observational single-surgeon case-control study (before-and-after pathway). A total of 20 consecutive patients were prospectively enrolled for the ERP-PD and compared with 24 consecutive patients previously treated during an equal time frame. Patients in the ERP-PD group had a significant shorter time to remove naso-gastric tube (median of 5 vs. 7 days, p = 0.0001), start liquid diet (median of 2 vs. 5 days, p < 0.0001), start solid food (median of 4 vs. 9 days, p < 0.0001), pass stools (median of 6 vs. 7 days, p = 0.002), and had shorter length of stay (median of 8.5 days vs. 13 days, p = 0.015) compared to the pre-pathway group. Postoperative complications were overall less frequent but not significantly different in the ERP-PD group (p = 0.077). No difference in mortality and readmission rates was found. Our findings support the feasibility and safety of ERP-PD. Improved patients' outcomes, significant bed day savings and increase National Health Service productivity are anticipated with implementation of ERP-PD on a larger scale. Copyright © 2012 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Sweet liking in patients with Parkinson's disease.

PubMed

Sienkiewicz-Jarosz, Halina; Scinska, Anna; Swiecicki, Lukasz; Lipczynska-Lojkowska, Wanda; Kuran, Wlodzimierz; Ryglewicz, Danuta; Kolaczkowski, Marcin; Samochowiec, Jerzy; Bienkowski, Przemyslaw

2013-06-15

Pleasant tastes and odors are considered phylogenetically old natural rewards and their hedonic evaluation is regarded as a good indicator of the reward system function. The primary aim of the present study was to compare pleasantness ratings of sucrose solutions (1-30%, w/w) and sweet liking/disliking status in 20 patients with Parkinson's disease (PD) and in 20 age-matched healthy controls. In addition, basic sensory aspects of gustatory (intensity ratings, electrogustometric thresholds) and olfactory function (identification abilities in the Sniffin' Stick test) were assessed in both groups. The number of odors rated as pleasant, unpleasant, and neutral was also compared. As expected, the PD patients showed a significant impairment in olfactory identification abilities. There were no differences between the PD patients and controls in electrogustometric thresholds. Rated intensity of higher sucrose concentrations did not differ between the groups. The PD patients tended to rate water taste as more intense in comparison with the controls. Pleasantness ratings of sucrose solutions, the proportion of subjects rating 30% sucrose as the most pleasant (sweet likers), and the number of odors rated as pleasant did not differ between the study groups. The present results suggest that PD does not lead to any obvious alterations in pleasantness ratings of chemosensory stimuli. The study requires replication in larger samples. Copyright © 2013. Published by Elsevier B.V.

Automatic Online Motor Control Is Intact in Parkinson's Disease With and Without Perceptual Awareness.

PubMed

Merritt, Kate E; Seergobin, Ken N; Mendonça, Daniel A; Jenkins, Mary E; Goodale, Melvyn A; MacDonald, Penny A

2017-01-01

In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson's disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients ( n = 14) and healthy controls ( n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls'. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses.

Automatic Online Motor Control Is Intact in Parkinson’s Disease With and Without Perceptual Awareness

PubMed Central

Seergobin, Ken N.; Mendonça, Daniel A.

2017-01-01

Abstract In the double-step paradigm, healthy human participants automatically correct reaching movements when targets are displaced. Motor deficits are prominent in Parkinson’s disease (PD) patients. In the lone investigation of online motor correction in PD using the double-step task, a recent study found that PD patients performed unconscious adjustments appropriately but seemed impaired for consciously-perceived modifications. Conscious perception of target movement was achieved by linking displacement to movement onset. PD-related bradykinesia disproportionately prolonged preparatory phases for movements to original target locations for patients, potentially accounting for deficits. Eliminating this confound in a double-step task, we evaluated the effect of conscious awareness of trajectory change on online motor corrections in PD. On and off dopaminergic therapy, PD patients (n = 14) and healthy controls (n = 14) reached to peripheral visual targets that remained stationary or unexpectedly moved during an initial saccade. Saccade latencies in PD are comparable to controls’. Hence, target displacements occurred at equal times across groups. Target jump size affected conscious awareness, confirmed in an independent target displacement judgment task. Small jumps were subliminal, but large target displacements were consciously perceived. Contrary to the previous result, PD patients performed online motor corrections normally and automatically, irrespective of conscious perception. Patients evidenced equivalent movement durations for jump and stay trials, and trajectories for patients and controls were identical, irrespective of conscious perception. Dopaminergic therapy had no effect on performance. In summary, online motor control is intact in PD, unaffected by conscious perceptual awareness. The basal ganglia are not implicated in online corrective responses. PMID:29085900

Study of telomere length and different markers of oxidative stress in patients with Parkinson's disease.

PubMed

Watfa, G; Dragonas, C; Brosche, T; Dittrich, R; Sieber, C C; Alecu, C; Benetos, A; Nzietchueng, R

2011-04-01

Many studies have shown that short telomere length (TL) is associated with high oxidative stress and various age-related diseases. Parkinson's disease (PD) is an age-related disease, and although its pathogenic mechanism is uncertain, oxidative stress is believed to be implicated in this pathology. The aim of this case-control study was to assess both TL and the different markers of oxidative stress in elderly patients with PD compared to age control subjects. 20 PD patients and 15 age-matched controls, >65 years were studied. TL was measured by Southern blotting from DNA samples extracted from white blood cells. Superoxide dismutase (SOD) activity and plasma levels of total glutathione and protein carbonyls were determined. There was a trend for lower TL in PD patients: 6.06 ± 0.81 kb in PD versus 6.45 ± 0.73 kb in controls (p = 0.08). No significant difference was found between the two groups in terms of oxidative stress markers. In controls, age was the main determinant of telomere shortening (r = -0.547; p = 0.03) whereas, in PD patients, telomere shortening was mainly dependent on plasmatic concentrations of carbonyl proteins (r= -0.544; p=0.044). In PD patients, a negative association was observed between plasma carbonyl protein levels and SOD activity (r= -0.622, p=0.004). In PD, TL is shorter in presence of high oxidative stress as measured by carbonyl protein levels. The absence of telomere attrition with age among patients with PD could reflect a telomere regulation by mechanisms other than age.

Temperament, character and anxiety sensitivity in panic disorder: a high-risk study.

PubMed

Perna, Giampaolo; di Pasquale, Danila; Grassi, Massimiliano; Vanni, Giovanna; Bellodi, Laura; Caldirola, Daniela

2012-01-01

Adult patients with panic disorder (PD) show high levels of harm avoidance and anxiety sensitivity. Peculiar temperament profiles and high anxiety sensitivity have been proposed as developmental risk factors for PD in adult age. Since familial-genetic influences play a role both in PD and in anxiety sensitivity and temperament profiles, this study aims to investigate the possible association between family history of PD and peculiar temperament-character profiles or high anxiety sensitivity in offspring of patients with PD. Thirty-four children of patients with PD with/without agoraphobia and 30 children of healthy subjects were compared. Temperament and character dimensions and anxiety sensitivity levels of children were obtained by the Junior Temperament and Character Inventory and the Childhood Anxiety Sensitivity Index. Children of patients with PD and children of healthy subjects differed neither in temperament and character dimensions nor in anxiety sensitivity levels. Our results show that family history of PD is not associated with peculiar temperament and character profiles or high anxiety sensitivity in children, suggesting that these factors may not be early expressions of familial vulnerability to PD. Since the sample is small and the study has a cross-sectional design, longitudinal studies in larger samples are warranted to confirm these findings and to clarify the role of anxiety sensitivity and temperament-character dimensions in the development of PD. Copyright © 2012 S. Karger AG, Basel.

Intrinsic brain connectivity predicts impulse control disorders in patients with Parkinson's disease.

PubMed

Tessitore, Alessandro; De Micco, Rosa; Giordano, Alfonso; di Nardo, Federica; Caiazzo, Giuseppina; Siciliano, Mattia; De Stefano, Manuela; Russo, Antonio; Esposito, Fabrizio; Tedeschi, Gioacchino

2017-12-01

Impulse control disorders can be triggered by dopamine replacement therapies in patients with PD. Using resting-state functional MRI, we investigated the intrinsic brain network connectivity at baseline in a cohort of drug-naive PD patients who successively developed impulse control disorders over a 36-month follow-up period compared with patients who did not. Baseline 3-Tesla MRI images of 30 drug-naive PD patients and 20 matched healthy controls were analyzed. The impulse control disorders' presence and severity at follow-up were assessed by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting-state networks. We also compared internetwork connectivity between patients. Finally, a multivariate Cox regression model was used to investigate baseline predictors of impulse control disorder development. At baseline, decreased connectivity in the default-mode and right central executive networks and increased connectivity in the salience network were detected in PD patients with impulse control disorders at follow-up compared with those without. Increased default-mode/central executive internetwork connectivity was significantly associated with impulse control disorders development (P < 0.05). Our findings demonstrated that abnormal brain connectivity in the three large-scale networks characterizes drug-naive PD patients who will eventually develop impulse control disorders while on dopaminergic treatment. We hypothesize that these divergent cognitive and limbic network connectivity changes could represent a potential biomarker and an additional risk factor for the emergence of impulse control disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Problem-solving ability and comorbid personality disorders in depressed outpatients.

PubMed

Harley, Rebecca; Petersen, Timothy; Scalia, Margaret; Papakostas, George I; Farabaugh, Amy; Fava, Maurizio

2006-01-01

Major depressive disorder (MDD) is associated with poor problem-solving abilities. In addition, certain personality disorders (PDs) that are common among patients with MDD are also associated with limited problem-solving skills. Attempts to understand the relationship between PDs and problem solving can be complicated by the presence of acute MDD. Our objective in this study was to investigate the relationships between PDs, problem-solving skills, and response to treatment among outpatients with MDD. We enrolled 312 outpatients with MDD in an open, fixed-dose, 8-week fluoxetine trial. PD diagnoses were ascertained via structured clinical interview before and after fluoxetine treatment. Subjects completed the Problem-Solving Inventory (PSI) at both time points. We used analyses of covariance (ANCOVAs) to assess relationships between PD diagnoses and PSI scores prior to treatment. Subjects were divided into three groups: those with PD diagnoses that remained stable after fluoxetine treatment (N=91), those who no longer met PD criteria after fluoxetine treatment (N=119), and those who did not meet criteria for a PD at any time point in the study (N=95). We used multiple chi(2) analyses to compare rates of MDD response and remission between the three PD groups. ANCOVA was also used to compare posttreatment PSI scores between PD groups. Prior to fluoxetine treatment, patients with avoidant, dependent, narcissistic, and borderline PDs reported significantly worse problem-solving ability than did patients without any PDs. Only subjects with dependent PD remained associated with poorer baseline problem-solving reports after the effects of baseline depression severity were controlled. Patients with stable PD diagnoses had significantly lower rates of MDD remission. Across PD groups, problem solving improved as MDD improved. No significant differences in posttreatment problem-solving were found between PD groups after controlling for baseline depression severity, baseline PSI score, and response to treatment. Treatment with fluoxetine is less likely to lead to remission of MDD in patients with stable PDs. More study is needed to investigate causal links between PDs, problem solving, and MDD treatment response. Published 2006 Wiley-Liss, Inc.

Postoperative Nutritional Effects of Early Enteral Feeding Compared with Total Parental Nutrition in Pancreaticoduodectomy Patients: A Prosepective, Randomized Study

PubMed Central

Park, Joon Seong; Chung, Hye-Kyung; Hwang, Ho Kyoung; Kim, Jae Keun

2012-01-01

The benefits of early enteral feeding (EEN) have been demonstrated in gastrointestinal surgery. But, the impact of EEN has not been elucidated yet. We assessed the postoperative nutritional status of patients who had undergone pancreaticoduodenectomy (PD) according to the postoperative nutritional method and compared the clinical outcomes of two methods. A prospective randomized trial was undertaken following PD. Patients were randomly divided into two groups; the EEN group received the postoperative enteral feed and the control group received the postoperative total parenteral nutrition (TPN) management. Thirty-eight patients were included in our analyses. The first day of bowel movement and time to take a normal soft diet was significantly shorter in EEN group than in TPN group. Prealbumin and transferrin were significantly reduced on post-operative day (POD) 7 and were slowly recovered until POD 90 in the TPN group than in the EEN group. EEN group rapidly recovered weight after POD 21 whereas it was gradually decreased in TPN group until POD 90. EEN after PD is associated with preservation of weight compared with TPN and impact on recovery of digestive function after PD. PMID:22379336

Quality of life in patients on chronic dialysis in South Africa: a comparative mixed methods study.

PubMed

Tannor, Elliot K; Archer, Elize; Kapembwa, Kenneth; van Schalkwyk, Susan C; Davids, M Razeen

2017-01-05

The increasing prevalence of treated end-stage renal disease and low transplant rates in Africa leads to longer durations on dialysis. Dialysis should not only be aimed at prolonging lives but also improve quality of life (QOL). Using mixed methods, we investigated the QOL of patients on chronic haemodialysis (HD) and peritoneal dialysis (PD). We conducted a cross-sectional study at Tygerberg Hospital in Cape Town, South Africa. All the PD patients were being treated with continuous ambulatory peritoneal dialysis. The KDQOL-SF 1.3 questionnaire was used for the quantitative phase of the study. Thereafter, focus-group interviews were conducted by an experienced facilitator in groups of HD and PD patients. Electronic recordings were transcribed verbatim and analysed manually to identify emerging themes. A total of 106 patients completed questionnaires and 36 of them participated in the focus group interviews. There was no difference between PD and HD patients in the overall KDQOL-SF scores. PD patients scored lower with regard to symptoms (P = 0.005), energy/fatigue (P = 0.025) and sleep (P = 0.023) but scored higher for work status (P = 0.005) and dialysis staff encouragement (P = 0.019) than those on HD. Symptoms and complications were verbalised more in the PD patients, with fear of peritonitis keeping some housebound. PD patients were more limited by their treatment modality which impacted on body image, sexual function and social interaction but there were less dietary and occupational limitations. Patients on each modality acknowledged the support received from family and dialysis staff but highlighted the lack of support from government. PD patients had little opportunity for interaction with one another and therefore enjoyed less support from fellow patients. PD patients experienced a heavier symptom burden and greater limitations related to their dialysis modality, especially with regards to social functioning. The mixed-methods approach helped to identify several issues affecting quality of life which are amenable to intervention.

Preoperative clinical and diagnostic characteristics of patients who require delayed IPP after primary Peyronies repair.

PubMed

Alphs, Hannah H; Navai, Neema; Köhler, Tobias S; McVary, Kevin T

2010-03-01

Penile vascular abnormalities occur in a high proportion of patients with Peyronie's disease (PD). Penile duplex ultrasonography (PDU) and dynamic infusion cavernosometry and cavernosography (DICC) are tools that can be used to help tailor individualized treatment for patients undergoing surgical intervention for their PD. However, precisely which parameters can be used to predict those patients with PD at risk for developing erectile dysfunction (ED) after intervention without inflatable penile prosthesis (IPP) has not been previously elucidated. To evaluate preoperative vascular parameters that predispose PD patients for developing ED after intervention without IPP. Twenty-six patients receiving surgical intervention for their PD at a single center were retrospectively identified. Of these, 11 (42.3%) opted for primary repair without placement of an IPP. Three (27.2%) of these 11 patients went on to develop ED postoperatively. We compared various demographic, PDU, and DICC parameters between patients who did and did not fail primary repair of their PD. Mean age and follow-up of patients who went on to develop ED after repair of PD without IPP were not significantly different (P < 0.05). Resistive index (RI) and end diastolic volume were significantly different between these two groups (P < 0.05), while peak systolic volume, flow to maintain, and pressure decay were not significantly different. An RI cutoff of <0.80 was found to identify all patients who would later develop ED and fail primary repair without IPP. Penile vascular assessment can aid in counseling patients about their risk of developing delayed ED after primary repair of PD. In our cohort of patients, PDU provided preoperative risk stratification for postoperative erectile dysfunction in men undergoing Peyronie's repair without IPP. We propose the prospective study of an RI cutoff to identify patients at risk of failing primary PD repair without IPP.

Trends in anemia management practices in patients receiving hemodialysis and peritoneal dialysis: a retrospective cohort analysis.

PubMed

Wetmore, James B; Peng, Yi; Monda, Keri L; Kats, Allyson M; Kim, Deborah H; Bradbury, Brian D; Collins, Allan J; Gilbertson, David T

2015-01-01

Recent changes in clinical practice guidelines and reimbursement policies may have affected the use of anemia-related medications and red blood cell (RBC) transfusions in peritoneal dialysis (PD) and hemodialysis (HD) patients. We sought to compare patterns of erythropoiesis-stimulating agents (ESA) and intravenous (IV) iron use, achieved hemoglobin levels, and RBC transfusion use in PD and HD patients. In quarterly cohorts of prevalent dialysis patients receiving persistent therapy (>3 months), 2007-2011, with Medicare Parts A and B coverage, we assessed ESA and IV iron use and dose, RBC transfusions, and hemoglobin levels. Quarterly transfusion rates were calculated. Observable PD and HD patients numbered 14,958 and 221,866 in Q1/2007 and 17,842 and 256,942 in Q4/2011. Adjusted ESA use was lower in PD (71.4-80.1%) than in HD (86.9-92.0%) patients, decreasing from 80.1% (Q1/2010) to 71.4% (Q4/2011) in PD patients, and from 92.0 to 86.9% in HD patients. The mean adjusted ESA dose decreased by 67.5% in PD and 58.4% in HD patients. IV iron use tended to increase, peaking at 39.3% for PD (Q3/2011) and 80.5% for HD (Q2/2011) patients. Adjusted mean hemoglobin levels fell from 11.7 to 10.6 mg/dl in PD and from 12.0 to 10.7 mg/dl in HD ESA users; adjusted transfusion rates increased from 2.4 to 3.0 per 100 patient-months in PD and from 2.6 to 3.3 in HD patients. In patients receiving persistent dialysis, dose and frequency of ESA administrations decreased during the period 2007-2011. Mean hemoglobin levels decreased by more than 1 g/dl, while transfusion rates increased by approximately 25%. © 2015 S. Karger AG, Basel.

A Comprehensive Analysis of Programmed Cell Death Ligand-1 Expression With the Clone SP142 Antibody in Non-Small-Cell Lung Cancer Patients.

PubMed

Takada, Kazuki; Toyokawa, Gouji; Okamoto, Tatsuro; Shimokawa, Mototsugu; Kozuma, Yuka; Matsubara, Taichi; Haratake, Naoki; Akamine, Takaki; Takamori, Shinkichi; Katsura, Masakazu; Shoji, Fumihiro; Oda, Yoshinao; Maehara, Yoshihiko

2017-09-01

Programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1) have been identified as novel targets for immunotherapy, with anti-PD-1 therapy currently the standard treatment for non-small-cell lung cancer (NSCLC) patients after the failure of first-line chemotherapy treatment. The recent phase II POPLAR and phase III OAK studies showed that atezolizumab, a representative PD-L1 inhibitor, exhibited a survival benefit compared with standard therapy in patients with NSCLC. We examined PD-L1 expression in NSCLC using the clone SP142 of POPLAR and OAK studies. PD-L1 expression in 499 surgically resected NSCLC patients was evaluated using immunohistochemistry using SP142. We set cutoff values as 1%, 5%, 10%, and 50%. The samples from 189 (37.9%), 119 (23.8%), 71 (14.2%), and 39 (7.8%) patients were positive for PD-L1 expression at cutoff values of 1%, 5%, 10%, and 50%, respectively. Fisher exact tests showed that PD-L1 positivity was significantly associated with male sex, smoking, advanced stage, the presence of vascular invasion, squamous cell carcinoma, and wild type epidermal growth factor receptor gene mutation status at all cutoff values. Univariate and multivariate survival analyses revealed that PD-L1-positive patients had a worse prognosis than PD-L1-negative patients only at the 1% cutoff value. Forest plot analyses showed that the 1% cutoff provided a more sensitive value for the prediction of postoperative prognosis. PD-L1 expression varied greatly according to different cutoff values. This study might be a useful reference to understand the results of POPLAR and OAK studies and to select patients likely to benefit from atezolizumab. Copyright © 2017 Elsevier Inc. All rights reserved.

Rotigotine Improves Abnormal Circadian Rhythm of Blood Pressure in Parkinson's Disease.

PubMed

Oka, Hisayoshi; Nakahara, Atuso; Umehara, Tadashi

2018-05-15

Cardiovascular autonomic failure is commonly associated with Parkinson's disease (PD), affecting the daily lives of patients. Rotigotine was recently reported not to influence cardiovascular autonomic responses in contrast to other dopaminergic drugs. The effect of rotigotine on daily blood pressure (BP) fluctuations might reflect autonomic failure in patients with PD. Twenty-five PD patients who were receiving rotigotine and 12 patients not receiving rotigotine were recruited. Systolic BP during the daytime and nighttime was measured by 24-h BP monitoring at an interval of 2 years. The patients were divided into 3 groups according to the BP fluctuation type: dippers (nocturnal fall in BP ≥10%), non-dippers (0-10%), and risers (< 0%). The time course of BP was compared between the patients given rotigotine and those not given rotigotine. Among the 25 patients who received rotigotine, the BP type worsened in 2 patients, was unchanged in 16 patients, and improved in 7 patients. Among the 12 patients who were not receiving rotigotine, the BP type worsened in 5 patients, was unchanged in 4 patients, and improved only in 3 patients (p = 0.042). Rotigotine improves the abnormal circadian rhythm of BP in patients with PD. Rotigotine was suggested to have favorable effects on cardiovascular autonomic responses and circadian rhythm in patients with PD. © 2018 S. Karger AG, Basel.

Mood and neural correlates of excessive daytime sleepiness in Parkinson's disease.

PubMed

Wen, M-C; Chan, L L; Tan, L C S; Tan, E K

2017-08-01

For patients with Parkinson's disease (PD), excessive daytime sleepiness (PD-EDS) is a debilitating non-motor symptom and may be affected by mood symptoms, especially depression and anxiety. Few neuroimaging works have attempted to identify the neural features of PD-EDS, but various findings were reported. The purpose of this study was to systematically review the literature on mood and neuroimaging correlates of PD-EDS. A MEDLINE, PubMed, EMBASE, and PsycInfo search for peer-reviewed original research articles on depression, anxiety, and neuroimaging in PD-EDS identified 26 studies on depression, nine on anxiety, and eight on neuroimaging. Half of the studies reported greater depression in PD-EDS-positive patients compared with PD-EDS-negative patients. There was a significantly positive correlation between depression and PD-EDS. Limited studies on anxiety in PD-EDS suggested a weak correlation between anxiety and EDS. For depression and anxiety, the effect sizes were medium when EDS was subjectively measured, but became small when EDS was objective measured. Current neuroimaging studies generally suggested diminished neural structural and functional features (eg, brain volume, white matter integrity as indicated by fractional anisotropy, and cerebral metabolism) in patients with PD-EDS. Future studies should apply objective and subjective measures of mood symptoms and EDS and improve the neuroimaging methodology via using multimodal techniques and whole-brain analysis to provide new clues on the mood and neural correlates of PD-EDS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The contribution of proprioceptive information to postural control in elderly and patients with Parkinson's disease with a history of falls.

PubMed

Bekkers, Esther M J; Dockx, Kim; Heremans, Elke; Vercruysse, Sarah; Verschueren, Sabine M P; Mirelman, Anat; Nieuwboer, Alice

2014-01-01

Proprioceptive deficits negatively affect postural control but their precise contribution to postural instability in Parkinson's disease (PD) is unclear. We investigated if proprioceptive manipulations differentially affect balance, measured by force plates, during quiet standing in 13 PD patients and 13 age-matched controls with a history of falls. Perceived limits of stability (LoS) were derived from the differences between maximal center of pressure (CoP) displacement in anterior-posterior (AP) and medio-lateral (ML) direction during a maximal leaning task. Task conditions comprised standing with eyes open (EO) and eyes closed (EC): (1) on a stable surface; (2) an unstable surface; and (3) with Achilles tendon vibration. CoP displacements were calculated as a percentage of their respective LoS. Perceived LoS did not differ between groups. PD patients showed greater ML CoP displacement than elderly fallers (EF) across all conditions (p = 0.043) and tended to have higher postural sway in relation to the LoS (p = 0.050). Both groups performed worse on an unstable surface and during tendon vibration compared to standing on a stable surface with EO and even more so with EC. Both PD and EF had more AP sway in all conditions with EC compared to EO (p < 0.001) and showed increased CoP displacements when relying on proprioception only compared to standing with normal sensory input. This implies a similar role of the proprioceptive system in postural control in fallers with and without PD. PD fallers showed higher ML sway after sensory manipulations, as a result of which these values approached their perceived LoS more closely than in EF. We conclude that despite a similar fall history, PD patients showed more ML instability than EF, irrespective of sensory manipulation, but had a similar reliance on ankle proprioception. Hence, we recommend that rehabilitation and fall prevention for PD should focus on motor rather than on sensory aspects.

Clinical Impact and Cost-Effectiveness of an Education Program for PD Patients: A Randomized Controlled Trial

PubMed Central

Ory-Magne, Fabienne; Arcari, Céline; Mohara, Christine; Pourcel, Laure; Derumeaux, Hélène; Bérard, Emilie; Bourrel, Robert; Molinier, Laurent; Brefel-Courbon, Christine

2016-01-01

Background Parkinson’s disease (PD) is characterized by its impact on quality of life, constituting a substantial economic burden on society. Education programs implicating patients more in the management of their illness and complementing medical treatment may be a beneficial adjunct in PD. This study assessed the impact of an education program on quality of life and its cost-effectiveness in PD patients. Methods This single-center, prospective, randomized study assessed an education program consisting of individual and group sessions over a 12-month period. A total of 120 PD patients were assigned to either the Treated by Behavioral Intervention group (TTBI) or the no TTBI group. The primary outcome criterion was quality of life assessed using PDQ39. The Unified Parkinson’s Disease Rating Scale (UPDRS) and psychological status were collected. An economic evaluation was performed, including calculations of incremental cost-effectiveness ratios (ICERs). Results After 12 months of follow-up, changes recorded in the PDQ39 between the groups were not significantly different but better changes were observed in each dimension in the TTBI group compared to the no TTBI group. UPDRS I, II and total score were significantly improved in TTBI group compared to the no TTBI group. Mean annual costs did not differ significantly between the two groups. Conclusion This study suggested that the education program positively impacts the perceived health of PD patients without increasing medical costs. PMID:27685455

Perceived Discrimination in Patients With Psychiatric Disorder and Turkish Migration Background in Germany.

PubMed

Müller, Matthias J; Koch, Eckhardt

2016-07-01

Perceived discrimination (PD) has a negative impact on the course of psychiatric disorders. We have investigated PD in inpatients with affective or anxiety disorder and Turkish migration background (TP) or native Germans (GP). Migration-related, clinical, and sociodemographic data of n = 62 TP and n = 62 GP, matched for age, sex, and psychiatric diagnoses, were retrospectively analyzed. PD was assessed as one of 10 questions related to migration and acculturation (yes/no, severity 0-10). PD prevalence rates were compared between TP and GP; relationships of PD with other variables were analyzed using bivariate correlations and multiple regression analyses. A PD prevalence of 26% in TP and 1% in GP was found (odds ratio, 21.2 [2.7-165.8]). Migration background was the strongest predictor of PD in the total group. Within the TP sample, asylum-seeking status and migration-related distress were significantly predictive of PD. In patients with psychiatric disorder in Germany, PD seems to be strongly related to migration-related distress.

Mucuna pruriens for Parkinson's disease: Low-cost preparation method, laboratory measures and pharmacokinetics profile.

PubMed

Cassani, Erica; Cilia, Roberto; Laguna, Janeth; Barichella, Michela; Contin, Manuela; Cereda, Emanuele; Isaias, Ioannis U; Sparvoli, Francesca; Akpalu, Albert; Budu, Kwabena Ofosu; Scarpa, Maria Teresa; Pezzoli, Gianni

2016-06-15

Parkinson's disease (PD) is a progressive neurological condition. Levodopa (LD) is the gold standard therapy for PD patients. Most PD patients in low-income areas cannot afford long-term daily Levodopa therapy. The aim of our study was to investigate if Mucuna pruriens (MP), a legume with high LD content that grows in tropical regions worldwide, might be potential alternative for poor PD patients. We analyzed 25 samples of MP from Africa, Latin America and Asia. We measured the content in LD in various MP preparations (dried, roasted, boiled). LD pharmacokinetics and motor response were recorded in four PD patients, comparing MP vs. LD+Dopa-Decarboxylase Inhibitor (DDCI) formulations. Median LD concentration in dried MP seeds was 5.29%; similar results were obtained in roasted powder samples (5.3%), while boiling reduced LD content up to 70%. Compared to LD+DDCI, MP extract at similar LD dose provided less clinical benefit, with a 3.5-fold lower median AUC. Considering the lack of a DDCI, MP therapy may provide clinical benefit only when content of LD is at least 3.5-fold the standard LD+DDCI. If long-term MP proves to be safe and effective in controlled clinical trials, it may be a sustainable alternative therapy for PD in low-income countries. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Five-year follow-up of a prospective non-randomised study comparing duodenum-preserving pancreatic head resection with classic Whipple procedure in the treatment of chronic pancreatitis.

PubMed

Möbius, C; Max, D; Uhlmann, D; Gumpp, K; Behrbohm, J; Horvath, K; Hauss, J; Witzigmann, H

2007-05-01

Three prospective randomised studies were conducted to compare pancreatoduodenectomy (PD) with duodenum-preserving pancreatic head resection (DPPHR) in patients suffering from chronic pancreatitis (cP). In these three series, the superiority of the duodenum-preserving technique with regard to quality of life (QOL) and pain relief has been demonstrated. Long-term follow-up investigations have not been published so far. The present paper reports on a 5-year follow-up study of a prospective, non-randomised trial comparing classic Whipple procedure (PD) with Beger DPPHR. Seventy patients were initially enrolled in this study. Fifty-one patients were left for the present long-term outcome analysis (PD, n = 24; DPPHR, n = 27). The follow-up included the following parameters: QOL, pain intensity, endocrine and exocrine function, and body mass index (BMI). The median follow-up was 63.5 (range 56-67) months. Two patients in the DPPHR group and none in the PD group underwent a re-operation. The QOL scores of the relevant symptom scales (nausea, pain, diarrhoea) and functional parameters (physical status, working ability, global QOL) were significantly better in the DPPHR group than in the PD group. Pain intensity as self-assessed by the patients was less pronounced in the DPPHR group (P < 0.001), whereas the frequency of acute episodes and analgesic medication did not differ between the two groups. No difference was observed between the two groups with regard to endocrine and exocrine function. The values of the median body mass index (BMI) in the PD group [23.4 (range 18.5-25.0) kg/m(2)] and in the DPPHR group [24.2 (range 17.9-27.8) kg/m(2)] were comparable. The 5-year outcome remained stable compared to the early post-operative data published elsewhere. This 5-year long-term outcome analysis documents the superiority of the Beger duodenum-preserving technique over the classic Whipple procedure in terms of QOL and pain intensity as self-assessed by the patients.

Restless legs syndrome, rapid eye movement sleep behavior disorder, and hypersomnia in patients with two parkin mutations.

PubMed

Limousin, Nadège; Konofal, Eric; Karroum, Elias; Lohmann, Ebba; Theodorou, Ioannis; Dürr, Alexandra; Arnulf, Isabelle

2009-10-15

Parkin gene mutations cause a juvenile parkinsonism. Patients with these mutations may commonly exhibit REM sleep behaviour disorders, but other sleep problems (insomnia, sleepiness, restless legs syndrome) have not been studied. The aim of this study was to evaluate the sleep-wake phenotype in patients with two parkin mutations, compared with patients with idiopathic Parkinson's disease (iPD). Sleep interview and overnight video-polysomnography, followed by multiple sleep latency tests, were assessed in 11 consecutive patients with two parkin mutations (aged 35-60 years, from seven families) and 11 sex-matched patients with iPD (aged 51-65 years). Sleep complaints in the parkin group included insomnia (73% patients versus 45% in the iPD group), restless legs syndrome (45%, versus none in the iPD group, P = 0.04), and daytime sleepiness (45%, versus 54% in the iPD group). Of the parkin patients, 45% had REM sleep without atonia, but only 9% had a definite REM sleep behavior disorder. All sleep measures were similar in the parkin and iPD groups. Two parkin siblings had a central hypersomnia, characterized by mean daytime sleep latencies of 3 min, no sleep onset REM periods, and normal nighttime sleep. Although the patients with two parkin mutations were young, their sleep phenotype paralleled the clinical and polygraphic sleep recording abnormalities reported in iPD, except that restless legs syndrome was more prevalent and secondary narcolepsy was absent.

The Association Between PD-L1 Expression and the Clinical Outcomes to Vascular Endothelial Growth Factor-Targeted Therapy in Patients With Metastatic Clear Cell Renal Cell Carcinoma

PubMed Central

Shin, Su-Jin; Jeon, Yoon Kyung; Cho, Yong Mee; Lee, Jae-Lyun; Chung, Doo Hyun; Park, Ji Young

2015-01-01

Background. Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are used as the first-line treatment for patients with metastatic clear cell renal cell carcinoma (mCCRCC). Recently, programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) blockade emerged as promising therapy for renal cell carcinoma. However, the expression pattern and prognostic implication of programmed death-ligands (PD-Ls) in mCCRCC patients receiving VEGF-TKI remain unclear. Patients and Methods. PD-L1 and PD-L2 expression in tumor cells and the quantities of PD-1+ tumor-infiltrating lymphocytes were immunohistochemically evaluated in 91 mCCRCC patients treated with VEGF-TKI, and their associations with VEGF-TKI responsiveness and clinical outcome were analyzed. Results. PD-L1 immunopositivity was observed in 17.6% and significantly associated with a high International Society of Urological Pathology grade (p = .031) and sarcomatoid features (p = .014). PD-L2 immunopositivity was observed in 39.6% and was not associated with any of the assessed clinicopathological variables. PD-L1-positive cases showed poor VEGF-TKI responsiveness (p = .012) compared with PD-L1-negative cases. In univariate survival analysis, PD-L1 immunopositivity was significantly associated with shorter overall survival (OS) (p = .037) and progression-free survival (PFS) (p = .043). Multivariate survival analysis revealed that PD-L1 expression was independently associated with poor OS (p = .038) and PFS (p = .013) in addition to tumor necrosis (p = .006; p = .029, respectively) and Memorial Sloan Kettering Cancer Center score (p = .018; p = .032, respectively). PD-L2 expression was neither associated with VEGF-TKI responsiveness nor patients’ outcome. Conclusion. PD-L1 expression was significantly related to lack of VEGF-TKI responsiveness and independently associated with shorter survival in mCCRCC patients after VEGF-TKI treatment. PD-L1 may have a predictive and prognostic value for determining the value of VEGF-TKI treatment in patients with mCCRCC. Implications for Practice: Vascular endothelial growth factor pathway (VEGF)-tyrosine kinase inhibitors (TKIs) are essential for the treatment of metastatic renal cell carcinoma patients, but the treatment suffers from a lack of predictive markers. This study demonstrates that PD-L1 expression is a predictor for unfavorable response to VEGF-TKI and a prognostic indicator for poor overall survival and progression-free survival in patients with metastatic clear cell renal cell carcinoma receiving VEGF-TKI. PMID:26424759

Hyperprogressors after Immunotherapy: Analysis of Genomic Alterations Associated with Accelerated Growth Rate.

PubMed

Kato, Shumei; Goodman, Aaron; Walavalkar, Vighnesh; Barkauskas, Donald A; Sharabi, Andrew; Kurzrock, Razelle

2017-08-01

Purpose: Checkpoint inhibitors demonstrate salutary anticancer effects, including long-term remissions. PD-L1 expression/amplification, high mutational burden, and mismatch repair deficiency correlate with response. We have, however, observed a subset of patients who appear to be "hyperprogressors," with a greatly accelerated rate of tumor growth and clinical deterioration compared with pretherapy, which was also recently reported by Institut Gustave Roussy. The current study investigated potential genomic markers associated with "hyperprogression" after immunotherapy. Experimental Design: Consecutive stage IV cancer patients who received immunotherapies (CTLA-4, PD-1/PD-L1 inhibitors or other [investigational] agents) and had their tumor evaluated by next-generation sequencing were analyzed ( N = 155). We defined hyperprogression as time-to-treatment failure (TTF) <2 months, >50% increase in tumor burden compared with preimmunotherapy imaging, and >2-fold increase in progression pace. Results: Amongst 155 patients, TTF <2 months was seen in all six individuals with MDM2/MDM4 amplification. After anti-PD1/PDL1 monotherapy, four of these patients showed remarkable increases in existing tumor size (55% to 258%), new large masses, and significantly accelerated progression pace (2.3-, 7.1-, 7.2- and 42.3-fold compared with the 2 months before immunotherapy). In multivariate analysis, MDM2/MDM4 and EGFR alterations correlated with TTF <2 months. Two of 10 patients with EGFR alterations were also hyperprogressors (53.6% and 125% increase in tumor size; 35.7- and 41.7-fold increase). Conclusions: Some patients with MDM2 family amplification or EGFR aberrations had poor clinical outcome and significantly increased rate of tumor growth after single-agent checkpoint (PD-1/PD-L1) inhibitors. Genomic profiles may help to identify patients at risk for hyperprogression on immunotherapy. Further investigation is urgently needed. Clin Cancer Res; 23(15); 4242-50. ©2017 AACR . ©2017 American Association for Cancer Research.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription.

PubMed

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 - 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. Copyright © 2016 International Society for Peritoneal Dialysis.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription

PubMed Central

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Background: Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Methods: Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Results: Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 – 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Conclusion: Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. PMID:26224788

UK Renal Registry 13th Annual Report (December 2010): Chapter 9: haemoglobin, ferritin and erythropoietin amongst UK adult dialysis patients in 2009: national and centre-specific analyses.

PubMed

Gilg, Julie; Webb, Lynsey; Feest, Terry; Fogarty, Damian

2011-01-01

The UK Renal Association (RA) and National Institute for Health and Clinical Excellence (NICE) have published Clinical Practice Guidelines which include recommendations for management of anaemia in established renal failure. To determine the extent to which the guidelines for anaemia management are met in the UK. Quarterly data were obtained regarding haemoglobin (Hb) and factors that influence Hb from renal centres in England, Wales, Northern Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent renal replacement therapy (RRT) cohorts for 2009. In the UK, in 2009 55% of patients commenced dialysis therapy with Hb x10.0 g/dl (median Hb 10.2 g/dl). The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile range (IQR) of 10.6 - 12.4 g/dl. Of HD patients 85% had Hb ≥ 10.0 g/dl. The median Hb of peritoneal dialysis (PD) patients in the UK was 11.7 g/dl (IQR 10.7-12.6 g/dl). Of UK PD patients, 88% had Hb ≥ 10.0 g/dl. The median ferritin in HD patients in EWNI was 441 mg/L (IQR 289-629) and 96% of HD patients had a ferritin ≥ 100 mg/L. The median ferritin in PD patients was 249 mg/L (IQR 142-412) with 86% of PD patients having a ferritin 5100 mg/L. In EWNI the mean Erythropoietin Stimulating Agent (ESA) dose was higher for HD than PD patients (9,507 vs. 6,212 IU/week). In 2009, 56% of prevalent HD patients had a Hb ≥ 10.5 and ≤ 12.5 g/dl compared with 54% in 2008 and 53% in 2007. Fifty-four percent of prevalent PD patients had a Hb ≥10.5 and ≤12.5 g/dl compared to 55% in 2008. Copyright © 2011 S. Karger AG, Basel.

Patterns of Cortical Synchronization in Isolated Dystonia Compared With Parkinson Disease

PubMed Central

Miocinovic, Svjetlana; de Hemptinne, Coralie; Qasim, Salman; Ostrem, Jill L.; Starr, Philip A.

2016-01-01

IMPORTANCE Isolated dystonia and Parkinson disease (PD) are disorders of the basal gangliothalamocortical network. They have largely distinct clinical profiles, but both disorders respond to deep brain stimulation (DBS) in the same subcortical targets using similar stimulation paradigms, suggesting pathophysiologic overlap. We hypothesized that, similar to PD, isolated dystonia is associated with elevated cortical neuronal synchronization. OBJECTIVE To investigate the electrophysiologic characteristics of the sensorimotor cortex arm-related area using a temporary subdural electrode strip in patients with isolated dystonia and PD undergoing DBS implantation in the awake state. DESIGN, SETTING, AND PARTICIPANTS An observational study recruited patients scheduled for DBS at the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center. Data were collected from May 1, 2008, through April 1, 2015. Findings are reported for 22 patients with isolated cervical or segmental dystonia (8 with [DYST-ARM] and 14 without [DYST] arm symptoms] and 14 patients with akinetic rigid PD. Data were analyzed from November 1, 2014, through May 1, 2015. MAIN OUTCOMES AND MEASURES Cortical local field potentials, power spectral density, and phase-amplitude coupling (PAC). RESULTS Among our 3 groups that together included 36 patients, cortical PAC was present in primary motor and premotor arm-related areas for all groups, but the DYST group was less likely to exhibit increased PAC (P = .008). Similar to what has been shown for patients with PD, subthalamic DBS reversibly decreased PAC in a subset of patients with dystonia who were studied before and during intraoperative test stimulation (n = 4). At rest, broadband gamma (50–200 Hz) power in the primary motor cortex was greater in the DYST-ARM and PD groups compared with the DYST group, whereas alpha (8–13 Hz) and beta (13–30 Hz) power was comparable in all 3 groups. During movement, the DYST-ARM group had impaired beta and low gamma desynchronization in the primary motor cortex. CONCLUSIONS AND RELEVANCE Isolated dystonia and PD have physiologic overlap with respect to high levels of motor cortex synchronization and reduction of cortical synchronization by subthalamic DBS, providing an explanation for their similar therapeutic response to basal ganglia stimulation. PMID:26409266

Enhanced creative thinking under dopaminergic therapy in Parkinson disease.

PubMed

Faust-Socher, Achinoam; Kenett, Yoed N; Cohen, Oren S; Hassin-Baer, Sharon; Inzelberg, Rivka

2014-06-01

Creative thinking requires a combination of originality, flexibility, and usefulness. Several reports described enhanced artistic creativity in Parkinson disease (PD) patients treated with dopaminergic agents. We aimed to examine PD patients' ability to perform creativity tasks compared to healthy controls and to verify whether creativity is related to an impulse control disorder (ICD) as a complication of dopaminergic therapy. Right-handed PD patients treated with dopamine agonists and/or levodopa, and age- and education- matched neurologically healthy controls were assessed using the Montreal Cognitive Assessment, semantic verbal fluency, Beck Depression Inventory, and Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease Rating Scale (QUIP-RS). Creativity assessment included Comprehension of Novel Metaphors (CNM), Remote Association Test, and Tel Aviv Creativity Test (TACT). Groups were compared using analyses of variance, t tests, and correlation analyses. Twenty-seven PD patients (age, mean ± standard deviation = 62 ± 7 years; education = 16 ± 3 years; disease duration = 5.8 ± 3.9 years) and 27 controls (age = 59 ± 9 years; education 17 ± 3 years) participated. PD patients performed significantly better than controls in divergent thinking tasks; specifically, the TACT-Visual for both fluency (33.48 ± 11.83 vs 25.59 ± 10.27, p = 0.034) and quality (15.78 ± 7.6 vs 11.19 ± 6.22, p = 0.025). Comprehension of Novel Metaphors was better in PD patients vs controls (0.71 ± 0.23 vs 0.55 ± 0.29, p = 0.04). QUIP-RS scores did not correlate with creativity measures. PD patients treated with dopaminergic drugs demonstrated enhanced verbal and visual creativity as compared to neurologically healthy controls. This feature was unrelated to ICD. Dopaminergic agents might act through the reduction of latent inhibition, resulting in widening of the associative network and enriched divergent thinking. © 2014 American Neurological Association.

Thoracic and cutaneous sarcoid-like reaction associated with anti-PD-1 therapy: longitudinal monitoring of PD-1 and PD-L1 expression after stopping treatment.

PubMed

Paolini, Léa; Poli, Caroline; Blanchard, Simon; Urban, Thierry; Croué, Anne; Rousselet, Marie-Christine; Le Roux, Sarah; Labarrière, Nathalie; Jeannin, Pascale; Hureaux, José

2018-06-13

Immune checkpoint inhibitors (ICI) target T cell inhibitory pathways that are responsible for cancer tolerance by down-modulating immune functions. ICI have revolutionized patients care with lung cancer. Nevertheless, restoring endogenous antitumor T-cell responses can induce immune related adverse events, such as sarcoidosis. We report here the first case of a thoracic and cutaneous sarcoid-like reaction in a patient with a relapsing unresectable non-small cell lung cancer (NSCLC) treated with nivolumab, an anti-PD-1 mAb. The expression of PD-1 and its ligands, PD-L1 and PD-L2, was assessed by flow cytometry on peripheral blood mononuclear cells (PBMC) and compared to patients who had discontinued nivolumab therapy without having developed any immune related adverse events. PD-L1 expression was transiently increased on B cells, T cells and monocytes, whereas PD-L2 expression was not modulated. PD-1 was transiently undetectable when PD-L1 was maximal, before returning to basal level. Sarcoidosis spontaneously resolved, without corticotherapy. This case sheds the light on a complex regulation of PD-L1 expression in vivo on PBMC after nivolumab arrest and triggers the question of monitoring the expression of immune checkpoint on immune cells during and after treatment with ICI.

PD-1+ CD8+ T cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients

PubMed Central

Wu, X; Zhang, H; Xing, Q; Cui, J; Li, J; Li, Y; Tan, Y; Wang, S

2014-01-01

Background: The blockade of PD-1–PD-L1 pathway is emerging as an effective therapeutic strategy for several advanced cancers. But the immune regulatory role of PD-1–PD-L1 pathway is not clear in colorectal cancer (CRC) patients. This study aims to evaluate the role of PD-1–PD-L1 pathway in CD8+ T-cell functions in tumour-draining lymph nodes (TDLNs) and tumours of CRC patients. Methods: PD-1 expression on CD8+ T cells was examined by flow cytometry, and PD-L1 expression in TDLNs and tumour tissues were examined by immunohistochemistry. Production of IFN-γ, IL-2 and expression of granzyme B, perforin in CD8+ T cells were detected by intracellular staining. Results: PD-1 expression is markedly upregulated on CD8+ T cells in TDLNs and tumours compared with that in peripheral blood. PD-1-expressing CD8+ T cells are competent for production of cytokine (IL-2 and IFN-γ) and perforin in the tumour-free lymph nodes (TFLNs), but exhibit exhausted phenotypes in tumours. In addition, PD-L1 is highly expressed in tumours rather than TFLNs, which is closely correlated with the impairment of IFN-γ production of tumour-infiltrating PD-1+ CD8+ T cells. Conclusions: Our findings suggest a suppressive effect of PD-1 on CD8+ T-cell function in tumours, but not in TFLNs. PMID:25093496

Subthalamic nucleus stimulation and spontaneous language production in Parkinson's disease: A double laterality problem.

PubMed

Batens, Katja; De Letter, Miet; Raedt, Robrecht; Duyck, Wouter; Vanhoutte, Sarah; Van Roost, Dirk; Santens, Patrick

2015-08-01

Asymmetric degeneration of dopaminergic neurons, are characteristic for Parkinson's disease (PD). Despite the lateralized representation of language, the correlation of asymmetric degeneration of nigrostriatal networks in PD with language performance has scarcely been examined. The laterality of dopamine depletion influences language deficits in PD and thus modulates the effects of subthalamic nucleus (STN) stimulation on language production. The spontaneous language production of patients with predominant dopamine depletion of the left (PD-left) and right (PD-right) hemisphere was compared in four stimulation conditions. PD-right made comparatively more verb inflection errors than PD-left. Bilateral STN stimulation improves spontaneous language production only for PD-left. The laterality of dopamine depletion influences spontaneous language production and the effect of STN stimulation on linguistic functions. However, it is probably only one of the many variables influencing the effect of STN stimulation on language production. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive functions in Parkinson's disease: relation to disease severity and hallucination.

PubMed

Wakamori, Takaaki; Agari, Takashi; Yasuhara, Takao; Kameda, Masahiro; Kondo, Akihiko; Shinko, Aiko; Sasada, Susumu; Sasaki, Tatsuya; Furuta, Tomohisa; Date, Isao

2014-04-01

We wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF). Eighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF. The mean MMSE score of PD patients was 27.4 ± 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 ± 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus. This is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression of PD-1 and PD-L1 in poorly differentiated neuroendocrine carcinomas of the digestive system: a potential target for anti-PD-1/PD-L1 therapy.

PubMed

Roberts, Jordan A; Gonzalez, Raul S; Das, Satya; Berlin, Jordan; Shi, Chanjuan

2017-12-01

Poorly differentiated neuroendocrine carcinoma of the digestive system has a dismal prognosis with limited treatment options. This study aimed to investigate expression of the PD-1/PD-L1 pathway in these tumors. Thirty-seven patients with a poorly differentiated neuroendocrine carcinoma of the digestive system were identified. Their electronic medical records, pathology reports, and pathology slides were reviewed for demographics, clinical history, and pathologic features. Tumor sections were immunohistochemically labeled for PD-1 and PD-L1, and expression of PD-1 and PD-L1 on tumor and tumor-associated immune cells was analyzed and compared between small cell and large cell neuroendocrine carcinomas. The mean age of patients was 61 years old with 18 men and 19 women. The colorectum (n=20) was the most common primary site; other primary sites included the pancreaticobiliary system, esophagus, stomach, duodenum, and ampulla. Expression of PD-1 was detected on tumor cells (n=6, 16%) as well as on tumor-associated immune cells (n=23, 63%). The 6 cases with PD-1 expression on tumor cells also had the expression on immune cells. Expression of PD-L1 was visualized on tumor cells in 5 cases (14%) and on tumor-associated immune cells in 10 cases (27%). There was no difference in PD-1 and PD-L1 expression between small cell and large cell neuroendocrine carcinomas. In conclusion, PD-1/PD-L1 expression is a frequent occurrence in poorly differentiated neuroendocrine carcinomas of the digestive system. Checkpoint blockade targeting the PD-1/PD-L1 pathway may have a potential role in treating patients with this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased Risk of Dementia in Patients With Chronic Obstructive Pulmonary Disease

PubMed Central

Liao, Kuang-Ming; Ho, Chung-Han; Ko, Shian-Chin; Li, Chung-Yi

2015-01-01

Abstract Neurodegenerative disease in patients with chronic obstructive pulmonary disease (COPD) was observed. We aim to clarify the risk of dementia in patients with COPD. The study used claims data from Taiwan's National Health Insurance Research Database. Subjects were those who received a discharge diagnosis of COPD between January 1, 2002 and December 31, 2011. Only the first hospitalization was enrolled, and the index date was the first day of admission. Patients younger than 40 years or those with a history of Alzheimer disease (AD) or Parkinson disease (PD) before the index date were excluded. The patients with COPD were then followed until receiving a diagnosis of AD or PD, death, or the end of the study. Control subjects were selected from hospitalized patients without a history of COPD, AD, or PD and were matched according to age (±3 years), gender, and the year of admission at a 2:1 ratio. The comorbidities were measured from 1 year before the index date based on the ICD-9-CM codes. The study included 8640 patients with COPD and a mean age of 68.76 (±10.74) years. The adjusted hazard ratio of developing dementia (AD or PD) was 1.74 (95% confidence interval = 1.55–1.96) in patients with COPD compared with patients without COPD after adjusting for age, gender, and comorbidities. This nationwide cohort study demonstrates that the risk of dementia, including AD and PD, is significantly increased in patients with COPD compared with individuals in the general population. PMID:26061317

Ischaemic stroke in patients with atrial fibrillation with chronic kidney disease undergoing peritoneal dialysis.

PubMed

Chan, Pak-Hei; Huang, Duo; Yip, Pok-Siu; Hai, Jojo; Tse, Hung-Fat; Chan, Tak-Mao; Lip, Gregory Y H; Lo, Wai-Kei; Siu, Chung-Wah

2016-05-01

Little is known about the ischaemic stroke risk and benefit of warfarin therapy for stroke prevention in chronic kidney disease (CKD) patients on peritoneal dialysis (PD) with concomitant atrial fibrillation (AF). Our objective was to determine the risk of ischaemic stroke in a 'real-world' cohort of PD patients with AF, and clinical benefit or harm of aspirin and warfarin. This is a single-centred observational study of Chinese patients with non-valvular AF. Hospitalizations with ischaemic stroke and intracranial haemorrhage (ICH) were recorded. Of 9810 patients from a hospital-based AF registry, 271 CKD patients on PD with AF (76.8 ± 12.5 years, CHA2DS2-VASc: 3.69 ± 1.83, and HAS-BLED: 2.07 ± 0.97) were identified. Amongst these PD patients, 24.7% received warfarin; 31.7% received aspirin; and 43.5% received no antithrombotic therapy. Amongst patients with no antithrombotic therapy, annual incidence of ischaemic stroke in PD patients was comparable with those non-CKD counterparts (9.32 vs. 9.30%/year). Similar to non-CKD patients, annual incidence of ischaemic stroke increased with increasing CHA2DS2-VASc score (CHA2DS2-VASc = 0-1: 5.76 vs. 5.70%/year, P = 1.00; and CHA2DS2-VASc ≥ 2: 10.80 vs. 9.94%/year, P = 0.78). Amongst PD patients, warfarin therapy was associated with lower risk of ischaemic stroke compared with aspirin [Hazard ratio (HR): 0.16, 95% confidence interval (CI): 0.04-0.66, P = 0.01] and no therapy (HR: 0.19, 95% CI: 0.06-0.65, P = 0.01), but not associated with a higher risk of ICH. In CKD patients on PD with AF, who had similar ischaemic stroke risk as non-CKD counterparts, warfarin therapy is associated with reduction in risk of ischaemic stroke without a higher risk of ICH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Quality of life in patients after total pancreatectomy is comparable with quality of life in patients who undergo a partial pancreatic resection.

PubMed

Epelboym, Irene; Winner, Megan; DiNorcia, Joseph; Lee, Minna K; Lee, James A; Schrope, Beth; Chabot, John A; Allendorf, John D

2014-03-01

Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases. We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test. Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected. Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection. Copyright © 2014. Published by Elsevier Inc.

Augmented superior rectus transposition procedure in Duane retraction syndrome compared with sixth nerve palsy.

PubMed

Akbari, Mohammadreza; Shomali, Setareh; Mirmohammadsadeghi, Arash; Fard, Masoud Aghsaei

2018-05-01

Superior rectus transposition (SRT) with medial rectus recession has been used for the treatment of sixth nerve palsy and esotropic Duane retraction syndrome (DRS). The purpose of this study was to compare the results of augmented SRT (with scleral fixation) without medial rectus recession in DRS and sixth nerve palsy. Patients with unilateral esotropic DRS (DRS group) and sixth nerve palsy were included in this prospective, comparative study and underwent SRT. Preoperative forced duction testing was negative or slightly positive in both groups. Prospective measurements were compared between the two groups. There were 11 patients in the DRS group and 11 patients in the sixth nerve palsy group. The mean preoperative esotropia decreased from 20.9 ± 6.0 prism diopter (PD) at far to 13.2 ± 5.8 PD in the DRS group (P = 0.003). The same measurement improved from 28.0 ± 8.5 PD to 8.4 ± 7.3 PD in the sixth nerve palsy group (P = 0.003). In the sixth nerve palsy group, the improvement in primary gaze esotropia and abnormal head posture was more than the DRS group (Both P < 0.001).The average dose effect for SRT was 7.8 ± 2.2 PD in the DRS group and 19.2 ± 4.6 PD in the sixth nerve palsy group. Although objective intorsion was significantly induced after SRT, subjective torsion was not significant after surgery in both groups. SRT appears to be more effective in improving primary gaze deviation and head posture in sixth nerve palsy compared with DRS. Subjective torsional and vertical diplopia were rare in both groups.

Safety and efficacy of anti-PD-L1 therapy in the woodchuck model of HBV infection

PubMed Central

Balsitis, Scott; Gali, Volodymyr; Mason, Pamela J.; Chaniewski, Susan; Levine, Steven M.; Wichroski, Michael J.; Feulner, Michael; Song, Yunling; Granaldi, Karen; Loy, James K.; Thompson, Chris M.; Lesniak, Jacob A.; Brockus, Catherine; Kishnani, Narendra; Menne, Stephan; Cockett, Mark I.; Iyer, Renuka; Mason, Stephen W.

2018-01-01

Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters. We used woodchucks infected with WHV to assess the safety and efficacy of anti-PD-L1 monoclonal antibody therapy (αPD-L1) in a variety of WHV infection states. Experimentally-infected animals lacked PD-1 or PD-L1 upregulation compared to uninfected controls, and accordingly, αPD-L1 treatment in lab-infected animals had limited antiviral effects. In contrast, animals with naturally acquired WHV infections displayed elevated PD-1 and PD-L1. In these same animals, combination therapy with αPD-L1 and entecavir (ETV) improved control of viremia and antigenemia compared to ETV treatment alone, but with efficacy restricted to a minority of animals. Pre-treatment WHV surface antigen (sAg) level was identified as a statistically significant predictor of treatment response, while PD-1 expression on peripheral CD8+ T cells, T cell production of interferon gamma (IFN-γ) upon in vitro antigen stimulation (WHV ELISPOT), and circulating levels of liver enzymes were not. To further assess the safety of this strategy, αPD-L1 was tested in acute WHV infection to model the risk of liver damage when the extent of hepatic infection and antiviral immune responses were expected to be the greatest. No significant increase in serum markers of hepatic injury was observed over those in infected, untreated control animals. These data support a positive benefit/risk assessment for blockade of the PD-1:PD-L1 pathway in CHB patients and may help to identify patient groups most likely to benefit from treatment. Furthermore, the efficacy of αPD-L1 in only a minority of animals, as observed here, suggests that additional agents may be needed to achieve a more robust and consistent response leading to full sAg loss and durable responses through anti-sAg antibody seroconversion. PMID:29444087

Diagnostic value of combined assessment of olfaction and sustantia nigra hyperechogenicity for Parkinson's disease.

PubMed

López Hernández, N; García Escrivá, A; Shalabi Benavent, M

2015-10-01

Hyposmia and substantia nigra hyperechogenicity (SN+) are characteristic markers of Parkinson's disease (PD), although their diagnostic value in isolation may be limited. We evaluated the combined prevalence of both disorders in patients diagnosed with PD and assessed their diagnostic yield compared to a sample with essential tremor (ET) and another group of healthy subjects. Patients diagnosed with PD and ET and treated in our outpatient clinic were enrolled. Olfaction was assessed using the "Sniffin' Sticks" odour identification test (SS-12) and hyperechogenicity of the substantia nigra (SN+) was assessed by transcranial duplex ultrasound. A total of 98 subjects were analysed, comprising 30 with PD, 21 with ET, and 47 controls. The respective prevalence rates of hyposmia (SS-12 < 8) and SN+ (area > .24cm(2)) were 70% and 83.3% in PD, 33.3% and 9.5% in ET, and 17% and 10.6% in controls. Both markers were present in 63% of patients with PD, none of the patients with ET, and only 2 of the controls. Combined use of substantia nigra sonography and olfactory testing with SS-12, two rapid, safe, and accessible tests, was more specific than each isolated marker for distinguishing patients with PD from patients with ET and control subjects. Since both markers have been described in very early phases of PD, combined use may be helpful in providing early diagnosis of PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

Impact of glucocerebrosidase mutations on motor and nonmotor complications in Parkinson's disease.

PubMed

Oeda, Tomoko; Umemura, Atsushi; Mori, Yuko; Tomita, Satoshi; Kohsaka, Masayuki; Park, Kwiyoung; Inoue, Kimiko; Fujimura, Harutoshi; Hasegawa, Hiroshi; Sugiyama, Hiroshi; Sawada, Hideyuki

2015-12-01

Homozygous mutations of the glucocerebrosidase gene (GBA) cause Gaucher disease (GD), and heterozygous mutations of GBA are a major risk factor for Parkinson's disease (PD). This study examined the impact of GBA mutations on the longitudinal clinical course of PD patients by retrospective cohort design. GBA-coding regions were fully sequenced in 215 PD patients and GD-associated GBA mutations were identified in 19 (8.8%) PD patients. In a retrospective cohort study, time to develop dementia, psychosis, wearing-off, and dyskinesia were examined. Survival time analysis followed a maximum 12-year observation (median 6.0 years), revealing that PD patients with GD-associated mutations developed dementia and psychosis significantly earlier than those without mutations (p < 0.001 and p = 0.017, respectively). Adjusted hazard ratios of GBA mutations were 8.3 for dementia (p < 0.001) and 3.1 for psychosis (p = 0.002). No statistically significant differences were observed for wearing-off and dyskinesia between the groups. N-isopropyl-p[(123)I] iodoamphetamine single-photon emission tomography pixel-by-pixel analysis revealed that regional cerebral blood flow was reduced in the bilateral parietal cortex, including the precuneus of GD-associated mutant PD patients, compared with matched PD controls without mutations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Impact of Obesity on Modality Longevity, Residual Kidney Function, Peritonitis, and Survival Among Incident Peritoneal Dialysis Patients.

PubMed

Obi, Yoshitsugu; Streja, Elani; Mehrotra, Rajnish; Rivara, Matthew B; Rhee, Connie M; Soohoo, Melissa; Gillen, Daniel L; Lau, Wei-Ling; Kovesdy, Csaba P; Kalantar-Zadeh, Kamyar

2018-06-01

The prevalence of severe obesity, often considered a contraindication to peritoneal dialysis (PD), has increased over time. However, mortality has decreased more rapidly in the PD population than the hemodialysis (HD) population in the United States. The association between obesity and clinical outcomes among patients with end-stage kidney disease remains unclear in the current era. Historical cohort study. 15,573 incident PD patients from a large US dialysis organization (2007-2011). Body mass index (BMI). Modality longevity, residual renal creatinine clearance, peritonitis, and survival. Higher BMI was significantly associated with shorter time to transfer to HD therapy (P for trend < 0.001), longer time to kidney transplantation (P for trend < 0.001), and, with borderline significance, more frequent peritonitis-related hospitalization (P for trend = 0.05). Compared with lean patients, obese patients had faster declines in residual kidney function (P for trend < 0.001) and consistently achieved lower total Kt/V over time (P for trend < 0.001) despite greater increases in dialysis Kt/V (P for trend < 0.001). There was a U-shaped association between BMI and mortality, with the greatest survival associated with the BMI range of 30 to < 35kg/m 2 in the case-mix adjusted model. Compared with matched HD patients, PD patients had lower mortality in the BMI categories of < 25 and 25 to < 35kg/m 2 and had equivalent survival in the BMI category ≥ 35kg/m 2 (P for interaction = 0.001 [vs < 25 kg/m 2 ]). This attenuation in survival difference among patients with severe obesity was observed only in patients with diabetes, but not those without diabetes. Inability to evaluate causal associations. Potential indication bias. Whereas obese PD patients had higher risk for complications than nonobese PD patients, their survival was no worse than matched HD patients. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Deep Brain Stimulation for Parkinson’s Disease with Early Motor Complications: A UK Cost-Effectiveness Analysis

PubMed Central

Fundament, Tomasz; Eldridge, Paul R.; Green, Alexander L.; Whone, Alan L.; Taylor, Rod S.; Williams, Adrian C.; Schuepbach, W. M. Michael

2016-01-01

Background Parkinson’s disease (PD) is a debilitating illness associated with considerable impairment of quality of life and substantial costs to health care systems. Deep brain stimulation (DBS) is an established surgical treatment option for some patients with advanced PD. The EARLYSTIM trial has recently demonstrated its clinical benefit also in patients with early motor complications. We sought to evaluate the cost-effectiveness of DBS, compared to best medical therapy (BMT), among PD patients with early onset of motor complications, from a United Kingdom (UK) payer perspective. Methods We developed a Markov model to represent the progression of PD as rated using the Unified Parkinson's Disease Rating Scale (UPDRS) over time in patients with early PD. Evidence sources were a systematic review of clinical evidence; data from the EARLYSTIM study; and a UK Clinical Practice Research Datalink (CPRD) dataset including DBS patients. A mapping algorithm was developed to generate utility values based on UPDRS data for each intervention. The cost-effectiveness was expressed as the incremental cost per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were undertaken to explore the effect of parameter uncertainty. Results Over a 15-year time horizon, DBS was predicted to lead to additional mean cost per patient of £26,799 compared with BMT (£73,077/patient versus £46,278/patient) and an additional mean 1.35 QALYs (6.69 QALYs versus 5.35 QALYs), resulting in an incremental cost-effectiveness ratio of £19,887 per QALY gained with a 99% probability of DBS being cost-effective at a threshold of £30,000/QALY. One-way sensitivity analyses suggested that the results were not significantly impacted by plausible changes in the input parameter values. Conclusion These results indicate that DBS is a cost-effective intervention in PD patients with early motor complications when compared with existing interventions, offering additional health benefits at acceptable incremental cost. This supports the extended use of DBS among patients with early onset of motor complications. PMID:27441637

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

PubMed

Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

2012-12-01

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. Copyright © 2012 Movement Disorder Society.

The pattern of verbal, visuospatial and procedural learning in Richardson variant of progressive supranuclear palsy in comparison to Parkinson's disease.

PubMed

Sitek, Emilia J; Wieczorek, Dariusz; Konkel, Agnieszka; Dąbrowska, Magda; Sławek, Jarosław

2017-08-29

Progressive supranuclear palsy (PSP) is regarded either within spectrum of atypical parkinsonian syndromes or frontotemporal lobar degeneration. We compared the verbal, visuospatial and procedural learning profiles in patients with PSP and Parkinson's disease (PD). Furthermore, the relationship between executive factors (initiation and inhibition) and learning outcomes was analyzed. Thirty-three patients with the clinical diagnosis of PSP-Richardson's syndrome (PSP-RS), 39 patients with PD and 29 age -and education -matched controls were administered Mini-Mental State Examination (MMSE), phonemic and semantic fluency tasks, Auditory Verbal Learning Test (AVLT), Visual Learning and Memory Test for Neuropsychological Assessment by Lamberti and Weidlich (Diagnosticum für Cerebralschädigung, DCS), Tower of Toronto (ToT) and two motor sequencing tasks. Patients with PSP-RS and PD were matched in terms of MMSE scores and mood. Performance on DCS was lower in PSP-RS than in PD. AVLT delayed recall was better in PSP-RS than PD. Motor sequencing task did not differentiate between patients. Scores on AVLT correlated positively with phonemic fluency scores in both PSP-RS and PD. ToT rule violation scores were negatively associated with DCS performance in PSP-RS and PD as well as with AVLT performance in PD. Global memory performance is relatively similar in PSP-RS and PD. Executive factors (initiation and inhibition) are closely related to memory performance in PSP-RS and PD. Visuospatial learning impairment in PSP-RS is possibly linked to impulsivity and failure to inhibit automatic responses.

Voice characteristics in the progression of Parkinson's disease.

PubMed

Holmes, R J; Oates, J M; Phyland, D J; Hughes, A J

2000-01-01

This study examined the acoustic and perceptual voice characteristics of patients with Parkinson's disease according to disease severity. The perceptual and acoustic voice characteristics of 30 patients with early stage PD and 30 patients with later stage PD were compared with data from 30 normal control subjects. Voice recordings consisted of prolongation of the vowel /a/, scale singing, and a 1-min monologue. In comparison with controls and previously published normative data, both early and later stage PD patients' voices were characterized perceptually by limited pitch and loudness variability, breathiness, harshness and reduced loudness. High modal pitch levels also characterized the voices of males in both early and later stages of PD. Acoustically, the voices of both groups of PD patients demonstrated lower mean intensity levels and reduced maximum phonational frequency ranges in comparison with normative data. Although less clear, the present data also suggested that the PD patients' voices were characterized by excess jitter, a high-speaking fundamental frequency for males and a reduced fundamental frequency variability for females. While several of these voice features did not appear to deteriorate with disease progression (i.e. harshness, high modal pitch and speaking fundamental frequency in males, fundamental frequency variability in females, low intensity and jitter), breathiness, monopitch and monoloudness, low loudness and reduced maximum phonational frequency range were all worse in the later stages of PD. Tremor was the sole voice feature which was associated only with later stage PD.

Alterations in regional homogeneity of resting-state brain activity in fatigue of Parkinson's disease.

PubMed

Li, Junyi; Yuan, Yongsheng; Wang, Min; Zhang, Jiejin; Zhang, Li; Jiang, Siming; Ding, Jian; Zhang, Kezhong

2017-10-01

Fatigue is a common complaint in patients with Parkinson's disease (PD). However, the neural bases of fatigue in PD remain uncertain. In this cross-sectional study, our aim was to study the change of the local brain function in PD patients with fatigue. Among 49 patients with PD, 17 of them had fatigue and the remaining 32 patients without fatigue, and 25 age- and gender-matched healthy controls were enrolled. All subjects were evaluated with Fatigue Severity Scale (FSS) and had a resting-state functional magnetic resonance imaging (rs-fMRI) scan. The fMRI images were analyzed using regional homogeneity (ReHo) to study the change of the local brain function. ReHo analysis controlling for gray matter volume, age, gender, and education showed decreased ReHo in the left anterior cingulate cortex (ACC) and the right superior frontal gyrus (dorsolateral part), and increased ReHo in the left postcentral gyrus and the right inferior frontal gyrus (orbital and triangular part), compared PD-F with PD-NF; In PD patients, the regional activity in the left ACC and the right superior frontal gyrus (dorsolateral part) was negatively correlated with the FSS scores, while that in the left postcentral gyrus, the right inferior frontal gyrus (orbital and triangular part) was positively correlated with the FSS scores. This study demonstrates that brain areas including frontal, postcentral and ACC regions indicative of sensory, motor, and cognitive systems are involved in fatigue in PD patients.

Cyclooxygenase-2 polymorphisms in Parkinson's disease.

PubMed

Håkansson, Anna; Bergman, Olle; Chrapkowska, Cecilia; Westberg, Lars; Belin, Andrea Carmine; Sydow, Olof; Johnels, Bo; Olson, Lars; Holmberg, Björn; Nissbrandt, Hans

2007-04-05

Accumulating evidence indicate that cyclooxygenase-2 (COX-2) is of pathophysiological importance for the neurodegeneration in Parkinson's disease (PD). For example, in a large epidemiological study, use of NSAIDs was associated with a lower risk of PD. Genetic variants of the COX-2 gene might therefore influence the risk of developing the disease. The genotype distribution of four common single nucleotide polymorphisms (SNPs) in the COX-2 gene (rs689466:A496G, rs20417:G926C, rs5277:G3050C, rs5275:C8473T) was analyzed in PD patients and control subjects in a Swedish population. No differences could be seen between the PD-patient and controls regarding the A496G, G926C, and G3050C SNPs, but the allele frequency of the C8473T SNP was found to differ when male patients were compared to controls (P = 0.007). In females no difference could be seen between PD-patients and controls. In conclusion, the results suggest a possible influence of the COX-2 C8473T SNP in PD, although it only seems to be of importance in men. (c) 2006 Wiley-Liss, Inc.

Technologies for Assessment of Motor Disorders in Parkinson’s Disease: A Review

PubMed Central

Oung, Qi Wei; Muthusamy, Hariharan; Lee, Hoi Leong; Basah, Shafriza Nisha; Yaacob, Sazali; Sarillee, Mohamed; Lee, Chia Hau

2015-01-01

Parkinson’s Disease (PD) is characterized as the commonest neurodegenerative illness that gradually degenerates the central nervous system. The goal of this review is to come out with a summary of the recent progress of numerous forms of sensors and systems that are related to diagnosis of PD in the past decades. The paper reviews the substantial researches on the application of technological tools (objective techniques) in the PD field applying different types of sensors proposed by previous researchers. In addition, this also includes the use of clinical tools (subjective techniques) for PD assessments, for instance, patient self-reports, patient diaries and the international gold standard reference scale, Unified Parkinson Disease Rating Scale (UPDRS). Comparative studies and critical descriptions of these approaches have been highlighted in this paper, giving an insight on the current state of the art. It is followed by explaining the merits of the multiple sensor fusion platform compared to single sensor platform for better monitoring progression of PD, and ends with thoughts about the future direction towards the need of multimodal sensor integration platform for the assessment of PD. PMID:26404288

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson's disease.

PubMed

Lowin, Julia; Sail, Kavita; Baj, Rakhi; Jalundhwala, Yash J; Marshall, Thomas S; Konwea, Henrietta; Chaudhuri, K R

2017-11-01

Parkinson's disease (PD) is an incurable, progressive neurological condition, with symptoms impacting movement, walking, and posture that eventually become severely disabling. Advanced PD (aPD) has a significant impact on quality-of-life (QoL) for patients and their caregivers/families. Levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper-/dyskinesia when available combinations of therapy have not given satisfactory results. To determine the cost-effectiveness of LCIG vs standard of care (SoC) for the treatment of aPD patients. A Markov model was used to evaluate LCIG vs SoC in a hypothetical cohort of 100 aPD patients with severe motor fluctuations from an Irish healthcare perspective. Model health states were defined by Hoehn & Yahr (H&Y) scale-combined with amount of time in OFF-time-and death. SoC comprised of standard oral therapy ± subcutaneous apomorphine infusion and standard follow-up visits. Clinical efficacy, utilities, and transition probabilities were derived from published studies. Resource use was estimated from individual patient-level data from Adelphi 2012 UK dataset, using Irish costs, where possible. Time horizon was 20 years. Costs and outcomes were discounted at 4%. Both one-way and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratio for LCIG vs SOC was €26,944/quality adjusted life year (QALY) (total costs and QALYs for LCIG vs SoC: €537,687 vs €514,037 and 4.37 vs 3.49, respectively). LCIG is cost-effective at a payer threshold of €45,000. The model was most sensitive to health state costs. LCIG is a cost-effective treatment option compared with SoC in patients with aPD.

UK Renal Registry 18th Annual Report: Chapter 11 2014 Multisite Dialysis Access Audit in England, Northern Ireland and Wales and 2013 PD One Year Follow-up: National and Centre-specific Analyses.

PubMed

Rao, Anirudh; Evans, Rebecca; Wilkie, Martin; Fluck, Richard; Kumwenda, Mick

2016-01-01

Data are presented from the third combined vascular and peritoneal dialysis access audit. In 2014, 53 centres in England, Wales and Northern Ireland (out of 62) returned data on first access from 4,339 incident haemodialysis (HD) patients and 1,090 incident peritoneal dialysis (PD) patients. Of the 5,429 incident patients, 20.1% started dialysis on PD, 27.8% started with an arteriovenous fistula (AVF), 1.0% with an arteriovenous graft (AVG), 27.1% on a tunnelled line (TL) and 24.0% on a non-tunnelled line (NTL). Older patients (565 years) were more likely to start haemodialysis using AVF compared to their younger counterparts (36.2% vs. 32.8%). Thirteen of the nineteen centres (68%) using the physician led percutaneous insertion technique had over 20% of their incident patients starting on PD when compared to only seven out of fourteen centres (50%) which used single technique (open surgical or laparoscopic) for their PD catheter insertion. Wide variations were apparent between centres for use of AVF as the first haemodialysis access ranging from 10–54%. Eight of the 49 centres were achieving close to the 65% target for AV fistula in their incident patients. Length of time known to nephrology services and likelihood of commencing dialysis using either an AVF or a PD catheter are strongly associated. Patients who were known to a nephrologist for over one year were more likely to start dialysis with AVF, as compared to those who were referred between 90–365 days (39.2% vs. 24.6%). Similarly, patients who were known to a nephrologist between 90 days and one year were more likely to start on PD when compared to patients who were referred <90 days prior to dialysis start (26.9% vs. 9.1%). By comparison, amongst the late presenters, only 3.5% had first access documented as an AVF and 87.3% started dialysis on either a tunnelled line or a non-tunnelled line. Initial surgical assessment was a key determinant of the likelihood of AVF formation. Of the incident patients known to renal services for longer than three months and in those assessed by a surgeon at least three months prior to starting dialysis, 71.4% started dialysis with an AVF whereas of those who were not seen by a surgeon only 10.8% did. Thirty one of the 38 centres were 2 or 3 standard deviations below the 85% target for prevalent haemodialysis patients with an AV fistula. For centres returning data on one-year peritoneal dialysis outcomes, the majority of centres (28/32) maintained 550% of patients on PD at one year, having censored for transplantation. This report demonstrates wide variations in practice between centres across several domains in the provision of dialysis access and further work will be required to understand the underlying reasons.

Health service costs and clinical gains of psychotherapy for personality disorders: a randomized controlled trial of day-hospital-based step-down treatment versus outpatient treatment at a specialist practice

PubMed Central

2013-01-01

Background Day-hospital-based treatment programmes have been recommended for poorly functioning patients with personality disorders (PD). However, more research is needed to confirm the cost-effectiveness of such extensive programmes over other, presumably simpler, treatment formats. Methods This study compared health service costs and psychosocial functioning for PD patients randomly allocated to either a day-hospital-based treatment programme combining individual and group psychotherapy in a step-down format, or outpatient individual psychotherapy at a specialist practice. It included 107 PD patients, 46% of whom had borderline PD, and 40% of whom had avoidant PD. Costs included the two treatment conditions and additional primary and secondary in- and outpatient services. Psychosocial functioning was assessed using measures of global (observer-rated GAF) and occupational (self-report) functioning. Repeated assessments over three years were analysed using mixed models. Results The costs of step-down treatment were higher than those of outpatient treatment, but these high costs were compensated by considerably lower costs of other health services. However, costs and clinical gains depended on the type of PD. For borderline PD patients, cost-effectiveness did not differ by treatment condition. Health service costs declined during the trial, and functioning improved to mild impairment levels (GAF > 60). For avoidant PD patients, considerable adjuvant health services expanded the outpatient format. Clinical improvements were nevertheless superior to the step-down condition. Conclusion Our results indicate that decisions on treatment format should differentiate between PD types. For borderline PD patients, the costs and gains of step-down and outpatient treatment conditions did not differ. For avoidant PD patients, the outpatient format was a better alternative, leaning, however, on costly additional health services in the early phase of treatment. Trial registration Clinical Trials NCT00378248 PMID:24268099

Predictive Value of Soluble Programmed Death-1 for Severe Sepsis and Septic Shock During the First Week in an Intensive Care Unit.

PubMed

Zhao, Yongzhen; Jia, Yumei; Li, Chunsheng; Shao, Rui; Fang, Yingying

2018-04-26

Programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) exists in both membrane-bound and soluble forms. In this study, we evaluated the predictive value of soluble PD-1 (sPD-1) for severity and 28-day mortality in patients with severe sepsis and septic shock during the first week in an intensive care unit (ICU). In this prospective cohort study, patients were classified into the severe sepsis group or the septic shock group according to the severity of their condition on ICU admission. All patients were also separated into the survivor or nonsurvivor groups according to their 28-day outcomes. Peripheral blood sPD-1 and soluble PD-L1 (sPD-L1) levels, PD-1 expression on CD4 and CD8 T cells, and PD-L1 expression on monocytes were measured and compared between the groups on days 1 and 7 after ICU admission. In all, 45 healthy volunteers and 112 patients were recruited. Serum sPD-1 levels were positively correlated with the severity of sepsis, sPD-L1 levels, PD-1 expression on CD4 or CD8 T cells, and PD-L1 expression on monocytes. The sPD-1 was an independent predictive factor for 28-day mortality both on day 1 and day 7. The area under the curve (AUC) of the sPD-1 on day 7 (0.871) was higher than that on day 1 (0.785) (P < 0.05), and better than the AUC of the percentages of PD-L1 on monocytes (0.770) on day 7 (P < 0.05). Serum sPD-1 shows valuable predictive ability for the severity and 28-day mortality of severe sepsis and septic shock during the first week of ICU treatment.

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency

PubMed Central

Lee, Jaewoong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack-Gyun

2017-01-01

Background We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. Methods In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. Results One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. Conclusions The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability. PMID:28028996

Genetic Profiles of Korean Patients With Glucose-6-Phosphate Dehydrogenase Deficiency.

PubMed

Lee, Jaewoong; Park, Joonhong; Choi, Hayoung; Kim, Jiyeon; Kwon, Ahlm; Jang, Woori; Chae, Hyojin; Kim, Myungshin; Kim, Yonggoo; Lee, Jae Wook; Chung, Nack Gyun; Cho, Bin

2017-03-01

We describe the genetic profiles of Korean patients with glucose-6-phosphate dehydrogenase (G6PD) deficiencies and the effects of G6PD mutations on protein stability and enzyme activity on the basis of in silico analysis. In parallel with a genetic analysis, the pathogenicity of G6PD mutations detected in Korean patients was predicted in silico. The simulated effects of G6PD mutations were compared to the WHO classes based on G6PD enzyme activity. Four previously reported mutations and three newly diagnosed patients with missense mutations were estimated. One novel mutation (p.Cys385Gly, labeled G6PD Kangnam) and two known mutations [p.Ile220Met (G6PD São Paulo) and p.Glu416Lys (G6PD Tokyo)] were identified in this study. G6PD mutations identified in Koreans were also found in Brazil (G6PD São Paulo), Poland (G6PD Seoul), United States of America (G6PD Riley), Mexico (G6PD Guadalajara), and Japan (G6PD Tokyo). Several mutations occurred at the same nucleotide, but resulted in different amino acid residue changes in different ethnic populations (p.Ile380 variant, G6PD Calvo Mackenna; p.Cys385 variants, Tomah, Madrid, Lynwood; p.Arg387 variant, Beverly Hills; p.Pro396 variant, Bari; and p.Pro396Ala in India). On the basis of the in silico analysis, Class I or II mutations were predicted to be highly deleterious, and the effects of one Class IV mutation were equivocal. The genetic profiles of Korean individuals with G6PD mutations indicated that the same mutations may have arisen by independent mutational events, and were not derived from shared ancestral mutations. The in silico analysis provided insight into the role of G6PD mutations in enzyme function and stability.

Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials.

PubMed

O'Connor, Jeremy M; Fessele, Kristen L; Steiner, Jean; Seidl-Rathkopf, Kathi; Carson, Kenneth R; Nussbaum, Nathan C; Yin, Emily S; Adelson, Kerin B; Presley, Carolyn J; Chiang, Anne C; Ross, Joseph S; Abernethy, Amy P; Gross, Cary P

2018-05-10

The US Food and Drug Administration (FDA) is increasing its pace of approvals for novel cancer therapeutics, including for immune checkpoint inhibitors of programmed cell death 1 protein (anti-PD-1 agents). However, little is known about how quickly anti-PD-1 agents reach eligible patients in practice or whether such patients differ from those studied in clinical trials that lead to FDA approval (pivotal clinical trials). To assess the speed with which anti-PD-1 agents reached eligible patients in practice and to compare the ages of patients treated in clinical practice with the ages of those treated in pivotal clinical trials. This retrospective cohort study, performed from January 1, 2011, through August 31, 2016, included patients from the Flatiron Health Network who were eligible for anti-PD-1 treatment of selected cancer types, which included melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). Cumulative proportions of eligible patients receiving anti-PD-1 treatment and their age distributions. The study identified 3089 patients who were eligible for anti-PD-1 treatment (median age, 66 [interquartile range, 56-75] years for patients with melanoma, 66 [interquartile range, 58-72] years for patients with RCC, and 67 [interquartile range, 59-74] years for patients with NSCLC; 1742 male [56.4%] and 1347 [43.6%] female; 2066 [66.9%] white). Of these patients, 2123 (68.7%) received anti-PD-1 treatment, including 439 eligible patients with melanoma (79.1%), 1417 eligible patients with NSCLC (65.6%), and 267 eligible patients with RCC (71.2%). Within 4 months after FDA approval, greater than 60% of eligible patients in each cohort had received anti-PD-1 treatment. Overall, similar proportions of older and younger patients received anti-PD-1 treatment during the first 9 months after FDA approval. However, there were significant differences in age between clinical trial participants and patients receiving anti-PD-1 treatment in clinical practice, with more patients being older than 65 years in clinical practice (range, 327 of 1365 [60.6%] to 46 of 72 [63.9%]) than in pivotal clinical trials (range, 38 of 120 [31.7%] to 223 of 544 [41.0%]; all P < .001). Anti-PD-1 agents rapidly reached patients in clinical practice, and patients treated in clinical practice differed significantly from patients treated in pivotal clinical trials. Future actions are needed to ensure that rapid adoption occurs on the basis of representative trial evidence.

The Role of the Frontal Lobe in Complex Walking Among Patients With Parkinson's Disease and Healthy Older Adults: An fNIRS Study.

PubMed

Maidan, Inbal; Nieuwhof, Freek; Bernad-Elazari, Hagar; Reelick, Miriam F; Bloem, Bas R; Giladi, Nir; Deutsch, Judith E; Hausdorff, Jeffery M; Claassen, Jurgen A H; Mirelman, Anat

2016-11-01

Gait is influenced by higher order cognitive and cortical control mechanisms. Functional near infrared spectroscopy (fNIRS) has been used to examine frontal activation during walking in healthy older adults, reporting increased oxygenated hemoglobin (HbO2) levels during dual task walking (DT), compared with usual walking. To investigate the role of the frontal lobe during DT and obstacle negotiation, in healthy older adults and patients with Parkinson's disease (PD). Thirty-eight healthy older adults (mean age 70.4 ± 0.9 years) and 68 patients with PD (mean age 71.7 ± 1.1 years,) performed 3 walking tasks: (a) usual walking, (b) DT walking, and (c) obstacles negotiation, with fNIRS and accelerometers. Linear-mix models were used to detect changes between groups and within tasks. Patients with PD had higher activation during usual walking (P < .030). During DT, HbO2 increased only in healthy older adults (P < .001). During obstacle negotiation, HbO2 increased in patients with PD (P = .001) and tended to increase in healthy older adults (P = .053). Higher DT and obstacle cost (P < .003) and worse cognitive performance were observed in patients with PD (P = .001). A different pattern of frontal activation during walking was observed between groups. The higher activation during usual walking in patients with PD suggests that the prefrontal cortex plays an important role already during simple walking. However, higher activation relative to baseline during obstacle negotiation and not during DT in the patients with PD demonstrates that prefrontal activation depends on the nature of the task. These findings may have important implications for rehabilitation of gait in patients with PD. © The Author(s) 2016.

Implementation of a standardized out-of-hospital management method for Parkinson dysphagia.

PubMed

Wei, Hongying; Sun, Dongxiu; Liu, Meiping

2017-12-01

Our objective is to explore the effectiveness and feasibility of establishing a swallowing management clinic to implement out-of-hospital management for Parkinson disease (PD) patients with dysphagia. Two-hundred seventeen (217) voluntary PD patients with dysphagia in a PD outpatient clinic were divided into a control group with 100 people, and an experimental group with 117 people. The control group was given dysphagia rehabilitation guidance. The experimental group was presented with the standardized out-of-hospital management method as overall management and information and education materials. Rehabilitation efficiency and incidence rate of dysphagia, as well as relevant complications of both groups were compared after a 6-month intervention. Rehabilitation efficiency and the incidence rate of dysphagia including relevant complications of patients treated with the standardized out-of-hospital management were compared with those seen in the control group. The differences have distinct statistics meaning (p<0.01). Establishing a swallowing management protocol for outpatient setting can effectively help the recovery of the function of swallowing, reduce the incidence rate of dysphagia complications and improve the quality of life in patients with PD.

Comprehensive malnutrition inflammation score as a marker of nutritional status in Chinese peritoneal dialysis patients.

PubMed

Chan, Jessie Ying Wing; Che, Kit I; Lam, Karry Mau Chu; Chow, Kai-Ming; Chung, Kwok-Yi; Li, Philip Kam-Tao; Szeto, Cheuk-Chun

2007-04-01

Malnutrition is common among peritoneal dialysis (PD) patients. However, the ideal marker of nutritional status in PD patients remained controversial. We studied 165 unselected adult PD patients. We compared the comprehensive Malnutrition-Inflammation Score (MIS) and the 7-point Subjective Global Assessment (SGA) score. The mean age was 59.2 +/- 11.5 years. Seventy patients were male. MIS significantly correlated with the SGA score (r =-0.667, P < 0.001). Of the 165 patients, 132 (80.0%) had similar classification of nutritional status by SGA and MIS (Group I); 17 (10.3%) were classified as normal by SGA but moderately malnourished by MIS (Group II), while 16 (9.7%) were classified as normal by MIS but moderately malnourished by SGA (Group III). Group II had been dialysed longer than Group I (71.7 +/- 50.3 vs 40.7 +/- 37.5 months, P = 0.011). As compared with Group I, Group III was more likely to require helper for PD exchange (37.5%vs 9.7%, P = 0.004), marginally more likely to be diabetic (62.5%vs 35.6%, P = 0.085) and had a slightly higher Charlson's comorbidity score (6.13 +/- 1.78 vs 4.98 +/- 2.1, P = 0.085), although the latter two were not statistically significant. MIS has a reasonable correlation with the conventional SGA score in PD patients. Patients with limited self-care capability, diabetes and multiple comorbidities probably had worse score (i.e. worse nutrition) revealed by SGA than by MIS, while patients who had been dialysed longer had worse score revealed by MIS than by SGA.

Self-Reported Executive Functioning in Everyday Life in Parkinson's Disease after Three Months of Subthalamic Deep Brain Stimulation.

PubMed

Pham, Uyen Ha Gia; Andersson, Stein; Toft, Mathias; Pripp, Are Hugo; Konglund, Ane Eidahl; Dietrichs, Espen; Malt, Ulrik Fredrik; Skogseid, Inger Marie; Haraldsen, Ira Ronit Hebolt; Solbakk, Anne-Kristin

2015-01-01

Objective. Studies on the effect of subthalamic deep brain stimulation (STN-DBS) on executive functioning in Parkinson's disease (PD) are still controversial. In this study we compared self-reported daily executive functioning in PD patients before and after three months of STN-DBS. We also examined whether executive functioning in everyday life was associated with motor symptoms, apathy, and psychiatric symptoms. Method. 40 PD patients were examined with the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), the Symptom Checklist 90-Revised (SCL-90-R), and the Apathy Evaluation Scale (AES-S). Results. PD patients reported significant improvement in daily life executive functioning after 3 months of STN-DBS. Anxiety scores significantly declined, while other psychiatric symptoms remained unchanged. The improvement of self-reported executive functioning did not correlate with motor improvement after STN-DBS. Apathy scores remained unchanged after surgery. Only preoperative depressed mood had predictive value to the improvement of executive function and appears to prevent potentially favorable outcomes from STN-DBS on some aspects of executive function. Conclusion. PD patients being screened for STN-DBS surgery should be evaluated with regard to self-reported executive functioning. Depressive symptoms in presurgical PD patients should be treated. Complementary information about daily life executive functioning in PD patients might enhance further treatment planning of STN-DBS.

Imposed Faster and Slower Walking Speeds Influence Gait Stability Differently in Parkinson Fallers.

PubMed

Cole, Michael H; Sweeney, Matthew; Conway, Zachary J; Blackmore, Tim; Silburn, Peter A

2017-04-01

To evaluate the effect of imposed faster and slower walking speeds on postural stability in people with Parkinson disease (PD). Cross-sectional cohort study. General community. Patients with PD (n=84; 51 with a falls history; 33 without) and age-matched controls (n=82) were invited to participate via neurology clinics and preexisting databases. Of those contacted, 99 did not respond (PD=36; controls=63) and 27 were not interested (PD=18; controls=9). After screening, a further 10 patients were excluded; 5 had deep brain stimulation surgery and 5 could not accommodate to the treadmill. The remaining patients (N=30) completed all assessments and were subdivided into PD fallers (n=10), PD nonfallers (n=10), and age-matched controls (n=10) based on falls history. Not applicable. Three-dimensional accelerometers assessed head and trunk accelerations and allowed calculation of harmonic ratios and root mean square (RMS) accelerations to assess segment control and movement amplitude. Symptom severity, balance confidence, and medical history were established before participants walked on a treadmill at 70%, 100%, and 130% of their preferred speed. Head and trunk control was lower for PD fallers than PD nonfallers and older adults. Significant interactions indicated head and trunk control increased with speed for PD nonfallers and older adults, but did not improve at faster speeds for PD fallers. Vertical head and trunk accelerations increased with walking speed for PD nonfallers and older adults, while the PD fallers demonstrated greater anteroposterior RMS accelerations compared with both other groups. The results suggest that improved gait dynamics do not necessarily represent improved walking stability, and this must be respected when rehabilitating gait in patients with PD. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Acting without being in control: Exploring volition in Parkinson's disease with impulsive compulsive behaviours.

PubMed

Ricciardi, Lucia; Haggard, Patrick; de Boer, Lieke; Sorbera, Chiara; Stenner, Max-Philipp; Morgante, Francesca; Edwards, Mark J

2017-07-01

Several aspects of volitional control of action may be relevant in the pathophysiology of impulsive-compulsive behaviours (ICB) in Parkinson's disease (PD). We aimed to explore multiple aspects of action control, assessing reward-related behaviour, inhibition (externally and internally triggered) and sense of agency in PD patients, with and without ICB compared to healthy subjects. Nineteen PD patients with ICB (PD-ICB), 19 PD without ICB (PD-no-ICB) and 19 healthy controls (HC) underwent a battery of tests including: Intentional Binding task which measures sense of agency; Stop Signal Reaction Time (SSRT) measuring capacity for reactive inhibition; the Marble task, assessing intentional inhibition; Balloon Analog Risk Task for reward sensitivity. One-way ANOVA showed significant main effect of group for action binding (p = 0.004, F = 6.27). Post hoc analysis revealed that PD-ICB had significantly stronger action binding than HC (p = 0.004), and PD-no-ICB (p = 0.04). There was no difference between PD-no-ICB and HC. SSRT did not differ between PD groups, whereas a significant difference between PD-no-ICB and HC was detected (p = 0.01). No other differences were found among groups in the other tasks. PD patients with ICB have abnormal performance on a psychophysical task assessing sense of agency, which might be related to a deficit in action representation at cognitive/experiential level. Yet, they have no deficit on tasks evaluating externally and internally triggered inhibitory control, or in reward-based decision-making. We conclude that impaired sense of agency may be a factor contributing to ICB in PD patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Objectifying facial expressivity assessment of Parkinson's patients: preliminary study.

PubMed

Wu, Peng; Gonzalez, Isabel; Patsis, Georgios; Jiang, Dongmei; Sahli, Hichem; Kerckhofs, Eric; Vandekerckhove, Marie

2014-01-01

Patients with Parkinson's disease (PD) can exhibit a reduction of spontaneous facial expression, designated as "facial masking," a symptom in which facial muscles become rigid. To improve clinical assessment of facial expressivity of PD, this work attempts to quantify the dynamic facial expressivity (facial activity) of PD by automatically recognizing facial action units (AUs) and estimating their intensity. Spontaneous facial expressivity was assessed by comparing 7 PD patients with 8 control participants. To voluntarily produce spontaneous facial expressions that resemble those typically triggered by emotions, six emotions (amusement, sadness, anger, disgust, surprise, and fear) were elicited using movie clips. During the movie clips, physiological signals (facial electromyography (EMG) and electrocardiogram (ECG)) and frontal face video of the participants were recorded. The participants were asked to report on their emotional states throughout the experiment. We first examined the effectiveness of the emotion manipulation by evaluating the participant's self-reports. Disgust-induced emotions were significantly higher than the other emotions. Thus we focused on the analysis of the recorded data during watching disgust movie clips. The proposed facial expressivity assessment approach captured differences in facial expressivity between PD patients and controls. Also differences between PD patients with different progression of Parkinson's disease have been observed.

SPECT neuroimaging and neuropsychological functions in different stages of Parkinson's disease.

PubMed

Paschali, Anna; Messinis, Lambros; Kargiotis, Odysseas; Lakiotis, Velissarios; Kefalopoulou, Zinovia; Constantoyannis, Costantinos; Papathanasopoulos, Panagiotis; Vassilakos, Pavlos

2010-06-01

The present study investigated differences and associations between cortical perfusion, nigrostriatal dopamine pathway and neuropsychological functions in different stages of Parkinson's disease (PD). We recruited 53 non-demented PD patients divided into four groups according to the Hoehn and Yahr (HY) staging system and 20 healthy controls who were used in the comparison of the neuropsychological findings. Each patient underwent two separate brain single photon emission computed tomography (SPECT) studies (perfusion and dopamine transporter binding) as well as neuropsychological evaluation. Perfusion images of each patient were quantified and compared with a normative database provided by the NeuroGam software manufacturers. Mean values obtained from the cortical areas and neuropsychological measures in the different groups were also compared by analysis of covariance (ANCOVA) controlling for disease duration and educational level. We found cognitive deficits especially in the late PD stages (HY 3, 4 and 5) compared to the early stages (HY 1 and 2) and associations between cognitive decrements and cortical perfusion deterioration mainly in the frontal and posterior cortical areas. Compared with controls, PD patients showed impairments of cognition and cerebral perfusion that increased with clinical severity. Furthermore, we found a significant correlation between the performance on the phonemic fluency task and regional cerebral blood flow (rCBF) in the left frontal lobe. Dopamine transporter binding in the left caudate nucleus significantly correlated with blood flow in the left dorsolateral prefrontal cortex (DLPFC), but not with measures of executive functions. There are significant cognitive and perfusion deficits associated with PD progression, implying a multifactorial neurodegeneration process apart from dopamine depletion in the substantia nigra pars compacta (SNc).

Modulating risky decision-making in Parkinson's disease by transcranial direct current stimulation.

PubMed

Benussi, A; Alberici, A; Cantoni, V; Manenti, R; Brambilla, M; Dell'Era, V; Gazzina, S; Manes, M; Cristillo, V; Padovani, A; Cotelli, M; Borroni, B

2017-05-01

Performance on gambling tasks in Parkinson's disease (PD) is of particular interest, as pathological gambling is often associated with dopamine replacement therapy in these patients. We aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) in modulating gambling behaviour in PD. We assessed the effects of cathodal tDCS over the right DLPFC during the Iowa Gambling Task in 20 patients with PD, compared with sham stimulation. We then conducted a second experimental design, assessing the effects of anodal tDCS over the right DLPFC. We observed that cathodal tDCS over the right DLPFC increased Iowa Gambling Task scores compared with sham stimulation. In the second experimental design, we did not find significant differences between anodal and sham tDCS. Cathodal tDCS over the right DLPFC possibly reduces the pathological overdrive in frontostriatal networks in patients with PD on dopaminergic medication, thus modulating impulsive and risky decision-making. © 2017 EAN.

Reconstruction Options for Pancreaticoduodenectomy in Patients with Prior Roux-en-Y Gastric Bypass.

PubMed

Shah, Mihir M; Martin, Benjamin M; Stetler, Jamil L; Patel, Ankit D; Davis, S Scott; Sarmiento, Juan M; Lin, Edward

2017-11-01

Patients with prior Roux-en-Y gastric bypass (RYGB) operations for weight loss present reconstruction challenges during a pancreaticoduodenectomy (PD). With over 60,000 RYGB performed annually, the increasing odds of encountering such patients during a PD make it imperative to understand the RYGB anatomy and anticipate reconstruction options. This article describes the possible reconstruction options and their rationale. We reviewed our PD reconstruction options, compared them to what have been described in the literature, and derived a consensus from internal conferences comprising bariatric and hepatopancreatobiliary surgeons to describe known reconstruction options. In general, reconstruction options can include one of three options: (1) remnant gastrectomy, (2) preservation of gastric remnant, or (3) reversal of gastric bypass. This article describes individualized reconstruction options for RYGB patients undergoing PD. The reconstruction options can be tailored to the needs of the patient.

Target lesion response predicts survival of patients with hepatocellular carcinoma retreated with transarterial chemoembolization.

PubMed

Zhang, Yong-Fa; Guo, Rong-Ping; OuYang, Han-Yue; Shen, Jing-Xian; Zhao, Jing; Tan, Guo-Sheng; Le, Yong; Wei, Wei; Shi, Ming

2016-10-01

The discontinuation rules of transarterial chemoembolization (TACE) for patients who were assessed as progressive disease (PD) but stage progression-free (SP-free: still belongs to Barcelona Clinic Liver Cancer B) after TACE are unclear. We aimed to evaluate the impact of the PD-pattern on the survival of these patients retreated with TACE. In total, 115 consecutive patients who were assessed as PD but SP-free after TACE and then underwent at least one subsequent TACE session were included. Sixty patients were assessed as PD with target lesion progression (TP), and 55 patients were assessed as PD with target lesion non-progression (TNP). Survival and treatment-related adverse events were compared between the two groups. Additional external validation was performed using a data set (n = 103) from another institution. Patients with TNP had significantly longer median post-progression survival (PPS) than those with TP (21.0 vs. 11.9 months, P = 0.004). After TACE retreatment, the incidence of liver dysfunction was significantly higher for patients with TP than for patients with TNP (45% vs. 20%, P = 0.031). In the multivariate analysis, the target lesion response was one of the most significant prognostic factors for PPS (HR = 2.01; 95% confidence interval: 1.23-3.27; P = 0.005). The findings were supported by an independent external cohort. Compared to patients with TNP, patients with TP might exhibit no improvement in survival and even present damaged liver function after retreatment with TACE. Target lesion response is useful as a clinical decision for repeated TACE in these patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of surgical outcomes between open and robot-assisted minimally invasive pancreaticoduodenectomy.

PubMed

Kim, Hyeong Seok; Han, Youngmin; Kang, Jae Seung; Kim, Hongbeom; Kim, Jae Ri; Koon, Wooil; Kim, Sun-Whe; Jang, Jin-Young

2018-02-01

Robot surgery is a new method that maintains advantages and overcomes disadvantages of conventional methods, even in pancreatic surgery. This study aimed to evaluate safety and benefits of robot-assisted minimally invasive pancreaticoduodenectomy (robot PD). This study included 237 patients who underwent PD between 2015 and 2017. Demographics and surgical outcomes were evaluated. Fifty-one patients underwent robot PD and 186 underwent open PD. Robot PD group had younger age (60.7 vs. 65.4 years, P = 0.006) and lower body mass index (22.7 vs. 24.0, P = 0.007). Robot PD group had lower proportion of patients with firm or hard pancreatic texture (15.7% vs. 38.2%, P = 0.004) and smaller pancreatic duct size (2.3 vs. 3.3 mm, P = 0.002). Two groups had similar operation time (robot vs. open: 335.6 vs. 330.1 min) and complications (15.7% vs. 21.0%), including postoperative pancreatic fistula rate (6.0% vs. 12.0%). Robot PD group had lower postoperative pain score (3.7 vs. 4.1 points, P = 0.008), and shorter postoperative stay (10.6 vs. 15.3 days, P = 0.001). Robot PD is comparable to open PD in early outcomes. Robot PD is safe and feasible and enables early recovery; indication for robot PD is expected to expand in the near future. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Anxiety in early Parkinson's disease: Validation of the Italian observer-rated version of the Parkinson Anxiety Scale (OR-PAS).

PubMed

Santangelo, Gabriella; Falco, Fabrizia; D'Iorio, Alfonsina; Cuoco, Sofia; Raimo, Simona; Amboni, Marianna; Pellecchia, Maria Teresa; Longo, Katia; Vitale, Carmine; Barone, Paolo

2016-08-15

Anxiety disorders are common in Parkinson's Disease (PD) and their identification is relevant even at early stages. The Parkinson Anxiety Scale (PAS) evaluates anxiety in PD; it was used only in the original validation study in PD patients mainly at 2-3 stages of Hoehn & Yahr system (H&Y). The study aimed to investigate psychometric properties of observer-rated version of the PAS (OR-PAS), prevalence rate of anxiety and its features, compared with diagnostic criteria in early PD patients. A sample of 101 PD patients with H&Y:1-2 underwent the OR-PAS. To assess convergent and divergent validity, PD patients underwent Beck Anxiety Inventory, and scales assessing depression, apathy, anhedonia and cognition. To diagnose anxiety disorders, Mini International Neuropsychiatric Inventory was used as gold standard. A "receiver operating characteristics" curve was obtained; positive and negative predictive values were calculated for different cut-off points of the OR-PAS and its subscales. There was no missing data, no floor and ceiling effects; mean score was 12.2±10.1; Cronbach's alpha was 0.899. The OR-PAS showed good convergent and divergent validity. Maximum discrimination was obtained with a cut-off score of 8.5. The anxiety occurred in 59 patients (58.4%). The OR-PAS is a reliable and valid screening instrument for assessing anxiety in patients at early PD. Anxiety was found in 58.4% of PD patients, demonstrating that anxiety occurs even at early stages. Copyright © 2016 Elsevier B.V. All rights reserved.

Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease

PubMed Central

Evatt, Marian L.; DeLong, Mahlon R.; Khazai, Natasha; Rosen, Ami; Triche, Shirley; Tangpricha, Vin

2009-01-01

Background A role for vitamin D deficiency in Parkinson disease (PD) has recently been proposed. Objective To compare the prevalence of vitamin D deficiency in a research database cohort of patients with PD with the prevalence in age-matched healthy controls and patients with Alzheimer disease (AD). Design Survey study and blinded comparison of plasma 25-hydroxyvitamin D (25[OH]D) concentrations of stored samples in a clinical research database at Emory University School of Medicine. Setting Referral center (PD and AD patients), primary care clinics, and community setting (controls). Participants Participants were recruited into the study between May 1992 and March 2007. Every fifth consecutively enrolled PD patient was selected from the clinical research database. Unrelated AD (n=97) and control (n=99) participants were randomly selected from the database after matching for age, sex, race, APOE genotype, and geographic location. Main Outcome Measures Prevalence of suboptimal vitamin D and mean 25(OH)D concentrations. Results Significantly more patients with PD (55%) had insufficient vitamin D than did controls (36%) or patients with AD (41%; P=.02, χ2 test). The mean (SD) 25(OH)D concentration in the PD cohort was significantly lower than in the AD and control cohorts (31.9 [13.6] ng/mL vs 34.8 [15.4] ng/mL and 37.0 [14.5] ng/mL, respectively; P=.03). Conclusions This report of 25(OH)D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin D in pathogenesis and clinical course of PD. PMID:18852350

Changes in functional organization and white matter integrity in the connectome in Parkinson's disease.

PubMed

Tinaz, Sule; Lauro, Peter M; Ghosh, Pritha; Lungu, Codrin; Horovitz, Silvina G

2017-01-01

Parkinson's disease (PD) leads to dysfunction in multiple cortico-striatal circuits. The neurodegeneration has also been associated with impaired white matter integrity. This structural and functional "disconnection" in PD needs further characterization. We investigated the structural and functional organization of the PD whole brain connectome consisting of 200 nodes using diffusion tensor imaging and resting-state functional MRI, respectively. Data from 20 non-demented PD patients on dopaminergic medication and 20 matched controls were analyzed using graph theory-based methods. We focused on node strength, clustering coefficient, and local efficiency as measures of local network properties; and network modularity as a measure of information flow. PD patients showed reduced white matter connectivity in frontoparietal-striatal nodes compared to controls, but no change in modular organization of the white matter tracts. PD group also showed reduction in functional local network metrics in many nodes distributed across the connectome. There was also decreased functional modularity in the core cognitive networks including the default mode and dorsal attention networks, and sensorimotor network, as well as a lack of modular distinction in the orbitofrontal and basal ganglia nodes in the PD group compared to controls. Our results suggest that despite subtle white matter connectivity changes, the overall structural organization of the PD connectome remains robust at relatively early disease stages. However, there is a breakdown in the functional modular organization of the PD connectome.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

PubMed Central

Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

2013-01-01

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms. PMID:24278399

Risk of dementia in peritoneal dialysis patients compared with hemodialysis patients.

PubMed

Wolfgram, Dawn F; Szabo, Aniko; Murray, Anne M; Whittle, Jeff

2015-01-01

Compared with similarly aged controls, patients with end-stage renal disease (ESRD) have a higher prevalence of cognitive impairment and more rapid cognitive decline, which is not explained by traditional risk factors alone. Since previous small studies suggest an association of cognitive impairment with dialysis modality, we compared incident dementia among patients initiating hemodialysis (HD) vs peritoneal dialysis (PD) in a large national cohort. This is a retrospective cohort study of incident dialysis patients in the United States from 2006 to 2008 with no diagnosis of dementia prior to beginning dialysis. We evaluated the effect of initial dialysis modality on incidence of dementia, diagnosed by Medicare claims data, adjusted for baseline demographic and clinical data from the USRDS registry. Our analysis included 121,623 patients, of whom 8,663 initiated dialysis on PD. The mean age of our cohort was 69.2 years. Patients who initiated PD had a lower cumulative incidence of dementia than those who initiated HD (1.0% vs 2.7%, 2.5% vs 5.3%, and 3.9% vs 7.3% at 1, 2, and 3 years, respectively). The risk of dementia for patients who started on PD was lower compared with those who started on HD, with a hazard ratio (HR) = 0.46 [0.41, 0.53], in an unadjusted model and HR 0.74 [0.64, 0.86] in a matched model. Dialysis modality is associated with incident dementia in a cohort of older ESRD patients. This finding warrants further investigation of the effect of dialysis modality on cognitive function and evaluation for possible mechanisms. Copyright © 2015 International Society for Peritoneal Dialysis.

Differences in early speech patterns between Parkinson variant of multiple system atrophy and Parkinson's disease.

PubMed

Huh, Young Eun; Park, Jongkyu; Suh, Mee Kyung; Lee, Sang Eun; Kim, Jumin; Jeong, Yuri; Kim, Hee-Tae; Cho, Jin Whan

2015-08-01

In Parkinson variant of multiple system atrophy (MSA-P), patterns of early speech impairment and their distinguishing features from Parkinson's disease (PD) require further exploration. Here, we compared speech data among patients with early-stage MSA-P, PD, and healthy subjects using quantitative acoustic and perceptual analyses. Variables were analyzed for men and women in view of gender-specific features of speech. Acoustic analysis revealed that male patients with MSA-P exhibited more profound speech abnormalities than those with PD, regarding increased voice pitch, prolonged pause time, and reduced speech rate. This might be due to widespread pathology of MSA-P in nigrostriatal or extra-striatal structures related to speech production. Although several perceptual measures were mildly impaired in MSA-P and PD patients, none of these parameters showed a significant difference between patient groups. Detailed speech analysis using acoustic measures may help distinguish between MSA-P and PD early in the disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI.

PubMed

Kamagata, Koji; Motoi, Yumiko; Hori, Masaaki; Suzuki, Michimasa; Nakanishi, Atsushi; Shimoji, Keigo; Kyougoku, Shinsuke; Kuwatsuru, Ryohei; Sasai, Keisuke; Abe, Osamu; Mizuno, Yoshikuni; Aoki, Shigeki; Hattori, Nobutaka

2011-04-01

To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD). Thirty-five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region-of-interest analysis. PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test). This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD. Copyright © 2011 Wiley-Liss, Inc.

Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial.

PubMed

Zhang, Lina; Zhang, Zhiqin; Chen, Yangmei; Qin, Xinyue; Zhou, Huadong; Zhang, Chaodong; Sun, Hongbin; Tang, Ronghua; Zheng, Jinou; Yi, Lin; Deng, Liying; Li, Jinfang

2013-08-01

Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable--mean adjusted total daily off time--decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

Association between subthalamic nucleus deep brain stimulation and weight gain: Results of a case-control study.

PubMed

Strowd, Roy E; Herco, Maja; Passmore-Griffin, Leah; Avery, Bradley; Haq, Ihtsham; Tatter, Stephen B; Tate, Jessica; Siddiqui, Mustafa S

2016-01-01

To evaluate whether weight change in patients with Parkinson's disease (PD) is different in those undergoing deep brain stimulation (DBS) of the subthalamic nucleus (STN) compared to those not undergoing DBS. A retrospective case-control study was performed in PD patients who had undergone STN DBS (cases) compared to matched PD patients without DBS (controls). Demographic and clinical data including Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were collected. Repeated measures mixed model regression was used to identify variables associated with weight gain. Thirty-five cases and 34 controls were identified. Baseline age, gender, diagnosis and weight were similar. Duration of diagnosis was longer in cases (6.3 vs 4.9 years, p=0.0015). At 21.3 months, cases gained 2.9 kg (+4.65%) while controls lost 1.8 kg (-3.05%, p<0.02). Postoperative UPDRS motor scores improved by 49% indicating surgical efficacy. Only younger age (p=0.0002) and DBS (p=0.008) were significantly associated with weight gain. In this case-control study, PD patients undergoing STN DBS experienced post-operative weight gain that was significantly different from the weight loss observed in non-DBS PD controls. Patients, especially overweight individuals, should be informed that STN DBS can result in weight gain. Copyright © 2015 Elsevier B.V. All rights reserved.

Smartphone- and internet-assisted self-management and adherence tools to manage Parkinson's disease (SMART-PD): study protocol for a randomised controlled trial (v7; 15 August 2014).

PubMed

Lakshminarayana, Rashmi; Wang, Duolao; Burn, David; Chaudhuri, K Ray; Cummins, Gemma; Galtrey, Clare; Hellman, Bruce; Pal, Suvankar; Stamford, Jon; Steiger, Malcolm; Williams, Adrian

2014-09-25

Nonadherence to treatment leads to suboptimal treatment outcomes and enormous costs to the economy. This is especially important in Parkinson's disease (PD). The progressive nature of the degenerative process, the complex treatment regimens and the high rates of comorbid conditions make treatment adherence in PD a challenge. Clinicians have limited face-to-face consultation time with PD patients, making it difficult to comprehensively address non-adherence. The rapid growth of digital technologies provides an opportunity to improve adherence and the quality of decision-making during consultation. The aim of this randomised controlled trial (RCT) is to evaluate the impact of using a smartphone and web applications to promote patient self-management as a tool to increase treatment adherence and working with the data collected to enhance the quality of clinical consultation. A 4-month multicentre RCT with 222 patients will be conducted to compare use of a smartphone- and internet-enabled Parkinson's tracker smartphone app with treatment as usual for patients with PD and/or their carers. The study investigators will compare the two groups immediately after intervention. Seven centres across England (6) and Scotland (1) will be involved. The primary objective of this trial is to assess whether patients with PD who use the app show improved medication adherence compared to those receiving treatment as usual alone. The secondary objectives are to investigate whether patients who receive the app and those who receive treatment as usual differ in terms of quality of life, quality of clinical consultation, overall disease state and activities of daily living. We also aim to investigate the experience of those receiving the intervention by conducting qualitative interviews with a sample of participants and clinicians, which will be administered by independent researchers. ISRCTN45824264 (registered 5 November 2013).

[Immunotherapy for renal cell carcinoma - current status].

PubMed

Grimm, Marc-Oliver; Foller, Susan

2018-04-01

Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo ® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma after prior VEGF targeted therapy. Nivolumab in combination with Ipilimumab will become a standard 1st line option for patients with intermediate and high risk profile according to IMDC. Further data are required regarding PD-1/PD-L1 inhibitors in combination with Bevacizumab and VEGFR-TKIs, respectively, including overall survival and side effect profile. © Georg Thieme Verlag KG Stuttgart · New York.

Functional Aspects of Gait in Essential Tremor: A Comparison with Age-Matched Parkinson's Disease Cases, Dystonia Cases, and Controls.

PubMed

Louis, Elan D; Rao, Ashwini K

2015-01-01

An understanding of the functional aspects of gait and balance has wide ramifications. Individuals with balance disorders often restrict physical activity, travel, and social commitments to avoid falling, and loss of balance confidence, itself, is a source of disability. We studied the functional aspects of gait in patients with essential tremor (ET), placing their findings within the context of two other neurological disorders (Parkinson's disease [PD] and dystonia) and comparing them with age-matched controls. We administered the six-item Activities of Balance Confidence (ABC-6) Scale and collected data on number of falls and near-falls, and use of walking aids in 422 participants (126 ET, 77 PD, 46 dystonia, 173 controls). Balance confidence was lowest in PD, intermediate in ET, and relatively preserved in dystonia compared with controls. This ordering reoccurred for each of the six ABC-6 items. The number of near-falls and falls followed a similar ordering. Use of canes, walkers, and wheelchairs was elevated in ET and even greater in PD. Several measures of balance confidence (ABC-6 items 1, 4, 5, and 6) were lower in torticollis cases than in those with blepharospasm, although the two groups did not differ with respect to falls or use of walking aids. Lower balance confidence, increased falls, and greater need for walking aids are variably features of a range of movement disorder patients compared to age-matched controls. While most marked among PD patients, these issues affected ET patients as well and, to a small degree, some patients with dystonia.

Effects of antidepressant treatment with rTMS and fluoxetine on brain perfusion in PD.

PubMed

Fregni, F; Ono, C R; Santos, C M; Bermpohl, F; Buchpiguel, C; Barbosa, E R; Marcolin, M A; Pascual-Leone, A; Valente, K D

2006-06-13

Although depression is highly prevalent in Parkinson disease (PD), little is known about the neural correlates associated with depression and antidepressant treatment in PD. To examine the effects of fluoxetine and repetitive transcranial magnetic stimulation (rTMS) on regional cerebral blood flow (rCBF) using SPECT in patients with PD and depression. Twenty-six patients were enrolled into two groups: One received active rTMS and placebo medication and the other sham rTMS and fluoxetine 20 mg/day. Brain SPECT was performed at baseline and after 2 and 8 weeks. Changes in rCBF were compared across timepoints and correlated with clinical scores. In addition, baseline rCBF of these patients was compared with that of 29 healthy, age-matched subjects. At baseline, patients with PD and depression showed significantly lower rCBF in the left prefrontal cortex, posterior cingulate gyrus, left insula, and right parietal cortex when compared with healthy controls. Both treatments induced significant clinical improvement and increases in rCBF in the posterior cingulate gyrus and decreases in rCBF in the right medial frontal gyrus. These changes were significantly correlated to the clinical outcome. Furthermore, the comparison between these two treatments revealed that whereas rTMS treatment was associated with an increased perfusion in the right and left prefrontal cortex, fluoxetine treatment was associated with a relative rCBF increase in the occipital lobe. Depression in patients with Parkinson disease is correlated with a dysfunction of the frontal-limbic network that can be modulated by two different antidepressant therapies.

Exenatide and the treatment of patients with Parkinson’s disease

PubMed Central

Aviles-Olmos, Iciar; Dickson, John; Kefalopoulou, Zinovia; Djamshidian, Atbin; Ell, Peter; Soderlund, Therese; Whitton, Peter; Wyse, Richard; Isaacs, Tom; Lees, Andrew; Limousin, Patricia; Foltynie, Thomas

2013-01-01

Background. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. Methods. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson’s disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). Results. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). Conclusion. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD. Trial registration. Clinicaltrials.gov NCT01174810. Funding. Cure Parkinson’s Trust. PMID:23728174

CXCR4–CXCL12–CXCR7, TLR2–TLR4, and PD-1/PD-L1 in colorectal cancer liver metastases from neoadjuvant-treated patients

PubMed Central

D'Alterio, Crescenzo; Nasti, Guglielmo; Polimeno, Marianeve; Ottaiano, Alessandro; Conson, Manuel; Circelli, Luisa; Botti, Giovanni; Scognamiglio, Giosuè; Santagata, Sara; De Divitiis, Chiara; Nappi, Anna; Napolitano, Maria; Tatangelo, Fabiana; Pacelli, Roberto; Izzo, Francesco; Vuttariello, Emilia; Botti, Gerardo; Scala, Stefania

2016-01-01

ABSTRACT A neoadjuvant clinical trial was previously conducted in patients with resectable colorectal cancer liver metastases (CRLM). At a median follow up of 28 months, 20/33 patients were dead of disease, 8 were alive with disease and 5 were alive with no evidence of disease. To shed further insight into biological features accounting for different outcomes, the expression of CXCR4–CXCL12–CXCR7, TLR2–TLR4, and the programmed death receptor-1 (PD-1)/programmed death-1 ligand (PD-L1) was evaluated in excised liver metastases. Expression profiles were assessed through qPCR in metastatic and unaffected liver tissue of 33 CRLM neoadjuvant-treated patients. CXCR4 and CXCR7, TLR2/TLR4, and PD-1/PD-L1 mRNA were significantly overexpressed in metastatic compared to unaffected liver tissues. CXCR4 protein was negative/low in 10/31, and high in 21/31, CXCR7 was negative/low in 16/31 and high in 15/31, CXCL12 was negative/low in 14/31 and high in 17/31 CRLM. PD-1 was negative in 19/30 and positive in 11/30, PD-L1 was negative/low in 24/30 and high in 6/30 CRLM. Stromal PD-L1 expression, affected the progression-free survival (PFS) in the CRLM population. Patients overexpressing CXCR4 experienced a worse PFS and cancer specific survival (CSS) (p = 0.001 and p = 0.0008); in these patients, KRAS mutation identified a subgroup with a significantly worse CSS (p < 0.01). Thus, CXCR4 and PD-L1 expression discriminate patients with the worse PFS within the CRLM evaluated patients. Within the CXCR4 high expressing patients carrying Mut-KRAS in CRLM identifies the worst prognostic group. Thus, CXCR4 targeting plus anti-PD-1 therapy should be explored to improve the prognosis of Mut-KRAS-high CXCR4-CRLMs. PMID:28123896

Abnormal ventral tegmental area-anterior cingulate cortex connectivity in Parkinson's disease with depression.

PubMed

Wei, Luqing; Hu, Xiao; Yuan, Yonggui; Liu, Weiguo; Chen, Hong

2018-07-16

Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease. The present study used resting-state fMRI and seed-based functional connectivity of putative dopaminergic midbrain regions (i.e., substantia nigra (SN) and ventral tegmental area (VTA)) to investigate the circuit-related abnormalities in PD with depression. The results showed that depressed PD (DPD) patients relative to healthy controls (HC) and non-depressed PD (NDPD) patients had increased functional connectivity between VTA and anterior cingulate cortex (ACC), demonstrating that dysfunctional mesocorticolimbic dopaminergic neurotransmission may be associated with depression in PD. Compared with HC, DPD and NDPD patients showed increased functional connectivity from SN to sensorimotor cortex, validating that alterations in the nigrostriatal circuitry could be responsible for cardinal motor features in PD. In addition, aberrant connectivity between VTA and ACC was correlated with the severity of depression in PD patients, further supporting that abnormal mesocorticolimbic system may account for depressive symptoms in PD. These results have provided potential circuit-level biomarkers of depression in PD, and suggested that resting state functional connectivity of midbrain dopaminergic nuclei may be useful for understanding the underlying pathology in PD with depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of oral health in peritoneal dialysis patients with and without diabetes mellitus.

PubMed

Eltas, Abubekir; Tozoğlu, Ummühan; Keleş, Mustafa; Canakci, Varol

2012-01-01

The incidence of chronic renal failure continues to rise worldwide, and although the oral and dental changes in individuals with this condition have been examined, investigations with diabetic peritoneal dialysis (PD) patients are limited. We therefore examined salivary pH, dry mouth, taste change, and mucosal ulceration in diabetic and nondiabetic uremic patients receiving PD. A total of 49 patients undergoing PD therapy were allocated to either the diabetic or the nondiabetic group. Salivary pH, dry mouth, taste change, and mucosal ulceration were determined for both groups. Salivary flow rate and pH were both lower in the diabetic group. Buffer capacity, dry mouth, taste change, and mucosal ulceration were all increased in that group. These findings were associated with level of glycosylated hemoglobin A1c. Our observations indicate that, compared with nondiabetic PD patients, patients with diabetes exhibit more severe oral uremic symptoms, including dry mouth, burning mouth syndrome, taste change, and mucosal ulcerations. The oral health in these patients should be followed.

Ameliorating Patient Stigma Amongst Staff Working With Personality Disorder: Randomized Controlled Trial of Self-Management Versus Skills Training.

PubMed

Clarke, Sue; Taylor, Georgina; Bolderston, Helen; Lancaster, Joanna; Remington, Bob

2015-11-01

Patients diagnosed with a personality disorder (PD) are often stigmatized by the healthcare staff who treat them. This study aimed to compare the impact on front-line staff of a self-management Acceptance and Commitment Therapy-based training intervention (ACTr) with a knowledge- and skills-based Dialectical Behaviour Training intervention (DBTr). A service-based randomized controlled trial was conducted comparing the effects of 2-day ACTr (N = 53) and DBTr (N = 47) staff workshops over 6 months. Primary outcome measures were staff attitudes towards patients and staff-patient relationships. For both interventions, staff attitudes, therapeutic relationship, and social distancing all improved pre- to postintervention, and these changes were maintained at 6-month follow-up. Although offering different resources to staff, both ACTr and DBTr were associated with an improved disposition towards PD patients. Future research could evaluate a combined approach, both for staff working with PD patients and those working with other stigmatized groups.

Subthalamic deep brain stimulation modulates conscious perception of sensory function in Parkinson's disease.

PubMed

Cury, Rubens G; Galhardoni, Ricardo; Teixeira, Manoel J; Dos Santos Ghilardi, Maria G; Silva, Valquiria; Myczkowski, Martin L; Marcolin, Marco A; Barbosa, Egberto R; Fonoff, Erich T; Ciampi de Andrade, Daniel

2016-12-01

Subthalamic deep brain stimulation (STN-DBS) is used to treat refractory motor complications in Parkinson disease (PD), but its effects on nonmotor symptoms remain uncertain. Up to 80% of patients with PD may have pain relief after STN-DBS, but it is unknown whether its analgesic properties are related to potential effects on sensory thresholds or secondary to motor improvement. We have previously reported significant and long-lasting pain relief after DBS, which did not correlate with motor symptomatic control. Here we present secondary data exploring the effects of DBS on sensory thresholds in a controlled way and have explored the relationship between these changes and clinical pain and motor improvement after surgery. Thirty-seven patients were prospectively evaluated before STN-DBS and 12 months after the procedure compared with healthy controls. Compared with baseline, patients with PD showed lower thermal and mechanical detection and higher cold pain thresholds after surgery. There were no changes in heat and mechanical pain thresholds. Compared with baseline values in healthy controls, patients with PD had higher thermal and mechanical detection thresholds, which decreased after surgery toward normalization. These sensory changes had no correlation with motor or clinical pain improvement after surgery. These data confirm the existence of sensory abnormalities in PD and suggest that STN-DBS mainly influenced the detection thresholds rather than painful sensations. However, these changes may depend on the specific effects of DBS on somatosensory loops with no correlation to motor or clinical pain improvement.

Mitochondrial DNA sequence analysis of four Alzheimer`s and Parkinson`s disease patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, M.D.; Shoffner, J.M.; Wallace, D.C.

1996-01-22

The mitochondrial DNA (mtDNA) sequence was determined on 3 patients with Alzheimer`s disease (AD) exhibiting AD plus Parkinson`s disease (PD) neuropathologic changes and one patient with PD. Patient mtDNA sequences were compared to the standard Cambridge sequence to identify base changes. In the first AD + PD patient, 2 of the 15 nucleotide substitutions may contribute to the neuropathology, a nucleotide pair (np) 4336 transition in the tRNA{sup Gln} gene found 7.4 times more frequently in patients than in controls, and a unique np 721 transition in the 12S rRNA gene which was not found in 70 other patients ormore » 905 controls. In the second AD + PD patient, 27 nucleotide substitutions were detected, including an np 3397 transition in the ND1 gene which converts a conserved methionine to a valine. In the third AD + PD patient, 2 polymorphic base substitutions frequently found at increased frequency in Leber`s hereditary optic neuropathy patients were observed, an np 4216 transition in ND1 and an np 13708 transition in the ND5 gene. For the PD patient, 2 novel variants were observed among 25 base substitutions, an np 1709 substitution in the 16S rRNA gene and an np 15851 missense mutation in the cytb gene. Further studies will be required to demonstrate a casual role for these base substitutions in neurodegenerative disease. 68 refs., 2 tabs.« less

Age 80 years and over is not associated with increased morbidity and mortality following pancreaticoduodenectomy.

PubMed

Kim, Sandy Y; Fink, Michael A; Perini, Marcos; Houli, Nezor; Weinberg, Laurence; Muralidharan, Vijayaragavan; Starkey, Graham; Jones, Robert M; Christophi, Christopher; Nikfarjam, Mehrdad

2018-05-01

Pancreaticoduodenectomy (PD) is associated with high morbidity, which is perceived to be increased in the elderly. To our knowledge there have been no Australian series that have compared outcomes of patients over the age of 80 undergoing PD to those who are younger. Patients who underwent PD between January 2008 and November 2015 were identified from a prospectively maintained database. A total of 165 patients underwent PD of whom 17 (10.3%) were aged 80 or over. The pre-operative health status, according to American Society of Anesthesiologists class was similar between the groups (P = 0.420). The 90-day mortality rates (5.9% in the elderly and 2% in the younger group; P = 0.355) and the post-operative complication rates (64.7% in the elderly versus 62.8% in the younger group; P = 0.88) were similar. Overall median length of hospital stay was also similar between the groups, but older patients were far more likely to be discharged to a rehabilitation facility than younger patients (47.1 versus 12.8%; P < 0.0001). Older patients with pancreatic adenocarcinoma (n = 10) had significantly lower median survival than the younger group (n = 69) (16.6 versus 22.5 months; P = 0.048). No significant differences were seen in the rate of complications following PD in patients aged 80 or over compared to younger patients, although there appears to be a shorter survival in the elderly patients treated for pancreatic cancer. Careful selection of elderly patients and optimal peri-operative care, rather than age should be used to determine whether surgical intervention is indicated in this patient group. © 2017 Royal Australasian College of Surgeons.

MicroRNAs and Target Genes As Biomarkers for the Diagnosis of Early Onset of Parkinson Disease

PubMed Central

Arshad, Ahmad R.; Sulaiman, Siti A.; Saperi, Amalia A.; Jamal, Rahman; Mohamed Ibrahim, Norlinah; Abdul Murad, Nor Azian

2017-01-01

Among the neurodegenerative disorders, Parkinson's disease (PD) ranks as the second most common disorder with a higher prevalence in individuals aged over 60 years old. Younger individuals may also be affected with PD which is known as early onset PD (EOPD). Despite similarities between the characteristics of EOPD and late onset PD (LODP), EOPD patients experience much longer disease manifestations and poorer quality of life. Although some individuals are more prone to have EOPD due to certain genetic alterations, the molecular mechanisms that differentiate between EOPD and LOPD remains unclear. Recent findings in PD patients revealed that there were differences in the genetic profiles of PD patients compared to healthy controls, as well as between EOPD and LOPD patients. There were variants identified that correlated with the decline of cognitive and motor symptoms as well as non-motor symptoms in PD. There were also specific microRNAs that correlated with PD progression, and since microRNAs have been shown to be involved in the maintenance of neuronal development, mitochondrial dysfunction and oxidative stress, there is a strong possibility that these microRNAs can be potentially used to differentiate between subsets of PD patients. PD is mainly diagnosed at the late stage, when almost majority of the dopaminergic neurons are lost. Therefore, identification of molecular biomarkers for early detection of PD is important. Given that miRNAs are crucial in controlling the gene expression, these regulatory microRNAs and their target genes could be used as biomarkers for early diagnosis of PD. In this article, we discussed the genes involved and their regulatory miRNAs, regarding their roles in PD progression, based on the findings of significantly altered microRNAs in EOPD studies. We also discussed the potential of these miRNAs as molecular biomarkers for early diagnosis. PMID:29163029

A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset.

PubMed

Jang, Bum-Sup; Kim, In Ah

2017-09-01

We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset. To validate the gene signature, 1045 patients were selected and divided into two clusters using a consensus clustering algorithm based on their radiosensitive (RS) or radioresistant (RR) designation according to their prognosis. Patients were also stratified as PD-L1-high or PD-L1-low based on the median value of CD274 mRNA expression level as surrogates of PD-L1. Patents assigned to the RS group had decreased risk of recurrence-free survival (RFS) rate than patients in the RR group by univariate analysis (HR 0.45, 95% CI 0.25-0.81, p=0.008) only when treated with RT. The RS group was independently associated with the PD-L1-high group, and CD274 mRNA expression was significantly higher in the RS group (p<0.001) than the RR group. In the PD-L1-high group, the RS group was associated with better RFS compared to the RR group (HR 0.37, 95% CI 0.16-0.87, p=0.022) in multivariate analysis. The level of PD-L1 expression may represent the immunogenicity of tumors, and thus, we speculated that the PD-L1-high group had more immunogenic tumors, which could be more sensitive to radiation-induced immunologic cell death. We first evaluated the predictive value of the radiosensitivity gene signature and described a relationship with this radiosensitivity gene signature and PD-L1. The radiosensitivity gene signature and PD-L1 status were important factors for prediction of the clinical outcome of RT in patients with invasive breast cancer and may be used for selecting patients who will benefit from RT combined with anti-PD1/PDL1 therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Alterations in conflict monitoring are related to functional connectivity in Parkinson's disease.

PubMed

Rosenberg-Katz, Keren; Maidan, Inbal; Jacob, Yael; Giladi, Nir; Mirelman, Anat; Hausdorff, Jeffrey M

2016-09-01

Patients with Parkinson's disease (PD) have difficulties in executive functions including conflict monitoring. The neural mechanisms underlying these difficulties are not yet fully understood. In order to examine the neural mechanisms related to conflict monitoring in PD, we evaluated 35 patients with PD and 20 healthy older adults while they performed a word-color Stroop paradigm in the MRI. Specifically, we focused on changes between the groups in task-related functional connectivity using psycho-physiological interaction (PPI) analysis. The anterior cingulate cortex (ACC), which is a brain node previously associated with the Stroop paradigm, was selected as the seed region for this analysis. Patients with PD, as compared to healthy controls, had reduced task-related functional connectivity between the ACC and parietal regions including the precuneus and inferior parietal lobe. This was seen only in the incongruent Stroop condition. A higher level of connectivity between the ACC and precuneus was correlated with a lower error rate in the conflicting, incongruent Stroop condition in the healthy controls, but not in the patients with PD. Furthermore, the patients also had reduced functional connectivity between the ACC and the superior frontal gyrus which was present in both the incongruent and congruent task condition. The present findings shed light on brain mechanisms that are apparently associated with specific cognitive difficulties in patients with PD. Among patients with PD, impaired conflict monitoring processing within the ACC-based fronto-parietal network may contribute to difficulties under increased executive demands. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peritonitis in children with automated peritoneal dialysis: a single-center study of a 10-year experience.

PubMed

Dotis, John; Myserlis, Pavlos; Printza, Nikoleta; Stabouli, Stella; Gkogka, Chrysa; Pavlaki, Antigoni; Papachristou, Fotios

2016-08-01

Peritoneal dialysis (PD) constitutes the preferred dialysis modality for children requiring renal replacement therapy with peritonitis being one of the most common complications of PD. This study was performed to evaluate the epidemiology, microbiology, and outcomes of PD-associated peritonitis in Greek children for a 10-year period. A total of 27 patients (16 males) with a mean age 121.8 ± 57.2 months were retrospective analyzed. Patients were on PD therapy for a mean duration of 45.2 ± 26.1 months. We found 23 episodes of PD-associated peritonitis occurred in 9 out of 27 patients (0.23 episodes/patient-year), with four patients experienced two or more peritonitis episodes. Gram-positive bacteria were responsible for 15 (65.2%) peritonitis episodes, with Staphylococcus aureus being the predominant specie isolated in 30.4% of cases. A total of seven episodes of exit-site infections (ESIs) were identified in five patients (0.069 episodes/patient-year) with the most common bacteria isolated being S. aureus (57.4%). Initial antibiotic treatment included intraperitoneal vancomycin plus ceftazidime in the majority of cases (82.6%). At the end of study, 12 (44.4%) patients remained on PD, 11 (41.8%) underwent renal transplantation, 2 (7.4%) shifted to hemodialysis and unfortunately, two patients (7.4%) died. Conclusively, our study revealed a noticeable low peritonitis and ESIs rate as compared to international data and represents the first evaluation of the characteristics and outcomes of peritonitis in the Greek pediatric PD population.

TEMPORAL TRENDS AND FACTORS ASSOCIATED WITH MEDICATION PRESCRIPTION PATTERNS IN PERITONEAL DIALYSIS PATIENTS.

PubMed

Campos, Ludimila G; Bragg-Gresham, Jennifer; Han, Yun; Moraes, Thyago P; Figueiredo, Ana E; Barretti, Pasqual; Balkrishnan, Rajesh; Saran, Rajiv; Pecoits-Filho, Roberto

2018-06-06

Patients on peritoneal dialysis (PD) suffer from a high burden of comorbidities, which are managed with multiple medications. Determinants of prescription patterns are largely unknown in this population. This study assesses temporal changes and factors associated with medication prescription in a nationally representative population of patients on PD under the universal coverage healthcare system in Brazil. Incident patients recruited in the Brazilian Peritoneal Dialysis Study (BRAZPD) from December 2004 to January 2011, stratified by prior hemodialysis (HD) treatment, were included in the analysis. Multivariable logistic regression was used to assess the association between medication prescription and socioeconomic factors. Yearly prevalent cross-sections were calculated to estimate prescription over time. Medication prescription was in general higher among patients who had previously received HD, compared with those who started renal replacement therapy (RRT) directly on PD. Prescription increased from baseline to 6 months of PD therapy, particularly in those who did not previously receive HD. After accounting for patient characteristics, significant associations were found between socioeconomic factors, geographic region, and medication prescription patterns. Finally, the prescription of all cardioprotective and anemia medications and phosphate binders increased significantly over time. In a PD population under universal coverage in a developing country, there was an increase in drug prescription during the first 6 months on PD, and a trend toward more liberal prescription of medications in later years. Independent from patient characteristics and comorbidities, socioeconomic factors influenced drug prescriptions that likely impact patient outcome, calling for public health action to decrease potential inequities in management of comorbidities in PD patients.

Dialysis Provision and Implications of Health Economics on Peritoneal Dialysis Utilization: A Review from a Malaysian Perspective

PubMed Central

Seong Hooi, Lai; Bavanandan, Sunita

2017-01-01

End-stage renal disease (ESRD) is managed by either lifesaving hemodialysis (HD) and peritoneal dialysis (PD) or a kidney transplant. In Malaysia, the prevalence of dialysis-treated ESRD patients has shown an exponential growth from 504 per million population (pmp) in 2005 to 1155 pmp in 2014. There were 1046 pmp patients on HD and 109 pmp patients on PD in 2014. Kidney transplants are limited due to lack of donors. Malaysia adopts public-private financing model for dialysis. Majority of HD patients were treated in the private sector but almost all PD patients were treated in government facilities. Inequality in access to dialysis is visible within geographical regions where majority of HD centres are scattered around developed areas. The expenditure on dialysis has been escalating in recent years but economic evaluations of dialysis modalities are scarce. Evidence shows that health policies and reimbursement strategies influence dialysis provision. Increased uptake of PD can produce significant economic benefits and improve patients' access to dialysis. As a result, some countries implemented a PD-First or Favored Policy to expand PD use. Thus, a current comparative costs analysis of dialysis is strongly recommended to assist decision-makers to establish a more equitable and economically sustainable dialysis provision in the future. PMID:29225970

Dialysis Provision and Implications of Health Economics on Peritoneal Dialysis Utilization: A Review from a Malaysian Perspective.

PubMed

Abdul Manaf, Mohd Rizal; Surendra, Naren Kumar; Abdul Gafor, Abdul Halim; Seong Hooi, Lai; Bavanandan, Sunita

2017-01-01

End-stage renal disease (ESRD) is managed by either lifesaving hemodialysis (HD) and peritoneal dialysis (PD) or a kidney transplant. In Malaysia, the prevalence of dialysis-treated ESRD patients has shown an exponential growth from 504 per million population (pmp) in 2005 to 1155 pmp in 2014. There were 1046 pmp patients on HD and 109 pmp patients on PD in 2014. Kidney transplants are limited due to lack of donors. Malaysia adopts public-private financing model for dialysis. Majority of HD patients were treated in the private sector but almost all PD patients were treated in government facilities. Inequality in access to dialysis is visible within geographical regions where majority of HD centres are scattered around developed areas. The expenditure on dialysis has been escalating in recent years but economic evaluations of dialysis modalities are scarce. Evidence shows that health policies and reimbursement strategies influence dialysis provision. Increased uptake of PD can produce significant economic benefits and improve patients' access to dialysis. As a result, some countries implemented a PD-First or Favored Policy to expand PD use. Thus, a current comparative costs analysis of dialysis is strongly recommended to assist decision-makers to establish a more equitable and economically sustainable dialysis provision in the future.

The impact of the peritoneal glucose load index on hydration status and inflammation in peritoneal dialysis patients.

PubMed

Hassan, Kamal; Hassan, Fadi; Edgem, Rabia; Moshe, Smadar; Hassan, Shadi

2015-02-01

To evaluate the impact of the peritoneal glucose load (PGL) on hydration status and inflammation in peritoneal dialysis (PD) patients. This cross-sectional study evaluated stable PD patients using a novel PGL index (PGLI), which was calculated as the net glucose content (g) in the PD solutions administered in the daily PD prescription divided by the dry body weight (kg) assessed by whole-body bioimpedance spectroscopy. The relationship between PGLI and glycosylated haemoglobin (HbA1c), fluid overload (FO), and inflammatory markers was investigated. A total of 43 stable PD patients participated in the study. Significant positive correlations were found between PGLI and HbA1c, FO, plasma high sensitivity C-reactive protein (hsCRP), and plasma interleukin-6 (IL-6) levels. HbA1c, FO, plasma hsCRP and plasma IL-6 levels were significantly higher in patients with PGLI >3 g/kg/day compared with those with PGLI ≤3 g/kg/day. PGLI values >3 g/kg/day may be associated with poor glycaemic control, over hydration and augmented inflammation. PGLI might be a useful tool for the quantitative assessment of the PGL and could be applied when managing PD patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Role of a Standardized Prism Under Cover Test in the Assessment of Dissociated Vertical Deviation.

PubMed

Klaehn, Lindsay D; Hatt, Sarah R; Leske, David A; Holmes, Jonathan M

2018-03-01

Dissociated vertical deviation (DVD) is commonly measured using a prism and alternate cover test (PACT), but some providers use a prism under cover test (PUCT). The aim of this study was to compare a standardized PUCT measurement with a PACT measurement, for assessing the magnitude of DVD. Thirty-six patients with a clinical diagnosis of DVD underwent measurement of the angle of deviation with the PACT, fixing with the habitually fixing eye, and with PUCT, fixing both right and left eyes. The PUCT was standardized, using a 10-second cover for each prism magnitude, until the deviation was neutralized. The magnitude of hyperdeviation by PACT and PUCT was compared for the non-fixing eye, using paired non-parametric tests. The frequency of discrepancies more than 4 prism diopters (PD) between PACT and PUCT was calculated. The magnitude of hyperdeviation was greater when measured with PUCT (range 8PD hypodeviation to 20PD hyperdeviation) vs. PACT (18PD hypodeviation to 25PD hyperdeviation) with a median difference of 4.5PD (range -5PD to 21PD); P < 0.0001. Eighteen (50%) of 36 measurements elicited >4PD hyperdeviation (or >4PD less hypodeviation) by PUCT than by PACT. A standardized 10-second PUCT yields greater values than a prism and alternate cover test in the majority of patients with DVD, providing better quantification of the severity of DVD, which may be important for management decisions.

PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer.

PubMed

Song, Minmin; Chen, Defeng; Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

2013-01-01

Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression.

Item Response Theory as an Efficient Tool to Describe a Heterogeneous Clinical Rating Scale in De Novo Idiopathic Parkinson's Disease Patients.

PubMed

Buatois, Simon; Retout, Sylvie; Frey, Nicolas; Ueckert, Sebastian

2017-10-01

This manuscript aims to precisely describe the natural disease progression of Parkinson's disease (PD) patients and evaluate approaches to increase the drug effect detection power. An item response theory (IRT) longitudinal model was built to describe the natural disease progression of 423 de novo PD patients followed during 48 months while taking into account the heterogeneous nature of the MDS-UPDRS. Clinical trial simulations were then used to compare drug effect detection power from IRT and sum of item scores based analysis under different analysis endpoints and drug effects. The IRT longitudinal model accurately describes the evolution of patients with and without PD medications while estimating different progression rates for the subscales. When comparing analysis methods, the IRT-based one consistently provided the highest power. IRT is a powerful tool which enables to capture the heterogeneous nature of the MDS-UPDRS.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors.

PubMed

Bernhard, Felix P; Heinzel, Sebastian; Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders.

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

PubMed Central

Binder, Gerhard; Weber, Karin; Apel, Anja; Roeben, Benjamin; Deuschle, Christian; Maechtel, Mirjam; Heger, Tanja; Nussbaum, Susanne; Gasser, Thomas; Maetzler, Walter; Berg, Daniela

2016-01-01

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: ≤3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders. PMID:26967642

Abnormal gait pattern emerges during curved trajectories in high-functioning Parkinsonian patients walking in line at normal speed

PubMed Central

Godi, Marco; Giardini, Marica; Arcolin, Ilaria; Nardone, Antonio; Giordano, Andrea; Schieppati, Marco

2018-01-01

Background Several patients with Parkinson´s disease (PD) can walk normally along straight trajectories, and impairment in their stride length and cadence may not be easily discernible. Do obvious abnormalities occur in these high-functioning patients when more challenging trajectories are travelled, such as circular paths, which normally implicate a graded modulation in the duration of the interlimb gait cycle phases? Methods We compared a cohort of well-treated mildly to moderately affected PD patients to a group of age-matched healthy subjects (HS), by deliberately including HS spontaneously walking at the same speed of the patients with PD. All participants performed, in random order: linear and circular walking (clockwise and counter-clockwise) at self-selected speed. By means of pressure-sensitive insoles, we recorded walking speed, cadence, duration of single support, double support, swing phase, and stride time. Stride length-cadence relationships were built for linear and curved walking. Stride-to-stride variability of temporal gait parameters was also estimated. Results Walking speed, cadence or stride length were not different between PD and HS during linear walking. Speed, cadence and stride length diminished during curved walking in both groups, stride length more in PD than HS. In PD compared to HS, the stride length-cadence relationship was altered during curved walking. Duration of the double-support phase was also increased during curved walking, as was variability of the single support, swing phase and double support phase. Conclusion The spatio-temporal gait pattern and variability are significantly modified in well-treated, high-functioning patients with PD walking along circular trajectories, even when they exhibit no changes in speed in straight-line walking. The increased variability of the gait phases during curved walking is an identifying characteristic of PD. We discuss our findings in term of interplay between control of balance and of locomotor progression: the former is challenged by curved trajectories even in high-functioning patients, while the latter may not be critically affected. PMID:29750815

Hippocampal perfusion predicts impending neurodegeneration in REM sleep behavior disorder.

PubMed

Dang-Vu, Thien Thanh; Gagnon, Jean-François; Vendette, Mélanie; Soucy, Jean-Paul; Postuma, Ronald B; Montplaisir, Jacques

2012-12-11

Patients with idiopathic REM sleep behavior disorder (IRBD) are at risk for developing Parkinson disease (PD) and dementia with Lewy bodies (DLB). We aimed to identify functional brain imaging patterns predicting the emergence of PD and DLB in patients with IRBD, using SPECT with (99m)Tc-ethylene cysteinate dimer (ECD). Twenty patients with IRBD were scanned at baseline during wakefulness using (99m)Tc-ECD SPECT. After a follow-up of 3 years on average, patients were divided into 2 groups according to whether or not they developed defined neurodegenerative disease (PD, DLB). SPECT data analysis comparing regional cerebral blood flow (rCBF) between groups assessed whether specific brain perfusion patterns were associated with subsequent clinical evolution. Regression analysis between rCBF and clinical markers of neurodegeneration (motor, color vision, olfaction) looked for neural structures involved in this process. Of the 20 patients with IRBD recruited for this study, 10 converted to PD or DLB during the follow-up. rCBF at baseline was increased in the hippocampus of patients who would later convert compared with those who would not (p < 0.05 corrected). Hippocampal perfusion was correlated with motor and color vision scores across all IRBD patients. (99m)Tc-ECD SPECT identifies patients with IRBD at risk for conversion to other neurodegenerative disorders such as PD or DLB; disease progression in IRBD is predicted by abnormal perfusion in the hippocampus at baseline. Perfusion within this structure is correlated with clinical markers of neurodegeneration, further suggesting its involvement in the development of presumed synucleinopathies.

Moral decision-making and theory of mind in patients with idiopathic Parkinson's disease.

PubMed

Rosen, Jan B; Brand, Matthias; Polzer, Christin; Ebersbach, Georg; Kalbe, Elke

2013-09-01

Cognitive impairments in theory of mind (ToM), executive processing, and decision-making are frequent and highly relevant symptoms in patients with Parkinson's disease (PD). These functions have been related to moral decision-making. Their association to moral decision-making in PD, however, has not been studied yet. It was hypothesized that moral decisions in patients with PD differ from those in healthy control participants, and that more egoistic decisions are related to ToM as well as executive dysfunctions in patients with PD. Nineteen patients with PD and 20 healthy control participants were examined with an everyday moral decision-making task, comprised of 10 low and 10 high emotional forced-choice moral dilemma short stories with egoistic and altruistic options. All participants received an elaborate neuropsychological test battery. Electrodermal skin conductance responses were recorded to examine possible unconscious emotional reactions during moral decision-making. The groups performed comparably in total scores of moral decision-making. Although ToM did not differ between groups, it was inversely related to altruistic moral decisions in the healthy control group, but not in patients with PD. Executive functions were not related to moral decision-making. No differences were found for skin conductance responses, yet they differed from zero in both groups. Our findings indicate that moral decisions do not differ between patients with PD and healthy control participants. However, different underlying processes in both groups can be presumed. While healthy control participants seem to apply ToM to permit egoistic moral decisions in low emotional dilemmas, patients with PD seem to decide independently from ToM. These mechanisms as well as neuropsychological and neurophysiological correlates are discussed.

Interaction effect of psychological distress and asthma control on productivity loss?

PubMed

Moullec, Grégory; FitzGerald, J Mark; Rousseau, Roxanne; Chen, Wenjia; Sadatsafavi, Mohsen

2015-06-01

Little is known about the potential synergistic effect of comorbid psychological distress (PD) and uncontrolled asthma (UA) on productivity loss. We estimated the productivity loss associated with the combination of these two potentially preventable conditions in employed adults with asthma. A population-based random sample of 300 adults with asthma in British Columbia, Canada, was prospectively recruited between Dec 2010 and Aug 2012. PD and productivity loss due to absenteeism and presenteeism was measured using validated instruments, and asthma control was ascertained using 2010 Global Initiative for Asthma management strategy. We used two-part regression models to study the contribution of UA and PD to productivity loss. Compared with reference group (controlled asthma (CA)+noPD), those with UA+noPD had CAD$286 (95%CI $276-297) weekly productivity loss, and those with CA+PD had CAD$465 ($445-485). Those with UA+PD had CAD$449 (437-462) in productivity loss. There was no significant interaction effect of PD with asthma control levels on productivity loss (p=0.22). In patients without PD, uncontrolled asthma was associated with a higher productivity loss than controlled asthma, but this was not the case in patients with PD. This finding can be explained by the fact that the contribution of PD to productivity loss is so large that there is no room for synergy with asthma control. Future studies should assess the impact of interventions that modify PD in patients with asthma. Copyright ©ERS 2015.

Efficacy of 1% Metformin Gel in Patients With Moderate and Severe Chronic Periodontitis: A Randomized Controlled Clinical Trial.

PubMed

Pradeep, A R; Patnaik, Kaushik; Nagpal, Kanika; Karvekar, Shruti; Guruprasad, C N; Kumaraswamy, K M

2017-10-01

The aim of this study is to investigate efficacy of metformin (MF) 1% gel as an adjunct to scaling and root planing (SRP) in the treatment of moderate and severe chronic periodontitis (CP). Seventy patients were categorized into two treatment groups: 1) SRP plus 1% MF and 2) SRP plus placebo. Clinical parameters were recorded at baseline and 3, 6, and 9 months. They included plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). Radiologic assessment of intrabony defects (IBDs) and percentage defect depth reduction (DDR%) was done at baseline and 6- and 9-month intervals using computer-aided software. PD, CAL, and DDR% were evaluated in two subgroups in both the placebo and MF group: 1) initial PD of 5 to 7 mm and 2) initial PD of >7 mm. Mean PD reduction and mean CAL gain was found to be greater in the MF group than the placebo group at all visits. Clinical parameters (PD, CAL) in both subgroups, with initial PDs of 5 to 7 and >7 mm, showed significant improvement in the 1% MF group compared with the placebo group. A significantly greater mean DDR% was found in the MF group than the placebo group at 6 and 9 months in both subgroups, 5 to 7 and >7 mm of initial PD. There was a greater decrease in PD and more CAL gain with significant IBD depth reduction at sites treated with SRP plus locally delivered MF in patients with CP in both initial PD = 5 to 7 and >7 mm subgroups compared with placebo.

Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.

PubMed

Saâda-Bouzid, E; Defaucheux, C; Karabajakian, A; Coloma, V P; Servois, V; Paoletti, X; Even, C; Fayette, J; Guigay, J; Loirat, D; Peyrade, F; Alt, M; Gal, J; Le Tourneau, C

2017-07-01

Pembrolizumab and nivolumab are immune checkpoint inhibitors targeting PD-1 that have recently been approved in pretreated recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. In the clinic, some patients seem not only not to benefit from anti-PD-L1/PD-1 agents but rather to experience an acceleration of tumor growth kinetics (TGK). We retrospectively compared TGK on immunotherapy and TGK on last treatment in patients with R/M HNSCC treated with PD-1/PD-L1 inhibitors in four French centers. The TGK ratio (TGKR, ratio of the slope of tumor growth before treatment and the slope of tumor growth on treatment) was calculated. Hyperprogression was defined as a TGKR ≥ 2. From September 2012 to September 2015, 34 patients were identified. Patterns of recurrence included exclusive loco-regional recurrence in 14 patients, exclusive distant metastases in 11 patients, and both in 9 patients. No pseudo-progression was observed. Hyperprogression was observed in 10 patients (29%), including 9 patients with at least a locoregional recurrence, and only 1 patient with exclusively distant metastases. Hyperprogression significantly correlated with a regional recurrence (TGKR ≥ 2: 90% versus TGKR < 2: 37%, P = 0.008), but not with local or distant recurrence. Hyperprogression was associated with a shorter progression-free survival (PFS) according to RECIST (P = 0.003) and irRECIST (P = 0.02), but not with overall survival (P = 0.77). Hyperprogression was observed in 29% of patients with R/M HNSCC treated with anti-PD-L1/PD-1 agents and correlated with a shorter PFS. It occurred in 39% of patients with at least a locoregional recurrence and 9% of patients with exclusively distant metastases. No pseudo-progressions were reported. Mechanisms and causality of hyperprogression should further be assessed through prospective controlled studies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Refining diagnosis of Parkinson's disease with deep learning-based interpretation of dopamine transporter imaging.

PubMed

Choi, Hongyoon; Ha, Seunggyun; Im, Hyung Jun; Paek, Sun Ha; Lee, Dong Soo

2017-01-01

Dopaminergic degeneration is a pathologic hallmark of Parkinson's disease (PD), which can be assessed by dopamine transporter imaging such as FP-CIT SPECT. Until now, imaging has been routinely interpreted by human though it can show interobserver variability and result in inconsistent diagnosis. In this study, we developed a deep learning-based FP-CIT SPECT interpretation system to refine the imaging diagnosis of Parkinson's disease. This system trained by SPECT images of PD patients and normal controls shows high classification accuracy comparable with the experts' evaluation referring quantification results. Its high accuracy was validated in an independent cohort composed of patients with PD and nonparkinsonian tremor. In addition, we showed that some patients clinically diagnosed as PD who have scans without evidence of dopaminergic deficit (SWEDD), an atypical subgroup of PD, could be reclassified by our automated system. Our results suggested that the deep learning-based model could accurately interpret FP-CIT SPECT and overcome variability of human evaluation. It could help imaging diagnosis of patients with uncertain Parkinsonism and provide objective patient group classification, particularly for SWEDD, in further clinical studies.

Limbic grey matter changes in early Parkinson's disease.

PubMed

Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Personality and Parkinson's disease: A meta-analysis.

PubMed

Santangelo, Gabriella; Garramone, Federica; Baiano, Chiara; D'Iorio, Alfonsina; Piscopo, Fausta; Raimo, Simona; Vitale, Carmine

2018-04-01

Personality changes are considered pre-motor features of Parkinson's disease (PD). Cross-sectional studies revealed that PD patients were more introvert, apprehensive, and cautious than healthy subjects (HS), whereas other studies failed to disclose these behavioural traits. Some studies found mixed results concerning Novelty Seeking (NS) and Harm Avoidance (HA) profiles in PD patients. To better clarify the personality profile in PD we performed a meta-analysis on studies exploring such topic according to both Cloninger's Psychobiological Model (PM) and Big Five Model (BFM) METHODS: The meta-analysis included 17 studies evaluating the personality in PD patients compared with HS. The outcomes were the dimensions of the temperament and character of the PM and personality traits of BFM. Effect sizes from data reported in the primary studies were computed using Hedges'g unbiased approach. Heterogeneity among the studies and publication bias were assessed. Meta-regressions were conducted with age at evaluation, gender, schooling, and type of personality trait tools as moderators. As for PM, PD patients scored higher on HA and lower on NS than HS. No difference was found on Reward Dependence, Perseverance/Persistence and on character level. As for BFM, higher levels of Neuroticism, but lower levels of Openness and Extraversion were associated with PD. The personality profile in PD is characterized by high Neuroticism and HA, and by low Openness, Extraversion and NS. The personality profile delineated in the present study on PD patients seems to reflect the premorbid one and might contribute to development and persistence of affective disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Global differences in dialysis modality mix: the role of patient characteristics, macroeconomics and renal service indicators.

PubMed

van de Luijtgaarden, Moniek W M; Jager, Kitty J; Stel, Vianda S; Kramer, Anneke; Cusumano, Ana; Elliott, Robert F; Geue, Claudia; MacLeod, Alison M; Stengel, Benedicte; Covic, Adrian; Caskey, Fergus J

2013-05-01

An increase in the dialysis programme expenditure is expected in most countries given the continued rise in the number of people with end-stage renal disease (ESRD) globally. Since chronic peritoneal dialysis (PD) therapy is relatively less expensive compared with haemodialysis (HD) and because there is no survival difference between PD and HD, identifying factors associated with PD use is important. Incidence counts for the years 2003-05 were available from 36 countries worldwide. We studied associations of population characteristics, macroeconomic factors and renal service indicators with the percentage of patients on PD at Day 91 after starting dialysis. With linear regression models, we obtained relative risks (RRs) with 95% confidence intervals (CIs). The median percentage of incident patients on PD was 12% (interquartile range: 7-26%). Determinants independently associated with lower percentages of patients on PD were as follows: patients with diabetic kidney disease (per 5% increase) (RR 0.93; 95% CI 0.89-0.97), health expenditure as % gross domestic product (per 1% increase) (RR 0.93; 95% CI 0.87-0.98), private-for-profit share of HD facilities (per 1% increase) (RR 0.996; 95% CI 0.99-1.00; P = 0.04), costs of PD consumables relative to staffing (per 0.1 increase) (RR 0.97; 95% CI 0.95-0.99). The factors associated with a lower percentage of patients on PD include higher diabetes prevalence, higher healthcare expenditures, larger share of private-for-profit centres and higher costs of PD consumables relative to staffing. Whether dialysis modality mix can be influenced by changing healthcare organization and funding requires additional studies.

The impact of sub-clinical over-hydration on left ventricular mass in peritoneal dialysis patients.

PubMed

Hassan, Kamal; Hassan, Dunia; Shturman, Alexander; Rubinchik, Irina; Fadi, Hassan; Shadi, Hassan; Atar, Shaul

2015-01-01

Left ventricular hypertrophy (LVH) represents a major predictor of the development of cardiovascular (CV) complications. Over-hydration (OH) is an important uremic risk factor associated with LVH and increased CV morbidity and mortality in peritoneal dialysis (PD) patients. In the present study we evaluated the prevalence of sub-clinical OH (SCOH) among PD patients and its effects on left ventricular mass (LVM). In this cross sectional study hydration status, blood pressure, glucose load, systemic inflammation and LVM were evaluated in 43 clinically stable patients on maintenance PD for 24-76 months. The hydration status was assessed by whole-body bio-impedance spectroscopy (BIS). Peripheral edema and any evidence of pulmonary congestion were considered clinical signs of OH. OH ≥ 1.5 L was detected in 26 (60.5%) of the study participants; the OH in 19 (73.1%) of them was sub-clinical. Only 23.5% (4/17) of patients with OH < 1.5 L had LVH compared to 68.4% (13/19) of those with SCOH ≥ 1.5 L (P = 0.007). Compared to patients with OH < 1.5 L, patients with SCOH ≥ 1.5 L had higher levels of blood pressure, peritoneal glucose load, plasma brain natriuretic peptide, high sensitive C-reactive protein, interleukin-6 and LVMI; and lower levels of serum albumin (P < 0.001). No significant differences were found between patients with clinical OH or SCOH with OH ≥ 1.5 L. SCOH is highly prevalent among PD patients and may contribute to the development of LVH. Considering the poor prognosis associated with over-hydrated PD patients, periodic assessment of hydration status using accurate BIS is suggested.

Panic Disorder and Agoraphobia in OCD patients: clinical profile and possible treatment implications.

PubMed

Torres, Albina R; Ferrão, Ygor A; Shavitt, Roseli G; Diniz, Juliana B; Costa, Daniel L C; do Rosário, Maria Conceição; Miguel, Euripedes C; Fontenelle, Leonardo F

2014-04-01

Panic Disorder (PD) and agoraphobia (AG) are frequently comorbid with obsessive-compulsive disorder (OCD), but the correlates of these comorbidities in OCD are fairly unknown. The study aims were to: 1) estimate the prevalence of PD with or without AG (PD), AG without panic (AG) and PD and/or AG (PD/AG) in a large clinical sample of OCD patients and 2) compare the characteristics of individuals with and without these comorbid conditions. A cross-sectional study with 1001 patients of the Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders using several assessment instruments, including the Dimensional Yale-Brown Obsessive-Compulsive Scale and the Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Bivariate analyses were followed by logistic regression models. The lifetime prevalence of PD was 15.3% (N=153), of AG 4.9% (N=49), and of PD/AG 20.2% (N=202). After logistic regression, hypochondriasis and specific phobia were common correlates of the three study groups. PD comorbidity was also associated with higher levels of anxiety, having children, major depression, bipolar I, generalized anxiety and posttraumatic stress disorders. Other independent correlates of AG were: dysthymia, bipolar II disorder, social phobia, impulsive-compulsive internet use, bulimia nervosa and binge eating disorder. Patients with PD/AG were also more likely to be married and to present high anxiety, separation anxiety disorder, major depression, impulsive-compulsive internet use, generalized anxiety, posttraumatic stress and binge eating disorders. Some distinct correlates were obtained for PD and AG in OCD patients, indicating the need for more specific and tailored treatment strategies for individuals with each of these clinical profiles. Copyright © 2014 Elsevier Inc. All rights reserved.

Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes.

PubMed

Choukem, S P; Sobngwi, E; Garnier, J P; Letellier, S; Mauvais-Jarvis, F; Calvo, F; Gautier, J-F

2015-09-01

Previously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels. In the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40 min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables. The maximum plasma glucose level after 200 min of glucose perfusion was 20.9±3.7 mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=-0.085, P=0.38). Neither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Plasmodium falciparum clearance with artemisinin-based combination therapy (ACT) in patients with glucose-6-phosphate dehydrogenase deficiency in Mali.

PubMed

Kone, Abdoulaye K; Sagara, Issaka; Thera, Mahamadou A; Dicko, Alassane; Guindo, Aldiouma; Diakite, Seidina; Kurantsin-Mills, Joseph; Djimde, Abdoulaye; Walcourt, Asikiya; Doumbo, Ogabara

2010-11-21

Artemisinin-based combination therapy (ACT) is currently the most effective medicine for the treatment of uncomplicated malaria. Artemisinin has previously been shown to increase the clearance of Plasmodium falciparum in malaria patients with haemoglobin E trait, but it did not increase parasite inhibition in an in vitro study using haemoglobin AS erythrocytes. The current study describes the efficacy of artemisinin derivatives on P. falciparum clearance in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD), a haemoglobin enzyme deficiency, not yet studied in the same context, but nonetheless is a common in malaria endemic areas, associated with host protection against uncomplicated and severe malaria. The impact of G6PD deficiency on parasite clearance with ACT treatment was compared between G6PD-deficient patients and G6PD-normal group. Blood samples from children and adults participants (1 to 70 years old) with uncomplicated P. falciparum malaria residing in Kambila, Mali were analysed. Study participants were randomly assigned to receive either artemether-lumefantrine (Coartem®) or artesunate plus mefloquine (Artequin™). A restriction-fragment length polymorphism analysis of PCR-amplified DNA samples was used to identify the (A-) allele of the gene mutation responsible for G6PD deficiency (G6PD*A-). 470 blood samples were thus analysed and of these, DNA was extracted from 315 samples using the QIAamp kit for PCR to identify the G6PD*A- gene. The DNA amplified from 315 samples using PCR showed that G6PD*A- deficiency was present in 56 participants (17.8%). The distribution of the specific deficiency was 1%, 7% and, 9.8% respectively for homozygous, hemizygous, and heterozygous genotypes. Before treatment, the median parasitaemia and other baseline characteristics (mean haemoglobin, sex and age groups) between G6PD deficiency (hemizygous, heterozygous, and homozygous) and G6PD-normal participants were comparable (p > 0.05). After treatment, parasite clearance did not change significantly whether the participants were G6PD deficient or G6PD normal on day 1 (OR = 1.3; CI = 0.70-2.47; p > 0.05) and on day 2 (OR = 0.859; CI = 0.097-7.61; p > 0.05). The presence of G6PD deficiency does not appear to significantly influence the clearance of P. falciparum in the treatment of uncomplicated malaria using ACT.

[Clinical effect of different sequences of debridement-antibiotic therapy in treatment of severe chronic periodontitis].

PubMed

Li, Yi; Xu, Li; Lu, Rui-fang; An, Yue-bang; Wang, Xian-e; Song, Wen-li; Meng, Huan-xi

2015-02-18

To evaluate the feasibility of full-mouth debridement (subgingival scaling and root planning, SRP) by 2 times within 1 week and compare the clinical effects of different sequences of debridement-antibiotic usage in patients with severe chronic periodontitis (CP). A double-blinded, placebo-controlled, randomized clinical trial was conducted in 30 severe CP patients (14 males and 16 females, 40.5 ± 8.4 years old on average from 35 to 60) receiving 3 different sequences of debridement-antibiotictherapy: Group A, antibiotic usage (metronidazole, MTZ, 0.2 g, tid, 7 d; amoxicillin, AMX 0.5 g, tid, 7 d) was started together with SRP (completed by 2 times in 7 d); Group B, antibiotic usage (MTZ 0.2 g, tid, 7 d; AMX 0.5 g, tid, 7 d) was started 1 d after SRP(completed by 2 times in 7 d); Group C, SRP alone[probing depth (PD), bleeding index (BI) and tooth mobility] was examined. The average full-mouth probing depth, the average full-mouth proximal probing depth (pPD), the percentage of sites with PD>5 mm (PD>5 mm%), the percentage of sites with proximal PD>5 mm (pPD>5 mm%), the average bleeding index (BI) and the percentage of sites with bleeding on probing (BOP%) were calculated. Clinical examinations were performed at baseline and 2 months post therapy. (1) Compared with baseline conditions, all the subjects showed clinical improvements in all the parameters evaluated 2 months post therapy, P<0.05. (2) Significant difference were observed in the average PD changes between Group A [(2.15 ± 0.42) mm], Group B [(1.76 ± 0.29) mm] and Group C [(1.57 ± 0.33) mm], P<0.05. No significant difference was observed in the average PD changes between Group B and Group C, P=0.354. Significant differences were observed in the average pPD changes between Group A [(2.45 ± 0.43)mm] and Group C[(1.90 ± 0.48) mm], P<0.05. No significant difference was observed in BI and BOP% changes between Group A,Group B and Group C. For patients with severe chronic periodontitis, it is safe and feasible to receive full-mouth SRP by 2 times within 1 week. The short-term (2 months) advantages in PD changes are observed in patients receiving SRP and antibiotic usage at the same time comparing with patients using antibiotics after SRP or SRP alone.

Eradication of Helicobacter pylori Infection Improves Levodopa Action, Clinical Symptoms and Quality of Life in Patients with Parkinson's Disease

PubMed Central

Hashim, Hasriza; Azmin, Shahrul; Razlan, Hamizah; Yahya, Nafisah Wan; Tan, Hui Jan; Manaf, M. Rizal Abdul; Ibrahim, Norlinah Mohamed

2014-01-01

Background Previous studies have demonstrated a higher prevalence of Helicobacter pylori (H. pylori) infection in patients with Parkinson's disease (PD) compared to controls. H. pylori infection affects levodopa absorption and its eradication significantly improves clinical response to levodopa. Here, we studied the prevalence of H. pylori infection and its eradication effects among our PD patients. Methods A prospective study involving idiopathic PD patients on levodopa therapy. 13C-urea breath test (UBT) was used to detect H. pylori. UBT-positive patients were given standard eradication therapy and followed up at 6 and 12 weeks in an open label single arm design. Repeat UBT was performed at 12 weeks. The UPDRS, PD NMQ, PD NMSS and PDQ-39 were administered at baseline and post-eradication (6 and 12 weeks). Levodopa ‘onset’ time and ON-duration were recorded. Results Of 82 patients recruited, 27 (32.9%) had positive UBT. H. pylori-positive patients had significantly poorer total UPDRS (p = 0.005) and PDQ39 (p<0.0001) scores compared to H. pylori-negative patients. At 12 weeks post-eradication, the mean levodopa onset time shortened by 14 minutes (p = 0.011). The mean ON duration time increased by 56 minutes at week 6 (p = 0.041) and 38 minutes at week 12 (p = 0.035). The total UPDRS scores (p<0.0001), scores for parts II (p = 0.001), III (p<0.0001) and IV (p = 0.009) were significantly better. The total PDQ-39 scores (p = 0.001) and subdomains mobility (p = 0.002), ADL (p = 0.001), emotional well being (p = 0.026) and stigma (p = 0.034) significantly improved. The PD NMSQ did not show significant improvement. Conclusions H. pylori eradication improved levodopa onset time, ON duration, motor severity and quality of life parameters. Screening and eradication of H. pylori is inexpensive and should be recommended in PD patients, particularly those with erratic response to levodopa. Trial Registration ClinicalTrials.gov NCT02112812 PMID:25411976

The effects of living distantly from peritoneal dialysis units on peritonitis risk, microbiology, treatment and outcomes: a multi-centre registry study

PubMed Central

2012-01-01

Background The aim of the study was to determine whether distance between residence and peritoneal dialysis (PD) unit influenced peritonitis occurrence, microbiology, treatment and outcomes. Methods The study included all patients receiving PD between 1/10/2003 and 31/12/2008, using ANZDATA Registry data. Results 365 (6%) patients lived ≥100 km from their nearest PD unit (distant group), while 6183 (94%) lived <100 km (local group). Median time to first peritonitis in distant patients (1.34 years, 95% CI 1.07-1.61) was significantly shorter than in local patients (1.68 years, 95% CI 1.59-1.77, p = 0.001), whilst overall peritonitis rates were higher in distant patients (incidence rate ratio 1.32, 95% CI 1.20-1.46). Living ≥100 km away from a PD unit was independently associated with a higher risk of S. aureus peritonitis (adjusted odds ratio [OR] 1.64, 95% CI 1.09-2.47). Distant patients with first peritonitis episodes were less likely to be hospitalised (64% vs 73%, p = 0.008) and receive antifungal prophylaxis (4% vs 10%, p = 0.01), but more likely to receive vancomycin-based antibiotic regimens (52% vs 42%, p < 0.001). Using multivariable logistic regression analysis of peritonitis outcomes, distant patients were more likely to be cured with antibiotics alone (OR 1.55, 95% CI 1.03-2.24). All other outcomes were comparable between the two groups. Conclusions Living ≥100 km away from a PD unit was associated with increased risk of S. aureus peritonitis, modified approaches to peritonitis treatment and peritonitis outcomes that were comparable to, or better than patients living closer to a PD unit. Staphylococcal decolonisation should receive particular consideration in remote living patients. PMID:22702659

Prospective memory performance in individuals with Parkinson's disease who have mild cognitive impairment.

PubMed

Costa, Alberto; Peppe, Antonella; Zabberoni, Silvia; Serafini, Francesca; Barban, Francesco; Scalici, Francesco; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-09-01

Prospective memory (PM) is the ability to keep in memory and realize future intentions. We aimed at investigating whether in Parkinson's disease (PD) PM deficits are related to mild cognitive impairment (MCI). Other aims were to investigate the cognitive abilities underlying PM performance, and the association between PM performance and measures of daily living functioning. The study included 15 PD patients with single domain MCI, 15 with multiple domain MCI, 17 PD patients without cognitive disorders (PDNC) and 25 healthy controls (HCs). All subjects were administered a PM procedure that included focal (PM cue is processed in the ongoing task) and nonfocal (PM cue is not processed in the ongoing task) conditions. PD patients were administered an extensive neuropsychological battery and scales to assess daily living abilities. PD patients with MCI (both single and multiple domains) showed lower accuracy on all PM conditions than both HC and PDNC patients. This was predicted by their scores on shifting indices. Conversely, PM accuracy of PDNC patients was comparable to HCs. Regression analyses revealed that PD patients' PM performance significantly predicted scores on daily living scales Conclusions: Results suggest that PM efficiency is not tout-court reduced in PD patients, but it specifically depends on the presence of MCI. Moreover, decreased executive functioning, but not episodic memory failure, accounts for a significant proportion of variance in PM performance. Finally, PM accuracy indices were found to be associated with measures of global daily living functioning and management of medication. (c) 2015 APA, all rights reserved).

Production of verbs related to body movement in amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD).

PubMed

Cousins, Katheryn A Q; Ash, Sharon; Grossman, Murray

2018-03-01

Theories of grounded cognition propose that action verb knowledge relies in part on motor processing regions, including premotor cortex. Accordingly, impaired action verb knowledge in patients with amyotrophic lateral sclerosis (ALS) and Parkinson's Disease (PD) is thought to be due to motor system degeneration. Upper motor neuron disease in ALS degrades the motor cortex and related pyramidal motor system, while disease in PD is centered in the basal ganglia and can spread to frontostriatal areas that are important to language functioning. These anatomical distinctions in disease may yield subtle differences in the action verb impairment between patient groups. Here we compare verbs where the body is the agent of the action to verbs where the body is the theme. To examine the role of motor functioning in body verb production, we split patient groups into patients with high motor impairment (HMI) and those with low motor impairment (LMI), using disease-specific measures of motor impairment. Regression analyses assessed how verb production in ALS and PD was related to motor system atrophy. We find a dissociation between agent- and theme-body verbs in ALS: ALS HMI were impaired for agent body verbs but not theme verbs, compared to ALS LMI. This dissociation was not present in PD patients, who instead show depressed production for all body verbs. Although patients with cognitive impairment were excluded from this study, cognitive performance significantly correlated with the production of theme verbs in ALS and cognitive/stative verbs in PD. Finally, regression analyses related the agent-theme dissociation in ALS to grey matter atrophy of premotor cortex. These findings support the view that motor dysfunction and disease in premotor cortex contributes to the agent body verb deficit in ALS, and begin to identify some distinct characteristics of impairment for verbs in ALS and PD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Peri-operative epidural may not be the preferred form of analgesia in select patients undergoing pancreaticoduodenectomy.

PubMed

Axelrod, Trevor M; Mendez, Bernardino M; Abood, Gerard J; Sinacore, James M; Aranha, Gerard V; Shoup, Margo

2015-03-01

Epidural analgesia has become the preferred method of pain management for major abdominal surgery. However, the superior form of analgesia for pancreaticoduodenecomy (PD), with regard to non-analgesic outcomes, has been debated. In this study, we compare outcomes of epidural and intravenous analgesia for PD and identify pre-operative factors leading to early epidural discontinuation. A retrospective review was performed on 163 patients undergoing PD between 2007 and 2011. We performed regression analyses to measure the predictive success of two groups of analgesia on morbidity and mortality and to identify predictors of epidural failure. Intravenous analgesia alone was given to 14 (9%) patients and 149 patients (91%) received epidural analgesia alone or in conjunction with intravenous analgesia. Morbidity and mortality were not significantly different between the two groups. Early epidural discontinuation was necessary in 22 patients (15%). Those older than 72 and with a BMI < 20 (n = 5) had their epidural discontinued in 80% of cases compared to 12% not meeting these criteria. However, early epidural discontinuation was not associated with increased morbidity and mortality. Epidural analgesia may be contraindicated in elderly, underweight patients undergoing PD given their increased risk of epidural-induced hypotension or malfunction. © 2014 Wiley Periodicals, Inc.

Two-point discrimination and kinesthetic sense disorders in productive age individuals with carpal tunnel syndrome.

PubMed

Wolny, Tomasz; Saulicz, Edward; Linek, Paweł; Myśliwiec, Andrzej

2016-06-16

The aim of this study was to evaluate two-point discrimination (2PD) sense and kinesthetic sense dysfunctions in carpal tunnel syndrome (CTS) patients compared with a healthy group. The 2PD sense, muscle force, and kinesthetic differentiation (KD) of strength; the range of motion in radiocarpal articulation; and KD of motion were assessed. The 2PD sense assessment showed significantly higher values in all the examined fingers in the CTS group than in those in the healthy group (p<0.01). There was a significant difference in the percentage value of error in KD of pincer and cylindrical grip (p<0.01) as well as in KD of flexion and extension movement in the radiocarpal articulation (p<0.01) between the studied groups. There are significant differences in the 2PD sense and KD of strength and movement between CTS patients compared with healthy individuals.

Two-point discrimination and kinesthetic sense disorders in productive age individuals with carpal tunnel syndrome

PubMed Central

Wolny, Tomasz; Saulicz, Edward; Linek, Paweł; Myśliwiec, Andrzej

2016-01-01

Objectives: The aim of this study was to evaluate two-point discrimination (2PD) sense and kinesthetic sense dysfunctions in carpal tunnel syndrome (CTS) patients compared with a healthy group. Methods: The 2PD sense, muscle force, and kinesthetic differentiation (KD) of strength; the range of motion in radiocarpal articulation; and KD of motion were assessed. Results: The 2PD sense assessment showed significantly higher values in all the examined fingers in the CTS group than in those in the healthy group (p<0.01). There was a significant difference in the percentage value of error in KD of pincer and cylindrical grip (p<0.01) as well as in KD of flexion and extension movement in the radiocarpal articulation (p<0.01) between the studied groups. Conclusions: There are significant differences in the 2PD sense and KD of strength and movement between CTS patients compared with healthy individuals. PMID:27108640

Robotic pancreaticoduodenectomy.

PubMed

Sola, Richard; Kirks, Russell C; Iannitti, David A; Vrochides, Dionisios; Martinie, John B

2016-01-01

Pancreaticoduodenectomy (PD) is considered one of the most complex and technically challenging abdominal surgeries performed by general surgeons. With increasing use of minimally invasive surgery, this operation continues to be performed most commonly in an open fashion. Open PD (OPD) is characterized by high morbidity and mortality rates in published series. Since the early 2000s, use of robotics for PD has slowly evolved. For appropriately selected patients, robotic PD (RPD) has been shown to have less intraoperative blood loss, decreased morbidity and mortality, shorter hospital length of stay, and similar oncological outcomes compared with OPD. At our high-volume center, we have found lower complication rates for RPD along with no difference in total cost when compared with OPD. With demonstrated non-inferior oncologic outcomes for RPD, the potential exists that RPD may be the future standard in surgical management for pancreatic disease. We present a case of a patient with a pancreatic head mass and describe our institution's surgical technique for RPD.

Deep brain stimulation of the subthalamic nucleus modulates reward processing and action selection in Parkinson patients.

PubMed

Wagenbreth, Caroline; Zaehle, Tino; Galazky, Imke; Voges, Jürgen; Guitart-Masip, Marc; Heinze, Hans-Jochen; Düzel, Emrah

2015-06-01

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for motor impairments in Parkinson's disease (PD) but its effect on the motivational regulation of action control is still not fully understood. We investigated whether DBS of the STN influences the ability of PD patients to act for anticipated reward or loss, or whether DBS improves action execution independent of motivational valence. 16 PD patients (12 male, mean age = 58.5 ± 10.17 years) treated with bilateral STN-DBS and an age- and gender-matched group of healthy controls (HC) performed a go/no-go task whose contingencies explicitly decouple valence and action. Patients were tested with (ON) and without (OFF) active STN stimulation. For HC, there was a benefit in performing rewarded actions when compared to actions that avoided punishment. PD patients showed such a benefit reliably only when STN stimulation was ON. In fact, the relative behavioral benefit for go for reward over go to avoid losing was stronger in the PD patients under DBS ON than in HC. In PD patients, rather than generally improving motor functions independent of motivational valence, modulation of the STN by DBS improves action execution specifically when rewards are anticipated. Thus, STN-DBS establishes a reliable congruency between action and reward ("Pavlovian congruency") and remarkably enhances it over the level observed in HC.

Levodopa Reduces the Phase lag Index of Parkinson's Disease Patients: A Magnetoencephalographic Study.

PubMed

Cao, Chunyan; Li, Dianyou; Zeng, Ke; Zhan, Shikun; Huang, Peng; Li, Xiaoli; Sun, Bomin

2018-06-01

As a method of measuring the phase difference between 2 signals, the phase lag index (PLI) of the alpha and beta bands in patients with Parkinson's disease (PD) was investigated by using magnetoencephalography (MEG). Eighteen PD patients were measured by MEG in the state of overnight withdrawal of levodopa and after levodopa treatment; meanwhile, Unified Parkinson's Disease Rating Scale (UPDRS) III scale was evaluated. Compared with healthy controls, alpha (8-13 Hz) PLI in the frontal and parietal areas elevated in PD patients, while the elevation was reversed by the levodopa treatment. The alterations of the UPDRS III total scale ( r s = 0.552, P = .013, n = 16) and the changes of akinesia scale ( r s = 0.622, P = .005, n = 16) were correlated to the change of beta (13-30 Hz) PLI in the left parietal area. The change of the UPDRS total scale was negatively correlated to duration of disease ( r s = 0.432, P = .047, n = 16). There was a negative correlation between the age of PD patients and the change of alpha PLI in the left frontal area ( r s = 0.519, P = .020, n = 16). PD patients showed a higher mu PLI in the sensorimotor area relative to the healthy controls. The improvement of motor symptoms of PD patients by levodopa was correlated to the inhibition of beta PLI in the sensorimotor area.

Objective measurements of the penile angulation are significantly different than self-estimated magnitude among patients with penile curvature.

PubMed

Liguori, Giovanni; Salonia, Andrea; Garaffa, Giulio; Chiriacò, Giovanni; Pavan, Nicola; Cavallini, Giorgio; Trombetta, Carlo

2018-01-01

The study was aimed to assess the presence of actual differences between the objective and the perceived magnitude of a curvature between patients affected by Peyronie's disease (PD) and congenital penile curvature (CPC). Wee analysed a cohort of 88 consecutive patients seeking medical help for either CPC or PD. All patients were invited to provide a self-made drawing of their penis in erection in order to obtain self-provided description of the deformity. An objective measurement of the deformity was also performed drawing two intersecting lines through the center of the distal and proximal straight section of the penile shaft. Our findings showed significant differences between patient self-estimation and the objective measurements of the penile angulation performed by trained experts, with only 32% of patients correctly assessing their own curvature. Overall, patients tended to overestimate (56%) their degree of curvature, but the results are different in patients with PD than those with CPC. In the 60 men (68%) who did not accurately assess their curvature, PD patients generally overestimated their curvature versus CPC patients (67% vs 16%). On the contrary CPC patients underestimated their curvature compared to PD (42% vs. 4%). In order to improve patients' satisfaction rates, the surgeon needs to take into consideration the patient's perception of the deformity when planning the type of surgical correction. Copyright® by the International Brazilian Journal of Urology.

Premorbid dietetic habits and risk for Parkinson's disease.

PubMed

Ayuso-Peralta, L; Jiménez-Jiménez, F J; Cabrera-Valdivia, F; Molina, J; Javier, M R; Almazán; De Pedro-Cuesta, J; Tabernero, C; Giménez-Roldán, S

1997-01-01

To evaluate the possible role of antioxidant (vitamins A, E, C, beta-carotene, zinc, selenium) or pro-oxidant (iron, copper, manganese) factors present in the diet, in the risk for Parkinson's disease (PD), we conducted a dietetic study (pre- and postmarriage) which included 91 foodstuffs. We interviewed separately 119 PD patients (64 males, 55 females, age 65.3 +/- 8.5 years, age at marriage 27.8 +/- 5.9 years) and their spouses (age 65.0 +/- 9.2 years, age at marriage 27.2 +/- 5.9 years) as the control group (C). Premarriage consumption for each foodstuff was classified into: (1) rarely of annually, (2) monthly, or (3) weekly; and postmarriage consumption (which included the period between age at marruage and age 40 years; only concordant answers were considered to be valid) into: (1) PD > Control, (2) Control > PD, and (3) PD = Control. The premarriage interview showed a trend towards a lower consumption of peas in PD patients as compared to controls. The postmarriage interview in PD patients showed a higher tendency for the consumption of rice, bluefish, liver paté and eggs, and a less consumption of tea than controls. We were unable to find any consistent trend towards a lower consumption of vitamins E and C during adulthood in PD patients, but they seemed to have eaten selenium-rich foodstuffs more frequently than controls. These results differ from those obtained by previous studies, and question the possible role of premorbid dietary habits on the risk for PD.

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression

PubMed Central

Wechalekar, Mihir D.; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M.; Pitzalis, Costantino; Smith, Malcolm D.; Friedman, Joshua R.; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J.; Fearon, Ursula

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception. PMID:29489833

Immune checkpoint inhibitor PD-1 pathway is down-regulated in synovium at various stages of rheumatoid arthritis disease progression.

PubMed

Guo, Yanxia; Walsh, Alice M; Canavan, Mary; Wechalekar, Mihir D; Cole, Suzanne; Yin, Xuefeng; Scott, Brittney; Loza, Mathew; Orr, Carl; McGarry, Trudy; Bombardieri, Michele; Humby, Frances; Proudman, Susanna M; Pitzalis, Costantino; Smith, Malcolm D; Friedman, Joshua R; Anderson, Ian; Madakamutil, Loui; Veale, Douglas J; Fearon, Ursula; Nagpal, Sunil

2018-01-01

Immune checkpoint blockade with therapeutic anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 (Ipilimumab) and anti-programmed death (PD)-1 (Nivolumab and Pembrolizumab) antibodies alone or in combination has shown remarkable efficacy in multiple cancer types, concomitant with immune-related adverse events, including arthralgia and inflammatory arthritis (IA) in some patients. Herein, using Nivolumab (anti-PD-1 antagonist)-responsive genes along with transcriptomics of synovial tissue from multiple stages of rheumatoid arthritis (RA) disease progression, we have interrogated the activity status of PD-1 pathway during RA development. We demonstrate that the expression of PD-1 was increased in early and established RA synovial tissue compared to normal and OA synovium, whereas that of its ligands, programmed death ligand-1 (PD-L1) and PD-L2, was increased at all the stages of RA disease progression, namely arthralgia, IA/undifferentiated arthritis, early RA and established RA. Further, we show that RA patients expressed PD-1 on a majority of synovial tissue infiltrating CD4+ and CD8+ T cells. Moreover, enrichment of Nivolumab gene signature was observed in IA and RA, indicating that the PD-1 pathway was downregulated during RA disease progression. Furthermore, serum soluble (s) PD-1 levels were increased in autoantibody positive early RA patients. Interestingly, most of the early RA synovium tissue sections showed negative PD-L1 staining by immunohistochemistry. Therefore, downregulation in PD-1 inhibitory signaling in RA could be attributed to increased serum sPD-1 and decreased synovial tissue PD-L1 levels. Taken together, these data suggest that agonistic PD1 antibody-based therapeutics may show efficacy in RA treatment and interception.

Comparison of caregiver strain in Parkinson's disease between Yamagata, Japan, and Maryland, The United States.

PubMed

Tanji, Haruko; Koyama, Shingo; Wada, Manabu; Kawanami, Toru; Kurita, Keiji; Tamiya, Gen; Saito, Naohiro; Suzuki, Kyoko; Kato, Takeo; Anderson, Karen E; Gruber-Baldini, Ann L; Fishman, Paul S; Reich, Stephen G; Weiner, William J; Shulman, Lisa M

2013-06-01

Japan and the United States (US) have different cultures of caregiving including differences in family structure and social programs that may influence caregiver strain. Differences in caregiver strain between regions in Japan and in the US have not been investigated in patient-spouse dyads in PD. To compare caregiver strain in spouses of PD patients between Yamagata, Japan and Maryland, US. Correlations between caregiver strain and patient/spousal variables are also examined. In Yamagata and Maryland, spouses of patients with PD completed questionnaires assessing caregiver strain. Patients and spouses completed scales assessing mental health, and medical co-morbidity. PD severity and disability were assessed with the Unified Parkinson's Disease Rating Scale and the Schwab and England Activities of Daily Living Scale. Results in the two regions were compared with Chi-square and Student's t-tests. Relationships between caregiver strain and patient/spousal variables were analyzed with univariate correlations and multivariate regression. 178 Spouse-patient pairs were assessed. The level of caregiver strain in PD did not differ between Yamagata, Japan and Maryland, US despite differences in demographics and social support programs in the two regions. Yamagata spouses reported physical, time and financial constraints, while Maryland spouses reported more emotional distress. In both regions, spousal depression was a significant contributor to caregiver strain. Different approaches to reduce caregiver strain will likely be necessary in Yamagata and Maryland since the contributing factors to caregiver strain are influenced by differences in culture and social supports in each country. Copyright © 2013 Elsevier Ltd. All rights reserved.

Does Response to Induction Chemotherapy Predict Survival for Locally Advanced Non-Small-Cell Lung Cancer? Secondary Analysis of RTOG 8804/8808

DOE Office of Scientific and Technical Information (OSTI.GOV)

McAleer, Mary Frances, E-mail: mfmcalee@mdanderson.or; Moughan, Jennifer M.S.; Byhardt, Roger W.

2010-03-01

Purpose: Induction chemotherapy (ICT) improves survival compared with radiotherapy (RT) alone in locally advanced non-small-cell lung cancer (LANSCLC) patients with good prognostic factors. Concurrent chemoradiotherapy (CCRT) is superior to ICT followed by RT. The question arises whether ICT response predicts the outcome of patients subsequently treated with CCRT or RT. Methods and Materials: Between 1988 and 1992, 194 LANSCLC patients were treated prospectively with ICT (two cycles of vinblastine and cisplatin) and then CCRT (cisplatin plus 63 Gy for 7 weeks) in the Radiation Therapy Oncology Group 8804 trial (n = 30) or ICT and then RT (60 Gy/6 wk)more » on Radiation Therapy Oncology Group 8808 trial (n = 164). Of the 194 patients, 183 were evaluable and 141 had undergone a postinduction assessment. The overall survival (OS) of those with complete remission (CR) or partial remission (PR) was compared with that of patients with stable disease (SD) or progressive disease (PD) after ICT. Results: Of the 141 patients, 6, 30, 99, and 6 had CR, PR, SD, and PD, respectively. The log-rank test showed a significant difference (p <0.0001) in OS when the response groups were compared (CR/PR vs. SD/PD). On univariate and multivariate analyses, a trend was seen toward a response to ICT with OS (p = 0.097 and p = 0.06, respectively). A squamous histologic type was associated with worse OS on univariate and multivariate analyses (p = 0.031 and p = 0.018, respectively). SD/PD plus a squamous histologic type had a hazard ratio of 2.25 vs. CR/PR plus a nonsquamous histologic type (p = 0.007) on covariate analysis. Conclusion: The response to ICT was associated with a significant survival difference when the response groups were compared. A response to ICT showed a trend toward, but was not predictive of, improved OS in LANSCLC patients. Patients with SD/PD after ICT and a squamous histologic type had the poorest OS. These data suggest that patients with squamous LANSCLC might benefit from immediate RT or CCRT.« less

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

PubMed Central

Bouwmans, Angela E. P.; Leentjens, Albert F. G.; Mess, Werner H.; Weber, Wim E. J.

2016-01-01

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. PMID:26881179

Cognitive training in Parkinson disease: cognition-specific vs nonspecific computer training.

PubMed

Zimmermann, Ronan; Gschwandtner, Ute; Benz, Nina; Hatz, Florian; Schindler, Christian; Taub, Ethan; Fuhr, Peter

2014-04-08

In this study, we compared a cognition-specific computer-based cognitive training program with a motion-controlled computer sports game that is not cognition-specific for their ability to enhance cognitive performance in various cognitive domains in patients with Parkinson disease (PD). Patients with PD were trained with either a computer program designed to enhance cognition (CogniPlus, 19 patients) or a computer sports game with motion-capturing controllers (Nintendo Wii, 20 patients). The effect of training in 5 cognitive domains was measured by neuropsychological testing at baseline and after training. Group differences over all variables were assessed with multivariate analysis of variance, and group differences in single variables were assessed with 95% confidence intervals of mean difference. The groups were similar regarding age, sex, and educational level. Patients with PD who were trained with Wii for 4 weeks performed better in attention (95% confidence interval: -1.49 to -0.11) than patients trained with CogniPlus. In our study, patients with PD derived at least the same degree of cognitive benefit from non-cognition-specific training involving movement as from cognition-specific computerized training. For patients with PD, game consoles may be a less expensive and more entertaining alternative to computer programs specifically designed for cognitive training. This study provides Class III evidence that, in patients with PD, cognition-specific computer-based training is not superior to a motion-controlled computer game in improving cognitive performance.

Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy.

PubMed

Moonen, A; Busch, O; Costantini, M; Finotti, E; Tack, J; Salvador, R; Boeckxstaens, G; Zaninotto, G

2017-11-01

A recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present study was to perform an economic analysis of the European achalasia trial. Patients with newly diagnosed achalasia were enrolled from to 2003 to 2008 in 14 centers in five European countries and were randomly assigned to either pneumatic dilation (PD) or laparoscopic Heller (LHM). The economic analysis was performed in the three centers in three different countries where most patients were enrolled (Amsterdam [NL], Leuven, [B] and Padova [I]) and then applied to all patients included in the study. The total raw costs of the two treatments per patient include the initial costs, the costs of complications, and the costs of retreatments. Two hundred and one patients, 107 (57 males and 50 females, mean age 46 CI: 43-49 years) were randomized to LHM and 94 (59 males and 34 females, mean age 46 CI 43-50 years) to PD. The total cost of PD per patient was quite comparable in the three different centers; €3397 in Padova, €3259 in Amsterdam and €3792 in Leuven. For LHM, the total costs per patient were highest in Amsterdam: €4488 in Padova, €6720 in Amsterdam, and €5856 in Leuven. In conclusion, the strategy of treating achalasia starting with PD appears the most economic approach, independent of the health system. © 2017 John Wiley & Sons Ltd.

Perioperative antimicrobial therapy in preventing infectious complications following pancreatoduodenectomy

PubMed Central

Barreto, Savio George; Singh, Amanjeet; Perwaiz, Azhar; Singh, Tanveer; Singh, Manish Kumar; Sharma, Sunil; Chaudhary, Adarsh

2017-01-01

Background & objectives: Infectious complications have been reported to occur in up to 45 per cent of patients, following pancreatoduodenectomy (PD). The incidence of perioperative infectious and overall complications is higher in patients undergoing preoperative invasive endoscopic procedures. The aim of the study was to compare the role of a carbapenem administered as three-once daily perioperative doses on infectious complications in patients at high risk for these complications versus those at low risk. Methods: A retrospective study with some secondary data collected from records was carried out on the data from a prospectively maintained surgical database of patients undergoing PD for pancreatic and periampullary lesions at a tertiary referral care centre, between June 2011 and May 2013. Patients were divided into two groups for comparison based on whether they underwent at least one preoperative endoscopic interventional procedure before PD (high-risk - intervention and low-risk - no intervention). All patients were administered three-once daily doses of ertapenem (1 g). Results: A total of 135 patients in two groups were comparable in terms of demographic and nutritional, surgical and histopathological factors. No significant difference between the two groups in terms of the overall morbidity (38.7 vs 35.7%), infectious complications (9.7 vs 4.8%), mortality (2.2 vs 2.4%) and mean post-operative hospital stay (9.2 vs 8.9 days) was observed. Interpretation & conclusions: Perioperative three-day course of once-daily administered ertapenem resulted in a non-significant difference in infectious and overall complications in high-risk patients undergoing PD as compared to the low-risk group. PMID:29434066

Social functioning and socioeconomic changes after introduction of regular dialysis treatment and impact of dialysis modality: a multi-centre survey of Japanese patients.

PubMed

Nakayama, Masaaki; Ishida, Mari; Ogihara, Masahiko; Hanaoka, Kazushige; Tamura, Masahito; Kanai, Hidetoshi; Tonozuka, Yukio; Marshall, Mark R

2015-08-01

Patient socialization and preservation of socioeconomic status are important patient-centred outcomes for those who start dialysis, and retention of employment is a key enabler. This study examined the influence of dialysis inception and modality upon these outcomes in a contemporary Japanese cohort. We conducted a survey of prevalent chronic dialysis patients from 5 dialysis centres in Japan. All patients who had been on peritoneal dialysis (PD) since dialysis inception were recruited, and matched with a sample of those on in-centre haemodialysis (ICHD). We assessed patients' current social functioning (Short Form 36 Health Survey), and evaluated changes to patient employment status, annual income, and general health condition from the pre-dialysis period to the current time. A total of 179 patients were studied (102 PD and 77 ICHD). There were no differences in social functioning by modality. Among them, 113 were employed in the pre-dialysis period with no difference by modality. Of these, 22% became unemployed after dialysis inception, with a corresponding decline in average working hours and annual income. The odds of unemployment after dialysis inception were 5.02 fold higher in those on ICHD compared to those on PD, after adjustment for covariates. There were no changes for those who were already unemployed in the pre-dialysis period. Employment status is significantly hampered by dialysis inception, although PD was associated with superior retention of employment and greater income compared to ICHD. This supports a positive role for PD in preservation of socioeconomic status and potentially other patient-centred outcomes. © 2015 Asian Pacific Society of Nephrology.

Spontaneous Swallowing during All-Night Sleep in Patients with Parkinson Disease in Comparison with Healthy Control Subjects.

PubMed

Uludag, Irem Fatma; Tiftikcioglu, Bedile Irem; Ertekin, Cumhur

2016-04-01

Spontaneous saliva swallows (SS) appear especially during sleep. The rate of SS was rarely investigated in all-night sleep in patients with Parkinson disease (PD). Dysphagia is a frequent symptom in PD, but the rate of SS was never studied with an all-night sleep electroencephalogram (EEG). A total of 21 patients with PD and 18 age-matched healthy controls were included in the study. Frequencies of SS and coughing were studied in all-night sleep recordings of patients with PD and controls. During all-night sleep, video-EEG 12-channel recording was used including the electromyography (EMG) of the swallowing muscles, nasal airflow, and recording of vertical laryngeal movement using a pair of EEG electrodes over the thyroid cartilage. The total number of SS was increased while the mean duration of sleep was decreased in PD when compared to controls. Sialorrhea and clinical dysphagia, assessed by proper questionnaires, had no effect in any patient group. The new finding was the so-called salvo type of consecutive SS in one set of swallowing. The amount of coughing was significantly increased just after the salvo SS. In PD, the rate of SS was not sufficient to demonstrate the swallowing disorder, such as oropharyngeal dysphagia, but the salvo type of SS was quite frequent. This is a novel finding and may contribute to the understanding of swallowing problems in patients with dysphagic or nondysphagic PD. © 2016 Associated Professional Sleep Societies, LLC.

Surgical treatment of pain in patients with chronic pancreatitis.

PubMed

Prochorov, Alexandermiddle Victorovich; Oldhafer, Karl-Jurgen; Tretyak, Stanislaw Ivanovich; Rashchynski, Siarhei Markovich; Donati, Marcello; Rashchynskaya, Nina Timofeevna; Audzevich, Dzmitry Anatolyevich

2012-06-01

The objectives of the research were to compare the outcomes of pancreatoduodenectomy (PD) (Kausch-Whipple or Traverso-Longmire) and resection with drainage operations (RDO) (Frey or Partingtone-Rochelle) in patients suffering from chronic pancreatitis (CP), in management of pain syndrome and quality of life provided by these kinds of surgical procedures. From 2002 to 2008 sixteen patients suffering from CP underwent PD and 16 underwent RDO. Treatment results for the two groups were analyzed with respect to postoperative complications and results of the questionnaire MOS SF-36 v.2(TM). In the immediate postoperative period more complications were observed in the PD group (a<0.05). In both groups a positive effect on removing the painful syndrome and improvement of the quality of life (p<0.01) were observed. In the PD group there were the best results of management by General Health difference criterion (a<0.01). A greater improvement of Physical Functiong value (a<0.01) was noticed in patients who underwent RDO. Both PD and RDO adequately remove pain syndrome and improve the quality of life in patients suffering from CP. Under equal conditions the preference should be given to RDO, as improvement in life quality of operated patients is greater.

Sleep spindle alterations in patients with Parkinson's disease

PubMed Central

Christensen, Julie A. E.; Nikolic, Miki; Warby, Simon C.; Koch, Henriette; Zoetmulder, Marielle; Frandsen, Rune; Moghadam, Keivan K.; Sorensen, Helge B. D.; Mignot, Emmanuel; Jennum, Poul J.

2015-01-01

The aim of this study was to identify changes of sleep spindles (SS) in the EEG of patients with Parkinson's disease (PD). Five sleep experts manually identified SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched control subjects. Each SS was given a confidence score, and by using a group consensus rule, 901 SS were identified and characterized by their (1) duration, (2) oscillation frequency, (3) maximum peak-to-peak amplitude, (4) percent-to-peak amplitude, and (5) density. Between-group comparisons were made for all SS characteristics computed, and significant changes for PD patients vs. control subjects were found for duration, oscillation frequency, maximum peak-to-peak amplitude and density. Specifically, SS density was lower, duration was longer, oscillation frequency slower and maximum peak-to-peak amplitude higher in patients vs. controls. We also computed inter-expert reliability in SS scoring and found a significantly lower reliability in scoring definite SS in patients when compared to controls. How neurodegeneration in PD could influence SS characteristics is discussed. We also note that the SS morphological changes observed here may affect automatic detection of SS in patients with PD or other neurodegenerative disorders (NDDs). PMID:25983685

Lack of association between the LRRK2 A419V variant and Asian Parkinson's disease.

PubMed

Gopalai, Aroma Agape; Lim, Shen Yang; Aziz, Zariah Abdul; Lim, Soo Kun; Tan, Li Ping; Chong, Yip Boon; Tan, Chong Tin; Puvanarajah, Santhi; Viswanathan, Shanti; Kuppusamy, Rishikesan; Tan, Ai Huey; Lim, Thien Thien; Eow, Gaik Bee; Norlinah, Mohamed Ibrahim; Li, Hui Hua; Zhao, Yi; Ahmad-Annuar, Azlina

2013-05-01

The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects. Eight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine. The heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624). A419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.

PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy.

PubMed

Gevensleben, Heidrun; Holmes, Emily Eva; Goltz, Diane; Dietrich, Jörn; Sailer, Verena; Ellinger, Jörg; Dietrich, Dimo; Kristiansen, Glen

2016-11-29

The rapid development of programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has generated an urgent need for biomarkers assisting the selection of patients eligible for therapy. The use of PD-L1 immunohistochemistry, which has been suggested as a predictive biomarker, however, is confounded by multiple unresolved issues. The aim of this study therefore was to quantify PD-L1 DNA methylation (mPD-L1) in prostate tissue samples and to evaluate its potential as a biomarker in prostate cancer (PCa). In the training cohort, normal tissue showed significantly lower levels of mPD-L1 compared to tumor tissue. High mPD-L1 in PCa was associated with biochemical recurrence (BCR) in univariate Cox proportional hazards (hazard ratio (HR)=2.60 [95%CI: 1.50-4.51], p=0.001) and Kaplan-Meier analyses (p<0.001). These results were corroborated in an independent validation cohort in univariate Cox (HR=1.24 [95%CI: 1.08-1.43], p=0.002) and Kaplan-Meier analyses (p=0.029). Although mPD-L1 and PD-L1 protein expression did not correlate in the validation cohort, both parameters added significant prognostic information in bivariate Cox analysis (HR=1.22 [95%CI: 1.05-1.42], p=0.008 for mPD-L1 and HR=2.58 [95%CI: 1.43-4.63], p=0.002 for PD-L1 protein expression). mPD-L1 was analyzed in a training cohort from The Cancer Genome Atlas (n=498) and was subsequently measured in an independent validation cohort (n=299) by quantitative methylation-specific real-time PCR. All patients had undergone radical prostatectomy. mPD-L1 is a promising biomarker for the risk stratification of PCa patients and might offer additional relevant prognostic information to the implemented clinical parameters, particularly in the setting of immune checkpoint inhibition.

The Contribution of Proprioceptive Information to Postural Control in Elderly and Patients with Parkinson’s Disease with a History of Falls

PubMed Central

Bekkers, Esther M. J.; Dockx, Kim; Heremans, Elke; Vercruysse, Sarah; Verschueren, Sabine M. P.; Mirelman, Anat; Nieuwboer, Alice

2014-01-01

Proprioceptive deficits negatively affect postural control but their precise contribution to postural instability in Parkinson’s disease (PD) is unclear. We investigated if proprioceptive manipulations differentially affect balance, measured by force plates, during quiet standing in 13 PD patients and 13 age-matched controls with a history of falls. Perceived limits of stability (LoS) were derived from the differences between maximal center of pressure (CoP) displacement in anterior–posterior (AP) and medio-lateral (ML) direction during a maximal leaning task. Task conditions comprised standing with eyes open (EO) and eyes closed (EC): (1) on a stable surface; (2) an unstable surface; and (3) with Achilles tendon vibration. CoP displacements were calculated as a percentage of their respective LoS. Perceived LoS did not differ between groups. PD patients showed greater ML CoP displacement than elderly fallers (EF) across all conditions (p = 0.043) and tended to have higher postural sway in relation to the LoS (p = 0.050). Both groups performed worse on an unstable surface and during tendon vibration compared to standing on a stable surface with EO and even more so with EC. Both PD and EF had more AP sway in all conditions with EC compared to EO (p < 0.001) and showed increased CoP displacements when relying on proprioception only compared to standing with normal sensory input. This implies a similar role of the proprioceptive system in postural control in fallers with and without PD. PD fallers showed higher ML sway after sensory manipulations, as a result of which these values approached their perceived LoS more closely than in EF. We conclude that despite a similar fall history, PD patients showed more ML instability than EF, irrespective of sensory manipulation, but had a similar reliance on ankle proprioception. Hence, we recommend that rehabilitation and fall prevention for PD should focus on motor rather than on sensory aspects. PMID:25505395

Cardiac abnormalities in Parkinson's disease and Parkinsonism.

PubMed

Scorza, Fulvio A; Fiorini, Ana C; Scorza, Carla A; Finsterer, Josef

2018-07-01

Though there is increasing evidence for primary cardiac disease in Parkinson's disease (PD) and Parkinsonism (PS), this evidence is hardly included in the general management of these patients. Literature review. PD is one of the most common age-related neurodegenerative disorders. Epidemiological studies have shown that PD is accompanied by high rates of premature death compared with the general population. In general, death in PD/PS is usually caused by determinant factors such as pneumonia, cerebrovascular, and cardiovascular disease. There is a significant body of literature demonstrating involvement of the heart in PD/PS. Cardiac involvement in PD/PS includes cardiac autonomic dysfunction, cardiomyopathy, coronary heart disease, arrhythmias, conduction defects, and sudden cardiac death (SCD), and sudden unexpected death in Parkinson's disease (SUDPAR). Cardiac abnormalities found in PD/PS are manifold but the most prominent is cardiac autonomic dysfunction. The frequency of coronary heart disease in PD is a matter of debate. Only rarely reported in PD/PS are cardiomyopathies, arrhythmias, and sudden cardiac death, and SUDPAR. It is particularly recommended that PD/PS patients are more intensively investigated cardiologically as soon as the diagnosis is established. Early recognition of cardiac involvement is important for preventing SCD and SUDPAR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Musculoskeletal problems in Parkinson's disease: neglected issues.

PubMed

Kim, Young Eun; Lee, Woong-Woo; Yun, Ji Young; Yang, Hui June; Kim, Han-Joon; Jeon, Beom S

2013-07-01

To identify the prevalence and clinical features of musculoskeletal problems in patients with Parkinson disease (PD) compared to controls. 400 PD patients and 138 age- and sex-matched controls were interviewed by physicians about their musculoskeletal problems. The prevalence of musculoskeletal problems was significantly higher in the PD group than in the control group (66.3% vs. 45.7%, P < 0.001). Commonly involved body sites were the low back, knee, and shoulder in that order. The low back was more frequently involved in the PD group than in the control group (44.3% vs. 24.6%, P < 0.001), and the shoulder tended to be more involved in the PD group than in the control group (15.0% vs. 8.7%, P = 0.061). However, the knee was similarly involved in both group (12.3% vs. 18.0%, P = 0.121). Among the past diagnoses associated with musculoskeletal problems, frozen shoulder, low back pain, osteoporosis and fracture were more common in the PD group than in the control group (P < 0.05). Older age, female, and a higher score on the Unified Parkinson's Disease Rating Scale I & II were associated with musculoskeletal problems in the PD group. Only 26.8% of the PD patients and 52.5% of the controls with musculoskeletal problems answered that their musculoskeletal problems were recovering. Furthermore, musculoskeletal problems in the PD group tended to receive less treatment than that of the control group (P = 0.052). Musculoskeletal problems were more common in the PD group than in the controls. Furthermore, despite PD patients having a higher prevalence, they did not receive adequate treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Propositional Density in Spoken and Written Language of Czech-Speaking Patients with Mild Cognitive Impairment

ERIC Educational Resources Information Center

Smolík, Filip; Stepankova, Hana; Vyhnálek, Martin; Nikolai, Tomáš; Horáková, Karolína; Matejka, Štepán

2016-01-01

Purpose Propositional density (PD) is a measure of content richness in language production that declines in normal aging and more profoundly in dementia. The present study aimed to develop a PD scoring system for Czech and use it to compare PD in language productions of older people with amnestic mild cognitive impairment (aMCI) and control…

Early Parkinson's disease patients on rasagiline present with better odor discrimination.

PubMed

Haehner, Antje; Habersack, Angela; Wienecke, Miriam; Storch, Alexander; Reichmann, Heinz; Hummel, Thomas

2015-11-01

The effects of rasagiline on olfaction in animal studies are convincing. However, apart from various anecdotal patient reports, they could not be reproduced in prospective studies in humans. Cross-sectional data of large patient groups are still missing. The aim of this study was therefore to determine the olfactory function in a broad heterogeneous Parkinson's disease (PD) population with and without rasagiline intake. In this single-center, cross-sectional study 224 PD patients with and without rasagiline (1 mg/day) participated. Seventy-four of them received rasagiline as mono, or adjunct therapy. One-hundred fifty patients were untreated or received PD medication other than rasagiline. Comprehensive olfactory testing was performed for phenyl-ethyl alcohol odor thresholds, odor discrimination, and odor identification. Olfactory function did not differ between the two treatment groups with disease duration up to 29 years. Rasagiline-treated patients with disease duration of less than 8 years, however, presented with significant better odor discrimination abilities compared to PD patients without rasagiline treatment. This effect was no longer evident in patients with longer disease duration and proofed to be independent of age, sex, and medication. Our results may suggest that rasagiline treatment has a positive effect on the processing of olfactory information in early PD.

Espresso Coffee for the Treatment of Somnolence in Parkinson’s Disease: Results of n-of-1 Trials

PubMed Central

Ferreira, Joaquim J.; Mestre, Tiago; Guedes, Leonor Correia; Coelho, Miguel; Rosa, Mário M.; Santos, Ana T.; Barra, Márcio; Sampaio, Cristina; Rascol, Olivier

2016-01-01

There is limited information available concerning the treatment of daytime somnolence associated with Parkinson’s disease (PD); the most frequently applied therapeutic strategies include decreasing the dose of dopamine agonists or adding potential wake-promoting agents. There is recent data from a placebo-controlled trial concluding on a non-significant trend in favor of caffeine. We aimed to evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD. To evaluate the efficacy of espresso-coffee in the treatment of daytime somnolence in PD, we have conducted multiple single-patient (n-of-1) clinical trials comparing regular espresso coffee to decaffeinated coffee in PD patients presenting moderate to severe daytime somnolence defined as an Epworth Sleepiness Scale score >9. Each single-patient (n-of-1) trial included a sequence of three crossovers (two treatment periods separated by two days of washout). Four patients were included in the studies and three completed the three pairs of treatment periods. In two of the four patients, espresso coffee was considered beneficial. This study concludes that multiple single patient trials are feasible in PD and suggests that espresso-coffee may have a beneficial effect on daytime somnolence in some patients. These results cannot be generalized beyond the patients included in these trials. PMID:27014181

Glucose-6-phosphate dehydrogenase deficiency and risk of invasive fungal disease in patients with acute myeloid leukemia.

PubMed

Sanna, Marco; Caocci, Giovanni; Ledda, Antonio; Orrù, Federica; Fozza, Claudio; Deias, Paola; Tidore, Gianni; Dore, Fausto; La Nasa, Giorgio

2017-11-01

Invasive fungal diseases (IFD) are still a leading cause of morbidity and mortality in patients with acute myeloid leukemia (AML). Glucose-6-phosphate dehydrogenase is an enzyme that leads to the production of NADPH, required to destroy microorganisms in the respiratory burst reaction of white blood cells. We evaluated the role of G6PD deficiency in susceptibility of IFD in 108 AML patients undergoing intensive chemotherapy. In all, 28 patients harbored G6PD deficiency (G6PD-), whereas 80 were normal (G6PD +). Incidence of IFD was significantly higher in G6PD- patients compared to G6PD + patients (35.7% vs. 5%, p = .0002, OR = 10, 95% CI = 2.96-37.5). Higher risk of mold infections (17.9% vs. 5%, p = .048, OR = 4.1, 95% CI = 1.0-16.6) and Candida sepsis (17.9% vs. 0%, p = .0009, OR = 37.68, 95% CI =2.0-707.1) was observed in G6PD - patients. The evaluation of G6PD activity may help to identify AML patients at higher risk of IFD, allowing to design more intensive surveillance and therapeutic strategies.

Parkinson's disease: diagnostic potential of high-resolution phase difference enhanced MR imaging at 3 T.

PubMed

Kakeda, Shingo; Korogi, Yukunori; Yoneda, Tetsuya; Watanabe, Keita; Moriya, Junji; Murakami, Yu; Sato, Toru; Hiai, Yasuhiro; Ohnari, Norihiro; Ide, Satoru; Okada, Kazumasa; Uozumi, Takenori; Tsuji, Sadatoshi; Hirai, Toshinori; Yamashita, Yasuyuki

2013-04-01

To determine whether it is possible to diagnose patients with Parkinson's disease (PD) on an individual basis using magnetic resonance imaging with phase difference enhanced imaging (PADRE). PADRE delineated the crural fibres as a layer of low signal intensity and the substantia nigra as a layer of medium signal intensity in a healthy volunteer, and showed a clear boundary between the crural fibres and the substantia nigra (BCS). Twenty-four PD patients and 24 control subjects were enrolled. Contrast ratios between the substantia nigra and occipital white matter were calculated, and two radiologists independently reviewed the PADRE findings regarding BCS obscuration. Mean contrast ratio in PD patients was significantly higher than in control subjects (0.56 vs 0.39, P < 0.01). The BCS on PADRE was obscured significantly more frequently in any subgroups with PD patients compared with control subjects (P < 0.01). The observation of BCS obscuration had a sensitivity, specificity and accuracy for the diagnosis of PD of 92 %, 88 % and 90 % for radiologist 1 and 83 %, 88 % and 85 % for radiologist 2, respectively. PADRE is able to identify PD in patients as a loss of delineation between the crural fibres and the substantia nigra on an individual basis.

Objectifying Facial Expressivity Assessment of Parkinson's Patients: Preliminary Study

PubMed Central

Patsis, Georgios; Jiang, Dongmei; Sahli, Hichem; Kerckhofs, Eric; Vandekerckhove, Marie

2014-01-01

Patients with Parkinson's disease (PD) can exhibit a reduction of spontaneous facial expression, designated as “facial masking,” a symptom in which facial muscles become rigid. To improve clinical assessment of facial expressivity of PD, this work attempts to quantify the dynamic facial expressivity (facial activity) of PD by automatically recognizing facial action units (AUs) and estimating their intensity. Spontaneous facial expressivity was assessed by comparing 7 PD patients with 8 control participants. To voluntarily produce spontaneous facial expressions that resemble those typically triggered by emotions, six emotions (amusement, sadness, anger, disgust, surprise, and fear) were elicited using movie clips. During the movie clips, physiological signals (facial electromyography (EMG) and electrocardiogram (ECG)) and frontal face video of the participants were recorded. The participants were asked to report on their emotional states throughout the experiment. We first examined the effectiveness of the emotion manipulation by evaluating the participant's self-reports. Disgust-induced emotions were significantly higher than the other emotions. Thus we focused on the analysis of the recorded data during watching disgust movie clips. The proposed facial expressivity assessment approach captured differences in facial expressivity between PD patients and controls. Also differences between PD patients with different progression of Parkinson's disease have been observed. PMID:25478003

Association of Serum Triglyceride Level and Gemfibrozil Consumption With Periodontal Status.

PubMed

Sayar, Ferena; Akhondi, Nasrin; Fallah, Soltanali; Moalemnia, Amir Abbas; Cheraghi, Azra

2017-05-01

Hyperlipidemia is a major risk factor for cardiovascular diseases. Considering the suggested association between periodontal and cardiovascular diseases, this study sought to assess the association, if any, between serum triglyceride (TG) levels and gemfibrozil consumption with periodontal parameters. This cross-sectional study was conducted on 90 participants, including 30 individuals with a normal lipid profile (group H), 30 patients with hypertriglyceridemia and not on medication (group N), and 30 patients with hypertriglyceridemia and taking gemfibrozil over a 3-month period (group M). Periodontal parameters including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index were measured at four sites of each tooth. Serum levels of total cholesterol (TC), TG, low-density lipoprotein, and high-density lipoprotein were measured. Mean values for PD and CAL in the two hypertriglyceridemic groups were significantly higher than those of the H group (P <0.001). After controlling for confounding variables, significant linear correlations were noted between PD and BOP, PD and TC, PD and TG, and CAL and TG in each group (P <0.01). Patients with hypertriglyceridemia had worse periodontal status than healthy controls. Patients with hypertriglyceridemia who were taking gemfibrozil did not show significant differences in CAL and PD compared with untreated patients with hypertriglyceridemia.

Medication burden in CKD-5D: impact of dialysis modality and setting.

PubMed

Parker, Kathrine; Nikam, Milind; Jayanti, Anuradha; Mitra, Sandip

2014-12-01

Medication adherence is thought to be around 50% in the general and dialysis population. Reducing the pill burden (PB) reduces regime complexity and can improve adherence. Increased adherence should lead to improvement in treatment outcomes and patient quality of life. There is currently little published data on PB in CKD-5D across dialysis modalities. This is a retrospective, single renal network study. All in-centre HD (MHD), peritoneal dialysis (PD) and home HD (HHD) patients were identified in the Greater Manchester East sector renal network. Information collected included age, sex, comorbidities, daily PB, dialysis vintage and adequacy. Data were retrieved from a customized renal database, clinic and discharge letters with cross validation from the general practitioner when needed. Two hundred and thirty-six prevalent dialysis patients were studied. HHD patients had a significantly lower PB (11 ± 7 pills/day) compared with PD and MHD (16 ± 7 pills/day). The HHD patients required fewer BP medications to meet the recommended target. HD setting was the only significant factor for reducing PB. For home therapies (HHD versus PD), weekly Kt/v and serum phosphate were significant factors influencing PB. When comparing all modalities, OR of PB ≥ 15/day for MHD versus HHD was 3.9 and PD versus HHD was 4.9. The influence of HHD is dominant above factors such as comorbidities or clinical variables in reducing PB for MHD. Higher clearances achieved by HHD could explain differences in PB with PD. This is the first comparative study of PB across all dialysis modalities and factors that influence it. The PB advantage in HHD may result in greater adherence and might contribute to the outcome benefit often seen with this modality. Higher clearances achieved by HHD could explain differences in PB with PD but the precise reasons for lower PB remain speculative and deserve further research in larger settings.

The role of the atrial electromechanical delay in predicting atrial fibrillation in beta-thalassemia major patients.

PubMed

Rago, Anna; Russo, Vincenzo; Papa, Andrea Antonio; Ciardiello, Carmine; Pannone, Bruno; Mayer, Maria Carolina; Cimmino, Giovanni; Nigro, Gerardo

2017-03-01

Paroxysmal atrial tachyarrhythmias frequently occur in beta-thalassemia major (β-TM) patients. The aim of the current study was to evaluate the atrial electromechanical delay (AEMD) in a large β-TM population with normal cardiac function and its relationship to atrial fibrillation (AF) onset. Eighty β-TM patients (44 men, 36 women), with a mean age of 36.2 ± 11.1 years, and 80 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of AF during a 5-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 6 months. Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead electrocardiogram (ECG). Compared to the healthy control group, the β-TM patients showed a statistically significant increase in inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD. Dividing the β-TM group into two subgroups (patients with or without AF), the inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD were significantly higher in the subgroup with AF compared to the subgroup without AF. There were significant good correlations of intra-left AEMD and inter-AEMD with PD. A cut-off value of 40.1 ms for intra-left AEMD had a sensitivity of 76.2% and a specificity of 97.5% in identifying β-TM patients with AF risk. A cut-off value of 44.8 ms for inter-AEMD had a sensitivity of 81.2% and a specificity of 98.7% in identifying this category of patients. Our results showed that the echocardiographic atrial electromechanical delay indices (intra-left and inter-AEMD) and the PD were significantly increased in β-TM subjects with normal cardiac function. PD and AEMD represent non-invasive, inexpensive, useful, and simple parameters to assess the AF risk in β-TM patients.

Polyneuropathy in levodopa-treated Parkinson's patients.

PubMed

Szadejko, Karol; Dziewiatowski, Krzysztof; Szabat, Krzysztof; Robowski, Piotr; Schinwelski, Michał; Sitek, Emilia; Sławek, Jarosław

2016-12-15

Recently published studies show that the prevalence of polyneuropathy (PNP) is higher in patients with Parkinson's disease (PD) than in age-matched controls. Its pathogenesis, however is a matter of controversy. The major hypothesis is the toxicity of high concentrations of homocysteine (Hcy) possibly related to levodopa (LD) therapy. The aim of the present study was to determine the prevalence of PNP, independent of other etiologies, and to determine the relationship to demographic and clinical factors in LD-treated Parkinson's patients. A total of 102 patients (51 patients with PD and 51 sex- and age-matched healthy controls) were enrolled in the study. The presence of any risk factors for PNP, ascertained from the history and laboratory tests, was an exclusion criterion. The Toronto Clinical Scoring System (TCSS) was used for clinical assessment of PNP. The objective assessment was based on electroneurography (ENG) studies in which motor nerves (peroneal and tibial nerves) as well as sensory nerves (sural and superficial peroneal nerves) were bilaterally examined. The severity of the disease was determined using the UPDRS scale (Unified Parkinson's Disease Rating Scale) and the Hoehn-Yahr (H-Y) scale. In the PD group, the clinical and neurophysiological indicators of PNP, manifested as a symmetrical and predominantly sensory axonal neuropathy, were more frequent then in the control group and observed in 43.1% vs. 13.7% and 15.7% vs. 2% of subjects respectively. The presence of PNP correlated with age and the severity of PD. Patients with PD and PNP had a higher level of Hcy as compared to PD patients without PNP, however the difference was not statistically significant. The frequency of PNP in PD patients is higher than in controls. The characteristics and discrepancy between the number of patients with clinical and ENG detected PNP may suggest the small fiber neuropathy (SFN) as the dominant form of neuropathy in PD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Progression Rate Associated Peripheral Blood Biomarkers of Parkinson's Disease.

PubMed

Fan, Yanxia; Xiao, Shuping

2018-06-23

Parkinson disease (PD) is one of the most frequent neurodegenerative disorders. The aim of this study was to identify blood biomarkers capable to discriminate PD patients with different progression rates. Differentially expressed genes (DEGs) were acquired by comparing the expression profiles of PD patients with rapid and slow progression rates, using an expression dataset from Gene Expression Omnibus (GEO) under accession code of GSE80599. Altered biological processes and pathways were revealed by functional annotation. Potential biomarkers of PD were identified by protein-protein interaction (PPI) network analysis. Critical transcription factors (TFs) and miRNAs regulating DEGs were predicted by TF analysis and miRNA analysis. A total of 225 DEGs were identified between PD patients with rapid and slow progression profiles. These genes were significantly enriched in biological processes and pathways related to fatty acid metabolism. Among these DEGs, ZFAND4, SRMS, UBL4B, PVALB, DIRAS1, PDP2, LRCH1, and MYL4 were potential progression rate associated biomarkers of PD. Additionally, these DEGs may be regulated by miRNAs of the miR-30 family and TFs STAT1 and GRHL3. Our results may contribute to our understanding of the molecular mechanisms underlying different PD progression profiles.

Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer.

PubMed

Chatterjee, Jayanta; Dai, Wei; Aziz, Nor Haslinda Abd; Teo, Pei Yun; Wahba, John; Phelps, David L; Maine, Christian J; Whilding, Lynsey M; Dina, Roberto; Trevisan, Giorgia; Flower, Kirsty J; George, Andrew J T; Ghaem-Maghami, Sadaf

2017-07-01

Purpose: We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer. Experimental Design: Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses. Results: Biomarkers from the discovery cohort that associated with PD-L1 + cells were found. PD-L1 + CD14 + cells and PD-L1 + CD11c + cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)-confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1 + and PD-L1 + CD14 + cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1 + expression on lymphocytes was associated with improved survival. Conclusions: Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti-PD-1/PD-L1 therapy in ovarian cancer. Clin Cancer Res; 23(13); 3453-60. ©2016 AACR . ©2016 American Association for Cancer Research.

Physical Function and Physical Activity in Peritoneal Dialysis Patients.

PubMed

Painter, Patricia L; Agarwal, Adhish; Drummond, Micah

2017-01-01

Physical functioning (PF) and physical activity (PA) are low in patients treated with maintenance hemodialysis (MHD). Little information exists on this topic in patients treated with peritoneal dialysis (PD). The objective of this study was to compare PF and PA in patients with Stage-5 chronic kidney disease (CKD) treated with PD and in-center MHD. Physical functioning was measured in 45 prevalent PD patients using standard physical performance measures that include gait speed, chair stand, standing balance, 6-minute-walk, incremental shuttle walk and self-reported PF using the short form (SF)-36 questionnaire. Physical activity was determined from self-report and using the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire. Scores for the short physical performance battery (SPPB) were calculated. In-center MHD patients were matched by age, gender, and diabetes status to the PD patients. Unadjusted comparisons showed significantly higher 6-minute-walk distance, shuttle-walk distance and hand-grip in the PD patients. Adjustment in multiple regression analysis resulted in only gait speed being significantly different between the groups. All test results in both groups were lower than reference values for age and gender in the general population, and were at the levels indicating impairment. Physical activity was not different between the 2 groups (average age 49 yrs), and both groups had weekly caloric expenditure from all exercise and from moderate-intensity exercise that was similar to older (> 70 yrs) community-dwelling adults. Adjusted association indicated that PA was significantly associated with shuttle-walk distance. Physical functioning and PA measures were low in both PD and MHD groups. Interventions to improve PA and PF should be strongly considered for both PD and MHD patients. Copyright © 2017 International Society for Peritoneal Dialysis.

PD-L1 inhibitors in the pipeline: Promise and progress.

PubMed

Vanella, Vito; Festino, Lucia; Strudel, Martina; Simeone, Ester; Grimaldi, Antonio M; Ascierto, Paolo A

2017-01-01

Checkpoint inhibitors have improved survival for patients with melanoma, non-small-cell lung cancer (NSCLC), bladder, head and neck and other cancers. Antibodies against PD-L1, including atezolizumab, avelumab and durvalumab, are also being developed and have been approved for various cancers. Compared with anti-CTLA-4 drugs, studies with anti-PD-1/PD-L1 agents have suggested higher response rates and improved survival. Targeting PD-L1 rather than PD-1 may also theoretically offer further benefit, with the potential for improved efficacy and reduced toxicity, although this has not been clearly shown by clinical experience to date. Anti-PD-L1 agents have shown good efficacy and manageable toxicity in several tumor types.

Reexperiencing symptoms, dissociation, and avoidance behaviors in daily life of patients with PTSD and patients with panic disorder with agoraphobia.

PubMed

Pfaltz, Monique C; Michael, Tanja; Meyer, Andrea H; Wilhelm, Frank H

2013-08-01

Panic attacks are frequently perceived as life threatening. Panic disorder (PD) patients may therefore experience symptoms of posttraumatic stress disorder (PTSD). The authors explored this in 28 healthy controls, 17 PTSD patients, and 24 PD patients with agoraphobia who completed electronic diaries 36 times during 1 week. Patient groups frequently reported dissociation as well as thoughts, memories, and reliving of their trauma or panic attacks. PTSD patients reported more trauma/panic attack thoughts (incidence rate ratio [IRR] = 2.9) and memories (IRR = 2.8) than PD patients. Patient groups relived their trauma or panic attacks equally frequently, and reported comparable bodily reactions and distress associated with trauma or panic attack memories. Clinical groups avoided trauma or panic attack reminders more often than healthy controls (avoidance of trauma- or panic attack-related thoughts (IRR = 8.0); avoidance of things associated with the trauma or panic attack (IRR = 40.7). PD patients avoided trauma or panic attack reminders less often than PTSD patients (avoidance of trauma- or panic attack-related thoughts [IRR = 2.5]; avoidance of things associated with the trauma or panic attack [IRR = 4.1]), yet these differences were nonsignificant when controlling for functional impairment. In conclusion, trauma-like symptoms are common in PD with agoraphobia and panic attacks may be processed similarly as trauma in PTSD. Copyright © 2013 International Society for Traumatic Stress Studies.

Scanning laser polarimetry and spectral domain optical coherence tomography for the detection of retinal changes in Parkinson's disease.

PubMed

Stemplewitz, Birthe; Keserü, Matthias; Bittersohl, Diana; Buhmann, Carsten; Skevas, Christos; Richard, Gisbert; Hassenstein, Andrea

2015-12-01

Whether retinal degeneration is part of the degenerative processes in patients with Parkinson's disease (PD) is still unclear. This cross-sectional study was undertaken to compare the retinal morphology of patients with PD and healthy controls using spectral domain optical coherence tomography (SD-OCT) and scanning laser polarimetry (SLP). Both eyes of patients with PD (n = 108) and healthy controls (n = 165) were examined using SD-OCT and SLP on the same day. Data on the thickness of the retinal nerve fibre layer (RNFL) of all quadrants and the macular area were acquired by OCT (Cirrus, Zeiss). The SLP device (Glaucoma diagnostics (GDx), Zeiss) measured the RNFL and calculated the nerve fibre index (NFI). All patients and probands were checked for concomitant ocular disorders by an ophthalmologist. Visual acuity, intraocular pressure (IOP), objective refraction and the anterior and posterior segment were assessed. Patients with PD showed a reduced macular volume and a reduced central subfield thickness in OCT examinations. The RNFL in the different quadrants did not differ significantly from that of controls. SLP data showed a reduced average RNFL thickness, a decreased thickness of the inferior quadrant and an increase of the NFI in patients with PD. PD may be associated with reduced thickness and volume of the macula and a reduced thickness of the RNFL in the inferior quadrant of the retina. Investigations using SD-OCT and SLP revealed distinct but significant differences between patients with PD and healthy controls. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Taste responses in patients with Parkinson's disease

PubMed Central

Sienkiewicz-Jaros..., H; Scinska, A; Kuran, W; Ryglewicz, D; Rogowski, A; Wrobel, E; Korkosz, A; Kukwa, A; Kostowski, W; Bienkowski, P

2005-01-01

Objective: Preclinical studies indicate that dopaminergic transmission in the basal ganglia may be involved in processing of both pleasant and unpleasant stimuli. Given this, the aim of the present study was to assess taste responses to sweet, bitter, sour, and salty substances in patients with Parkinson's disease (PD). Methods: Rated intensity and pleasantness of filter paper discs soaked in sucrose (10–60%), quinine (0.025–0.5%), citric acid (0.25–4.0%), or sodium chloride (1.25–20%) solutions was evaluated in 30 patients with PD and in 33 healthy controls. Paper discs soaked in deionised water served as control stimuli. In addition, reactivity to 100 ml samples of chocolate and vanilla milk was assessed in both groups. Taste detection thresholds were assessed by means of electrogustometry. Sociodemographic and neuropsychiatric data, including cigarette smoking, alcohol consumption, tea and coffee drinking, depressive symptoms, and cognitive functioning were collected. Results: In general, perceived intensity, pleasantness, and identification of the sucrose, quinine, citric acid, or sodium chloride samples did not differ between the PD patients and controls. Intensity ratings of the filter papers soaked in 0.025% quinine were significantly higher in the PD patients compared with the control group. No inter-group differences were found in taste responses to chocolate and vanilla milk. Electrogustometric thresholds were significantly (p = 0.001) more sensitive in the PD patients. Conclusions: PD is not associated with any major alterations in responses to pleasant or unpleasant taste stimuli. Patients with PD may present enhanced taste acuity in terms of electrogustometric threshold. PMID:15607993

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients.

PubMed

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B Paul; Ito, Yasuhiko

2017-01-01

We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

The combination of anti-KIR monoclonal antibodies with anti-PD-1/PD-L1 monoclonal antibodies could be a critical breakthrough in overcoming tumor immune escape in NSCLC.

PubMed

He, Yayi; Liu, Sangtian; Mattei, Jane; Bunn, Paul A; Zhou, Caicun; Chan, Daniel

2018-01-01

The anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) monoclonal antibody has a good effect in the treatment of non-small cell lung cancer (NSCLC), but not all PD-1/PD-L1 positive patients can get benefit from it. Compensatory expression of other immune checkpoints may be correlated with the poor efficacy of anti-PD-1/PD-L1 monoclonal antibodies. The inhibitory human leukocyte antigen (HLA)/killer cell Ig-like receptor (KIR) can effectively block the killing effect of natural killer (NK) cells on tumors. Our previous studies have confirmed that high expression of KIR was correlated with poor prognosis of NSCLC. Inhibitory KIR expression was positively correlated with the expression of PD-1. The expressions of KIR 2D (L1, L3, L4, S4) (BC032422/ADQ31987/NP_002246/NP_036446, Abcam) and PD-1 (NAT 105, Cell marque) proteins was assessed by immunohistochemistry. The expression of inhibitory KIR in tumor cells or tumor infiltrating lymphocytes (TILs) is associated with PD-1 expression. Among PD-1 positive patients, 76.3% were KIR 2D (L1, L3, L4, S4) positive on tumor cells, and 74.6% were KIR 2D (L1, L3, L4, S4) positive on TILs. We compared the expression of inhibitory KIR before and after treatment with nivolumab in 11 patients with NSCLC. We found that five (45.5%) patients had positive expression of inhibitory KIR in tumor tissue after being treated with anti-PD-1 monoclonal antibodies, two of whom exhibited a significant increase in expression of inhibitory KIR, and three showed no change. PD-1 expression was correlated with KIR 2D (L1, L3, L4, S4) on tumor cells or TILs. The resistance to anti-PD-1 monoclonal antibody treatment might be related to KIR. The inhibitory HLA/KIR could combine with the PD-1/PD-L1 signaling pathway negatively regulating NSCLC tumor immunity.

Nutritional status, fecal elastase-1, and 13C-labeled mixed triglyceride breath test in the long-term after pancreaticoduodenectomy.

PubMed

Muniz, Cinara Knychala; dos Santos, José Sebastião; Pfrimer, Karina; Ferrioli, Eduardo; Kemp, Rafael; Marchini, Júlio Sérgio; Cunha, Selma Freire

2014-04-01

This study aimed to compare the body composition, dietary intake and serum levels of vitamins and minerals, and exocrine pancreatic function in patients late after pancreaticoduodenectomy (PD) and healthy subjects. Fifteen patients (PD group) who had undergone PD over 1 year before the study and 15 health volunteers (control group) were included in the study. All volunteers underwent dietary intake evaluation, body composition, laboratory data, exocrine pancreatic function by elastase-1, and carbon (C )-labeled triglycerides in breath tests. The PD group subjects also underwent upper gastrointestinal endoscopy and small intestinal bacterial overgrowth analysis. Nutrient intake was adequate, and there were no differences in body mass index and mineral serum levels between the groups. The PD group showed lower serum levels of retinol, α-tocopherol, and ascorbic acid. Small intestinal bacterial overgrowth occurred in 39% of the patients. Fecal elastase-1 was lower in the PD group. The PD group had a higher C peak time; the cumulative label C recovery in 7 hours was similar in both groups. Fecal elastase-1 decreased, and the excretion of C in breath was similar to healthy controls. Although the data point toward an adaptation in the absorptive capacity of fats, A, C, and E hypovitaminosis indicate that some absorptive insufficiency persists late after PD.

CALCIPROTEIN PARTICLE FORMATION IN PERITONEAL DIALYSIS EFFLUENT IS DEPENDENT ON DIALYSATE CALCIUM CONCENTRATION.

PubMed

Cai, Michael M; Smith, Edward R; Kent, Annette; Huang, Louis; Hewitson, Tim D; McMahon, Lawrence P; Holt, Stephen G

2018-05-23

The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo Method: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo , compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.

Long-term effects of transference interpretation in dynamic psychotherapy of personality disorders.

PubMed

Høglend, P; Dahl, H-S; Hersoug, A G; Lorentzen, S; Perry, J C

2011-10-01

Only a few treatment studies of personality disorders (PD) patients are on longer-term psychotherapy, general outcome measures are used, and follow-up periods are usually short. More studies of long-term therapies, using outcome measures of core psychopathology, are needed. This study is a dismantling randomized controlled clinical trial, specifically designed to study long-term effects of transference interpretation. Forty-six patients with mainly cluster C personality disorders were randomly assigned to 1 year of dynamic psychotherapy with or without transference interpretations. The outcome measures were remission from PD, improvement in interpersonal functioning, and use of mental health resources in the 3-year period after treatment termination. After therapy with transference interpretation PD-patients improved significantly more in core psychopathology and interpersonal functioning, the drop-out rate was reduced to zero, and use of health services was reduced to 50%, compared to therapy without this ingredient. Three years after treatment termination, 73% no longer met diagnostic criteria for any PD in the transference group, compared to 44% in the comparison group. PD-patients with co-morbid disorders improved in both treatment arms in this study. However, transference interpretation improved outcome substantially more. Long-term psychotherapy that includes transference interpretation is an effective treatment for cluster C personality disorders and milder cluster B personality disorders. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

[Sleep disorders associated with essential tremor and Parkinson's disease].

PubMed

Chen, Juping; Yao, Jianxin; Chen, Li; Miao, Hong; Mao, Chengjie; Liu, Chunfeng

2015-01-20

To evaluate the sleep quality and explore the manifestations of sleep disorders for 62 essential tremor (ET) patients, 60 normal controls and 62 Parkinson's disease (PD) patients. A total of 62 ET patients, 60 normal controls and 62 PD patients from June 2009 to December 2013 were recruited. All of them were outpatients at Second Affiliated Hospital, Soochow University and Hospital of Changshu Hospital of Traditional Chinese Medicine. Sleep was assessed with Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). The global PSQI score was 4.7 ± 2.5 in controls, 6.0 ± 4.0 in ET cases and 7.4 ± 3. 7 in PD cases. PD cases had the highest PSQI score, followed by ET (intermediate) and lowest scores in controls (F = 9.022, P = 0.000). A poor quality of sleep was observed in normal controls (23/62, 38.3%) compared to ET cases (34/62, 54.8%) and PD cases (40/62, 64.5%) (χ² = 8.555, P = 0.014 when comparing all three groups and χ² = 1.206, P = 0.272 when ET vs PD). The ESS score increased from normal controls (4.4 ± 2.5) to ET cases (6.3 ± 4.8) and PD cases (8.2 ± 4.2). An ESS score ≥ 10 (an indicator of greater than normal levels of daytime sleepiness) was observed in 6 (10.0%) normal controls, compared to ET cases (16, 25.8%) and PD cases (20, 32.3%) (χ² = 9.047, P = 0.011 when comparing all three groups and χ² = 0.626, P = 0.429 when ET vs PD). For normal controls, ET and PD patients, the factor scores of subjective sleep were 0.6 ± 0.7, 0.8 ± 0.8 and 1.1 ± 0.7; the factor scores of quality sleep latency 0.6 ± 0.7, 0.9 ± 0.9 and 1.1 ± 1.0; the factor scores of sleep duration 0.6 ± 0.8, 0.7 ± 1.0 and 1.0 ± 0.9; the factor scores of sleep efficiency 0.6 ± 0.8, 0.9 ± 0.9 and 1.0 ± 1.0; the factor scores of sleep disturbances 1.2 ± 0.6, 1.2 ± 0.5 and 1.7 ± 0.7; the factor scores of daytime dysfunction 1.2 ± 1.0, 1.3 ± 1.0 and 2.0 ± 1.1 respectively. There were inter-group statistical differences in subjective sleep (F = 7.709, P = 0.001), quality sleep latency (F = 4.414, P = 0.013), sleep duration (F = 4.464, P = 0.013), sleep efficiency (F = 3.201, P = 0.043), sleep disturbances (F = 12.594, P = 0.000) and daytime dysfunction (F = 9.022, P = 0.000) . However, no inter-group statistical differences existed in use of sleeping medication (F = 1.200, P = 0.304). There were statistical differences in subjective sleep (P < 0.05), sleep efficiency (P < 0.05) and daytime dysfunction (P < 0.05) between ET and PD patients. Some sleep scores in ET are intermediate between those of PD cases and normal controls. And it suggests that a mild form of sleep dysregulation may be present in ET.

Effect of mutant variants of the KRAS gene on PD-L1 expression and on the immune microenvironment and association with clinical outcome in lung adenocarcinoma patients.

PubMed

Falk, Alexander T; Yazbeck, Nathalie; Guibert, Nicolas; Chamorey, Emmanuel; Paquet, Agnès; Ribeyre, Lydia; Bence, Coraline; Zahaf, Katia; Leroy, Sylvie; Marquette, Charles-Hugo; Cohen, Charlotte; Mograbi, Baharia; Mazières, Julien; Hofman, Véronique; Brest, Patrick; Hofman, Paul; Ilié, Marius

2018-07-01

The effect of anti-PD-1/PD-L1 inhibitors on lung adenocarcinomas (LADCs) with KRAS mutations is debatable. We examined the association between specific mutant KRAS proteins and the immune infiltrates with the outcome of patients with LADCs. In 219 LADCs harboring either wild-type (WT) or mutated KRAS gene, we quantified the density of several immune markers by immunohistochemistry followed by automated digital image analysis. Data were correlated to clinicopathological parameters and outcome of patients. Tumors harboring mutant KRAS-G12 V had a significantly higher PD-L1 expression compared to other tumors (p = 0.044), while mutant KRAS-G12D tumors showed an increase in the density of CD66b+ cells (p = 0.001). High PD-L1 expression in tumor cells was associated to improved overall survival (OS) in KRAS mutant patients (p = 0.012), but not in the WT population (p = 0.385), whereas increased PD-L1 expression in immune cells correlated to poor OS of KRAS-WT patients (p = 0.025), with no difference in patients with KRAS mutations. KRAS mutational status can affect the immune microenvironment and survival of LADC patients in a heterogeneous way, implying that specific mutant KRAS variants expressed by the tumor should be considered when stratifying patients for immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Long-Term Outcomes of Single-Port Laparoscopic Placement of Peritoneal Dialysis Catheter.

PubMed

Pan, Alan; Poi, Mun J; Matos, Jesus; Jiang, Jenny S; Kfoury, Elias; Echeverria, Angela; Bechara, Carlos F; Lin, Peter H

2016-07-01

Laparoscopic insertion of peritoneal dialysis (PD) catheter has become a preferred method compared to the traditional open technique for PD catheter insertion. We retrospectively report the outcome of 1-port laparoscopic placement PD catheters in our institution. A total of 263 patients with end-stage renal disease who underwent single-trocar laparoscopic PD catheter insertion during a recent 6-year period were reviewed. Laparoscopic technique involves introducing a PD catheter over a stiff guidewire into the abdominal cavity through a 10-mm laparoscopic port. Pertinent clinical variables, procedural complications, and follow-up outcome were analyzed. There were 182 men and 81 women. The mean age was 56 years. Technical success was 95.8%. Catheter occlusion was the most common early complications (<6 months) that occurred in 4 (1.5%) patients. Late complications (> 6 months) including catheter occlusion, cuff extrusion, catheter leakage, catheter migration, infection, and hernia occurred in 5 patients (1.9%), 2 patients (0.8%), 3 patients (1.1%), 3 patients (1.1%), 6 patients (2.3%), and 4 patients (1.5), respectively. Mean follow-up time was 39 ± 18 months. Catheter survival rate at 1, 2, 3, 4, and 5 years was 96%, 94%, 90%, 85%, and 82%, respectively. Laparoscopic PD catheter implantation via a single-trocar utilizing a stiff guidewire technique is feasible and safe. This method can result in low complication and high catheter survival rate. © The Author(s) 2016.

Characterization of PD-1 upregulation on tumor-infiltrating lymphocytes in human and murine gliomas and preclinical therapeutic blockade.

PubMed

Dejaegher, Joost; Verschuere, Tina; Vercalsteren, Ellen; Boon, Louis; Cremer, Jonathan; Sciot, Raf; Van Gool, Stefaan W; De Vleeschouwer, Steven

2017-11-01

Blockade of the immune checkpoint molecule programmed-cell-death-protein-1 (PD-1) yielded promising results in several cancers. To understand the therapeutic potential in human gliomas, quantitative data describing the expression of PD-1 are essential. Moreover, due the immune-specialized region of the brain in which gliomas arise, differences between tumor-infiltrating and circulating lymphocytes should be acknowledged. In this study we have used flow cytometry to quantify PD-1 expression on tumor-infiltrating T cells of 25 freshly resected glioma cell suspensions (10 newly and 5 relapsed glioblastoma, 10 lower grade gliomas) and simultaneously isolated circulating T cells. A strong upregulation of PD-1 expression in the tumor microenvironment compared to the blood circulation was seen in all glioma patients. Additionally, circulating T cells were isolated from 15 age-matched healthy volunteers, but no differences in PD-1 expression were found compared to glioma patients. In the murine GL261 malignant glioma model, there was a similar upregulation of PD-1 on brain-infiltrating lymphocytes. Using a monoclonal PD-1 blocking antibody, we found a marked prolonged survival with 55% of mice reaching long-term survival. Analysis of brain-infiltrating cells 21 days after GL261 tumor implantation showed a shift in infiltrating lymphocyte subgroups with increased CD8+ T cells and decreased regulatory T cells. Together, our results suggest an important role of PD-1 in glioma-induced immune escape, and provide translational evidence for the use of PD-1 blocking antibodies in human malignant gliomas. © 2017 UICC.

Major Complications of Pneumatic Dilation and Heller Myotomy for Achalasia: Single Center Experience and Systematic Review of the Literature

PubMed Central

Lynch, Kristle L; Pandolfino, John E; Howden, Colin W; Kahrilas, Peter J

2013-01-01

Background & Aims Pneumatic dilation (PD) and laparoscopic Heller myotomy (LHM) can be definitive therapies for achalasia; recent data suggest comparable efficacy. However, risk must also be considered. We reviewed the major complication rate of PD and LHM in a high volume center and reviewed the corresponding literature. Methods We reviewed 12 years of our institution’s achalasia treatment experience. During this interval a consistent technique of PD was used utilizing Rigiflex dilators. Medical records were reviewed for post-procedure complications. We administered a telephone survey and examined medical records to assess efficacy of treatment. We also performed a systematic review of the literature for comparable clinical data and examined 80 reports encompassing 12,494 LHM and PD procedures. Results At our center, 463 achalasia patients underwent 567 PD or LHM procedures. 78% of the PDs used a 30 mm Rigiflex dilator. 157/184 (85%) patients underwent 1 or 2 PD without any subsequent treatment. There were seven clinically significant perforations; one from PD and 6 from LHM. There were no resultant deaths from these perforations; two deaths occurred within 30 days of LHM from unrelated causes. Complications and deaths post-PD were significantly fewer than those post-LHM (p=.02). Conclusions Esophageal perforation from PD at our high-volume center was less common than often reported and lower than that associated with LHM. We conclude that, in the hands of experienced operators using conservative technique, PD has fewer major complications and deaths than LHM. PMID:23032978

[PD1/PD-L1 immunohistochemistry in thoracic oncology: Where are we?

PubMed

Hofman, Paul; Ilié, Marius; Lassalle, Sandra; Long, Elodie; Bence, Coraline; Butori, Catherine; Hofman, Véronique

2017-02-01

The assays for the assessment of the PD-L1 status by immunohistochemistry are available in clinical studies in thoracic oncology to predict response to immunotherapies targeting the PD-1/PD-L1 pathway. With the arrival of this new class of molecules in second line and very soon in first line of treatment for patients with advanced or metastatic non-small cell lung cancer, these tests will certainly be required in routine once these new drugs will be granted marketing authorization. The rapid introduction of these "companion" or "complementary" tests seems essential to select patients to benefit from these effective but also expensive and sometimes toxic therapies. Although challenged by some oncologists (as some patients not expressing PD-L1 may sometimes respond to PD-1/PD-L1 blockade), the anti-PD-L1 immunohistochemically approach seems inevitable in 2017. This new activity developed in the pathology laboratories raises several questions: which anti-PD-L1 clone should be used? On which device? What threshold of positivity should be considered? Should PD-L1 expression be assessed on tumor cells as well as on the immune cells? What controls should be used? Comparative studies are underway or have been already implemented in order to answer some of these questions. This review addresses the different evaluation criteria for immunohistochemistry using the main anti-PD-L1 antibodies used to date as well the recently published studies using these antibodies in thoracic oncology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Increased PD-1+CD154+ Tfh cells are possibly the most important functional subset of PD-1+ T follicular helper cells in adult patients with minimal change disease.

PubMed

Li, Tao; Shi, Yunpeng; Sun, Weixia; Wang, Haifeng; Wang, Quan; Jiang, Yanfang

2018-02-01

T follicular helper (Tfh) cells, especially programmed cell death protein 1 (PD-1) + Tfh cells, exert important functions in the normal immune response. The purpose of this study was to determine the frequency of different subsets of PD-1 + Tfh cells and their functional effects in adult patients with minimal change disease (MCD). The frequencies of circulating PD-1 + , PD-1 + CD154 + , and PD-1 + interleukin (IL)-21 + Tfh cells, and CD38 + CD19 + and CD38 + CD19 + CD40 + B cells, as well as serum IL-2, IL-4, IL-17A, IL-6, IL-21, and interferon (IFN)-γ were significantly increased in the MCD patients compared with the healthy controls (HCs) (P < 0.05). However, no significant difference was found in PD-1 + BCL-6 + or PD-1 + ICOS + Tfh cells. Furthermore, the percentages of PD-1 + Tfh and PD-1 + CD154 + Tfh cells were negatively correlated with the estimated glomerular filtration rate (eGFR), but positively correlated with the 24-h urinary protein concentration and serum IL-21 level. The percentages of PD-1 + Tfh and PD-1 + CD154 + Tfh cells were positively correlated with the percentages of CD38 + plasma cells and active CD38 + CD40 + plasma cells, respectively. After an 8-12-week treatment with prednisolone, the percentages of PD-1 + , PD-1 + CD154 + , and PD-1 + IL-21 + Tfh cells as well as the serum level of IL-21 were significantly reduced; in contrast, the serum levels of IL-4 and IL-10 were increased (P < 0.05). We conclude that increased PD-1 + CD154 + Tfh cells are possibly the most important functional subset of PD-1 + Tfh cells and may contribute towards the pathogenesis of MCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fibromyalgia and psychiatric disorders.

PubMed

Fietta, Pierluigi; Fietta, Pieranna; Manganelli, Paolo

2007-08-01

Fibromyalgia (FM) is a common and polymorphic syndrome, characterized by long-lasting, widespread musculoskeletal pain, in the presence of 11 or more tender points located at specific anatomical sites. A heterogeneous series of disturbances, mainly involving autonomic, neuroendocrine and neuropsychic systems, is usually present. Even if subjective, the chronic psychophysical suffering state of FM adversely affects the patient's quality of life, performance and mood. Cognitive behavioural therapy and antidepressant drugs are useful in FM treatment, suggesting a close link between the syndrome and psychiatric, psychological and behavioural factors. Our aim was to evaluate the personality profiles of FM patients, as well as the aggregation and relationships between FM and psychiatric disorders (PD), reviewing the available evidences in current literature on this comorbidity. Personality variables associated with psychological vulnerability are frequent in FM patients. Personality disorders are rarely reported. Compared with controls, FM patients show a significantly higher prevalence of depressive and anxiety disorders, reported in 20-80% and 13-63.8% of cases, respectively. This high variability may depend on the psychosocial characteristics of patients, since most of the studies were performed on tertiary care consulting patients, however, even referring to the lower percentages, the occurrence of PD is significantly higher in FM subjects compared to the general population (7%). Moreover, elevated frequencies of PD have been detected in relatives of FM patients. The FM/PD aggregation suggests a common physiopathology, and alterations of neurotransmitter systems may constitute the shared underlying factor.

Reduced dopamine transporter binding predates impulse control disorders in Parkinson's disease.

PubMed

Vriend, Chris; Nordbeck, Anna H; Booij, Jan; van der Werf, Ysbrand D; Pattij, Tommy; Voorn, Pieter; Raijmakers, Pieter; Foncke, Elisabeth M J; van de Giessen, Elsmarieke; Berendse, Henk W; van den Heuvel, Odile A

2014-06-01

Impulse control disorders (ICD) are relatively common in Parkinson's disease (PD) and generally are regarded as adverse effects of dopamine replacement therapy, although certain demographic and clinical risk factors are also involved. Previous single-photon emission computed tomography (SPECT) studies showed reduced ventral striatal dopamine transporter binding in Parkinson patients with ICD compared with patients without. Nevertheless, these studies were performed in patients with preexisting impulse control impairments, which impedes clear-cut interpretation of these findings. We retrospectively procured follow-up data from 31 medication-naïve PD patients who underwent dopamine transporter SPECT imaging at baseline and were subsequently treated with dopamine replacement therapy. We used questionnaires and a telephone interview to assess medication status and ICD symptom development during the follow-up period (31.5 ± 12.0 months). Eleven patients developed ICD symptoms during the follow-up period, eight of which were taking dopamine agonists. The PD patients with ICD symptoms at follow-up had higher baseline depressive scores and lower baseline dopamine transporter availability in the right ventral striatum, anterior-dorsal striatum, and posterior putamen compared with PD patients without ICD symptoms. No baseline between-group differences in age and disease stage or duration were found. The ICD symptom severity correlated negatively with baseline dopamine transporter availability in the right ventral and anterior-dorsal striatum. The results of this preliminary study show that reduced striatal dopamine transporter availability predates the development of ICD symptoms after dopamine replacement therapy and may constitute a neurobiological risk factor related to a lower premorbid dopamine transporter availability or a more pronounced dopamine denervation in PD patients susceptible to ICD. © 2014 International Parkinson and Movement Disorder Society.

Quantifying daily physical activity and determinants in sedentary patients with Parkinson's disease.

PubMed

Dontje, M L; de Greef, M H G; Speelman, A D; van Nimwegen, M; Krijnen, W P; Stolk, R P; Kamsma, Y P T; Bloem, B R; Munneke, M; van der Schans, C P

2013-10-01

Although physical activity is beneficial for Parkinson's disease (PD) patients, many do not meet the recommended levels. The range of physical activity among sedentary PD patients is unknown, as are factors that determine this variability. Hence, we aimed to (1) assess daily physical activity in self-identified sedentary PD patients; (2) compare this with criteria of a daily physical activity guideline; and (3) identify determinants of daily physical activity. Daily physical activity of 586 self-identified sedentary PD patients was measured with a tri-axial accelerometer for seven consecutive days. Physical fitness and demographic, disease-specific, and psychological characteristics were assessed. Daily physical activity was compared with the 30-min activity guideline. A linear mixed-effects model was estimated to identify determinants of daily physical activity. Accelerometer data of 467 patients who fulfilled all criteria revealed that >98% of their day was spent on sedentary to light-intensity activities. Eighty-two percent of the participants were 'physically inactive' (0 days/week of 30-min activity); 17% were 'semi-active' (1-4 days/week of 30-min activity). Age, gender, physical fitness, and scores on the Unified Parkinson's Disease Rating Scale explained 69% of the variability in daily physical activity. Performance-based measurements confirmed that most self-identified sedentary PD patients are 'physically inactive'. However, the variance in daily physical activity across subjects was considerable. Higher age, being female, and lower physical capacity were the most important determinants of reduced daily physical activity. Future therapeutic interventions should aim to improve daily physical activity in these high-risk patients, focusing specifically on modifiable risk factors. Copyright © 2013 Elsevier Ltd. All rights reserved.

Is the Whipple procedure harmful for long-term outcome in treatment of chronic pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving pancreatoduodenectomy and Frey procedure in chronic pancreatitis.

PubMed

Bachmann, Kai; Tomkoetter, Lena; Kutup, Asad; Erbes, Johannes; Vashist, Yogesh; Mann, Oliver; Bockhorn, Maximilian; Izbicki, Jakob R

2013-11-01

The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P < 0.001) and pain score (P < 0.001). PD and Frey procedure provide good and permanent pain relief and improvement of the quality of life in long-term follow-up. In addition, a longer survival was found after the organ sparing resection. Together with better short-term results, the organ-sparing procedure seems to be favorable in treatment of chronic pancreatitis.

Sensitivity to reward and punishment in Parkinson's disease: an analysis of behavioral patterns using a modified version of the Iowa gambling task.

PubMed

Kobayakawa, Mutsutaka; Tsuruya, Natsuko; Kawamura, Mitsuru

2010-08-01

Studies using the Iowa gambling task (IGT) have shown that patients with Parkinson's disease (PD) make disadvantageous choices characterized by immediate large rewards and delayed larger punishments. These results can be interpreted in two ways: either PD patients are hypersensitive to immediate outcomes and/or insensitive to delayed consequences or PD patients are hypersensitive to rewards and/or insensitive to punishments. In this study, we used a modified IGT in which selection of cards from the disadvantageous decks leads to immediate, small punishments and delayed, smaller rewards and selection of cards from the advantageous decks leads to immediate, large punishments and delayed larger rewards. We then compared the results obtained using this modified IGT with those obtained using the original IGT. If the PD patients were hypersensitive to the immediate outcomes of decisions, they would make disadvantageous choices in both the original and the modified IGTs. Differences between the results of the original and modified tasks would indicate impairments in balancing reward and punishment. In our analysis, PD patients selected advantageous decks and gained as much as normal subjects during the modified IGT, but they selected disadvantageous decks during the original IGT. These results indicate that the decision-making difficulties of PD patients are caused by their inability to balance reward and punishment and their hypersensitivity to reward and/or insensitivity to punishment.

Time for a strategy in night-time dopaminergic therapy? An objective sensor-based analysis of nocturnal hypokinesia and sleeping positions in Parkinson's disease.

PubMed

Sringean, Jirada; Anan, Chanawat; Thanawattano, Chusak; Bhidayasiri, Roongroj

2017-02-15

Nocturnal hypokinesia is a common night-time symptom in patients with Parkinson's disease (PD). However, there is still little understanding of the nature, and variations of severity of this symptom. To evaluate the severity of nocturnal hypokinesia and sleep positions in PD patients using multisite wearable sensors. Nocturnal parameters and sleep positions in 18 PD couples were assessed and compared using wearable sensors (limbs and trunk) for one night in their homes. Nocturnal parameters included number, velocity, acceleration, degree, limb movements and the number of times they got out of bed. PD patients had significantly fewer episodes of turns in bed than their spouses (p=0.043), which was associated with significantly slower speed (p=0.005), acceleration (p=0.005) and fewer degrees (p=0.017). When we split the night into the first and second half, significant findings were mainly demonstrated in the second half of the night, including significantly fewer turns (p=0.02) with smaller degrees (p=0.017), slower speed (p=0.005) and acceleration (p=0.007). No significant differences in these parameters were shown in the first half of the night except for smaller degrees of turn in bed in PD patients (p=0.028) and slower acceleration (p=0.037). In addition, PD patients spent significantly more time in a supine position compared to their spouses (p=0.031) with significantly less time in a prone position (p=0.041). Nocturnal hypokinesia gets worse as the night progresses. Treatment of nocturnal hypokinesia should aim at providing a continuous dopaminergic delivery that can achieve a sustained therapeutic level of dopamine throughout the night. Copyright © 2016 Elsevier B.V. All rights reserved.

Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease.

PubMed

Zhao, Na; Xiao, Jianqiu; Zheng, Zhiyong; Fei, Guoqiang; Zhang, Feng; Jin, Lirong; Zhong, Chunjiu

2015-04-01

Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is correlated with Parkinson's disease (PD). However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene (both promoter and coding regions) were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms (SNPs). High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/iron metabolism. The frequencies of eight SNPs (one intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

Performance of the CareStart Glucose-6-Phosphate Dehydrogenase (G6PD) Rapid Diagnostic Test in Gressier, Haiti

PubMed Central

von Fricken, Michael E.; Weppelmann, Thomas A.; Eaton, Will T.; Masse, Roseline; Beau de Rochars, Madsen V. E.; Okech, Bernard A.

2014-01-01

Administering primaquine (PQ) to treat malaria patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency can pose a serious risk of drug-induced hemolysis (DIH). New easy to use point-of-care rapid diagnostic tests are being developed as an alternative to labor-intensive spectrophotometric methods, but they require field testing before they can be used at scale. This study screened 456 participants in Gressier, Haiti using the Access Bio CareStart qualitative G6PD rapid detection test compared with the laboratory-based Trinity Biotech quantitative spectrophotometric assay. Findings suggest that the CareStart test was 90% sensitive for detecting individuals with severe deficiency and 84.8% sensitive for detecting individuals with moderate and severe deficiency compared with the Trinity Biotech assay. A high negative predictive value of 98.2% indicates excellent performance in determining those patients able to take PQ safely. The CareStart G6PD test holds much value for screening malaria patients to determine eligibility for PQ therapy. PMID:24778197

Performance of the CareStart glucose-6-phosphate dehydrogenase (G6PD) rapid diagnostic test in Gressier, Haiti.

PubMed

von Fricken, Michael E; Weppelmann, Thomas A; Eaton, Will T; Masse, Roseline; Beau de Rochars, Madsen V E; Okech, Bernard A

2014-07-01

Administering primaquine (PQ) to treat malaria patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency can pose a serious risk of drug-induced hemolysis (DIH). New easy to use point-of-care rapid diagnostic tests are being developed as an alternative to labor-intensive spectrophotometric methods, but they require field testing before they can be used at scale. This study screened 456 participants in Gressier, Haiti using the Access Bio CareStart qualitative G6PD rapid detection test compared with the laboratory-based Trinity Biotech quantitative spectrophotometric assay. Findings suggest that the CareStart test was 90% sensitive for detecting individuals with severe deficiency and 84.8% sensitive for detecting individuals with moderate and severe deficiency compared with the Trinity Biotech assay. A high negative predictive value of 98.2% indicates excellent performance in determining those patients able to take PQ safely. The CareStart G6PD test holds much value for screening malaria patients to determine eligibility for PQ therapy. © The American Society of Tropical Medicine and Hygiene.

Dopamine agonists and delusional jealousy in Parkinson's disease: a cross-sectional prevalence study.

PubMed

Poletti, Michele; Perugi, Giulio; Logi, Chiara; Romano, Anna; Del Dotto, Paolo; Ceravolo, Roberto; Rossi, Giuseppe; Pepe, Pasquale; Dell'Osso, Liliana; Bonuccelli, Ubaldo

2012-11-01

Delusional jealousy (DJ) has been described in patients with Parkinson's disease (PD) on dopaminergic therapy, but a role for dopaminergic therapy in DJ has not been established. The current cross-sectional study on DJ investigated its association with dopaminergic therapies compared with their associations with hallucinations and its prevalence in PD patients. Eight hundred five consecutive patients with PD were enrolled between January 2009 and June 2010. DJ was identified in 20 patients (2.48%) and hallucinations in 193 patients (23.98%). In the multivariate logistic regression analyses, dopamine agonists were significantly associated with DJ (odds ratio, 18.1; 95% CI, 3.0-infinity; P = .0002) but not with hallucinations (odds ratio, 0.73; 95% CI, 0.49-1.10; P = .133). These findings suggest that dopamine agonist treatment represents a risk factor for DJ in PD independent of the presence of a dementing disorder, and the presence of this additional nonmotor side effect should be investigated in this clinical population. Copyright © 2012 Movement Disorder Society.

Quantitative Susceptibility Mapping of the Midbrain in Parkinson’s Disease

PubMed Central

Du, Guangwei; Liu, Tian; Lewis, Mechelle M.; Kong, Lan; Wang, Yi; Connor, James; Mailman, Richard B.; Huang, Xuemei

2017-01-01

Background Parkinson’s disease (PD) is marked pathologically by dopamine neuron loss and iron overload in the substantia nigra pars compacta. Midbrain iron content is reported to be increased in PD based on magnetic resonance imaging (MRI) R2* changes. Because quantitative susceptibility mapping is a novel MRI approach to measure iron content, we compared it with R2* for assessing midbrain changes in PD. Methods Quantitative susceptibility mapping and R2* maps were obtained from 47 PD patients and 47 healthy controls. Midbrain susceptibility and R2* values were analyzed by using both voxel-based and region-of-interest approaches in normalized space, and analyzed along with clinical data, including disease duration, Unified Parkinson’s Disease Rating Scale (UPDRS) I, II, and III sub-scores, and levodopa-equivalent daily dosage. All studies were done while PD patients were “on drug.” Results Compared with controls, PD patients showed significantly increased susceptibility values in both right (cluster size = 106 mm3) and left (164 mm3) midbrain, located ventrolateral to the red nucleus that corresponded to the substantia nigra pars compacta. Susceptibility values in this region were correlated significantly with disease duration, UPDRS II, and levodopa-equivalent daily dosage. Conversely, R2* was increased significantly only in a much smaller region (62 mm3) of the left lateral substantia nigra pars compacta and was not significantly correlated with clinical parameters. Conclusion The use of quantitative susceptibility mapping demonstrated marked nigral changes that correlated with clinical PD status more sensitively than R2*. These data suggest that quantitative susceptibility mapping may be a superior imaging biomarker to R2* for estimating brain iron levels in PD. PMID:26362242

P wave dispersion in patients with hypochondriasis.

PubMed

Atmaca, Murad; Korkmaz, Hasan; Korkmaz, Sevda

2010-11-26

P wave dispersion (Pd), defined as the difference between the maximum and the minimum P wave duration, has been associated with anxiety. Thus, we wondered whether Pd in hypochondriasis which is associated with anxiety differed from that in healthy controls. Pd was measured in 30 hypochondriac patients and same number of physically and mentally healthy age- and gender-matched controls. Hamilton Depression Rating (HDRS) and Hamilton Anxiety Rating Scales (HARS) were scored. The heart rate and left atrium (LA) sizes were not significantly different between groups. However, both Pmax and Pmin values of the patients were significantly higher than those of healthy controls. As for the main variable investigated in the present study, the corrected Pd was significantly longer in the patient group compared to control group. On the basis of this study, we can conclude that Pd may be related to hypochondriasis though our sample is too small to allow us to obtain a clear conclusion. Future studies with larger sample evaluating the effects of treatment are required. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PD-L1 expression and presence of TILs in small intestinal neuroendocrine tumours

PubMed Central

Lamarca, Angela; Nonaka, Daisuke; Breitwieser, Wolfgang; Ashton, Garry; Barriuso, Jorge; McNamara, Mairéad G.; Moghadam, Sharzad; Rogan, Jane; Mansoor, Wasat; Hubner, Richard A.; Clark, Christopher; Chakrabarty, Bipasha; Valle, Juan W.

2018-01-01

Background The extent of resistance to immune surveillance in patients with well-differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs) is unknown. Methods Patients diagnosed with Wd Si-NETs (excluding appendix, which are considered to have a different biology to other midgut NETs) were eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in archival tissue by immunohistochemistry (IHC); reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results. Results Of 109 patients screened, 62 were eligible: 54.8% were male; median age was 63.7 years (95%-CI 59.7-67.2); disease stage II: 4.8%, III: 40.3% and IV: 54.8%; 41.9% were functional. Analysed samples (67.1% from primary tumours, 32.9% from metastases) were of grade 1 (67.1%) or 2 (32.86%) with a median Ki-67 of 2%. From the total of 62 eligible patients, 70 and 63 samples were suitable for IHC and RT-qPCR analysis, respectively. PD-L1 expression within tumour cells and TILs were identified in 12.8% and 24.3% of samples respectively; 30% of samples showed PD-L1 expression within tumour cells and/or TILs. PD-1 was present in TILs in 22.8% of samples. Majority of samples showed significant presence of CD4+ (focal 42.86%; moderate 2.86%) and CD8+ (focal 92.86%; moderate 4.29%) TILs. IHC findings were confirmed with RT-qPCR; which showed higher expression levels of PD-L1 (p-value 0.007) and PD-1 (p-value 0.001) in samples positive for IHC compared to negative-IHC. Conclusions Thirty-percent of patients express PD-L1 within tumour cells and/or TILs. Identification of presence of TILs was also significant and warrant the investigation of immunotherapy in this setting. PMID:29599916

Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease.

PubMed

Videnovic, Aleksandar; Noble, Charleston; Reid, Kathryn J; Peng, Jie; Turek, Fred W; Marconi, Angelica; Rademaker, Alfred W; Simuni, Tanya; Zadikoff, Cindy; Zee, Phyllis C

2014-04-01

Diurnal fluctuations of motor and nonmotor symptoms and a high prevalence of sleep-wake disturbances in Parkinson disease (PD) suggest a role of the circadian system in the modulation of these symptoms. However, surprisingly little is known regarding circadian function in PD and whether circadian dysfunction is involved in the development of sleep-wake disturbances in PD. To determine the relationship between the timing and amplitude of the 24-hour melatonin rhythm, a marker of endogenous circadian rhythmicity, with self-reported sleep quality, the severity of daytime sleepiness, and disease metrics. A cross-sectional study from January 1, 2009, through December 31, 2012, of 20 patients with PD receiving stable dopaminergic therapy and 15 age-matched control participants. Both groups underwent blood sampling for the measurement of serum melatonin levels at 30-minute intervals for 24 hours under modified constant routine conditions at the Parkinson's Disease and Movement Disorders Center of Northwestern University. Twenty-four hour monitoring of serum melatonin secretion. Clinical and demographic data, self-reported measures of sleep quality (Pittsburgh Sleep Quality Index) and daytime sleepiness (Epworth Sleepiness Scale), and circadian markers of the melatonin rhythm, including the amplitude, area under the curve (AUC), and phase of the 24-hour rhythm. Patients with PD had blunted circadian rhythms of melatonin secretion compared with controls; the amplitude of the melatonin rhythm and the 24-hour AUC for circulating melatonin levels were significantly lower in PD patients (P < .001). Markers of the circadian phase were not significantly different between the 2 groups. Compared with PD patients without excessive daytime sleepiness, patients with excessive daytime sleepiness (Epworth Sleepiness Scale score ≥10) had a significantly lower amplitude of the melatonin rhythm and 24-hour melatonin AUC (P = .001). Disease duration, Unified Parkinson's Disease Rating Scale scores, levodopa equivalent dose, and global Pittsburgh Sleep Quality Index score in the PD group were not significantly related to measures of the melatonin circadian rhythm. Circadian dysfunction may underlie excessive sleepiness in PD. The nature of this association needs to be explored further in longitudinal studies. Approaches aimed to strengthen circadian function, such as timed exposure to bright light and exercise, might serve as complementary therapies for the nonmotor manifestations of PD.

White matter correlates of anxiety sensitivity in panic disorder.

PubMed

Kim, Min-Kyoung; Kim, Borah; Kiu Choi, Tai; Lee, Sang-Hyuk

2017-01-01

Anxiety sensitivity (AS) refers to a fear of anxiety-related sensations and is a dispositional variable especially elevated in patients with panic disorder (PD). Although several functional imaging studies of AS in patients with PD have suggested the presence of altered neural activity in paralimbic areas such as the insula, no study has investigated white matter (WM) alterations in patients with PD in relation to AS. The objective of this study was to investigate the WM correlates of AS in patients with PD. One-hundred and twelve right-handed patients with PD and 48 healthy control (HC) subjects were enrolled in this study. The Anxiety Sensitivity Inventory-Revised (ASI-R), the Panic Disorder Severity Scale (PDSS), the Albany Panic and Phobia Questionnaire (APPQ), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were administered. Tract-based spatial statistics were used for diffusion tensor magnetic resonance imaging analysis. Among the patients with PD, the ASI-R total scores were significantly correlated with the fractional anisotropy values of the WM regions near the insula, the splenium of the corpus callosum, the tapetum, the fornix/stria terminalis, the posterior limb of the internal capsule, the retrolenticular part of the internal capsule, the posterior thalamic radiation, the sagittal striatum, and the posterior corona radiata located in temporo-parieto-limbic regions and are involved in interoceptive processing (p<0.01; threshold-free cluster enhancement [TFCE]-corrected). These WM regions were also significantly correlated with the APPQ interoceptive avoidance subscale and BDI scores in patients with PD (p<0.01, TFCE-corrected). Correlation analysis among the HC subjects revealed no significant findings. There has been no comparative study on the structural neural correlates of AS in PD. The current study suggests that the WM correlates of AS in patients with PD may be associated with the insula and the adjacent temporo-parieto-limbic WM regions, which may play important roles in interoceptive processing in the brain and in depression in PD. Copyright © 2016 Elsevier B.V. All rights reserved.

Mutations in the glucocerebrosidase gene are common in patients with Parkinson's disease from Eastern Canada.

PubMed

Han, Fabin; Grimes, David A; Li, Fang; Wang, Ting; Yu, Zhe; Song, Na; Wu, Shichao; Racacho, Lemuel; Bulman, Dennis E

2016-01-01

Mutations in the β-glucocerebrosidase gene (GBA) have been implicated as a risk factor for Parkinson's disease (PD). However, GBA mutations in PD patients of different ethnic origins were reported to be inconsistent. We sequenced all exons of the GBA gene in 225 PD patients and 110 control individuals from Eastern Canada. Two novel GBA variants of c.-119 A/G and S(-35)N, five known GBA mutations of R120W, N370S, L444P, RecNciI and RecTL mutation (del55/D409H/RecNciI) as well as two non-pathological variants of E326K and T369M were identified from PD patients while only one mutation of S13L and two non-pathological variants of E326K and T369M were found in the control individuals. The frequency of GBA mutations within PD patients (4.4%) is 4.8 times higher than the 0.91% observed in control individuals (X(2) = 2.91, p = 0.088; odds ratio = 4.835; 95% confidence interval = 2.524-9.123). The most common mutations of N370S and L444P accounted for 36.0% (9/25) of all the GBA mutations in this Eastern Canadian PD cohort. The frequency (6.67%) of E326K and T369M in PD patients is comparable to 7.27% in control individuals (X(2) = 0.042, p = 0.8376), further supporting that these two variants have no pathological effects on PD. Phenotype analysis showed that no significant difference in family history, age at onset and cognitive impairment was identified between the GBA mutation carriers and non-GBA mutation carriers. GBA mutations were found to be a common genetic risk factor for PD in Eastern Canadian patients.

Hospital care for mental health and substance abuse conditions in Parkinson's disease.

PubMed

Willis, Allison W; Thibault, Dylan P; Schmidt, Peter N; Dorsey, E Ray; Weintraub, Daniel

2016-12-01

The objective of this study was to examine mental health conditions among hospitalized individuals with Parkinson's disease in the United States. This was a serial cross-sectional study of hospitalizations of individuals aged ≥60 identified in the Nationwide Inpatient Sample dataset from 2000 to 2010. We identified all hospitalizations with a diagnosis of PD, alcohol abuse, anxiety, bipolar disorder, depression, impulse control disorders, mania, psychosis, substance abuse, and attempted suicide/suicidal ideation. National estimates of each mental health condition were compared between hospitalized individuals with and without PD. Hierarchical logistic regression models determined which inpatient mental health diagnoses were associated with PD, adjusting for demographic, payer, geographic, and hospital characteristics. We identified 3,918,703 mental health and substance abuse hospitalizations. Of these, 2.8% (n = 104, 437) involved a person also diagnosed with PD. The majority of mental health and substance abuse patients were white (86.9% of PD vs 83.3% of non-PD). Women were more common than men in both groups (male:female prevalence ratio, PD: 0.78, 0.78-0.79, non-PD: 0.58, 0.57-0.58). Depression (adjusted odds ratio 1.32, 1.31-1.34), psychosis (adjusted odds ratio 1.25, 1.15-1.33), bipolar disorder (adjusted odds ratio 2.74, 2.69-2.79), impulse control disorders (adjusted odds ratio 1.51, 1.31-1.75), and mania (adjusted odds ratio 1.43, 1.18-1.74) were more likely among PD patients, alcohol abuse was less likely (adjusted odds ratio 0.26, 0.25-0.27). We found no PD-associated difference in suicide-related care. PD patients have unique patterns of acute care for mental health and substance abuse. Research is needed to guide PD treatment in individuals with pre-existing psychiatric illnesses, determine cross provider reliability of psychiatric diagnoses in PD patients, and inform efforts to improve psychiatric outcomes. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Dietary habits in Parkinson's disease: Adherence to Mediterranean diet.

PubMed

Cassani, Erica; Barichella, Michela; Ferri, Valentina; Pinelli, Giovanna; Iorio, Laura; Bolliri, Carlotta; Caronni, Serena; Faierman, Samanta A; Mottolese, Antonia; Pusani, Chiara; Monajemi, Fatemeh; Pasqua, Marianna; Lubisco, Alessandro; Cereda, Emanuele; Frazzitta, Giuseppe; Petroni, Maria L; Pezzoli, Gianni

2017-09-01

Our objective is to describe the dietary habits, food preferences and adherence to Mediterranean diet (MeDi) of a large sample of Italian Parkinson's Disease (PD) patients compared to a group of controls. Dietary habits of 600 PD patients from throughout Italy and 600 controls matched by gender, age, education, physical activity level and geographical residence, were collected using the ON-GP Food Frequency Questionnaire. Then, we compared patients by disease duration and the presence of swallowing disturbances. Overall, adherence of PD patients (males, 53.8%; mean disease duration, 9.2 ± 7.0 years) to MeDi was similar to controls (score, 4.8 ± 1.7 vs. 4.9 ± 1.6; P = 0.294). Patients consumed less alcohol and fish and drank significantly less water, coffee, and milk which resulted also in lower total fluids intake. On the contrary, they ate more fruit, cooked vegetables, cereals and baked items, more dressings and more sweets in general. Disease duration was associated with increased intake of several food groups but it was not associated with changes in MeDi score (P = 0.721). Patients with swallowing disturbances (n = 72) preferred softer and more viscous food but preferences did not result in differences in dietary pattern. However, patients with dysphagia drank less fluids (P = 0.043). PD patients presented different dietary habits and food preferences compared to the general population and adherence to MeDi was not associated with disease duration. Self-reported dysphagia was associated with reduced intake of fluids. These aspects may be amenable to change in order to improve the management of nutritional issues in this patient population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropsychological functions and rCBF SPECT in Parkinson's disease patients considered candidates for deep brain stimulation.

PubMed

Paschali, Anna; Messinis, Lambros; Lyros, Epameinondas; Constantoyannis, Costas; Kefalopoulou, Zinovia; Lakiotis, Velissarios; Papathanasopoulos, Panagiotis; Vassilakos, Paulos

2009-11-01

In the present study, we examined relationships between neuropsychological functions and brain single photon emission computed tomography (SPECT) regional cerebral blood flow (rCBF) observed at presurgical evaluation for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in advanced Parkinson's disease (PD) patients. Twenty advanced non-demented PD patients, candidates for DBS surgery, underwent perfusion brain SPECT study and neuropsychological assessment prior to surgery (range: 30-50 days). Patients were further assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale. During all assessments patients were "on" standard medication. NeuroGam software, which permits voxel by voxel analysis, was used to compare the brain perfusion of PD patients with a normal database adjusted for sex and age. Neuropsychological scores were compared to age, education and sex-adjusted normative databases. Our results indicated that the distribution of rCBF showed significant differences when compared to an age- and sex-adjusted normative database. We found impaired blood flow in 17 (85%) of our patients in the left prefrontal lobe, in 14 (70%) in the right prefrontal lobe and in 11 (55%) in the left frontal and right parietal lobes. Neuropsychological testing revealed that 18 (90%) of our patients had significant impairments in measures of executive functions (set-shifting) and 15 (75%) in response inhibition. Furthermore, we found significant correlations between measures of visual attention, executive functions and the right frontal lobe region. The presence of widespread blood flow reduction was observed mainly in the frontal lobes of dementia-free patients with advanced PD. Furthermore, performance on specific cognitive measures was highly related to perfusion brain SPECT findings.

A mobile cloud-based Parkinson's disease assessment system for home-based monitoring.

PubMed

Pan, Di; Dhall, Rohit; Lieberman, Abraham; Petitti, Diana B

2015-03-26

Parkinson's disease (PD) is the most prevalent movement disorder of the central nervous system, and affects more than 6.3 million people in the world. The characteristic motor features include tremor, bradykinesia, rigidity, and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients' motor performance but often leads to levodopa-induced adverse effects, such as dyskinesia and motor fluctuation. Clinicians must regularly monitor patients in order to identify these effects and other declines in motor function as soon as possible. Current clinical assessment for Parkinson's is subjective and mostly conducted by brief observations made during patient visits. Changes in patients' motor function between visits are hard to track and clinicians are not able to make the most informed decisions about the course of therapy without frequent visits. Frequent clinic visits increase the physical and economic burden on patients and their families. In this project, we sought to design, develop, and evaluate a prototype mobile cloud-based mHealth app, "PD Dr", which collects quantitative and objective information about PD and would enable home-based assessment and monitoring of major PD symptoms. We designed and developed a mobile app on the Android platform to collect PD-related motion data using the smartphone 3D accelerometer and to send the data to a cloud service for storage, data processing, and PD symptoms severity estimation. To evaluate this system, data from the system were collected from 40 patients with PD and compared with experts' rating on standardized rating scales. The evaluation showed that PD Dr could effectively capture important motion features that differentiate PD severity and identify critical symptoms. For hand resting tremor detection, the sensitivity was .77 and accuracy was .82. For gait difficulty detection, the sensitivity was .89 and accuracy was .81. In PD severity estimation, the captured motion features also demonstrated strong correlation with PD severity stage, hand resting tremor severity, and gait difficulty. The system is simple to use, user friendly, and economically affordable. The key contribution of this study was building a mobile PD assessment and monitoring system to extend current PD assessment based in the clinic setting to the home-based environment. The results of this study proved feasibility and a promising future for utilizing mobile technology in PD management.

Increase of Reproductive Life Span Delays Age of Onset of Parkinson’s Disease

PubMed Central

Frentzel, Dominik; Judanin, Grigorij; Borozdina, Olga; Klucken, Jochen; Winkler, Jürgen; Schlachetzki, Johannes C. M.

2017-01-01

One striking observation in Parkinson’s disease (PD) is the remarkable gender difference in incidence and prevalence of the disease. Data on gender differences with regard to disease onset, motor and non-motor symptoms, and dopaminergic medication are limited. Furthermore, whether estrogen status affects disease onset and progression of PD is controversially discussed. In this retrospective single center study, we extracted clinical data of 226 ambulatory PD patients and compared age of disease onset, disease stage, motor impairment, non-motor symptoms, and dopaminergic medication between genders. We applied a matched-pairs design to adjust for age and disease duration. To determine the effect of estrogen-related reproductive factors including number of children, age at menarche, and menopause on the age of onset, we applied a standardized questionnaire and performed a regression analysis. The male to female ratio in the present PD cohort was 1.9:1 (147 men vs. 79 women). Male patients showed increased motor impairment than female patients. The levodopa equivalent daily dose was increased by 18.9% in male patients compared to female patients. Matched-pairs analysis confirmed the increased dose of dopaminergic medication in male patients. No differences were observed in age of onset, type of medication, and non-motor symptoms between both groups. Female reproductive factors including number of children, age at menarche, and age at menopause were positively associated with a delay of disease onset up to 30 months. The disease-modifying role of estrogen-related outcome measures warrants further clinical and experimental studies targeting gender differences, specifically hormone-dependent pathways in PD. PMID:28871235

Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

PubMed

Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin

2015-04-01

In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

Clinical application of eye movement tasks as an aid to understanding Parkinson's disease pathophysiology.

PubMed

Fukushima, Kikuro; Fukushima, Junko; Barnes, Graham R

2017-05-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder of the basal ganglia. Most PD patients suffer from somatomotor and oculomotor disorders. The oculomotor system facilitates obtaining accurate information from the visual world. If a target moves slowly in the fronto-parallel plane, tracking eye movements occur that consist primarily of smooth-pursuit interspersed with corrective saccades. Efficient smooth-pursuit requires appropriate target selection and predictive compensation for inherent processing delays. Although pursuit impairment, e.g. as latency prolongation or low gain (eye velocity/target velocity), is well known in PD, normal aging alone results in such changes. In this article, we first briefly review some basic features of smooth-pursuit, then review recent results showing the specific nature of impaired pursuit in PD using a cue-dependent memory-based smooth-pursuit task. This task was initially used for monkeys to separate two major components of prediction (image-motion direction memory and movement preparation), and neural correlates were examined in major pursuit pathways. Most PD patients possessed normal cue-information memory but extra-retinal mechanisms for pursuit preparation and execution were dysfunctional. A minority of PD patients had abnormal cue-information memory or difficulty in understanding the task. Some PD patients with normal cue-information memory changed strategy to initiate smooth tracking. Strategy changes were also observed to compensate for impaired pursuit during whole body rotation while the target moved with the head. We discuss PD pathophysiology by comparing eye movement task results with neuropsychological and motor symptom evaluations of individual patients and further with monkey results, and suggest possible neural circuits for these functions/dysfunctions.

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

PubMed Central

Morelle, Johann; Sow, Amadou; Hautem, Nicolas; Bouzin, Caroline; Crott, Ralph

2015-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport. PMID:25636412

Gene Expression Differences in Peripheral Blood of Parkinson’s Disease Patients with Distinct Progression Profiles

PubMed Central

Soreq, Lilach; Lobo, Patrícia P.; Mestre, Tiago; Coelho, Miguel; Rosa, Mário M.; Gonçalves, Nilza; Wales, Pauline; Mendes, Tiago; Gerhardt, Ellen; Fahlbusch, Christiane; Bonifati, Vincenzo; Bonin, Michael; Miltenberger-Miltényi, Gabriel; Borovecki, Fran; Soreq, Hermona; Ferreira, Joaquim J.; F. Outeiro, Tiago

2016-01-01

The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson’s disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention. PMID:27322389

Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma

PubMed Central

Merryman, Reid W.; Kim, Haesook T.; Zinzani, Pier Luigi; Carlo-Stella, Carmelo; Ansell, Stephen M.; Perales, Miguel-Angel; Avigdor, Abraham; Halwani, Ahmad S.; Houot, Roch; Marchand, Tony; Dhedin, Nathalie; Lescaut, Willy; Thiebaut-Bertrand, Anne; François, Sylvie; Stamatoullas-Bastard, Aspasia; Rohrlich, Pierre-Simon; Labussière Wallet, Hélène; Castagna, Luca; Santoro, Armando; Bachanova, Veronika; Bresler, Scott C.; Srivastava, Amitabh; Kim, Harim; Pesek, Emily; Chammas, Marie; Reynolds, Carol; Ho, Vincent T.; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.

2017-01-01

Anti–programmed cell death protein 1 (PD-1) monoclonal antibodies are being increasingly tested in patients with advanced lymphoma. Following treatment, many of those patients are likely to be candidates for allogeneic hematopoietic stem cell transplant (HSCT). However, the safety and efficacy of HSCT may be affected by prior PD-1 blockade. We conducted an international retrospective analysis of 39 patients with lymphoma who received prior treatment with a PD-1 inhibitor, at a median time of 62 days (7-260) before HSCT. After a median follow-up of 12 months, the 1-year cumulative incidences of grade 2-4 and grade 3-4 acute graft-versus-host disease (GVHD) were 44% and 23%, respectively, whereas the 1-year incidence of chronic GVHD was 41%. There were 4 treatment-related deaths (1 from hepatic sinusoidal obstruction syndrome, 3 from early acute GVHD). In addition, 7 patients developed a noninfectious febrile syndrome shortly after transplant requiring prolonged courses of steroids. One-year overall and progression-free survival rates were 89% (95% confidence interval [CI], 74-96) and 76% (95% CI, 56-87), respectively. One-year cumulative incidences of relapse and nonrelapse mortality were 14% (95% CI, 4-29) and 11% (95% CI, 3-23), respectively. Circulating lymphocyte subsets were analyzed in 17 patients. Compared with controls, patients previously treated with PD-1 blockade had significantly decreased PD-1+ T cells and decreased ratios of T-regulatory cells to conventional CD4 and CD8 T cells. In conclusion, HSCT after PD-1 blockade appears feasible with a low rate of relapse. However, there may be an increased risk of early immune toxicity, which could reflect long-lasting immune alterations triggered by prior PD-1 blockade. PMID:28073785

Overexpression of G6PD is associated with high risks of recurrent metastasis and poor progression-free survival in primary breast carcinoma.

PubMed

Pu, Haihong; Zhang, Qingyuan; Zhao, Chunbo; Shi, Lei; Wang, Yan; Wang, Jingxuan; Zhang, Minghui

2015-11-25

The present study aimed to investigate the expression of CYP27A1, CYP7B1, insulin-like growth factor-1 (IGF-1), glucose-6-phosphate-dehydrogenase (G6PD), glutathione S-transferase P1 (GSTP1), and pyruvate kinase isoform M2 (PKM2) in breast carcinoma tissue and evaluate their prognostic value for progression-free survival (PFS) and overall survival (OS). A total of 20 patients treated with surgery for primary breast carcinoma were enrolled: 10 cases diagnosed with recurrent metastasis (A), along with their corresponding metastases specimen (AM) and 10 cases with no evidence of recurrence or metastasis (B). Baseline characteristics of patients including age, lymph node metastasis, molecular subtypes, tumor staging and size, and pathological classification were all collected. Immunohistochemistry was performed to detect the protein expression in tumor specimens. Elevated G6PD protein levels were noted in group A compared with group AM and B (both P < 0.05), and PKM2 expression was also higher in group A when compared to group AM (P = 0.019), but similar with group B (P > 0.05). No association between clinicopathological parameters and the two proteins expression was observed. The G6PD protein expression was strongly associated with PFS of breast carcinoma patients (P = 0.021) but not for OS. According to the Kaplan-Meier analysis, mean PFS time of patients with G6PD-negative and G6PD-positive expression tumor were 71.36 ± 6.53 and 32.25 ± 5.67 months, respectively (P = 0.002). The G6PD protein could be served as a potential prognostic biomarker for primary breast carcinoma, and overexpression of G6PD protein predicted a high risk of recurrent metastasis and poor PFS during follow-up.

Quality-of-life perception by Parkinson's disease patients and caregivers.

PubMed

Balash, Y; Korczyn, A D; Knaani, J; Migirov, A A; Gurevich, T

2017-08-01

The quality-of-life (QoL) perception by Parkinson's disease (PD) patients and their caregivers (CG) has not been studied in depth. To examine patient/proxy agreements on the PD QoL Questionnaire (PDQ-39), the Scale of Quality of Life of Care-Givers (SQLC) and the Multidimensional Caregiver Strain Index (MCSI). Patients with PD and their CG completed the above-mentioned questionnaires about themselves and each other. The intraclass correlations between their scores (paired t test) were compared. Twelve patient-CG pairs were studied. Agreements for QoL items were strong and comparable for the total scores of the PDQ-39, SQLC and MCSI questionnaires (75.4% ± 14%; 78.1% ± 14.1% and 78.2% ± 14.3%, respectively). Agreements ranged from moderate to strong (0.57-0.88, P≤.05) for the patients' physical condition (PDQ-39 items 3, 5, 6, 8, 12-15, 23, 24, 35), mental concentration (item 31) and depression (item 17). Disagreements were apparent in 20%-25% of the pairs and were particularly significant for PDQ-39 items #33 and #25 (embarrassment of patients in public and distressing dreams or hallucinations), in which the CG gave higher scores than the patients. Agreements between patients with PD and CG were generally good for most, but not all, of the PDQ-39, SQLC and MCSI domains. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer

PubMed Central

Lu, Biyan; Wang, Chenliang; Zhang, Junxiao; Huang, Lanlan; Wang, Xiaoyan; Timmons, Christine L.; Hu, Jun; Liu, Bindong; Wu, Xiaojian; Wang, Lei; Wang, Jianping; Liu, Huanliang

2013-01-01

Background Programmed death ligand-1 (PD-L1) has been identified as a factor associated with poor prognosis in a range of cancers, and was reported to be mainly induced by PTEN loss in gliomas. However, the clinical effect of PD-L1 and its regulation by PTEN has not yet been determined in colorectal cancer (CRC). In the present study, we verified the regulation of PTEN on PD-L1 and further determined the effect of PTEN on the correlation between PD-L1 expression and clinical parameters in CRC. Methods/Results RNA interference approach was used to down-regulate PTEN expression in SW480, SW620 and HCT116 cells. It was showed that PD-L1 protein, but not mRNA, was significantly increased in cells transfected with siRNA PTEN compared with the negative control. Moreover, the capacity of PTEN to regulate PD-L1 expression was not obviously affected by IFN-γ, the main inducer of PD-L1. Tissue microarray immunohistochemistry was used to detect PD-L1 and PTEN in 404 CRC patient samples. Overexpression of PD-L1 was significantly correlated with distant metastasis (P<0.001), TNM stage (P<0.01), metastatic progression (P<0.01) and PTEN expression (P<0.001). Univariate analysis revealed that patients with high PD-L1 expression had a poor overall survival (P<0.001). However, multivariate analysis did not support PD-L1 as an independent prognostic factor (P = 0.548). Univariate (P<0.001) and multivariate survival (P<0.001) analysis of 310 located CRC patients revealed that high level of PD-L1 expression was associated with increased risks of metastatic progression. Furthermore, the clinical effect of PD-L1 on CRC was not statistically significant in a subset of 39 patients with no PTEN expression (distant metastasis: P = 0.102; TNM stage: P = 0.634, overall survival: P = 0.482). Conclusions PD-L1 can be used to identify CRC patients with high risk of metastasis and poor prognosis. This clinical manifestation may be partly associated with PTEN expression. PMID:23785454

Asymmetries in reactive and anticipatory balance control are of similar magnitude in Parkinson's disease patients.

PubMed

Boonstra, Tjitske A; van Kordelaar, Joost; Engelhart, Denise; van Vugt, Jeroen P P; van der Kooij, Herman

2016-01-01

Many Parkinson's disease (PD) patients show asymmetries in balance control during quiet stance and in response to perturbations (i.e., reactive balance control) in the sagittal plane. In addition, PD patients show a reduced ability to anticipate to self-induced disturbances, but it is not clear whether these anticipatory responses can be asymmetric too. Furthermore, it is not known how reactive balance control and anticipatory balance control are related in PD patients. Therefore, we investigated whether reactive and anticipatory balance control are asymmetric to the same extent in PD patients. 14 PD patients and 10 controls participated. Reactive balance control (RBC) was investigated by applying external platform and force perturbations and relating the response of the left and right ankle torque to the body sway angle at the excited frequencies. Anticipatory postural adjustments (APAs) were investigated by determining the increase in the left and right ankle torque just before the subjects released a force exerted with the hands against a force sensor. The symmetry ratio between the contribution of the left and right ankle was used to express the asymmetry in reactive and anticipatory balance control; the correlation between the two ratio's was investigated with Spearman's rank correlation coefficients. PD patients were more asymmetric in anticipatory (p=0.026) and reactive balance control (p=0.004) compared to controls and the symmetry ratios were significantly related (ρ=0.74; p=0.003) in PD patients. These findings suggest that asymmetric reactive balance control during bipedal stance may share a common pathophysiology with asymmetries in the anticipation of voluntary perturbations during, for instance, gait initiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of physical exercise programs on cognitive function in Parkinson’s disease patients: A systematic review of randomized controlled trials of the last 10 years

PubMed Central

Iop, Rodrigo da Rosa; de Oliveira, Laiana Cândido; Boll, Alice Mathea; de Alvarenga, José Gustavo Souza; Gutierres Filho, Paulo José Barbosa; de Melo, Lídia Mara Aguiar Bezerra; Xavier, André Junqueira; da Silva, Rudney

2018-01-01

Background Given the relative importance of cognitive impairment, there was considerable interest in identifying the cognitive profile of PD patients, in order to ensure specific and appropriate therapeutic interventions. Purpose To determine the effects of physical exercise programs on cognitive function in PD patients, compared with the control group. Data sources Medline, Cochrane, Scopus, PEDro and Web of Science (last searched in September 2016). Study selection Randomized clinical trials examining the effects of physical exercise programs and cognitive function in PD patients. Nine studies fulfilled the selection criteria and were included in this review. Data extraction Characteristics of the publication, characteristics of the participants, test used for cognitive screening, cognitive domain assessed, tools used to assess cognitive function, characteristics of the experimental intervention, characteristics of the control group, mean results and standard deviation of function cognitive. The PEDro score was used to evaluate methodological quality. Data synthesis Most eligible studies showed good methodological quality based on the PEDro scale. Studies have shown that adapted tango for PD patients, cognitive training combined with motor training, and treadmill training promote the preservation or improvement of cognitive function in PD patients. Limitations The diversity of cognitive tests used to assess cognitive function and the high heterogeneity identified between the physical exercise programs. Conclusions Physical exercise programs promote positive and significant effects on global cognitive function, processing speed, sustained attention and mental flexibility in PD patients, at a mild to moderate stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3 times a week for about 60 minutes and for a period of 24 weeks produced larger improvements in cognition. PMID:29486000

Effects of physical exercise programs on cognitive function in Parkinson's disease patients: A systematic review of randomized controlled trials of the last 10 years.

PubMed

da Silva, Franciele Cascaes; Iop, Rodrigo da Rosa; de Oliveira, Laiana Cândido; Boll, Alice Mathea; de Alvarenga, José Gustavo Souza; Gutierres Filho, Paulo José Barbosa; de Melo, Lídia Mara Aguiar Bezerra; Xavier, André Junqueira; da Silva, Rudney

2018-01-01

Given the relative importance of cognitive impairment, there was considerable interest in identifying the cognitive profile of PD patients, in order to ensure specific and appropriate therapeutic interventions. To determine the effects of physical exercise programs on cognitive function in PD patients, compared with the control group. Medline, Cochrane, Scopus, PEDro and Web of Science (last searched in September 2016). Randomized clinical trials examining the effects of physical exercise programs and cognitive function in PD patients. Nine studies fulfilled the selection criteria and were included in this review. Characteristics of the publication, characteristics of the participants, test used for cognitive screening, cognitive domain assessed, tools used to assess cognitive function, characteristics of the experimental intervention, characteristics of the control group, mean results and standard deviation of function cognitive. The PEDro score was used to evaluate methodological quality. Most eligible studies showed good methodological quality based on the PEDro scale. Studies have shown that adapted tango for PD patients, cognitive training combined with motor training, and treadmill training promote the preservation or improvement of cognitive function in PD patients. The diversity of cognitive tests used to assess cognitive function and the high heterogeneity identified between the physical exercise programs. Physical exercise programs promote positive and significant effects on global cognitive function, processing speed, sustained attention and mental flexibility in PD patients, at a mild to moderate stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3 times a week for about 60 minutes and for a period of 24 weeks produced larger improvements in cognition.

l-DOPA and Freezing of Gait in Parkinson’s Disease: Objective Assessment through a Wearable Wireless System

PubMed Central

Suppa, Antonio; Kita, Ardian; Leodori, Giorgio; Zampogna, Alessandro; Nicolini, Ettore; Lorenzi, Paolo; Rao, Rosario; Irrera, Fernanda

2017-01-01

Freezing of gait (FOG) is a leading cause of falls and fractures in Parkinson’s disease (PD). The episodic and rather unpredictable occurrence of FOG, coupled with the variable response to l-DOPA of this gait disorder, makes the objective evaluation of FOG severity a major clinical challenge in the therapeutic management of patients with PD. The aim of this study was to examine and compare gait, clinically and objectively, in patients with PD, with and without FOG, by means of a new wearable system. We also assessed the effect of l-DOPA on FOG severity and specific spatiotemporal gait parameters in patients with and without FOG. To this purpose, we recruited 28 patients with FOG, 16 patients without FOG, and 16 healthy subjects. In all participants, gait was evaluated clinically by video recordings and objectively by means of the wearable wireless system, during a modified 3-m Timed Up and Go (TUG) test. All patients performed the modified TUG test under and not under dopaminergic therapy (ON and OFF therapy). By comparing instrumental data with the clinical identification of FOG based on offline video-recordings, we also assessed the performance of the wearable system to detect FOG automatically in terms of sensitivity, specificity, positive and negative predictive values, and finally accuracy. TUG duration was longer in patients than in controls, and the amount of gait abnormalities was prominent in patients with FOG compared with those without FOG. l-DOPA improved gait significantly in patients with PD and particularly in patients with FOG mainly by reducing FOG duration and increasing specific spatiotemporal gait parameters. Finally, the overall wireless system performance in automatic FOG detection was characterized by excellent sensitivity (93.41%), specificity (98.51%), positive predictive value (89.55%), negative predictive value (97.31%), and finally accuracy (98.51%). Our study overall provides new information on the beneficial effect of l-DOPA on FOG severity and specific spatiotemporal gait parameters as objectively measured by a wearable sensory system. The algorithm here reported potentially opens to objective long-time sensing of FOG episodes in patients with PD. PMID:28855889

Cortisol stress response in post-traumatic stress disorder, panic disorder, and major depressive disorder patients.

PubMed

Wichmann, Susann; Kirschbaum, Clemens; Böhme, Carsten; Petrowski, Katja

2017-09-01

Previous research has focussed extensively on the distinction of HPA-axis functioning between patient groups and healthy volunteers, with relatively little emphasis on a direct comparison of patient groups. The current study's aim was to analyse differences in the cortisol stress response as a function of primary diagnosis of panic disorder (PD), post-traumatic stress disorder (PTSD), and major depressive disorder (MDD). A total of n=30 PD (mean age±SD: 36.07±12.56), n=23 PTSD (41.22±10.17), n=18 MDD patients (39.00±14.93) and n=47 healthy control (HC) individuals (35.51±13.15) participated in this study. All the study participants were female. The Trier Social Stress Test (TSST) was used for reliable laboratory stress induction. Blood sampling accompanied the TSST for cortisol and ACTH assessment. Panic-related, PTSD-specific questionnaires and the Beck Depression Inventory II were handed out for the characterisation of the study groups. Repeated measure ANCOVAs were conducted to test for main effects of time or group and for interaction effects. Regression analyses were conducted to take comorbid depression into account. 26.7% of the PD patients, 43.5% of the PTSD patients, 72.2% of the MDD patients and 80.6% of the HC participants showed a cortisol stress response upon the TSST. ANCOVA revealed a cortisol hypo-responsiveness both in PD and PTSD patients, while no significant group differences were seen in the ACTH concentrations. Additional analyses showed no impact of comorbid depressiveness on the cortisol stress response. MDD patients did not differ in the hormonal stress response neither compared to the HC participants nor to the PD and PTSD patients. Our main findings provide evidence of a dissociation between the cortisol and ACTH concentrations in response to the TSST in PTSD and in PD patients, independent of comorbid depression. Our results further support overall research findings of a cortisol hypo-responsiveness in PD patients. A hypo-response pattern was also seen in the PTSD patients agreeing with previous finding on the cortisol stress reactivity following TSST stress induction in these patients. Patients with a primary MDD diagnosis showed descriptively higher cortisol concentrations compared to the anxiety patients, and lower cortisol concentrations as the healthy individuals. The limitations of the study and implications for future studies will be discussed. Copyright © 2017. Published by Elsevier Ltd.

The effect of PD-L1 testing on the cost-effectiveness and economic impact of immune checkpoint inhibitors for the second-line treatment of NSCLC.

PubMed

Aguiar, P N; Perry, L A; Penny-Dimri, J; Babiker, H; Tadokoro, H; de Mello, R A; Lopes, G L

2017-09-01

Immune checkpoint inhibitors improve outcomes compared with chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel. The model used outcomes data from randomized clinical trials (RCTs) and drug acquisition costs from the United States. Thereafter, we used epidemiologic data to estimate the economic impact of the treatment. We included four RCTs (2 with nivolumab, 1 with pembrolizumab, and 1 with atezolizumab). The incremental quality-adjusted life year (QALY) for nivolumab was 0.417 among squamous tumors and 0.287 among non-squamous tumors and the incremental cost-effectiveness ratio (ICER) were $155 605 and $187 685, respectively. The QALY gain in the base case for atezolizumab was 0.354 and the ICER was $215 802. Compared with treating all patients, the selection of patients by PD-L1 expression improved incremental QALY by up to 183% and decreased the ICER by up to 65%. Pembrolizumab was studied only in patients whose tumors expressed PD-L1. The QALY gain was 0.346 and the ICER was $98 421. Patient selection also reduced the budget impact of immunotherapy. The use of PD-L1 expression as a biomarker increases cost-effectiveness of immunotherapy but also diminishes the number of potential life-years saved. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Efficacy of rasagiline and selegiline in Parkinson's disease: a head-to-head 3-year retrospective case-control study.

PubMed

Cereda, Emanuele; Cilia, Roberto; Canesi, Margherita; Tesei, Silvana; Mariani, Claudio Bruno; Zecchinelli, Anna Lena; Pezzoli, Gianni

2017-06-01

Monoamine oxidase type B (MAO-B) inhibitors, such as selegiline and rasagiline, can be used as monotherapy or adjuvant therapy to levodopa in Parkinson's disease (PD). Data on long-term efficacy of MAO-B inhibitors are limited with no head-to-head comparison available to date. The aim of this case-control retrospective study was to analyze data from patients with PD attending the Parkinson Institute (Milan, Italy) over a 6-year period (2009-2015) and compare the effects of selegiline and rasagiline on levodopa treatment outcomes. Patients with PD treated with either selegiline (n = 85) or rasagiline (n = 85) for 3 years as well as a control group of patients (N = 170) who have never received MAO-B inhibitors, were matched for gender, disease duration (±1 year) and age (±1 year) at baseline assessment (ratio 1:1:2). The Unified PD Rating Scale and the Hoehn-Yahr staging system were used for clinical comparisons. At baseline, mean PD duration was 6.5 years and clinical features were comparable across all three groups. After a mean follow-up of approximately 37 months, no differences in clinical progression of motor and non-motor symptoms were observed between the three groups. However, MAO-B inhibitor use was associated with ~2-fold lower change in daily dose of levodopa (p < 0.001) and lower dyskinesia scores (p = 0.028) than non-users. No intra-class differences were observed between selegiline and rasagiline. Long-term use of MAO-B inhibitors resulted in a significant reduction in levodopa requirements and a lower frequency of dyskinesias in patients with PD. Selegiline and rasagiline had equal efficacy in controlling motor symptoms in PD patients on optimized therapy.

Functional sensibility of the hand in leprosy patients.

PubMed

van Brakel, W H; Kets, C M; van Leerdam, M E; Khawas, I B; Gurung, K S

1997-03-01

The aims of this cross-sectional comparative study was to compare the results of Semmes-Weinstein monofilament testing (SWM) and moving 2-point discrimination (M2PD) with four tests of functional sensibility: recognition of objects, discrimination of size and texture and detection of dots. Ninety-eight leprosy in- and outpatients at Green Pastures Hospital in Pokhara, Nepal were tested with each of the above tests and the results were compared to see how well they agreed. Using the tests of functional sensibility as reference points, we examined the validity of the SWM and M2PD as predictors of functional sensibility. There was definite, but only moderate correlation between thresholds of monofilaments and M2PD and functional sensibility of the hand. A normal result with the SWM and/or M2PD had a good predictive value for normal functional sensibility. Sensitivity was reasonable against recognition of objects and discrimination of textures as reference tests (80-90% and 88-93%), but poor against discrimination of size and detection of dots (50-75% and 43-65%). Specificity was high for most combinations of SWM or M2PD with any of the tests of functional sensibility (85-99%). Above a monofilament threshold of 2 g, the predictive value of an abnormal test was 100% for dot detection and 83-92% for textural discrimination. This indicates that impairment of touch sensibility at this level correlates well with loss of dot detection and textural discrimination in patients with leprous neuropathy. For M2PD the pattern was very similar. Above a threshold of 5 mm, 95-100% of affected hands had loss of dot detection and 73-80% had loss of textural discrimination. Monofilament testing and M2PD did not seem suitable as proxy measures of functional sensibility of the hand in leprosy patients. However, a normal threshold with monofilaments and/or M2PD had a good predictive value for normal functional sensibility. Above a monofilament threshold of 2 g and/or a M2PD threshold of 5 mm, textural discrimination was abnormal in most hands.

Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility.

PubMed

Martin-Bastida, A; Lao-Kaim, N P; Loane, C; Politis, M; Roussakis, A A; Valle-Guzman, N; Kefalopoulou, Z; Paul-Visse, G; Widner, H; Xing, Y; Schwarz, S T; Auer, D P; Foltynie, T; Barker, R A; Piccini, P

2017-02-01

To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies. © 2016 EAN.

PD-L1 gene polymorphisms and low serum level of PD-L1 protein are associated to type 1 diabetes in Chile.

PubMed

Pizarro, Carolina; García-Díaz, Diego F; Codner, Ethel; Salas-Pérez, Francisca; Carrasco, Elena; Pérez-Bravo, Francisco

2014-11-01

Type 1 diabetes (T1D) has a complex etiology in which genetic and environmental factors are involved, whose interactions have not yet been completely clarified. In this context, the role in PD-1 pathway and its ligands 1 and 2 (PD-L1 and PD-L2) have been proposed as candidates in several autoimmune diseases. The aim of this work was to determine the allele and haplotype frequency of six gene polymorphisms of PD-ligands (PD-L1 and PD-L2) in Chilean T1D patients and their effect on serum levels of PD-L1 and autoantibody profile (GAD65 and IA2). This study cohort comprised 205 T1D patients and 205 normal children. We performed genotypic analysis of PD-L1 and PD-L2 genes by TaqMan method. Determination of anti-GAD65 and anti-IA-2 autoantibodies was performed by ELISA. The PD-L1 serum levels were measured. The allelic distribution of PD-L1 variants (rs2297137 and rs4143815) showed differences between T1D patients and controls (p = 0.035 and p = 0.022, respectively). No differences were detected among the PD-L2 polymorphisms, and only the rs16923189 showed genetic variation. T1D patients showed decreased serum levels of PD-L1 compared to controls: 1.42 [0.23-7.45] ng/mL versus 3.35 [0.49-5.89] ng/mL (p < 0.025). In addition, the CGG haplotype in PD-L1 associated with T1D (constructed from rs822342, rs2297137 and rs4143815 polymorphisms) showed an OR = 1.44 [1.08 to 1.93]. Finally, no association of these genetic variants was observed with serum concentrations of PD ligands or auto-antibody profile, although a correlation between PD-L1 ligand serum concentration and the age at disease onset was detected. Two polymorphism of PD-L1 are presented in different allelic variants between T1D and healthy subjects, also PDL-1 serum levels are significantly lowered in diabetics patients. Moreover, the age of onset of the disease determine differences between serum ligand levels in diabetics, being lower in younger. These results points to a possible establishment of PDL-1 as a genetic and biochemical marker for T1D onset, at least in Chilean population. Copyright © 2014 John Wiley & Sons, Ltd.

Visualization of nigrosome 1 and its loss in PD

PubMed Central

Schwarz, Stefan T.; Pitiot, Alain; Stephenson, Mary C.; Lowe, James; Bajaj, Nin; Bowtell, Richard W.; Auer, Dorothee P.; Gowland, Penny A.

2013-01-01

Objective: This study assessed whether high-resolution 7 T MRI allowed direct in vivo visualization of nigrosomes, substructures of the substantia nigra pars compacta (SNpc) undergoing the greatest and earliest dopaminergic cell loss in Parkinson disease (PD), and whether any disease-specific changes could be detected in patients with PD. Methods: Postmortem (PM) midbrains, 2 from healthy controls (HCs) and 1 from a patient with PD, were scanned with high-resolution T2*-weighted MRI scans, sectioned, and stained for iron and neuromelanin (Perl), TH, and calbindin. To confirm the identification of nigrosomes in vivo on 7 T T2*-weighted scans, we assessed colocalization with neuromelanin-sensitive T1-weighted scans. We then assessed the ability to depict PD pathology on in vivo T2*-weighted scans by comparing data from 10 patients with PD and 8 age- and sex-matched HCs. Results: A hyperintense, ovoid area within the dorsolateral border of the otherwise hypointense SNpc was identified in the HC brains on in vivo and PM T2*-weighted MRI. Location, size, shape, and staining characteristics conform to nigrosome 1. Blinded assessment by 2 neuroradiologists showed consistent bilateral absence of this nigrosome feature in all 10 patients with PD, and bilateral presence in 7/8 HC. Conclusions: In vivo and PM MRI with histologic correlation demonstrates that high-resolution 7 T MRI can directly visualize nigrosome 1. The absence of nigrosome 1 in the SNpc on MRI scans might prove useful in developing a neuroimaging diagnostic test for PD. PMID:23843466

Regional cerebral blood flow in Parkinson disease with nonpsychotic visual hallucinations.

PubMed

Oishi, N; Udaka, F; Kameyama, M; Sawamoto, N; Hashikawa, K; Fukuyama, H

2005-12-13

Patients with Parkinson disease (PD) often experience visual hallucinations (VH) with retained insight (nonpsychotic) but the precise mechanism remains unclear. To clarify which neural substrates participate in nonpsychotic VH in PD, the authors evaluated regional cerebral blood flow (rCBF) changes in patients with PD and VH. The authors compared 24 patients with PD who had nonpsychotic VH (hallucinators) and 41 patients with PD who had never experienced VH (non-hallucinators) using SPECT images with N-isopropyl-p-[(123)I]iodoamphetamine. There were no significant differences in age, sex, duration of disease, doses of PD medications, Hoehn and Yahr scale, or Mini-Mental State Examination (MMSE) scores between the two groups. The rCBF data were analyzed using statistical parametric mapping (SPM). The rCBF in the right fusiform gyrus was lower in the hallucinators than in the non-hallucinators (corrected p < 0.05 at cluster levels). The hallucinators revealed higher rCBF in the right superior and middle temporal gyri than the non-hallucinators (uncorrected p < 0.001). These significant differences were demonstrated after MMSE scores and duration of disease, which are the relevant factors associated with VH, were covariated out. Nonpsychotic visual hallucinations in Parkinson disease (PD) may be associated with hypoperfusion in the right fusiform gyrus and hyperperfusion in the right superior and middle temporal gyri. These temporal regions are important for visual object recognition and these regional cerebral blood flow changes are associated with inappropriate visual processing and are responsible for nonpsychotic visual hallucinations in PD.

Lack of motivation: a new modifiable risk factor for peritonitis in patients undergoing peritoneal dialysis?

PubMed

Paudel, Klara; Namagondlu, Girish; Samad, Nasreen; McKitty, Khadija; Fan, Stanley L

2015-03-01

Can we identify modifiable risk factors for peritonitis in patients undergoing peritoneal dialysis (PD)? We aimed to determine whether housing standard, PD exchange technique or patient motivation might be modifiable risks for peritonitis. We also explored the relationship between lack of motivation and depression. Nurse home visits assessed PD exchange technique, environment and patient motivation. Motivation scores were correlated separately with an Apathy Evaluation Score and a depression score using PHQ-9 questionnaires. Home hygiene, exchange technique and motivation were above average in 53%, 56% and 60%, respectively in 104 patients undergoing PD. After 15 months, 25.9% patients developed peritonitis but nurses' ratings of homes and exchange techniques were not predictive. Low patient motivation was predictive. Patients rated to have above or below median motivation had significantly different Apathy Scores (p = 0.0002). Unmotivated depressed patients were significantly more likely to develop peritonitis compared to motivated depressed patients. Lack of motivation predicted peritonitis particularly if associated with depression. Further studies are required focusing on specific motivation scoring schemes and the psychosocial support that might lead to better outcomes. © 2014 European Dialysis and Transplant Nurses Association/European Renal Care Association.

Identification of three novel LRRK2 mutations associated with Parkinson's disease in a Calabrian population.

PubMed

Anfossi, Maria; Colao, Rosanna; Gallo, Maura; Bernardi, Livia; Conidi, M Elena; Frangipane, Francesca; Vasso, Franca; Puccio, Gianfranco; Clodomiro, Alessandra; Mirabelli, Maria; Curcio, Sabrina A M; Torchia, Giusi; Smirne, Nicoletta; Di Lorenzo, Raffaele; Maletta, Raffaele; Bruni, Amalia C

2014-01-01

LRRK2 mutations are common in familial and sporadic Parkinson's disease (PD) cases. We present a screening of the most frequently mutated exons of LRRK2 in Calabrian population. Eighty-eight PD patients diagnosed according to standard criteria, underwent screening for LRRK2 mutations in exons 19, 21, 24, 25, 27, 29, 31, 32, 33, 35, 38, 40, 41, and 48. Eight LRRK2 variations were identified in nine patients affected by PD, including three novel missense variations (p.Phe1227Leu, p.Gly1520Ala, p.Ile2020Ser) and five previously identified mutations (p.Ala1151Thr, IVS31+3A>G, p.Arg1514Gln, p.Gly2019Ser, p.Thr2356Ile). LRRK2 frequency mutations were approximately 10.2% in all PD patients, 12% in familial, 8% in sporadic cases. The p.Gly2019Ser mutation was found in 2.3% of the total cohort and in 3.2% of sporadic cases. The clinical features of LRRK2-associated with PD in our patients were similar to those of idiopathic PD although most LRRK2 mutated patients presented with bradykinesia instead of tremor; 33.3% developed dementia. We identified three novel LRRK2 mutations and reported a higher frequency in Calabria compared to previously reported data possibly due to the relative genetic isolation of the Calabrian population. These findings contribute to the understanding of the role of LRKK2 variations in PD and provide additional genetic insight into this disease.

Preserved serotonin transporter binding in de novo Parkinson's disease: negative correlation with the dopamine transporter.

PubMed

Strecker, Karl; Wegner, Florian; Hesse, Swen; Becker, Georg-Alexander; Patt, Marianne; Meyer, Philipp M; Lobsien, Donald; Schwarz, Johannes; Sabri, Osama

2011-01-01

Recent imaging and neuropathological studies indicate reduced serotonin transporter (SERT) in advanced Parkinson's disease (PD). However, data on SERT in early PD patients are sparse. Following the hypothesis that the serotonergic system is damaged early in PD, the aim of our study was to investigate SERT availability by means of PET imaging. Since the loss of dopaminergic neurons is the pathologic hallmark of PD and SERT might be associated with psychiatric co-morbidity, we further sought to correlate SERT availability with the availability of dopamine transporter (DAT) and depressive or motor symptoms in early PD. We prospectively recruited nine early PD patients (4 female, 5 male; 42-76 years) and nine age matched healthy volunteers (5 female, 4 male; 42-72 years). Diagnosis of PD was confirmed by the UK brain bank criteria and DAT imaging. SERT availability was measured by means of [11C]DASB PET. For neuropsychiatric assessment done on the day of PET we applied UPDRS parts I, II and III, Beck's Depression Inventory, Hamilton Rating Scale for Depression, Mini-Mental State Examination and Demtect. SERT was not reduced in any of 14 investigated regions of interest in the nine PD patients compared to healthy controls (p>0.13). SERT was negatively associated with DAT in the striatum (r=-0.69; p=0.04) but not within the midbrain. There was no correlation of SERT availability with depressive symptoms. No alteration of SERT binding in our patients suggests that the serotonergic system is remarkably preserved in early PD. Correlation with DAT might point to a compensatory regulation of the serotonergic system in early stages of PD.

Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.

PubMed

Rocha, Natalia Pessoa; Assis, Frankcinéia; Scalzo, Paula Luciana; Vieira, Érica Leandro Marciano; Barbosa, Izabela Guimarães; de Souza, Mariana Soares; Christo, Paulo Pereira; Reis, Helton José; Teixeira, Antonio Lucio

2018-02-01

Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.

Self-awareness of memory function in Parkinson's disease in relation to mood and symptom severity.

PubMed

Sitek, Emilia J; Sołtan, Witold; Wieczorek, Dariusz; Robowski, Piotr; Sławek, Jarosław

2011-03-01

In clinical practice, discrepancies are observed between self and proxy reports of various aspects of Parkinson's disease (PD). This study aimed at assessing self-awareness of memory function in PD both by comparing patients' and caregivers' questionnaire ratings of the patients' memory and by correlating subjective ratings with verbal learning results. Forty-five patient-proxy pairs participated in the study. Self-Rating Scale of Memory Functions was used as a questionnaire subjective measure. Auditory Verbal Learning Test (AVLT) was applied to assess verbal memory, Stroop test to assess cognitive control and Mini-Mental State Examination (MMSE) for global cognitive assessment. Patient self-reports did not diverge appreciably from proxy reports when global scores were considered, but patient-proxy consistency was low for individual items with the exception of those referring to verbal recall. Both patient and proxy ratings were moderately correlated with the objective measures. Patient-proxy discrepancies were associated with lower verbal learning, poor cognitive control and more severe PD symptomatology. Moreover, depression was associated with patients' overestimation of symptoms. Self-awareness of memory function is relatively well preserved in PD, but is negatively affected by depressive symptoms. Patient-proxy discrepancies increase also with disease severity, degree of memory problems and cognitive control deficits. Caregivers seem to be unaware of the specificity of memory problems in PD and report only some of them, mainly those related to verbal recall.

Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson's disease: historical overview and future prospects.

PubMed

Nagatsu, Toshiharu

2017-06-01

Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro-Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987, we detected PREP activity in human cerebrospinal fluid (CSF) using highly sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl-coumarin amide as a new synthetic substrate, and found a marked decrease in its activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) as compared with its level in control patients without neurological diseases. In 2013, Hannula et al. found co-localization of PREP with α-synuclein in the postmortem PD brain. Several recent studies also suggest that the level of PREP in the brain of PD patients may be related to dopamine (DA) cell death via promotion of α-synuclein oligomerization and that inhibitors of PREP may play a neuroprotective role in PD. Although the relationship between another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II) and dipeptidyl peptidase IV (DPP IV), and α-synuclein in the PD brain is not yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was significantly increased in PD patients. This review discusses the possibility of PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.

Impaired sequential and partially compensated probabilistic skill learning in Parkinson's disease.

PubMed

Kemény, Ferenc; Demeter, Gyula; Racsmány, Mihály; Valálik, István; Lukács, Ágnes

2018-06-08

The striatal dopaminergic dysfunction in Parkinson's disease (PD) has been associated with deficits in skill learning in numerous studies, but some of the findings remain controversial. Our aim was to explore the generality of the learning deficit using two widely reported skill learning tasks in the same group of Parkinson's patients. Thirty-four patients with PD (mean age: 62.83 years, SD: 7.67) were compared to age-matched healthy adults. Two tasks were employed: the Serial Reaction Time Task (SRT), testing the learning of motor sequences, and the Weather Prediction (WP) task, testing non-sequential probabilistic category learning. On the SRT task, patients with PD showed no significant evidence for sequence learning. These results support and also extend previous findings, suggesting that motor skill learning is vulnerable in PD. On the WP task, the PD group showed the same amount of learning as controls, but they exploited qualitatively different strategies in predicting the target categories. While controls typically combined probabilities from multiple predicting cues, patients with PD instead focused on individual cues. We also found moderate to high correlations between the different measures of skill learning. These findings support our hypothesis that skill learning is generally impaired in PD, and can in some cases be compensated by relying on alternative learning strategies. © 2018 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Genetic Architecture of MAPT Gene Region in Parkinson Disease Subtypes

PubMed Central

Pascale, Esterina; Di Battista, Maria Elena; Rubino, Alfonso; Purcaro, Carlo; Valente, Marcella; Fattapposta, Francesco; Ferraguti, Giampiero; Meco, Giuseppe

2016-01-01

The microtubule-associated protein tau (MAPT) region has been conceptualized as a model of the interaction between genetics and functional disease outcomes in neurodegenerative disorders, such as Parkinson disease (PD). Indeed, haplotype-specific differences in expression and alternative splicing of MAPT transcripts affect cellular functions at different levels, increasing susceptibility to a range of neurodegenerative processes. In order to evaluate a possible link between MAPT variants, PD risk and PD motor phenotype, we analyzed the genetic architecture of MAPT in a cohort of PD patients. We observed a statistically significant association between the H1 haplotype and PD risk (79.5 vs 69.5%; χ2 = 9.9; OR, 1.7; 95% CI, 1.2–2.4; p = 0.002). The effect was more evident in non tremor dominant (TD) PD subjects (NTD-PD) (82 vs 69.5%; χ2 = 13.6; OR, 2.03; 95% CI, 1.4–3; p = 0.0003), while no difference emerged between PD subgroup of tremor dominant patients (TD-PD) and control subjects. Examination of specific intra-H1 variations showed that the H1h subhaplotype was overrepresented in NTD-PD patients compared with controls (p = 0.007; OR, 2.9; 95% CI, 1.3–6.3). Although we cannot exclude that MAPT variation may be associated with ethnicity, our results may support the hypothesis that MAPT H1 clade and a specific H1 subhaplotype influence the risk of PD and modulate the clinical expression of the disease, including motor phenotype. PMID:27147968

Effects of various factors on sleep disorders and quality of life in Parkinson's disease.

PubMed

Telarovic, Srdjana; Mijatovic, Dragana; Telarovic, Irma

2015-12-01

In Parkinson's disease (PD), sleep disorders (SD) occur as a result of the neurochemical changes in sleep centres, neurodegenerative changes in dopaminergic neurons, and other factors. The most common SD include excessive daytime sleepiness, insomnia, restless legs syndrome and nocturia. The aim of the study was to compare quality of sleep, as a factor that greatly impacts quality of life (QoL), between PD patients and a control group and to further examine SD in the PD group with focus on incidence and SD types as well as on effects various factors (age, sex, PD characteristics, medication usage) have on these disorders. The study included 110 patients who met the criteria for the diagnosis of PD and 110 age-matched healthy controls. We used the Pittsburgh Sleep Quality Index, PD Sleep Scale, Epworth Sleepiness Scale, PD QoL Questionnaire-8 and PD Questionnaire-39 (items 30 and 33). In the group with PD, we considered the duration of the disease, the stage of disease according to the Hoehn and Yahr scale, medications and their impact on the SD. The average duration of the disease was 6 years and the mean stage was 2.44. The result showed significant differences in the sleep quality between groups. In the PD group, SD differences were also found according to gender, duration of the disease and medication usage. The most common SD were fragmented sleep, insomnia and nocturia. To improve the QoL of PD patients, it is necessary to pay more attention to detecting and solving SD.

Effects of dopaminergic replacement therapy on motor speech disorders in Parkinson's disease: longitudinal follow-up study on previously untreated patients.

PubMed

Rusz, Jan; Tykalová, Tereza; Klempíř, Jiří; Čmejla, Roman; Růžička, Evžen

2016-04-01

Although speech disorders represent an early and common manifestation of Parkinson's disease (PD), little is known about their progression and relationship to dopaminergic replacement therapy. The aim of the current study was to examine longitudinal motor speech changes after the initiation of pharmacotherapy in PD. Fifteen newly-diagnosed, untreated PD patients and ten healthy controls of comparable age were investigated. PD patients were tested before the introduction of antiparkinsonian therapy and then twice within the following 6 years. Quantitative acoustic analyses of seven key speech dimensions of hypokinetic dysarthria were performed. At baseline, PD patients showed significantly altered speech including imprecise consonants, monopitch, inappropriate silences, decreased quality of voice, slow alternating motion rates, imprecise vowels and monoloudness. At follow-up assessment, preservation or slight improvement of speech performance was objectively observed in two-thirds of PD patients within the first 3-6 years of dopaminergic treatment, primarily associated with the improvement of stop consonant articulation. The extent of speech improvement correlated with L-dopa equivalent dose (r = 0.66, p = 0.008) as well as with reduction in principal motor manifestations based on the Unified Parkinson's Disease Rating Scale (r = -0.61, p = 0.02), particularly reflecting treatment-related changes in bradykinesia but not in rigidity, tremor, or axial motor manifestations. While speech disorders are frequently present in drug-naive PD patients, they tend to improve or remain relatively stable after the initiation of dopaminergic treatment and appear to be related to the dopaminergic responsiveness of bradykinesia.

Dopaminergic Therapy Increases Go Timeouts in the Go/No-Go Task in Patients with Parkinson’s Disease

PubMed Central

Yang, Xue Q.; Lauzon, Brian; Seergobin, Ken N.; MacDonald, Penny A.

2018-01-01

Parkinson’s disease (PD) is characterized by resting tremor, rigidity and bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms, but can have complex effects on cognition. Impulse control is an essential cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity involves the inability to withhold pre-potent, automatic, erroneous responses. In contrast, cognitive impulsivity refers to improper risk-reward assessment guiding behavior. Informed by our previous research, we anticipated that dopaminergic therapy would decrease motor impulsivity though it is well known to enhance cognitive impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off their normal dopaminergic medication. Participants completed cognitive, mood, and physiological measures. PD patients on medication had a significantly higher proportion of Go trial Timeouts (i.e., trials in which Go responses were not completed prior to a deadline of 750 ms) compared to off medication (p = 0.01). No significant ON-OFF differences were found for Go trial or No-go trial response times (RTs), or for number of No-go errors. We interpret that dopaminergic therapy induces a more conservative response set, reflected in Go trial Timeouts in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in PD patients. This is in contrast to the widely recognized effects of dopaminergic therapy on cognitive impulsivity leading in some patients to impulse control disorders. Understanding the nuanced effects of dopaminergic treatment in PD on cognitive functions such as impulse control will clarify therapeutic decisions. PMID:29354045

Programmed death-1 gene polymorphism (PD-1.5 C/T) is associated with gastric cancer.

PubMed

Savabkar, Sanaz; Azimzadeh, Pedram; Chaleshi, Vahid; Nazemalhosseini Mojarad, Ehsan; Aghdaei, Hamid Asadzadeh

2013-01-01

This study aimed to determine the association between PD-1.5C/T (rs2227981, +7785) and the risk of gastric cancer (GC) in an Iranian population. Gastric cancer is the fourth most common cancer in the world. The programmed death 1 (PD-1) is a member of the CD28 super family. PD-1 is a negative regulator of T-cell effector mechanisms which decrease immune responses against cancer. we conducted case- control study to investigate the association of PD-1.5 C/T polymorphism in 122 GC patients and 166 control individuals. DNA was extracted from blood specimens. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The frequency of CC, CT and TT genotypes was 53.6%, 42.2% and 4.2% in control group and 41%, 54.1% and 4.9% in gastric cancer patients respectively. CC genotype was more frequent in control individuals than in patients but we found no statically significant association. The frequencies of PD-1.5CT genotypes were significantly higher in GC patient compared with control individuals (OR= 1.77, 95% CI= 1.077-2.931; P=0.026). Allele distribution was similar in patients and healthy individuals (p = 0.061).Frequency of C and T alleles was 74.7%, 25.3% in control individuals and 68.03% and 31.97% in gastric cancer patients respectively. These results suggest that PD-1.5 C/T polymorphism may affect the GC risk and prognosis in an Iranian population.

When fruits lose to animals: Disorganized search of semantic memory in Parkinson's disease.

PubMed

Tagini, Sofia; Seyed-Allaei, Shima; Scarpina, Federica; Toraldo, Alessio; Mauro, Alessandro; Cherubini, Paolo; Reverberi, Carlo

2018-04-16

The semantic fluency task is widely used in both clinical and research settings to assess both the integrity of the semantic store and the effectiveness of the search through it. Our aim was to investigate whether nondemented Parkinson's disease (PD) patients show an impairment in the strategic exploration of the semantic store and whether the tested semantic category has an impact on multiple measures of performance. We compared 74 nondemented PD patients with 254 healthy subjects in a semantic fluency test using relatively small (fruits) and large (animals) semantic categories. Number of words produced, number of explored semantic subcategories, and degree of order in the produced sequences were computed as dependent variables. PD patients produced fewer words than healthy subjects did, regardless of the category. Number of subcategories was also lower in PD patients than in healthy subjects, without a significant difference between categories. Critically, PD patients' sequences were less semantically organized than were those of controls, but this effect appeared in only the smaller category (fruits), thus pointing to a lack of strategy in exploring the semantic store. Our results show that the semantic fluency deficit in PD patients has a strategic component, even though that may not be the only cause of the impaired performance. Furthermore, our evidence suggests that the semantic category used in the test influences performance, hence providing an explanation for the failure by previous studies, which often used large categories such as animals, to detect strategy deficits in PD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

What is the effect on comorbid personality disorder of brief panic-focused psychotherapy in patients with panic disorder?

PubMed

Keefe, John R; Milrod, Barbara L; Gallop, Robert; Barber, Jacques P; Chambless, Dianne L

2018-03-01

No studies of psychotherapies for panic disorder (PD) have examined effects on comorbid personality disorders (PersD), yet half such patients have a PersD. In a randomized trial for PD with and without agoraphobia comparing Cognitive-Behavioral Therapy (CBT) and Panic-Focused Psychodynamic Psychotherapy (PFPP), PersD was assessed pre-to-post treatment with the Structured Clinical Interview for the Diagnosis of Axis-II Disorders (SCID-II). For patients completing therapy (n = 118, 54 with PersD), covariance between panic and SCID-II criteria improvements was analyzed. SCID-II diagnostic remission and recovery were evaluated. Comparative efficacy of PFPP versus CBT for improving PersD was analyzed both for the average patient, and as a function of PersD severity. 37 and 17% of PersD patients experienced diagnostic PersD remission and recovery, respectively. Larger reductions in PersD were related to more panic improvement, with a modest effect size (r = 0.28). Although there was no difference between treatments in their ability to improve PersD for the average patient (d = 0.01), patients meeting more PersD criteria did better in PFPP compared to CBT (P = .007), with PFPP being significantly superior at 11 criteria and above (d = 0.66; 3 more criteria lost). PersD presenting in the context of primary PD rarely resolves during psychotherapies focused on PD, and change in PersD only moderately tracks panic improvements, indicating non-overlap of the constructs. Patients receiving panic-focused psychotherapies may require additional treatment for their PersD. PFPP may be superior at improving severe PersD, but replication of this finding is required. © 2017 Wiley Periodicals, Inc.