Neuroepidemiology of Parkinson’s disease in an urban area of Iran : from screening and prevalence to nutritional, clinical and psychiatric features and quality of life

Background. Parkinson’s disease (PD) is the second most common neurodegenerative disorder with complex presentations consisting of different motor and non-motor symptoms. The multisystem and progressive nature of PD has made it a complicated entity with broad variation in manifestations and reciprocal effects on several aspects of daily life. Aims. This doctoral thesis investigated different neuroepidemiologic aspects of PD and parkinsonism including its screening and prevalence in the urban area of Tehran, Iran, nutritional status and risk factors for malnutrition, clinical and psychiatric features, healthrelated quality of life (HRQoL) and its determinants in Iranian PD patients. For this purpose, we also aimed to validate several questionnaires and make a new screening instrument. Study I. Psychometric properties of the Persian-translated version of the short-form Parkinson’s disease questionnaire (PDQ-8) were assessed in 114 Iranian patients with PD consecutively recruited from an outpatient Movement Disorder Clinic. The Cronbach’s alpha coefficient of the entire PDQ-8 was 0.740 (95% CI: 0.661-0.806). Replacement of PDQ-8 items with other questions with the highest internal consistency within each dimension of the long-form PDQ (PDQ-39) did not further improve reliability. The Persian version of the PDQ-8 was shown to be a valid and reliable instrument to assess HRQoL in Iranian PD population especially in mental and behavioral aspects. PDQ-8 is a practical and informative instrument in daily clinical practice where clinicians are in shortage of time and need a validated self-reported brief questionnaire. Study II. To develop a new instrument for screening of parkinsonism in community-based surveys, a comprehensive questionnaire consisting of 25 items on different PD symptoms was filled in 157 patients with parkinsonism and 110 controls. Using the concept of clinical utility index (CUI), six items on “stiffness & rigidity”, “tremor & shaking”, “troublesome buttoning”, “troublesome arm swing”, “feet stuck to floor” and “slower daily activity” demonstrated good validity (CUI≥0.64) to be included in the new screening tool . We introduced a new set of six items to screen parkinsonism, which showed higher diagnostic values [area under curve (AUC)=0.977] compared to the previously developed questionnaires. This new instrument could be used in population-based surveys to screen parkinsonism in poor-resource settings. Study III. Following a random multistage sampling of the households within the network of “Health Centers” with 374 subunits in all 22 urban districts of Tehran, 20,621 individuals answered the baseline checklist and the screening questionnaire developed in study II. Data from 19,500 persons aged ≥30 years were entered in the final analysis. A total number of 157 cases were positively screened for parkinsonism that resulted in age- and sex-adjustment prevalence rates of 222.9/100,000 (95% CI: 160-300) and 285/100,000 (95% CI: 240-329) based on the real Tehran population and “WHO World Standard Population”, respectively. The male/female ratio of probable parkinsonism was 1.62 and there was a steady increase by advancing age. The calculated rates for the prevalence of parkinsonism in our study are closer to the reports from some European and Middle-East countries, higher than reports from the Eastern Asian and African populations, and lower than Australia. The prevalence rate of >200/100,000 for parkinsonism in Tehran, Iran is considered as a medium-to-high rate. Study IV. Nutritional status was evaluated in 143 Iranian PD patients and 145 age- and sexmatched controls by means of the validated Persian version of the mini-nutritional assessment (MNA). The mean of total MNA score was not significantly different between the two groups [24.4 (SD=3.8) in controls vs. 25.1 (SD=3.4) in PD patients, p=0.094]. Three (2.1%) PD patients were suffering from malnutrition and another 37 (25.9%) were at risk of malnutrition; while in control group similar feature was observed (2.0% malnourished and 35.2% at risk of malnutrition, p=0.228). Our findings indicated similar nutritional status among mild-to-moderate PD patients and matched controls from the same community. However, nearly one third of PD population were either malnourished or at risk of malnutrition necessitating more attention towards nutritional assessment in PD. Study V. Factors affecting nutritional status were investigated in 150 PD patients including a comprehensive list of motor and non-motor scales. The total score of the Unified Parkinson's disease rating scale (UPDRS) scale (r=-0.613, p<0.001) and PD duration (r=-0.284, p=0.002) had a significant inverse correlation with the total MNA score. A higher Hoehn and Yahr stage [2.5 vs. 2.0, p<0.001], more severe anxiety [8.8 vs. 5.9, p=0.002], depression [9.0 vs. 3.6, p<0.001] and fatigue [5.4 vs. 4.2, p<0.001] were observed in PD patients with nutritional insufficiency. Except for stigma, all other domains of the HRQoL significantly correlated with the total MNA score. We showed that disease duration, severity of motor and psychiatric symptoms (depression, anxiety) and fatigue associated with nutritional status in PD, which itself affected different aspects of HRQoL especially the emotional well-being and mobility. Study VI. A broad spectrum of demographic, motor and non-motor characteristics were evaluated in 157 PD patients consisting of comorbidity profile, nutritional status, UPDRS (total items), psychiatric symptoms (depression, anxiety), fatigue and psychosocial functioning through physical examination, validated questionnaires and scales. Structural equation model (SEM) and multivariate regressions were applied to find determinants of Parkinson’s disease severity index (PDSI) and different domains of HRQoL (PDQ-39). Female sex, anxiety, depression and UPDRS-part II scores were the significant independent determinants of PDSI. A structural model consisting of global motor, global non-motor and co-morbidity indicator as three main components was able to predict 89% of the variance in HRQoL. However, outstanding heterogeneities in the pattern and determinants of HRQoL were found among different PD phenotypes. Conclusions. We showed a medium-to-high prevalence rate for suspicious parkinsonism in Iranian population living in the urban area of Tehran by means of a novel 6-item screening instrument. Similar nutritional status was found in mild-to-moderate PD patients and matched controls from the same community. Yet, approximately one third of people with mild-tomoderate PD were either malnourished or at risk of malnutrition. Duration of PD, severity of motor symptoms, depression, anxiety and fatigue associated with nutritional status in PD patients. Motor symptoms affecting activities of daily living (ADL), depression, anxiety and female sex were found to be the strongest independent determinants of HRQoL in Iranian PD population. Clear heterogeneities were found in the pattern and determinants of HRQoL in different PD phenotypes, which should be considered during the assessments and developing personalized interventions to improve life quality in PD patients with different prominent features

PhD Education Challenges - Doctoral Candidates’ Perspectives

Doctoral training was included in the Bologna system as the third cycle. The important consequence of this change is that the doctoral studies became more structured, and most universities now train doctors in a shorter time period than in the past, mostly in 3 to 4 years. The National Association of PhD students from Serbia (Doktoranti Srbije) conducted the same survey in the form of a questionnaire three years in a row (2010-2012). In 2010 the survey received 335 responses, in 2011 there were 557 responses and in 2012 there were 625. The survey results showed that doctoral candidates recognise supervision as a key issue that need to be improved. Surveyed individuals emphasised the impact of the supervisor’s engagement on the quality of their PhD projects. Supportiveness is the quality that PhD students value the most. This involves supervisors being encouraging, and aware that students' lives extend beyond the PhD. Other key areas for improvement, according to Serbian PhD candidates, are financing and mobility, especially international mobility

Medium-to-high prevalence of screening-detected parkinsonism in the urban area of Tehran, Iran: Data from a community-based door-to-door study

Introduction: Parkinsonism occurs in all ethnic groups worldwide; however, there are wide variations in the prevalence rates reported from different countries, even for neighboring regions. The huge socioeconomic burden of parkinsonism necessitates the need for prevalence studies in each country. So far, there is neither data registry nor prevalence information on parkinsonism in the Iranian population. The aim of our study was to estimate the prevalence rate of probable parkinsonism in a huge urban area in Iran, Tehran using a community-based door-to-door survey. Materials and methods: We used a random multistage sampling of the households within the network of health centers consisting of 374 subunits in all 22 districts throughout the entire urban area of Tehran. Overall, 20,621 individuals answered the baseline checklist and screening questionnaire and data from 19,500 persons aged �30 years were entered in the fnal analysis. Health care professionals used a new six-item screening questionnaire for parkinsonism, which has been previously shown to have a high validity and diagnostic value in the same population. Results: A total of 157 cases were screened for parkinsonism using the validated six-item questionnaire. After age and sex adjustment based on the Tehran population, the prevalence of parkinsonism was calculated as 222.9 per 100,000. Using the World Health Organization�s World Standard Population, the standardized prevalence rate of parkinsonism was 285 per 100,000 (95 confdence interval 240-329). The male:female ratio of probable parkinsonism was calculated as 1.62, and there was a signifcant increase in the screening rate by advancing age. Conclusion: The calculated rates for the prevalence of parkinsonism in our study are closer to reports from some European and Middle Eastern countries, higher than reports from Eastern Asian and African populations, and lower than Australia. The prevalence rate of >200 in 100,000 for parkinsonism in Tehran, Iran could be considered a medium-to-high rate. © 2015 Fereshtehnejad et al

Mortality in Iranian patients with Parkinson's disease: Cumulative impact of cardiovascular comorbidities as one major risk factor

Mortality rate, life expectancy, survival, and the impact of comorbidities on them in people with Parkinson's disease (PD) need to be assessed in settings with different sociodemographic backgrounds. We investigated mortality features in Iranian PD patients focusing on the role of cardiovascular multimorbidity on their survival. Data on mortality and comorbidity profile was gathered in a cohort of 190 individuals with idiopathic PD referred to a Movement Disorders Clinic. Standardized mortality ratio (SMR) compared to the Tehran general population was 3.44 and the life expectancy at birth was 67.4 (95 CI: 59.1-75.8) yr. Patients with at least one cardiovascular comorbidity had a shorter survival time after PD onset (14.0 versus 29.2 yr, p = 0.012). The hazard ratio for death increased 2.8 times (95 CI: 1.5-5.2, p = 0.002) with one additional cardiovascular comorbidity. Among all comorbid conditions, stroke showed the strongest independent effect on mortality in PD patients HR = 13.1 (95% CI: 2.4-71.7), p = 0.003 . Conclusively, life expectancy was slightly lower in Iranian PD patients compared to the general population, while the SMR was high. Cardiometabolic multimorbidity substantially decreased survival in people with PD. Our study highlights the need for assessment, prevention, and treatment of cardiovascular morbidities in parkinsonian patients, given their effect on survival. © 2015 Seyed-Mohammad Fereshtehnejad et al

The effect of interferon-beta1a on relapses and progression of disability in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis

Objectives: In 85 of young adults with multiple sclerosis (MS), onset is a subacute clinically isolated syndrome (CIS) of the optic nerves, brain stem or spinal cord. The advent of disease-modifying treatments for MS has increased attention on early stages of the disease. Therefore, the aim of this study was to evaluate the effect of interferon on relapses and progression of disability in patients with a CIS. Patients and methods: This randomized, clinical trial was conducted in 25 patients who presented with a CIS indicative of MS. They were evaluated in two groups: 11 patients who were receiving interferon-beta1a (Rebif, Serono) subcutaneous injections three times a week (group A), and 14 patients who were not receiving disease-modifying treatment (group B). The progression of disability was determined using the Kurtzke Expanded Disability Status Scale (EDSS) and the numbers of new relapses were recorded during 21 months of follow-up. Results: The mean numbers of new relapses and changes in EDSS at the end of study period were 0.68 (standard deviation S.D. = 0.80) and -1.09 (S.D. = 0.49), and 1.79 (S.D. = 1.05) and -0.64 (S.D. = 0.49) in groups A and B, respectively. Statistical analysis showed that disease-modifying treatment with interferon-beta1a may reduce relapses (P = 0.007) and prevent progressive disability (P = 0.034). Conclusion: Interferon-beta1a significantly delayed progression to disability and incidence of new relapses. © 2007 Elsevier B.V. All rights reserved

Delayed versus same-day percutaneous nephrolithotomy in patients with aspirated cloudy urine.

INTRODUCTION: We present our experience in continuing percutaneous nephrolithotomy (PCNL) versus delayed PCNL when purulent fluid is aspirated during access to the pyelocaliceal system. MATERIALS AND METHODS: This randomized controlled study was carried out on patients who had purulent urine in the pyelocaliceal system at the initial puncturing during PCNL. Patients with recent untreated urinary tract infection, thick or foul pus in aspirated urine, fever, and immunocompromised condition were excluded. Thirty-one patients were randomly divided into 2 groups. In group 1, PCNL was continued, but in group 2, nephrostomy tube was placed and PCNL was performed 10 days later after documented sterile nephrostomy urine. The preoperative and postoperative findings were compared. RESULTS: There were 16 and 15 patients in groups 1 and 2, respectively. All patients had negative urine cultures for microorganisms, preoperatively. The purulent aspirated fluid was infected in 43.8 and 40.0 of the patients in groups 1 and 2, respectively. Postoperative fever was seen in 25.0 and 26.7 of the patients, respectively. No statistical differences were observed between the two groups in terms of bacteriuria, bacteremia, positive calculus cultures, or stone-free rates, and duration of hospitalization between groups 1 and 2, respectively. More analysis with linear regression model showed that postoperative positive blood culture (P < .001), fever (P = .001), and postoperative positive urine culture (P = .02) correlated with duration of hospitalization. CONCLUSION: In the absence of untreated recent UTI and aspiration of thick or foul pus, continuing PCNL can be safe while purulent urine is encountered

Heterogeneous determinants of quality of life in different phenotypes of Parkinson's disease

Objectives Health-related quality of life (HRQoL) is considered a very important outcome indicator in patients with Parkinson's disease (PD). A broad list of motor and non-motor features have been shown to affect HRQoL in PD, however, there is a dearth of information about the complexity of interrelationships between determinants of HRQoL in different PD phenotypes. We aimed to find independent determinates and the best structural model for HRQoL, also to investigate the heterogeneity in HRQoL between PD patients with different phenotypes regarding onset-age, progression rate and dominant symptom. Methods A broad spectrum of demographic, motor and non-motor characteristics were collected in 157 idiopathic PD patients, namely comorbidity profile, nutritional status, UPDRS (total items), psychiatric symptoms (depression, anxiety), fatigue and psychosocial functioning through physical examination, validated questionnaires and scales. Structural equation model (SEM) and multivariate regressions were applied to find determinants of Parkinson's disease summary index (PDSI) and different domains of HRQoL (PDQ-39). Results Female sex, anxiety, depression and UPDRS-part II scores were the significant independent determinants of PDSI. A structural model consisting of global motor, global non-motor and co-morbidity indicator as three main components was able to predict 89 of the variance in HRQoL. In older-onset and slow-progression phenotypes, the motor domain showed smaller contribution on HRQoL and the majority of its effects were mediated through non-motor features. Comorbidity component was a significant determinant of HRQoL only among older-onset and non-tremor-dominant PD patients. Fatigue was not a significant indicator of non-motor component to affect HRQoL in rapid-progression PD. Conclusions Our findings showed outstanding heterogeneities in the pattern and determinants of HRQoL among PD phenotypes. These factors should be considered during the assessments and developing personalized interventions to improve HRQOL in PD patients with different phenotypes or prominent feature. © 2015 Fereshtehnejad et al

Arterial blood gas and spirometry parameters affect the length of stay in hospitalized asthmatic patients

Background: Asthma is a common condition in general medical practice, and it accounts for about 1 of all ambulatory hospital visits. Nowadays, hospitalization rates for asthma have actually been increased in some demographic subgroups despite recent advances in treatment. Understanding the underlying factors that contribute to hospitalization and especially duration of the hospitalization of asthmatics could help elucidate the recent rise in morbidity and also reduce the high demand on health care systems of the disease. The aim of this study was to evaluate factors affecting the duration of hospitalization for Iranian patients with asthma. Methods: This study was conducted on 55 asthmatic patients (diagnosis of asthma was in accordance with the criteria of the American Thoracic Society). The study was performed on patients hospitalized in Rasoul-e- Akram hospital in Tehran, Iran during the period 2005-2006. During hospitalization, the patients' most common complaints were recorded as the symptoms and signs of the medical condition, results of physical examinations, spirometry, arterial blood gas analysis (ABG), and ICU admission. Results: There were 18(32.7) male and 37(67.3) female patients with a mean age of 54.96 (SD=17.54) years. The mean duration of hospitalization was 8.31(SD=4.69) days that ranged between 2 and 23 days. The mean baseline arterial PH (p=0.039, RPearso = -0.362), baseline arterial HCO3 (p=0.042, RPearson = 0.361), changes of FEV1 after bronchodilator (p=0.041, RPearson = -0.363) and patient's age (p=0.002, RPearson=0.0433) were determined as factors affecting duration of hospitalization. Conclusion: Our results showed that more attention needs to be given to the findings of arterial blood gas and spirometry which can potentially affect the duration of hospitalization of asthmatic patients