Determinants of health-related quality of life in people with Parkinson’s disease: a path analysis

Purpose:
To identify the demographic factors, impairments and activity limitations that contribute to health-related quality of life (HRQOL) in people with idiopathic Parkinson’s disease (PD).

Method:
Two hundred and ten individuals with idiopathic PD who participated in the baseline assessment of a randomized clinical trial were included. The Parkinson’s Disease Questionnaire-39 summary index was used to quantify HRQOL. In order to provide greater clarity regarding the determinants of HRQOL, path analysis was used to explore the relationships between the various predictors in relation to the functioning and disability framework of the International Classification of Functioning model.

Results:
The two models of HRQOL that were examined in this study had a reasonable fit with the data. Activity limitations were found to be the strongest predictor of HRQOL. Limitations in performing self-care activities contributed the most to HRQOL in Model 1 (β = 0.38; p < 0.05), while limitations in functional mobility had the largest contribution in Model 2 (β = −0.31; p < 0.0005). Self-reported history of falls was also found to have a significant and direct relationship with HRQOL in both models (Model 1 β = −0.11; p < 0.05; Model 2 β = −0.21; p < 0.05).

Conclusions:
Health-related quality of life in PD is associated with self-care limitations, mobility limitations, self-reported history of falls and disease duration. Understanding how these factors are inter-related may assist clinicians focus their assessments and develop strategies that aim to minimize the negative functional and social sequelae of this debilitating disease.

Rural living and health-related quality of life in Australians with Parkinson's disease

Introduction: The motor and non-motor symptoms associated with idiopathic Parkinson’s disease (PD) may compromise the health-related quality of life (HRQOL) of some individuals living with this debilitating condition. Although growing evidence suggests that PD may be more prevalent in rural communities, there is little information about the life quality of these individuals. This study examines whether HRQOL ratings vary in relation to rural and metropolitan life settings.
Methods: An analytic cross-sectional study was conducted to compare the HRQOL of two separate samples of people with PD living in metropolitan Melbourne and rural Victoria. The metropolitan sample consisted of 210 individuals who had participated in the baseline assessment for an existing clinical trial. The rural sample comprised 24 participants who attended community-based rehabilitation programs and support groups in rural Victoria. Health-related quality of life was quantified using the Parkinson’s Disease Questionnaire-39 (PDQ-39).
Results: The HRQOL of participants in rural Australia differed from individuals living in a large metropolitan city (p=0.025). Participants in rural Australia reported worse overall HRQOL, after controlling for differences in disease duration. Their overall HRQOL was lower than for city dwellers. Rural living was also found to be a significant negative predictor of HRQOL (β=0.14; 95% CI -1.27 to -0.08; _p=0.027).
Conclusion: The findings of this study suggest that some people with PD living in rural Victoria perceive their HRQOL to be relatively poor. In order to minimise the debilitating consequences of this disease, further studies examining the factors that may contribute to the HRQOL of individuals living in rural and remote areas are required.

Quantifying the profile and progression of impairments, activity, participation, and quality of life in people with Parkinson disease : protocol for a prospective cohort study

Background Despite the finding that Parkinson disease (PD) occurs in more than one in every 1000 people older than 60 years, there have been few attempts to quantify how deficits in impairments, activity, participation, and quality of life progress in this debilitating condition. It is unclear which tools are most appropriate for measuring change over time in PD.
Methods and design This protocol describes a prospective analysis of changes in impairments, activity, participation, and quality of life over a 12 month period together with an economic analysis of costs associated with PD. One-hundred participants will be included, provided they have idiopathic PD rated I-IV on the modified Hoehn & Yahr (1967) scale and fulfil the inclusion criteria. The study aims to determine which clinical and economic measures best quantify the natural history and progression of PD in a sample of people receiving services from the Victorian Comprehensive Parkinson's Program, Australia. When the data become available, the results will be expressed as baseline scores and changes over 3 months and 12 months for impairment, activity, participation, and quality of life together with a cost analysis.
Discussion This study has the potential to identify baseline characteristics of PD for different Hoehn & Yahr stages, to determine the influence of disease duration on performance, and to calculate the costs associated with idiopathic PD. Valid clinical and economic measures for quantifying the natural history and progression of PD will also be identified.

The health profile of people living with Parkinson's Disease managed in a comprehensive care setting

Background: Globally there are few reports of the impairments, disabilities and medications used in people living with idiopathic Parkinson’s disease. Caregiver characteristics and caregiver burden have seldom been reported. We examined the health status in a large cohort of people living with Parkinson’s disease and their caregivers managed in a comprehensive health care setting.

Methods/Design: A prospective, cross sectional analysis of impairments, disabilities and Parkinson’s disease medication use was conducted in a sample of 100 people with Parkinson’s disease rated I-IV on the modified Hoehn & Yahr scale. Participants were recruited from the Victorian Comprehensive Parkinson Program in Melbourne, Australia. Their caregivers were invited to provide their views on the burden of care, services provided and support received.

Results: The severity of impairments and disabilities was strongly associated with disease duration (mean of 5.5 years). Those with long standing disease or more severe disease also used more Parkinson’s disease medications and participated in fewer social roles than people who were newly diagnosed or mildly affected. The severity of impairments was strongly correlated with limitations in performing activities of daily living. Limitations in performing daily activities were also found to be a significant contributing factor for health-related quality of life (PDQ-39 SI β=0.55, p=0.000; EQ-5D SI β=0.43, p=0.001). People with Parkinson’s disease lived at home with relatives. The average caregiver was a spouse or child providing approximately 3.5 hours of care per day, with the capacity to provide 9.4 hours per day and had provided care for four years. Additional support was high (63%) for 2.5 hours per day.

Conclusion: The comprehensive care setting of this cohort describes a relatively benign condition despite a wide range of disease duration and severity. This report provides a baseline with which to compare other delivery models.

Concerns and worries in people living with inflammatory bowel disease (IBD): A mixed methods study.

OBJECTIVE: This mixed-methods study aimed to explore concerns and worries related to living with inflammatory bowel disease (IBD). METHODS: Overall, 294 patients with a clinically established diagnosis of IBD were enrolled in this cross-sectional study. Concerns and worries were measured with one open-ended question. Measures of anxiety and depressive symptoms and disease activity were also administered. A thematic analysis was conducted and thematic map created. Spearman's rho was used to identify univariate correlations between predictors and the main themes. Binary logistic regression was used to test the predictors of the main themes. RESULTS: Despite the majority of study participants being in IBD remission (74%, n=217), all but 11 reported significant IBD-related concerns. Twenty two percent reported symptoms of depression and 41% of anxiety. Four themes were identified: Quality of life (51%); Unpredictability (35%); Symptoms (34%) and Treatments (19%). Males and older people were less concerned about Quality of life (OR=.597, 95% CI: .363-.980 and OR=.980, 95% CI: .965-.995, respectively). Those in remission were less concerned about Symptoms (OR=.510, 95% CI: .281- .926) while those with longer disease duration worried more about the Symptoms (OR=1.035, 95% CI: 1.010-1.061). Males were less concerned about Treatments (OR=.422, 95% CI: .229-.777). CONCLUSION: IBD patients report significant disease-related concerns even when in remission. Further exploration of what predicts patient concerns may help in shaping health-care delivery so that it better addresses patient needs.

Colon cancer surveillance in inflammatory bowel disease: unclear gain but no psychological pain?

BACKGROUND: Surveillance for colorectal neoplasia in inflammatory bowel disease (IBD) is widely practised despite a lack of convincing mortality reduction. The psychological impact of this approach is largely unexplored. AIM: To examine psychological well-being among IBD subjects undergoing colonoscopic surveillance for colorectal cancer (CRC). METHODS: A cross-sectional study was performed by interrogating an IBD database for subjects currently enrolled in colonoscopic surveillance programmes. Identified surveillance subjects were age- and gender-matched with IBD control subjects not meeting surveillance criteria. Subjects were mailed a questionnaire including demographic details, the Short Form 36 (SF-36) survey to assess quality of life, the Spielberger State-Trait Personality Inventory, the Multidimensional Health Locus of Control, and a Risk Perception Questionnaire. RESULTS: One hundred and thirty-nine of 286 (49%) subjects responded, 53% male, 46% Crohn disease. Fifty-six per cent respondents were in the surveillance group. Surveillance subjects were older (55.4 vs 51.1 years; P = .048) with longer disease duration, but otherwise had comparable demographics with controls. Overall, quality of life was not significantly different between cohorts (mean SF-36 63.82 vs 65.48; P = 0.70). Groups did not differ on any locus of control classification (P = 0.52), nor was there any difference between mean scores on 'state' subscales of the Spielberger State-Trait Personality Inventory: anxiety (P = 0.91), curiosity (P = 0.12), anger (P = 0.81) or depression (P = 0.70). Both groups grossly overestimated their perceived lifetime risk of CRC at 50%, with no difference between surveillance and control subjects (P = 1.0). CONCLUSIONS: Enrolment in colonoscopic colon cancer surveillance does not appear to impair psychological well-being in individuals with IBD despite longer disease duration. IBD patients overestimate their risk of CRC.

Ankylosing spondylitis patients commencing biologic therapy have high baseline levels of comorbidity: a report from the Australian Rheumatology Association Database

Aims: To compare the baseline characteristics of a population-based cohort of patients with ankylosing spondylitis (AS) commencing biological therapy to the reported characteristics of bDMARD randomised controlled trials (RCTs) participants.
Methods: Descriptive analysis of AS participants in the Australian Rheumatology Association Database (ARAD) who were commencing bDMARD therapy.
Results: Up to December 2008, 389 patients with AS were enrolled in ARAD. 354 (91.0%) had taken bDMARDs at some time, and 198 (55.9%) completed their entry questionnaire prior to or within 6 months of commencing bDMARDs. 131 (66.1%) had at least one comorbid condition, and 24 (6.8%) had a previous malignancy (15 nonmelanoma skin, 4 melanoma, 2 prostate, 1 breast, cervix, and bowel). Compared with RCT participants, ARAD participants were older, had longer disease duration and higher baseline disease activity.
Conclusions: AS patients commencing bDMARDs in routine care are significantly different to RCT participants and have significant baseline comorbidities.

Malondialdehyde plasma concentration correlates with declarative and working memory in patients with recurrent depressive disorder

Oxidative stress has been implicated in the cognitive decline, especially in memory impairment. The purpose of this study was to determine the concentration of malondialdehyde (MDA) in patients with recurrent depressive disorders (rDD) and to define relationship between plasma levels of MDA and the cognitive performance. The study comprised 46 patients meeting criteria for rDD. Cognitive function assessment was based on: The Trail Making Test , The Stroop Test, Verbal Fluency Test and Auditory-Verbal Learning Test. The severity of depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Statistically significant differences were found in the intensity of depression symptoms, measured by the HDRS on therapy onset versus the examination results after 8 weeks of treatment (P < 0.001). Considering the 8-week pharmacotherapy period, rDD patients presented better outcomes in cognitive function tests. There was no statistically significant correlation between plasma MDA levels, and the age, disease duration, number of previous depressive episodes and the results in HDRS applied on admission and on discharge. Elevated levels of MDA adversely affected the efficiency of visual-spatial and auditory-verbal working memory, short-term declarative memory and the delayed recall declarative memory. 1. Higher concentration of plasma MDA in rDD patients is associated with the severity of depressive symptoms, both at the beginning of antidepressants pharmacotherapy, and after 8 weeks of its duration. 2. Elevated levels of plasma MDA are related to the impairment of visual-spatial and auditory-verbal working memory and short-term and delayed declarative memory.

Sex as a determinant of relapse incidence and progressive course of multiple sclerosis

The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48 362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10−12). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10−12). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.

Retinal nerve fibre layer thinning associated with diabetic peripheral neuropathy

Aims
To investigate the relationship between retinal nerve fibre layer thickness and peripheral neuropathy in patients with Type 2 diabetes, particularly in those who are at higher risk of foot ulceration.

Methods
Global and sectoral retinal nerve fibre layer thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). The level of neuropathy was assessed in 106 participants (82 with Type 2 diabetes and 24 healthy controls) using the 0–10 neuropathy disability score. Participants were stratified into four neuropathy groups: none (0–2), mild (3–5), moderate (6–8), and severe (9–10). A neuropathy disability score ‡ 6 was used to define those at higher risk of foot ulceration. Multivariable regression analysis was performed to assess the effect of neuropathy disability scores, age, disease duration and retinopathy on RNFL thickness.

Results
Inferior (but not global or other sectoral) retinal nerve fibre layer thinning was associated with higher neuropathy disability scores (P = 0.03). The retinal nerve fibre layer was significantly thinner for the group with neuropathy disability scores ‡ 6 in the inferior quadrant (P < 0.005). Age, duration of disease and retinopathy levels did not significantly influence retinal nerve fibre layer thickness. Control participants did not show any significant differences in thickness measurements from the group with diabetes and no neuropathy (P > 0.24 for global and all sectors).

Conclusions
Inferior quadrant retinal nerve fibre layer thinning is associated with peripheral neuropathy in patients with Type 2 diabetes, and is more pronounced in those at higher risk of foot ulceration.

Visual sensitivity loss in the central 30° of visual field is associated with diabetic peripheral neuropathy

Aims/hypothesis
Impaired central vision has been shown to predict diabetic peripheral neuropathy (DPN). Several studies have demonstrated diffuse retinal neurodegenerative changes in diabetic patients prior to retinopathy development, raising the prospect that non-central vision may also be compromised by primary neural damage. We hypothesise that type 2 diabetic patients with DPN exhibit visual sensitivity loss in a distinctive pattern across the visual field, compared with a control group of type 2 diabetic patients without DPN.

Methods
Increment light sensitivity was measured by standard perimetry in the central 30° of visual field for two age-matched groups of type 2 diabetic patients, with and without neuropathy (n = 40/30). Neuropathy status was assigned using the neuropathy disability score. Mean visual sensitivity values were calculated globally, for each quadrant and for three eccentricities (0–10°, 11–20° and 21–30°). Data were analysed using a generalised additive mixed model (GAMM).

Results
Global and quadrant between-group visual sensitivity mean differences were marginally but consistently lower (by about 1 dB) in the neuropathy cohort compared with controls. Between-group mean differences increased from 0.36 to 1.81 dB with increasing eccentricity. GAMM analysis, after adjustment for age, showed these differences to be significant beyond 15° eccentricity and monotonically increasing. Retinopathy levels and disease duration were not significant factors within the model (p = 0.90).

Conclusions/interpretation
Visual sensitivity reduces disproportionately with increasing eccentricity in type 2 diabetic patients with peripheral neuropathy. This sensitivity reduction within the central 30° of visual field may be indicative of more consequential loss in the far periphery.

Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications

It has been postulated that schizophrenia (SZ) is related to a lower expression of brain-derived neurotrophic factor (BDNF). In the past few years, an increasing number of divergent clinical studies assessing BDNF in serum and plasma have been published. It is now possible to verify the relationship between BDNF levels and severity of symptoms in SZ as well as the effects of antipsychotic drugs on BDNF using meta-analysis. The aims of this study were to verify if peripheral BDNF is decreased in SZ, whether its levels are correlated with positive and negative symptomatology and if BDNF levels change after antipsychotic treatment. This report consists of two distinct meta-analyses of peripheral BDNF in SZ including a total of 41 studies and more than 7000 participants: (1) peripheral BDNF levels in serum and plasma were moderately reduced in SZ compared with controls. Notably, this decrease was accentuated with the disease duration. However, the extent of peripheral BDNF level decrease did not correlate with the severity of positive and negative symptoms. (2) In plasma, but not serum, peripheral BDNF levels are consistently increased after antipsychotic treatment irrespective of the patient's response to medication. In conclusion, there is compelling evidence that there are decreased levels of peripheral BDNF in SZ, in parallel to previously described reduced cerebral BDNF expression. It remains unclear whether these systemic changes are causally related to the development of SZ or if they are merely a pathologic epiphenomenon.Molecular Psychiatry advance online publication, 30 September 2014; doi:10.1038/mp.2014.117.

Oxidant/antioxidant imbalance is an inherent feature of depression

BACKGROUND: 50% to 60% of the people who have recovered from the first episode of depression experience a relapse. The immune system of the people suffering from depression is in a permanent state of pathological pro-inflammatory readiness. There are some reports that depressive episodes cause sensitization of immune-inflammatory pathways and that staing of depression (e.g. number of depressive episodes) is correlated with immune-inflammatory markers. The main objective of the study was to delineate whether recurrent major depression (rDD) is characterized by alterations in selected immune-inflammatory biomarkers as compared with first episode of depression (ED-I), i.e. expression of mRNA and enzymatic activity of manganese superoxide dismutase (MnSOD, SOD-2), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS, NOS-2), and cyclooxygenase-2 (COX-2). METHODS: The study was carried out in a group of 131 patients: ED-I group - 42 patients, rDD group - 89 patients. Depression severity was assessed with the 17-item Hamilton Depression Rating Scale (HDRS). The number of depression episodes and the disease duration periods were recorded in each patient. For the patients, HDRS was administered at admission during the symptomatic phase, which would generally be either before or shortly after modification of the previous antidepressant drug regimen. Reassessment of the mental condition was conducted after 8 weeks of the pharmacological treatment also with the use of the HDRS scale. RESULTS: No significant statistical differences were found between the analysed groups as regards the intensity of depressive disorders. No differences in the expression of MnSOD, MPO, COX-2 and i-NOS genes on the level of both mRNA and protein were observed between both groups. No significant interrelation was noticed between the number of depression episodes experienced and the expression of selected genes on the mRNA level and protein level. CONCLUSIONS: There is no significant difference in MnSOD, MPO, COX-2 and i-NOS between patients with recurrent depressive disorders and those in a first episode of depression. These findings suggest that these enzymes are trait markers of depression and are not related to staging of depression.

Changing risk behaviours for non-communicable disease in New Zealand working men - is workplace intervention effective?

Aims. To evaluate the effectiveness of a health promotion
programme targeting dietary behaviours and physical
activity among male hourly-paid workers and to explore
demographic and attitudinal influences on dietary patterns
at baseline.
Methods. A controlled field trial compared workers at one
intervention and one control worksite. The intervention
comprised nutrition displays in the cafeteria and monthly
30-minute workshops for six months. Key outcome
measures at six and twelve-months were self-reported
dietary and lifestyle behaviours, nutrition knowledge, body
mass index (BMI), waist circumference and blood pressure.
Results. 132 men at the intervention site and 121 men at the
control site participated in the study and a high retention rate
(94% at 6-months and 89% at 12-months) was achieved. At
baseline, 40% of the total sample (253) were obese, 30% had
elevated blood pressure, 59% indicated an excessive fat intake
and 92% did not meet the recommended vegetable and fruit
intake. The intervention reduced fat intake, increased
vegetable intake and physical activity, improved nutrition
knowledge and reduced systolic blood pressure when
compared to the control site. There was no difference in
change in mean BMI or waist circumference. Reduction in
BMI was associated with reduction in fat intake.
Discussion. Low intensity workplace intervention can
significantly improve reported health behaviours and
nutrition knowledge although the impact on more
objective measures of risk was variable. A longer duration
or more intensive intervention may be required to achieve
further reduction in risk factors.