Persian version of brief infant sleep questionnaire (BISQ): a psychometric evaluation.

BACKGROUND: The high prevalence of sleep problems and their negative consequences on children and parents highlight the need to design early screening instruments to evaluate sleep problems in early childhood. We aimed to determine the validity and reliability of the Brief Infant Sleep Questionnaire (BISQ) among the Iranian population. METHODS AND MATERIALS: This study included 646 one-year-old infants by random sampling from the PERSIAN birth cohort study. Following the forward-backward translation of the BISQ, its psychometric properties, including construct validity in terms of concurrent and convergent validities as well as reliability, were evaluated. RESULTS: The CVIs and CVR ranged between 0.8 and 1.00 for all items. Therefore, we keep all the items of the original version of the BISQ in the Persian BISQ. Concurrent validity was assessed by comparing items of the Persian BISQ among different maternal views regarding their infant's sleep. All BISQ items were significantly different among the two levels of maternal view about the infant's sleep problem except daytime sleep duration. The convergent validity of the BISQ was evaluated by calculating the correlation between BISQ items and the ISQ (infant sleep questionnaire) total score as a similar tool. ISQ score was adequately correlated with nocturnal sleep latency and the number of waking at night (rs ranged from 0.59 to 0.72). In addition, the associations of mothers' and infants' demographic variables and nutritional and gestational variables with BISQ items were presented to confirm construct validity. Strong correlations were found between the repeated sleep measures for sleep arrangement, sleep position, and sleep situation (kappa ranged from 0.65 to 0.84), nocturnal sleep duration, daytime sleep duration number of wakings at night, night waking duration, nocturnal sleep latency and sleep-onset time (ICC ranged 0.91 to 0.99). CONCLUSION: The Persian version of the BISQ is a reliable and valid measure for assessing sleep problems in infants. It would be helpful to be utilized for the early diagnosis of infants' sleep problems.

Phenotype and genotype heterogeneity of PLA2G6-associated neurodegeneration in a cohort of pediatric and adult patients.

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by mutations in the PLA2G6 gene is a rare neurodegenerative disorder that presents with four sub-groups. Infantile neuroaxonal dystrophy (INAD) and PLA2G6-related dystonia-parkinsonism are the main two subtypes. In this cohort, we reviewed clinical, imaging, and genetic features of 25 adult and pediatric patients harboring variants in the PLA2G6. METHODS: An extensive review of the patients' data was carried out. Infantile Neuroaxonal Dystrophy Rating Scale (INAD-RS) was used for evaluating the severity and progression of INAD patients. Whole-exome sequencing was used to determine the disease's underlying etiology followed by co-segregation analysis using Sanger sequencing. In silico prediction analysis based on the ACMG recommendation was used to assess the pathogenicity of genetic variants. We aimed to survey a genotype-genotype correlation in PLA2G6 considering all reported disease-causing variants in addition to our patients using the HGMD database and the chi-square statistical approach. RESULTS: Eighteen cases of INAD and 7 cases of late-onset PLAN were enrolled. Among 18 patients with INAD, gross motor regression was the most common presenting symptom. Considering the INAD-RS total score, the mean rate of progression was 0.58 points per month of symptoms (Standard error 0.22, lower 95% - 1.10, and upper 95% - 0.15). Sixty percent of the maximum potential loss in the INAD-RS had occurred within 60 months of symptom onset in INAD patients. Among seven adult cases of PLAN, hypokinesia, tremor, ataxic gate, and cognitive impairment were the most frequent clinical features. Various brain imaging abnormalities were also observed in 26 imaging series of these patients with cerebellar atrophy being the most common finding in more than 50%. Twenty unique variants in 25 patients with PLAN were detected including nine novel variants. Altogether, 107 distinct disease-causing variants from 87 patient were analyzed to establish a genotype-phenotype correlation. The P value of the chi-square test did not indicate a significant relationship between age of disease onset and the distribution of reported variants on PLA2G6. CONCLUSION: PLAN presents with a wide spectrum of clinical symptoms from infancy to adulthood. PLAN should be considered in adult patients with parkinsonism or cognition decline. Based on the current knowledge, it is not possible to foresee the age of disease onset based on the identified genotype.

Efficacy and safety of miglustat in the treatment of GM2 gangliosidosis: A systematic review.

BACKGROUND: Since the results of previous studies regarding the safety and efficacy of miglustat in GM2 gangliosidosis (GM2g) were inconsistent, we aimed to assess miglustat therapy in GM2g patients. METHODS: This study followed the latest version of PRISMA. We included the observational or interventional studies reporting GM2g patients under miglustat therapy by searching PubMed, Web of Science, and Scopus. Data extracted included the natural history of individual patient data, as well as the safety and efficacy of miglustat in GM2g patients. The quality assessment was performed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: A total of 1023 records were identified and reduced to 621 after removing duplicates. After screening and applying the eligibility criteria, 10 articles and 2 abstracts met the inclusion criteria. Overall, the studies represented 54 patients with GM2g under treatment with miglustat and 22 patients with GM2g in the control group. Among patients with available data, 14 and 54 have been diagnosed with Sandhoff disease and Tay-Sachs disease, respectively. Patients included in this review consisted of 23 infantile, 4 late-infantile, 18 juvenile, and 31 adult-onset GM2g. CONCLUSIONS: Although miglustat should not be considered a definite treatment for GM2g, it appears that patients, particularly those with infantile or late-infantile GM2g, could benefit from miglustat therapy to some extent. We also make some suggestions regarding future studies presenting their findings in a standard format to facilitate pooling the available data in such rare diseases for a more comprehensive conclusion.

White matter tracts alterations underpinning reward and conflict processing.

BACKGROUND: Reinforcement sensitivity theory (RST) is proposed as a neurobiological system that eventually led to emotion and motivation-based constructs of personality. Traditionally segmented into the behavioral activation system (BAS) and the behavioral inhibition system (BIS), RST is commonly used to describe personality and behavior. Although there have been studies linking gray matter alterations with BIS/BAS subscales, the role of white matter (WM) alterations is yet controversial. We aimed to investigate the specific WM tracts associated with BIS/BAS scores. METHODS: 220 healthy participants (mean age = 39.14 ± 20.23, 80 (35.7 %) females) were evaluated using the BIS/BAS questionnaire from the LEMON database. Diffusion MRI connectometry (DMRI) was used to investigate the WM correlates of BIS/BAS subscales in each gender group. Multiple regression models with the covariates of age, handedness, and education were fitted to address the correlation of local connectomes with BIS/BAS components. RESULTS: DMRI connectometry revealed that the quantitative anisotropy (QA) value of the splenium of the corpus callosum, right cerebellum, middle cerebellar peduncle, and superior cerebellar peduncle, had a significant negative correlation with each BIS/BAS subscale. In contrast, the QA value in the body of the corpus callosum and bilateral cingulum showed a positive correlation with BIS/BAS subscales. CONCLUSION: The integrity of WM in certain tracts is associated with behavioral activation and inhibition. This finding expands our knowledge of the neural networks associated with risk-taking and reward-seeking behaviors.

The First Report of Iranian Registry of Patients with Spinal Muscular Atrophy.

BACKGROUND: Insufficient amounts of survival motor neuron protein is leading to one of the most disabling neuromuscular diseases, spinal muscular atrophy (SMA). Before the current study, the detailed characteristics of Iranian patients with SMA had not been determined. OBJECTIVE: To describe the key demographic, clinical, and genetic characteristics of patients with SMA registered in the Iranian Registry of SMA (IRSMA). METHODS: IRSMA has been established since 2018, and the demographic, clinical, and genetic characteristics of patients with SMA were recorded according to the methods of treat neuromuscular disease (TREAT-NMD) project. RESULTS: By October 1, 2022, 781 patients with 5q SMA were registered. Of them, 164 patients died, the majority of them had SMA type 1 and died during the first 20 months of life. The median survival of patients with type 1 SMA was 23 months. The consanguinity rate in 617 alive patients was 52.4%, while merely 24.8% of them had a positive family history. The most common type of SMA in live patients was type 3. Morbidities were defined as having scoliosis (44.1%), wheelchair dependency (36.8%), tube feeding (8.1%), and requiring mechanical ventilation (9.9%). Most of the registered patients had a homozygous deletion of SMN1, while the frequency of patients with higher copy numbers of SMN2, was less in more severe types of the disease. Earlier onset of the disease was significantly seen in patients with lower copy numbers of SMN2. The neuronal apoptosis inhibitory protein (NAIP) gene deletion was associated with a higher incidence of more severe types of SMA, higher dependency on ventilators, tube feeding, and earlier onset of the disease. CONCLUSIONS: The IRSMA is the first established Iranian nationwide registry of patients with SMA. Using this registry, decision-makers, researchers, and practitioners can precisely understand the epidemiology, characteristics, and genetics of patients with SMA in Iran.

Effect of parenting intervention through "Care for Child Development Guideline" on early child development and behaviors: a randomized controlled trial.

BACKGROUND: Several studies showed that parenting intervention programs play a core component in early child development. Considering the limited healthcare resources in developing countries, group-session intervention based on care for child development (CCD) guideline might be cost-effective. METHODS: This randomized controlled trial was conducted at an outpatient public Pediatrics clinic in Isfahan, Iran. We included 210 pregnant women aged 18-45 years in their third trimester and followed their children for 18 months. The intervention group underwent 5 educational group sessions, each lasting for almost 45 minutes. The main outcomes were the children's development and socio-emotional behavior problems based on Bayley Scales of Infant and Toddler Development-III (BSID-III) at 12 months and the Children Behavior Checklist (CBCL) at 18 months. RESULTS: Overall, data of 181 children were included in the current study, including 80 in the intervention group and 101 controls. The adjusted median/mean differences between intervention and control groups using median/linear regression were not significant for all BSID-III domains except for median differences for cognitive score based on BSID-III (ß (SE): - 4.98(2.31), p:0.032) and mean differences for anxiety/depression score based on CBCL (ß (SE): - 2.54(1.27), p:0.046). CONCLUSION: In this study, parenting interventions through CCD group sessions were significantly effective on just one subscale of children's socio-emotional behavior domains based on CBCL and one domain of children's development based on BSID-III. There might be a ceiling or floor effects for the BSID-III and CBCL assessment, respectively, leaving little room for improvement as almost all children have achieved their full developmental potential in our study. TRIAL REGISTRATION: IRCT20190128042533N2, Date of registration: 16/01/2020, www.irct.ir.

Latent Class Analysis of knowledge, Attitude, and Practice of a Population-Based Sample of Iranian Pregnant Women toward COVID-19.

Background: The aim of the study is to identify latent class (LC)-derived patterns of women's knowledge, attitude, and practice (KAP) toward coronavirus disease 2019 (COVID-19) in Iran. Materials and Methods: This cross-sectional survey of 2029 women, who participated in the PERSIAN Birth Cohort, was conducted in Isfahan, Iran. KAP was assessed by shortened and validated form of a recently used questionnaire in Iran. LC analysis was used to discover underlying response patterns of KAP toward COVID-19 using Mplus 8.0 software. Results: Three classes were identified: Class 1 (n = 514, 25.33%) "Low knowledge and poor practice, Class 2 (n = 423, 22.08%) "Moderate knowledge and proper practice," and Class 3 (n = 1092, 53.82%) "Low knowledge and proper practice." The lowest rate of positive attitude was seen in Class 3. Women living in rural areas, as well as those with lower education, were more likely to member classes with improper practice. Conclusion: The findings suggest that the LCA approach can provide important information reflecting different levels of adoption of protection toward COVID-19 infection. The results may be useful to conducting health-care programs during the outbreaks.

Paroxysmal hemicrania in children and adolescents: A systematic review.

OBJECTIVE: We aimed to report the accessible demographic, clinical, and radiological characteristics of reported pediatric paroxysmal hemicrania (PH). INTRODUCTION: It has been a while since PH in a child was first described. However, it is still unknown whether children's PH follows the same patterns as adults. METHODS: This study followed the latest version of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). PubMed, Web of Science, and Scopus were searched systematically without time limitation. We included all English-language, peer-reviewed articles, including observational or interventional studies reporting PH cases in children or adolescents based on the International Classification of Headache Disorders (ICHD) criteria. Data extracted included PH class; sex; age; age of onset; frequency, duration, site, severity, and quality of pains; triggers; and autonomic and migrainous symptoms, as well as a sense of restlessness/agitation, response to treatment, laboratory investigations, imaging, comorbidity, and family history. For quality assessment, two independent reviewers (MB and VM) assessed the methodological quality of the included studies through the Joanna Briggs Institute's critical appraisal checklist. RESULTS: A total of 182 records were identified and reduced to 116 after removing duplicates. After screening, 22 articles met the inclusion criteria. Overall, the studies represented 35 children or adolescents with PH. We found a boy-to-girl ratio of 1.125:1. Onset occurred at a broad range of 1 to 14 years old. The mean age of onset among reported cases in children and adolescents was 6.5 years, while the mean age of diagnosis was 8.2 years. [Correction added on 22 August 2022, after first online publication: In the preceding sentence, 6.3 and 7.9 years were changed to 6.5 and 8.2 years, respectively.] The attacks' frequency and duration were greatly varied. Left-sided pain occurred twice as often as right-sided pain. The characteristics of the pain were usually severe in intensity. In nearly all of the cases, it was accompanied by ipsilateral cranial autonomic features. While most attacks were spontaneous, there were some common triggers. The physical examination, electroencephalogram, and brain magnetic resonance imaging had normal findings. Almost all patients benefited from indomethacin and showed complete responses to treatment, while some needed combination treatment of indomethacin with other medications. CONCLUSION: Although pediatric-onset PH has similar features to adult-onset PH, there are some challenges with ICHD criteria for younger children that limit the ability to confidently assign a diagnosis. Moreover, owing to concomitant migrainous features, PH may be confused with migraine in children and adolescents.

Parental Occupational Exposure and Neurodevelopmental Disorders in Offspring: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Parental occupational exposures might be associated with neurodevelopmental disorders (NDDs) in offspring. We aimed to conduct a systematic review and meta-analysis to summarize and synthesize the current literature and to estimate the pooled magnitude of the underlying association(s) between parental occupational exposures and subsequent risk of NDDs. RECENT FINDINGS: In the meta-analysis of 20 included studies, significant associations were found between parental occupational exposure to pesticides or solvents and the risk of attention deficit hyperactivity disorder in offspring. Prenatal occupational exposure to pesticides was significantly associated with motor development or cognition disorders in children. Furthermore, some evidence showed that metals might have a role in the development of autism spectrum disorders. Further studies need to identify the level of parental occupational exposures that can be significantly associated with NDDs. Moreover, utilizing standardized outcome and exposure scales is recommended to incorporate paternal, maternal, and parental as well as both prenatal and postnatal exposure in future studies.

Changes in Lifestyle Behaviors of Children and Adolescents during the COVID-19 Pandemic and the Impact on the Development of Non-Communicable Diseases: A Narrative Review.

Background: Quarantine restrictions have changed the usual lifestyle habits of children and adolescents. In this review, we summarize how the COVID-19 outbreak changed lifestyle during childhood and discuss potential short- and long-term effects of NCD high-risk behaviors on health outcomes. Methods: literature search was conducted in Medline database (PubMed), Scopus, Embase, Web of Science, and Google Scholar. All studies that assessed the relationship between COVID-19 outbreak and lifestyle changes were included. Results: NCD risk factors such as unhealthy diet, physical inactivity, prolonged screen time and sedentary behavior, disrupted sleep schedules and sleep quality, as well as mental disorders during COVID19 in childhood, may increase the susceptibility to NCDs in adulthood. These changes in lifestyle behaviors have short and long-term cardio-metabolic and psychological health outcomes. Since it is not clear when COVID-19 is completely controlled, assessment of the interactions between COVID-19 and lifestyle activities in the pediatric age group is critical. Conclusion: The pandemic of coronavirus disease 2019 (COVID-19) has greatly influenced all levels of health systems. During the COVID-19 pandemic, prevention and management of non-communicable diseases (NCDs) will need to be prioritized even further.

Injection of Paraquat in the Neck: A Rare Complicated Case Report.

Paraquat is a highly toxic compound and a widely used herbicide that causes serious morbidity and mortality. The most well-known route of poisoning is oral ingestion, whereas parenteral injection of paraquat is individually uncommon. We present a case who injected paraquat in his neck in an attempt to commit suicide. His general condition got worsened gradually over 3 days. He received early hemodialysis in 4 h after self-injection and then supportive treatment in intensive care unit. Early hemodialysis helped him survive, but during hospitalization, some rare complications occurred, and unfortunately, he died after 3 months. Despite the high-risk route of poisoning, the patient survived for 3 months. Our patient was protected from renal and hepatic damage may be because of early hemodialysis but suffered from central nervous system and pulmonary damage.

Knowledge, Attitudes, and Practices toward COVID-19 among Persian Birth Cohort Participants.

BACKGROUND: Knowledge, attitudes, and practices (KAP) toward COVID-19 play an important role in controlling the outbreak. The present study aimed to investigate the KAP of a group of women toward COVID-19 during the second wave of the outbreak in Iran. METHOD AND MATERIAL: A cross-sectional survey of 2862 women was conducted in May and June 2020 in two centers of Persian birth cohort. The survey instrument was a self-reported questionnaire Multivariable linear regression analysis to identify factors associated with knowledge and practice. toward COVID-19 and multinomial logistic regression analyses to identify factors associated with attitudes. Unstandardized regression coefficients (ß) and odds ratios and their 95% confidence intervals were used to quantify the associations between variables and KAP. RESULT: Good knowledge and optimistic attitudes toward the successful control of COVID-19 was seen among participants. Overall, about 57.3% (1640), 41.1% (1176), and 1.6% (46) of respondents were categorized as low (score <50%), moderate (score: 50%-80%), and high (score > 80%) proper practice, respectively. Eighty-five individuals with COVID-19 experience (3.0%) had lower knowledge score (79.91 ± 17.93 vs. 83.81 ± 13.88, P < 0.001) and lower proper practice score (40.22 ± 16.57 vs. 47.96 ± 16.15, respectively, P < 0.001) compared to those who were not infected. A higher level of knowledge was associated with appropriate practice in both groups of positive attitudes (χ2 = 32.23, P < 0.001) and negative attitudes (χ2 = 31.49, P < 0.001). CONCLUSION: This survey recorded good knowledge and relatively good attitudes among women. Special health policies plan should be taken for target populations among women during the COVID-19 pandemic.

A meta-analysis on the effect of telemedicine on the management of attention deficit and hyperactivity disorder in children and adolescents.

INTRODUCTION: This study aims to report the effect sizes of telemedicine treatments on the symptom domains of paediatric ADHD. METHODS: In this systematic review and meta-analysis, electronic databases, i.e. PubMed, Scopus, Web of Science and Embase, were searched for articles published up to December 2020. The inclusion criteria were as follows: children or adolescents diagnosed for ADHD or other hyperkinetic disorders; randomized controlled trials (RCTs); efficacy established with parents and teachers or self-rating scales at least for one of the following domains: inattention, cognitive function, hyperactivity, hyperactivity/impulsivity or oppositional behaviours. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. RESULTS: From 310 records reduced to 228 after removing duplicates, overall 12 studies were fulfilled our inclusion criteria. They consisted of 708 participants (358 with telemedicine intervention and 350 controls). The telemedicine interventions varied from computerized training programmes with phone calls to videoconferencing programmes, virtual reality classrooms or games. The most applicable method consisted of computerized training programmes with phone calls. Pooling results of all studies with available data on each subscale showed a significant effect of telemedicine on inattention/cognitive function (standardized mean difference (SMD) = 0.26, 95% CI: 0.16, 0.36), hyperactivity/impulsivity (SMD = 0.29, 95% CI: 0.06, 0.52), and oppositional behaviours (SMD = 0.72, 95% CI: 0.24, 1.20) subscales in ADHD. Almost all studies had an overall unclear risk of bias. The source of outcome assessment (parents, teachers or self-report questionnaire) was addressed as a potential confounding factor. In almost all symptom domains, the satisfaction from the treatment was higher in parents than in teachers. CONCLUSIONS: The clinical effects of telemedicine on the treatment of ADHD showed a small effect size for inattention/cognitive function, hyperactivity/impulsivity and oppositional behaviours.

Estimation of Cardiovascular Disease Risk Factors in the Undefined Participants of Campaign in Isfahan in 2017.

BACKGROUND: The cardiovascular mortality rate in Iran has been reported 65% of all death recently. Despite the high prevalence of cardiovascular diseases (CVD) risk factors and its burden in developing countries, public awareness of CVD symptoms and its risk factors are very low, leading to poor control of these risk factors. METHODS: Our study is a cross-sectional study that was conducted in an undefined sample of 163 individuals who participated in a public health campaign. We used a validated questionnaire containing demographic, cardiovascular history, family history, lifestyle (exercise, smoking, alcohol, and environment), stress, sleep, bowel toxicity, blood sugar, inflammation/pain, and diet parts for estimating total cardiovascular risk factor. RESULTS: 52.7% of our participants were male. The mean age of our participants was 42.6 ± 47.27 years. Half of our participants (50.3%%) were between 30 and 60 years. 12.3% of the participants were diagnosed with CVD. 12.8% were smokers and 25.8% were passive smokers. 73% of our participants had a high level of stress in their individual and work life. 35.5% of participants sleep less than 6 h per night. Half of them complained of initial or intermittent insomnia. 51.5% of our participants were at high or very high risk for CVD with three or more relative risks. There was a significant association between total cardiovascular risk and blood pressure, weight, sleep, and lifestyle in our population. CONCLUSIONS: More than half of our participants were on high or very high risk for CVD. The most common risk of CVD events in our participants is attributed to hypertension. Weight, sleep, and lifestyle were other modifiable risks that had a significant association with CVD in our study.

Association of serum 25-hydroxyvitamin D concentration with anthropometric measures in children and adolescents: the CASPIAN-V study.

BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) concentrations reflect vitamin D status, with deficiency implicated as an underlying factor for many adverse health effects. This study aims to analyze the association between vitamin D status and different anthropometric measures in a large pediatric population. METHODS: This nationwide cross-sectional study was conducted in 2019 in blood samples obtained from school students of 30 provinces in Iran. Participants were 2596 children and adolescents aged 7-18 years. Weight, height, waist circumference (WC), hip circumference (HC), neck circumference (NC), and wrist circumference (WrC) were measured. Body mass index (BMI) and waist-to-height ratio (W/HtR) were calculated. Serum 25(OH)D concentrations were measured using chemiluminescent immunoassay. RESULTS: Participants consisted of 55% boys, 71.3% urban inhabitants, with a mean (SD) age of 12.1 (3.0) years. Overall, vitamin D deficiency was documented in 10.6% of participants, insufficiency in 60.4%, and sufficiency in 29% of the population studied. The mean of BMI and WC was higher in the vitamin D deficient than in the vitamin D sufficient group (19.31 kg/m2 and 69.24 cm vs. 18.34 kg/m2 and 65.73 cm, respectively, P < 0.01). Multivariate linear regression models revealed a significant association of vitamin D insufficiency with WC and W/HtR (P < 0.05). Likewise, in the multivariate regression models, vitamin D deficiency was associated with BMI, WC, and W/HtR (P < 0.05). CONCLUSION: Our findings on the inverse association between vitamin D status and some anthropometric measures underscore the importance of providing vitamin D by fortification and supplementation programs of vitamin D for the pediatric population. LEVEL OF EVIDENCE: V.

Evaluation of non-motor symptoms and their impact on quality of life in patients with Parkinson's disease, Isfahan, Iran.

Background: Parkinson's disease (PD) is diagnosed on the basis of motor symptoms, but non-motor symptoms (NMS) have high prevalence in PD and often antecede motor symptoms for years and cause severe disability. This study was conducted to determine the prevalence of NMS in patients with PD. Methods: This cross-sectional study was performed in Isfahan, Iran, on patients with PD. The prevalence of NMS was evaluated by the NMS questionnaire, the NMS scale, and Parkinson's disease questionnaire-39 (PDQ-39). The Mini-Mental Status Examination (MMSE) was used for assessing cognition. Results: A total of 81 patients, including 60 men and 21 women, were recruited for this study. The prevalence of NMS was 100%, and the most commonly reported symptom was fatigue (87.7%); there was a strong correlation between NMS and the quality of life (QOL) of patients with PD (P < 0.001). Conclusion: This study showed that NMS are highly prevalent in the PD population and adversely affect QOL in these patients. Early diagnosis and treatment can improve QOL and can help in disability management of patients with PD.