Adjunctive bright light treatment with gradual advance in unipolar major depressive disorder with evening chronotype - A randomized controlled trial.

BACKGROUND: Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. METHOD: Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. RESULTS: A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. CONCLUSIONS: The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.

The association between sleep patterns and obesity in older adults.

BACKGROUND: Reduced sleep duration has been increasingly reported to predict obesity. However, timing and regularity of sleep may also be important. In this study, the cross-sectional association between objectively measured sleep patterns and obesity was assessed in two large cohorts of older individuals. METHODS: Wrist actigraphy was performed in 3053 men (mean age: 76.4 years) participating in the Osteoporotic Fractures in Men Study and 2985 women (mean age: 83.5 years) participating in the Study of Osteoporotic Fractures. Timing and regularity of sleep patterns were assessed across nights, as well as daytime napping. RESULTS: Greater night-to-night variability in sleep duration and daytime napping were associated with obesity independent of mean nocturnal sleep duration in both men and women. Each 1 h increase in the standard deviation of nocturnal sleep duration increased the odds of obesity 1.63-fold (95% confidence interval: 1.31-2.02) among men and 1.22-fold (95% confidence interval: 1.01-1.47) among women. Each 1 h increase in napping increased the odds of obesity 1.23-fold (95% confidence interval: 1.12-1.37) in men and 1.29-fold (95% confidence interval: 1.17-1.41) in women. In contrast, associations between later sleep timing and night-to-night variability in sleep timing with obesity were less consistent. CONCLUSIONS: In both older men and women, variability in nightly sleep duration and daytime napping were associated with obesity, independent of mean sleep duration. These findings suggest that characteristics of sleep beyond mean sleep duration may have a role in weight homeostasis, highlighting the complex relationship between sleep and metabolism.

Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.

Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.

Restless legs symptoms increased during COVID-19 pandemic. International ICOSS-survey.

BACKGROUND AND OBJECTIVES: Restless legs syndrome (RLS) has been associated with anxiety, depression, insomnia, lifestyle factors and infections. We aimed to study the prevalence of symptoms of RLS during the COVID-19 pandemic versus pre-pandemic. We hypothesized that pre-existing RLS symptoms worsened and pandemic-related factors may have triggered new symptoms of RLS. METHODS: Adults (≥18 years) from fifteen countries across four continents participated in an online survey between May and August 2020. The harmonized questionnaire included a validated single question on RLS with response alternatives from 1 to 5 on a scale from never to every/almost every evening or night. Other measures were the Insomnia Severity Index (ISI), measures of symptoms of anxiety (GAD-2) and depression (PHQ-2), and questions on different pandemic-related factors. RESULTS: Altogether, 17 846 subjects (63.8 % women) were included in the final analyses. The mean age was 41.4 years (SD 16.1). During the pandemic, symptoms of RLS (≥3 evenings/nights per week) were more common 9.1 % (95 % CI 8.7-10.1) compared to 5.4 % (95 % CI 4.9-6.0) before the pandemic (P < 0.0001). Alltogether 1.3 % (95 % CI 1.1-1.6) respondents had new-onset symptoms (≥3 evenings/nights per week). Moderate-severe insomnia was strongly associated with RLS symptoms. The occurrences of new-onset RLS symptoms were 5.6 % (95 % CI 0.9-13.0) for participants reporting COVID-19 and 1.1 % (95 % CI 0.7-1.5) for non-COVID-19 participants. In the fully adjusted logistic regression model, the occurrence of new-onset RLS symptoms was associated with younger age, social restrictions and insomnia severity. In a similar analysis, RLS symptoms (≥3 evenings/nights per week) were associated with lower education, financial hardship, sleep apnea symptoms, use of hypnotics, insomnia severity, symptoms of depression and possible post-traumatic stress disorder. DISCUSSION: Our findings indicate that RLS symptoms were more common during the pandemic than before. Usually, the prevalence of RLS increases with age. However, during the pandemic, new-onset symptoms of RLS were more common in younger age groups. This may be due to the pandemic-related factors being more pronounced in the younger compared to the older. The association between insomnia, psychiatric symptoms and RLS warrants clinical attention.

Natural history and predictors for progression of mild childhood obstructive sleep apnoea.

AIMS: The natural history of mild childhood obstructive sleep apnoea (OSA) was examined and factors associated with disease progression were identified. METHODS: Subjects were recruited from an epidemiological study which examined the prevalence of OSA in Chinese children aged 6-13 years. The first 56 consecutive children identified with mild OSA (apnoea-hypopnoea index 1-5) were invited for a repeat assessment 2 years after the diagnosis. RESULTS: 45 children participated in the follow-up study, in 13 of whom (29%) the OSA was found to have worsened. Compared with those in whom OSA had not worsened, the worsened OSA group had a greater increase in waist circumference, a higher prevalence of large tonsils (occupying > or =50% of the airway) at both baseline and follow-up, and a higher prevalence of habitual snoring at both baseline and follow-up. The presence of large tonsils had a positive predictive value of 53% and a negative predictive value of 83% for worsening OSA over a 2-year period. Multivariate linear regression analysis showed that the change in obstructive apnoea-hypopnoea index was associated with age at baseline (beta (SE) = -0.92 (0.34), p = 0.009), gender (male = 1; female = 0) (beta (SE) = 4.69 (1.29), p<0.001), presence of large tonsils at baseline (beta (SE) = 4.36 (1.24), p = 0.001), change in waist circumference (beta (SE) = 0.30 (0.09), p = 0.002) and persistently large tonsils (beta (SE) = 5.69 (1.36), p<0.001) over the 2-year period. CONCLUSIONS: Mild OSA in the majority of children does not resolve spontaneously. Subjects with tonsillar hypertrophy, especially boys, should be closely monitored to allow early detection of worsening OSA. Weight control should be stressed in the management of childhood OSA.

Association between physical activity and cardiovascular risk in Chinese youth independent of age and pubertal stage.

BACKGROUND: Childhood and adolescence are critical periods of habit formation with substantial tracking of lifestyle and cardiovascular risk into adulthood. There are various guidelines on recommended levels of physical activity in youth of school-age. Despite the epidemic of obesity and diabetes in China, there is a paucity of data in this regard in Chinese youth. We examined the association of self-reported level of physical activity and cardiovascular risk in Hong Kong Chinese youth of school-age. METHODS: This was a cross-sectional study conducted in 2007-8 in a school setting with 2119 Hong Kong Chinese youth aged 6-20 years. Physical activity level was assessed using a validated questionnaire, CUHK-PARCY (The Chinese University of Hong Kong: Physical Activity Rating for Children and Youth). A summary risk score comprising of waist circumference, blood pressure, fasting plasma glucose and lipids was constructed to quantify cardiovascular risk. RESULTS: In this cohort, 21.5% reported high level of physical activity with boys being more active than girls (32.1% versus 14.1%, p < 0.001). Regression analysis showed physical activity level, sex and pubertal stage were independently associated with cardiovascular risk score. CONCLUSION: Self-reported level of physical activity is associated with cardiovascular risk factors in Chinese youth after adjusting for sex and pubertal stage.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is suggested to be associated with cardiac structural abnormalities and dysfunction but existing evidence is limited and the treatment effect on echocardiographic outcome remains controversial. OBJECTIVE: To examine the presence of subclinical cardiac abnormalities in childhood OSA and the effects of treatment on cardiac changes. METHODS: Polysomnography (PSG) and echocardiographic examinations were performed in 101 children aged between 6 and 13 years who were invited from a community based questionnaire survey. They were classified into a reference group (apnoea-hypopnoea index (AHI) <1, n = 35), mild OSA group (AHI 1-5, n = 39) and moderate to severe group (AHI >5, n = 27) based on the PSG results. Treatments, including adenotonsillectomy or nasal steroids, were offered to the mild and moderate to severe OSA groups. RESULTS: The moderate to severe OSA group had greater right ventricular (RV) systolic volume index (RVSVI), lower RV ejection fraction (RVEF) and higher RV myocardial performance index (RVMPI) than the reference group. They also had more significant left ventricular (LV) diastolic dysfunction and remodelling with larger interventricular septal thickness index (IVSI) and relative wall thickness than those with lower AHI values. The moderate to severe OSA group had an increased risk of abnormal LV geometry compared with the reference group (odds ratio 4.21 (95% CI 1.35 to 13.12)). Log transformed AHI was associated with RVSVI (p = 0.0002), RVEF (p = 0.0001) and RVMPI (p<0.0001), independent of the effect of obesity. Improvement in RVMPI, IVSI and E/e' were observed in those with a significant reduction in AHI (>50%) comparing 6 month with baseline data. CONCLUSIONS: OSA is an independent risk factor for subclinical RV and LV dysfunction, and improvement in AHI is associated with reversibility of these abnormalities.

Association between painful physical symptoms and clinical outcomes in East Asian patients with major depressive disorder: a 3-month prospective observational study.

AIMS: Reports from non-Asian populations indicate that painful physical symptoms (PPS) are associated with poorer clinical and functional outcomes in major depressive disorder (MDD). The purpose of this study is to report comparative changes in disease severity, treatment patterns and quality of life observed in East Asian patients with MDD, with and without PPS, as assessed prospectively over a 3-month observation period. METHODS: This observational study enrolled 909 patients with MDD in psychiatric care settings in China, Hong Kong, Korea, Malaysia, Singapore and Taiwan. Patients were classified as PPS positive (PPS+) or negative (PPS-) based on mean modified Somatic Symptom Inventory scores of >or= 2 or < 2 respectively. The Clinical Global Impression of Severity (CGI-S) and 17-item Hamilton Depression Rating Scale (HAMD(17)) determined depression severity; a visual analogue scale (VAS) determined pain severity; and the EuroQoL (EQ-5D) assessed well-being after 3 months observation. RESULTS: Of the 909 enrollees, 355/471 (75.4%) of PPS+ patients and 363/438 (82.9%) of PPS- patients completed the study (p = 0.006). PPS+ patients improved less than PPS- patients on depression, pain and quality of life measures during the study (HAMD(17) p < 0.001, CGI-S p < 0.001, VAS p = 0.008 and EQ-5D p = 0.004). Fewer PPS+ patients (46.5%) achieved remission compared with PPS- patients (69.4%, p < 0.001). CONCLUSION: As the presence of PPS is associated with poorer outcomes in East Asian MDD patients, clinical management should aim to address both the mental and PPS associated with MDD.

Ambulatory blood pressure in children with obstructive sleep apnoea: a community based study.

BACKGROUND: Childhood obstructive sleep apnoea (OSA) is increasingly being recognised. Its effects on blood pressure (BP) elevation and hypertension are still controversial. OBJECTIVE: To evaluate the association between OSA and ambulatory BP in children. METHODS: Children aged 6-13 years from randomly selected schools were invited to undergo overnight sleep study and ambulatory BP monitoring after completing a validated OSA questionnaire. OSA was diagnosed if the obstructive apnoea-hypopnoea index (AHI) was >1, and normal controls had AHI <1 and snoring <3 nights per week. Children with OSA were subdivided into a mild group (AHI 1-5) and moderate to severe group (AHI >5). RESULTS: 306 subjects had valid sleep and daytime BP data. Children with OSA had significantly higher BP than normal healthy children during both sleep and wakefulness. BP levels increased with the severity of OSA, and children with moderate to severe disease (AHI >5) were at significantly higher risk for nocturnal systolic (OR 3.9 (95% CI 1.4 to 10.5)) and diastolic (OR 3.3 (95% CI 1.4 to 8.1)) hypertension. Multiple linear regression revealed a significant association between oxygen desaturation index and AHI with daytime and nocturnal BP, respectively, independent of obesity. CONCLUSIONS: OSA was associated with elevated daytime and nocturnal BP, and is an independent predictor of nocturnal hypertension. This has important clinical implications as childhood elevated BP predicts future cardiovascular risks. Future studies should examine the effect of therapy for OSA on changes in BP.

Narcolepsy in Southern Chinese patients: clinical characteristics, HLA typing and seasonality of birth.

OBJECTIVE: To report clinical characteristics, human leukocyte antigen (HLA) typing and seasonality of birth of a series of 54 Southern Chinese patients suffering from narcolepsy. METHODS: All subjects underwent detailed medical and psychiatric interviews and a standardised nocturnal polysomnogram followed by a daytime Multiple Sleep Latency Test. Each subject also completed a set of sleep questionnaires. HLA typing was performed in 91% of subjects. RESULTS: A total of 78% and 22% of patients were diagnosed with suffering from cataplectic and non-cataplectic narcolepsy, respectively. The majority (n = 47, 87%) of patients were referred to our sleep clinic for excessive daytime sleepiness (EDS). The cataplectic narcolepsy differed from non-cataplectic narcolepsy by having more rapid eye movement (REM)-related clinical symptoms (more sleep paralysis and sleep-related hallucination) and sleep disturbances (shorter REM latency), as well as tighter association with HLA DQB1*0602. A bi-modal peak pattern was observed at 11 and 39 years old. A similar bi-modal pattern also occurred for EDS and cataplexy. Excess winter births were observed for this series of patients. 81% of patients with cataplectic narcolepsy were DQB1*0602-positive. There were no differences between early- and late-onset cases in the association with positive DQB1*0602 (71.4% vs 60%). Narcolepsy had prominent pernicious effects on various social, academic, family and mental aspects in our patients. CONCLUSIONS: In our Southern Chinese narcolepsy series, bi-modal peak pattern of age of onset, excess winter birth and tight association of HLA DQB1*0602 with cataplectic narcolepsy were found.

Fahr's disease: a differential diagnosis of frontal lobe syndrome.

Fahr's disease refers to a rare syndrome characterised by symmetrical and bilateral intracranial calcification. The basal ganglia are the most common site of involvement and most cases present with extra-pyramidal symptoms. We describe two men with Fahr's diseases who presented with prominent frontal lobe symptoms. The first man presented with frequent uncontrollable bursts of laughter and crying spells. He later developed mild dysarthric speech and choreoathetoid movement. The second man presented with progressive changes in personality and behaviour. In both cases, there were no parkinsonian features. Computed tomographic scans of both patients demonstrated extensive symmetrical calcification over the basal ganglia and dentate nuclei. A repeated imaging scan in the second patient revealed progressive cerebral atrophy but reduction in the calcification. No underlying cause for the bilateral calcification was found. As frontal lobe symptoms are usually inconspicuous in the early stage, the presence of these symptoms might be overlooked in clinical practice when compared with those suffering from prominent movement disorders.