Jikoshu-kyofu in Singapore.

OBJECTIVE: Jikoshu-kyofu (JKF), a condition characterised by a fear of offending others through emitting foul body odour, was first described in Japan in the 1960s. Although initially thought to be a culture-bound syndrome, it has been described in other countries. It is well established that there are two variants, a non- delusional and a delusional variant. METHOD: We describe two cases of JKF who sought treatment from a hospital in Singapore, compare and contrast their characteristics, and in view of overlaps with other conditions, discuss differential diagnoses. RESULTS: Both cases involved women with fairly similar symptomatology except that the first case was younger, had overvalued ideas (but not delusions), an earlier age of onset and good treatment response, while the other had delusions, late age of onset, became too distressed to continue working and was initially resistant to treatment. CONCLUSION: It appears that the delusional variant may have a longer symptomatic duration before presentation, poorer insight, more resistance to treatment and multiple physician consultations, as well as greater impairment of socio-occupational functioning in contrast to the non-delusional variant.

Setting the clinical context to non-motor symptoms reflected by Park-pain, Park-sleep, and Park-autonomic subtypes of Parkinson's disease.

Non-motor symptoms (NMS) of Parkinson's disease (PD) are well described in both clinical practice and the literature, enabling their management and enhancing our understanding of PD. NMS can dominate the clinical pictures and NMS subtypes have recently been proposed, initially based on clinical observations, and later confirmed in data driven analyses of large datasets and in biomarker-based studies. In this chapter, we provide an update on what is known about three common subtypes of NMS in PD. The pain (Park-pain), sleep dysfunction (Park-sleep), and autonomic dysfunction (Park-autonomic), providing an overview of their individual classification, clinical manifestation, pathophysiology, diagnosis, and potential treatments.

Treatment of apathy in Parkinson's disease: A bayesian network meta-analysis of randomised controlled trials.

Background: Apathy is an important but unrecognised aspect of Parkinson's disease (PD). The optimal therapeutic options for apathy remain unclear. Early recognition and treatment of apathy can reduce the significant burden of disease for patients and their caregivers. Here we conducted a meta-analysis to evaluate the comparative efficacy of different treatment modalities of apathy in PD (CRD42021292099). Methods: We screened Medline, Embase, and PsycINFO databases for articles on therapies for apathy in PD. The outcome of interest is the reduction in apathy scores post-intervention and is measured by standardised mean differences (SMD) with 95% credible intervals (CrI). We included only randomised controlled trials examining interventions targeted at reducing apathy. Results: Nineteen studies involving 2372 patients were included in the quantitative analysis. The network meta-analysis found pharmacotherapy to be the most efficacious treatment, significantly better than brain stimulation (SMD -0.43, 95% CrI -0.78 to -0.07), exercise-based interventions (SMD -0.66, 95% CrI -1.25 to -0.08), supplements (SMD -0.33, 95% CrI -0.67 to 0), and placebo (SMD -0.38, 95% CrI -0.56 to -0.23). Subgroup analysis of pharmacotherapy versus placebo found similar efficacy of dopamine agonists (SMD -0.36, 95% CI -0.59 to -0.12, P = 0.003) and alternative medications (SMD -0.42, 95% CI -0.61 to -0.23, P < 0.001). The remaining comparisons and subgroup analyses did not demonstrate any significant treatment effects. Conclusion: Our meta-analysis of randomised controlled trials showed that pharmacotherapy is the most efficacious treatment option, with dopamine agonists having similar efficacy as other medications. Further research is needed to determine the optimal management strategy.

Safety attitudes, burnout and well-being among healthcare workers during the COVID-19 pandemic: an Indo-Pacific regional cross-sectional study.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact in Asia and has placed significant burden on already stretched healthcare systems. We examined the impact of COVID-19 on the safety attitudes among healthcare workers (HCWs), as well as their associated demographic and occupational factors, and measures of burnout, depression and anxiety. Methods: A cross-sectional survey study utilising snowball sampling was performed involving doctors, nurses and allied health professions from 23 hospitals in Singapore, Malaysia, India and Indonesia between 29 May 2020 and 13 July 2020. This survey collated demographic data and workplace conditions and included three validated questionnaires: the Safety Attitudes Questionnaire (SAQ), Oldenburg Burnout Inventory and Hospital Anxiety and Depression Scale. We performed multivariate mixed-model regression to assess independent associations with the SAQ total percentage agree rate (PAR). Results: We obtained 3,163 responses. The SAQ total PARs were found to be 35.7%, 15.0%, 51.0% and 3.3% among the respondents from Singapore, Malaysia, India and Indonesia, respectively. Burnout scores were highest among respondents from Indonesia and lowest among respondents from India (70.9%-85.4% vs. 56.3%-63.6%, respectively). Multivariate analyses revealed that meeting burnout and depression thresholds and shifts lasting ≥12 h were significantly associated with lower SAQ total PAR. Conclusion: Addressing the factors contributing to high burnout and depression and placing strict limits on work hours per shift may contribute significantly towards improving safety culture among HCWs and should remain priorities during the pandemic.

Impact of Covid-19 on research and training in Parkinson's disease.

The Coronavirus Disease 2019 (Covid-19) pandemic and the consequent restrictions imposed worldwide have posed an unprecedented challenge to research and training in Parkinson's disease (PD). The pandemic has caused loss of productivity, reduced access to funding, an oft-acute switch to digital platforms, and changes in daily work protocols, or even redeployment. Frequently, clinical and research appointments were suspended or changed as a solution to limit the risk of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spread and infection, but since the care and research in the field of movement disorders had traditionally been performed at in-person settings, the repercussions of the pandemic have even been more keenly felt in these areas. In this chapter, we review the implications of this impact on neurological research and training, with an emphasis on PD, as well as highlight lessons that can be learnt from how the Covid-19 pandemic has been managed in terms of restrictions in these crucial aspects of the neurosciences. One of the solutions brought to the fore has been to replace the traditional way of performing research and training with remote, and therefore socially distanced, alternatives. However, this has introduced fresh challenges in international collaboration, contingency planning, study prioritization, safety precautions, artificial intelligence, and various forms of digital technology. Nonetheless, in the long-term, these strategies will allow us to mitigate the adverse impact on PD research and training in future crises.

Spotlight on non-motor symptoms and Covid-19.

The Coronavirus Disease 2019 (Covid-19) pandemic has profoundly affected the quality of life (QoL) and health of the general population globally over the past 2 years, with a clear impact on people with Parkinson's Disease (PwP, PD). Non-motor symptoms have been widely acknowledged to hold a vital part in the clinical spectrum of PD, and, although often underrecognized, they significantly contribute to patients' and their caregivers' QoL. Up to now, there have been numerous reports of newly emerging or acutely deteriorating non-motor symptoms in PwP who had been infected by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), while some of these symptoms, like fatigue, pain, depression, anxiety and cognitive impairment, have also been identified as part of the long-COVID syndrome due to their persistent nature. The subjacent mechanisms, mediating the appearance or progression of non-motor symptoms in the context of Covid-19, although probably multifactorial in origin, remain largely unknown. Such mechanisms might be, at least partly, related solely to the viral infection per se or the lifestyle changes imposed during the pandemic, as many of the non-motor symptoms seem to be prevalent even among Covid-19 patients without PD. Here, we summarize the available evidence and implications of Covid-19 in non-motor PD symptoms in the acute and chronic, if applicable, phase of the infection, with a special reference on studies of PwP.

Stress and cortisol in Parkinson's disease.

Stress is ubiquitous with many factors contributing to its effects, including psychological responses and associated biological factors, including cortisol related physiological responses, and inflammation. Also in Parkinson's disease there is growing evidence for the role of stress in some key symptoms, even stretching to the prodromal stage. Here we discuss the possible contributions of the range and nature of stress in PD and we aim to summarize the current knowledge about the role of stress-related responses on motor and non-motor symptoms, the underlying pathophysiology, and the potential implications for treatment.

Executive function but not episodic memory decline associated with visual hallucinations in Parkinson's disease.

INTRODUCTION: Visual hallucinations (VH) have a significant impact on quality of life for people with Parkinson's disease (PD). A major reason for this is the well-established link with cognitive impairment, but there is still a need for more longitudinal studies examining the specific cognitive domains which may be affected. The aim of this study was to profile decline in cognition associated with VH in a cohort of 69 individuals with PD over 1 year. METHOD: Visual hallucinations assessments were carried out every 3 months. Executive function and episodic memory were assessed at baseline and 1 year. All evaluations were performed via phone interviews. The presence or absence of VH was categorized based on the entirety of the year's data (i.e., no episodes and >0 episodes). We also defined a persistent VH group who had VH present at more than one time point and compared these with a no-VH group and a group with transient VH (i.e., only one episode). RESULTS: Linear mixed-effect models showed that VH were associated with more rapid overall cognitive decline (-0.26, t = -2.39, p = .02), which was driven by executive function (-0.28, t = -2.48, p = .02). Persistent VH were associated with decline in executive function (-0.33, t = -2.4, p = .02), while no relationship was found for non-persistent VH, suggesting that persistent VH be the major driver of this relationship. CONCLUSION: This finding brings greater clarity to the relationship between cognitive decline and VH in PD. Future research should examine the robustness of this phenotype for biomarkers studies and treatment interventions.

Identifying and responding to fatigue and apathy in Parkinson's disease: a review of current practice.

Introduction: Fatigue and apathy are two key non-motor symptoms in Parkinson's disease (PD), with documented negative impact on Quality of life (QoL) and a frequent burden for caregivers.Areas covered: In this review, the authors comment on the latest pathophysiology, clinical phenomenology, the most frequently used scales for fatigue and apathy in PD with a focus on available therapeutic strategies.Expert opinion:The identification of fatigue and apathy in PD is mainly hampered by the lack of a clear consensus on these subjective symptoms. The pathophysiological processes remain unclear, and the large variation in prevalence is likely due to the heterogeneous PD populations and the lack of an enriched cohort of people with fatigue and/or apathy as main symptoms. Treatment strategies, and especially level 1 evidence for specific treatments for fatigue and apathy in PD, remain scarce. The best evidence to date is doxepin, rasagiline and levodopa infusion therapy (for fatigue), and rivastigmine (for apathy). Further efforts should be made to properly identify these two major symptoms in PD, to correctly detect those who may benefit most from tailored personalized interventions.

Amyloid-ß and Parkinson's disease.

Parkinson's disease (PD) is the second commonest neurodegenerative disorder in the world with a rising prevalence. The pathophysiology is multifactorial but aggregation of misfolded α-synuclein is considered to be a key underpinning mechanism. Amyloid-ß (Aß) and tau deposition are also comorbid associations and especially Aß deposition is associated with cognitive decline in PD. Some existing evidence suggests that low cerebrospinal fluid (CSF) Aß42 is predictive of future cognitive impairment in PD. Recent studies also show that CSF Aß is associated with the postural instability and gait difficulties (PIGD) or the newly proposed cholinergic subtype of PD, a possible risk factor for cognitive decline in PD. The glial-lymphatic system, responsible for convective solute clearance driven by active fluid transport through aquaporin-4 water channels, may be implicated in brain amyloid deposition. A better understanding of the role of this system and more specifically the role of Aß in PD symptomatology, could introduce new treatment and repurposing drug-based strategies. For instance, apomorphine infusion has been shown to promote the degradation of Aß in rodent models. This is further supported in a post-mortem study in PD patients although clinical implications are unclear. In this review, we address the clinical implication of cerebral Aß deposition in PD and elaborate on its metabolism, its role in cognition and motor function/gait, and finally assess the potential effect of apomorphine on Aß deposition in PD.

Exploring hyperhidrosis and related thermoregulatory symptoms as a possible clinical identifier for the dysautonomic subtype of Parkinson's disease.

OBJECTIVE: To identify associated (non-)motor profiles of Parkinson's disease (PD) patients with hyperhidrosis as a dominant problem. METHODS: This is a cross-sectional, exploratory, analysis of participants enrolled in the Non-motor Longitudinal International Study (NILS; UKCRN No: 10084) at the Parkinson's Centre at King's College Hospital (London, UK). Hyperhidrosis scores (yes/no) on question 28 of the Non-Motor Symptom Questionnaire were used to classify patients with normal sweat function (n = 172) and excessive sweating (n = 56) (Analysis 1; n = 228). NMS scale (NMSS) question 30 scores were used to stratify participants based on hyperhidrosis severity (Analysis 2; n = 352) using an arbitrary severity grading: absent score 0 (n = 267), mild 1-4 (n = 49), moderate 5-8 (n = 17), and severe 9-12 (n = 19). NMS burden, as well as PD sleep scale (PDSS) scores were then analysed along with other correlates. RESULTS: No differences were observed in baseline demographics between groups in either analysis. Patients with hyperhidrosis exhibited significantly higher total NMSS burden compared to those without (p < 0.001). Secondary analyses revealed higher dyskinesia scores, worse quality of life and PDSS scores, and higher anxiety and depression levels in hyperhidrosis patients (p < 0.001). Tertiary analyses revealed higher NMSS item scores for fatigue, sleep initiation, restless legs, urinary urgency, and unexplained pain (p < 0.001). CONCLUSIONS: Chronic hyperhidrosis appears to be associated with a dysautonomia dominant subtype in PD patients, which is also associated with sleep disorders and a higher rate of dyskinesia (fluctuation-related hyperhidrosis). These data should prompt the concept of hyperhidrosis being used as a simple clinical screening tool to identify PD patients with autonomic symptoms.

Restless legs syndrome - the under-recognised non-motor burden: a questionnaire-based cohort study.

Objectives: Non-motor symptoms (NMS) range from neuropsychiatric to pain and are an important but underexplored feature of restless legs syndrome (RLS). There are currently no tools available which enable the holistic assessment of NMS in RLS in clinical practice. The primary aim of this study was to systematically assess NMS prevalence and burden in patients with RLS using the NMS Questionnaire (NMSQuest) validated for Parkinson's disease. Methods: Patients with idiopathic RLS according to the criteria of the international RLS study group (IRLSSG) were included. Patients underwent a physical examination and clinical interview as well as completed the NMS Questionnaire and the international restless legs syndrome study group (IRLSSG) rating scale. Results: Seventy-four patients with primary RLS were included (mean age 64.6 ± 14.4 years, 62.2% female, mean disease duration 23.5 ± 17.8 years, mean Levodopa equivalent daily dose 63.3 ± 67.4 mg). On average patients reported an IRLSSG rating scale score of 24.8 ± 8.2 (maximum 40) and NMSQuest score of 9.9 ± 5.0 (maximum 30). Patients reported a minimum of two NMS with the majority (39.2%) reporting a moderate NMS burden, followed by severe (28.4%) and very severe (17.6%) burden. The most frequent NMS were insomnia (89.2%) followed by nocturia (70.3%), feeling sad (59.5%), forgetfulness (54.1%), urgency (47.3%), feeling anxious (43.2%), unexplained pain (41.9%), difficulty concentrating (40.5%) and dizziness (40.5%). There were no significant differences in NMSQuest total scores according to disease duration and gender (p = 0.739, p = 0.849). Conclusion: In conclusion, this study is one of the first to address NMS in RLS systematically and the data underlines the need to holistically assess NMS in RLS in order to deliver true value-based healthcare for these patients.

Assessment and Management of Neuropsychiatric Symptoms in Parkinson's Disease.

Neuropsychiatric symptoms are highly prevalent in Parkinson's disease and associated with decreased quality of life and adverse health outcomes. In this review, the assessment and management of common neuropsychiatric symptoms are discussed: depression, anxiety, psychosis, cognitive impairment, dementia and apathy. Validated assessment scales are now available for the majority of symptoms. Balancing dopaminergic therapy plays an important role in their management as increasing doses of dopaminergic agents might address depression and anxiety related to 'off' phases, non-motor fluctuations and apathy, while dose reduction might alleviate psychotic symptoms. More targeted treatment is possible through medications utilising different pathways. Although efficacy profiles of individual agents require further exploration, antidepressants as a drug class have shown utility in depression and anxiety in Parkinson's disease. Psychological therapies, especially cognitive behavioural approaches, are effective. Pimavanserin allows the treatment of psychosis in Parkinson's disease without directly affecting the dopaminergic and cholinergic system. The cholinergic system is currently the only target in Parkinson's disease dementia, and antagonists of this system, as are many psychotropic drugs, need to be used with caution. Management of apathy largely relies on non-pharmacological strategies adapted from dementia care, with antidepressants being ineffective and the role of stimulant therapy needing further evaluation.

Pramipexole in the treatment of REM sleep behaviour disorder: A critical review.

While widely accepted as a first-line treatment for rapid eye movement sleep (REM) behaviour disorder, clonazepam (CNZP) has side effects that limit its applicability. Pramipexole is a possible alternative, but limited literature on its effectiveness exists. This review aims to summarize the available data on the use of pramipexole in REM sleep behaviour disorder. A systematic search of major databases was conducted to look for published and on-going trials. This search yielded a total of five articles, all of which are observational in nature. Factors associated with effectiveness include low doses (less than 1.5mg/day) and idiopathic rapid eye movement sleep behaviour disorder/absence of neurodegenerative disease. Overall, the evidence is inconclusive. This is due to the lack of randomised controlled trials and the challenges in interpreting polysomgraphy findings in rapid eye movement sleep behaviour disorder. Suggestions are given on how future trials evaluating pramipexole treatment in rapid eye movement sleep behaviour disorder could overcome current methodological issues in extant literature.

Burden of blood transmitted infections in substance users admitted for inpatient treatment in Singapore and the associated factors.

INTRODUCTION: There is paucity of local data on the prevalence of blood transmitted infections (BTIs), such as hepatitis B, hepatitis C and human immunodeficiency virus (HIV) infections, among illicit drug users. This study aimed to examine the prevalence of BTIs among substance dependent inpatients and identify the factors associated with BTIs. METHODS: We conducted a retrospective analysis of clinical notes of 170 inpatients with a diagnosis of substance dependence who were admitted at the National Addictions Management Service, Singapore, between 1 June 2009 and 31 May 2010. RESULTS: Majority of the 170 inpatients were male (88.2%) and Chinese (58.2%). The mean age of the patients was 43.1 years, and the main drug of abuse was opioids (86.5%). BTIs were found in 70 (41.2%) inpatients; the prevalence of hepatitis B, hepatitis C and HIV infections was 3.7%, 39.6% and 0%, respectively. Lifetime intravenous drug use, but not needle-sharing, was more common among inpatients who were positive for BTIs (p < 0.01). Logistic regression analysis showed that lifetime intravenous drug use (OR 4.3, 95% CI 1.7- 10.8, p < 0.01) was the only significant predictor of BTIs. CONCLUSION: A large proportion (41.2%) of the substance users seeking help was positive for at least one BTI. Lifetime intravenous drug users were found to be more than four times more likely to have a BTI. Early detection and prevention is essential to improve prognosis.

Ministry of Health Clinical Practice Guidelines: Anxiety Disorders.

The Ministry of Health (MOH) has developed the clinical practice guidelines on Anxiety Disorders to provide doctors and patients in Singapore with evidence-based treatment for anxiety disorders. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on anxiety disorders, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.