Convolutional Neural Network for Freezing of Gait Detection Leveraging the Continuous Wavelet Transform on Lower Extremities Wearable Sensors Data.

Freezing of Gait is the most disabling gait disturbance in Parkinson's disease. For the past decade, there has been a growing interest in applying machine learning and deep learning models to wearable sensor data to detect Freezing of Gait episodes. In our study, we recruited sixty-seven Parkinson's disease patients who have been suffering from Freezing of Gait, and conducted two clinical assessments while the patients wore two wireless Inertial Measurement Units on their ankles. We converted the recorded time-series sensor data into continuous wavelet transform scalograms and trained a Convolutional Neural Network to detect the freezing episodes. The proposed model achieved a generalisation accuracy of 89.2% and a geometric mean of 88.8%.

Periventricular white matter hyperintensity burden and cognitive impairment in early Parkinson's disease.

BACKGROUND AND PURPOSE: This study quantified the total brain and periventricular white matter hyperintensity (WMH) burdens in patients with early Parkinson's disease (PD) and explored their associations with cardiovascular risk factors and cognitive performance. METHODS: A total of 175 non-demented patients with early PD who had undergone baseline brain magnetic resonance imaging were included. Comprehensive neurocognitive testing was conducted to identify PD with mild cognitive impairment (PD-MCI) and to evaluate performances in individual cognitive domains. Cardiovascular risk was expressed as a modified Framingham 10-year cardiovascular risk score (mFRS). RESULTS: A total of 53.7% of this early PD cohort fulfilled the diagnostic criteria for PD-MCI. An increase in mFRS was significantly associated with increases in the total brain WMH (P = 0.015) and periventricular WMH (P = 0.040) burden, independent of age and gender. The periventricular WMH burden was significantly associated with PD-MCI (P = 0.046) in early PD, independent of cardiovascular risk factors. Patients in the 5th quintile of periventricular WMH burden were 8.6 times more likely to have PD-MCI compared with patients in the 1st quintile of periventricular WMH burden (P = 0.004). However, total brain WMH burden was not associated with PD-MCI (P = 0.158). In individual cognitive domains, heavier periventricular WMH burden was associated with worse executive function and visuospatial function independent of cardiovascular risk factors. CONCLUSION: Periventricular WMHs are a useful imaging biomarker for cognitive impairment in early PD. Cardiovascular risk factors, although associated with periventricular WMHs, were unable to fully explain the association between periventricular WMHs and cognitive impairment in early PD.

Antibiotic management of acute pharyngitis in primary care.

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice.

No association of DNM3 with age of onset in Asian Parkinson's disease.

BACKGROUND AND PURPOSE: Genetic variability in DNM3 has been shown to modify age of onset of Parkinson's disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab-Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the DNM3 locus was associated with age of PD onset in both carriers and non-carriers of LRRK2 risk variants in Asians. METHODS: We analyzed the association of DNM3 rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian LRRK2 risk variants. RESULTS: DNM3 rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non-carriers. CONCLUSIONS: DNM3 rs2421947 was not associated with age of PD onset in LRRK2 risk variant carriers and non-carriers in Chinese samples. Further studies in other Asian populations will be of interest.

Non-motor symptoms in early Parkinson's disease with different motor subtypes and their associations with quality of life.

BACKGROUND AND PURPOSE: The aim of this study was to examine non-motor symptoms in different Parkinson's disease (PD) motor subtypes and their associations with quality of life (QoL). METHODS: A total of 132 patients with early PD with comprehensive motor examinations and non-motor symptom assessments were included. Motor subtypes were classified based on Stebbins' method. Non-motor symptoms were assessed by the Non-Motor Symptom Scale (NMSS) and validated by more comprehensive instruments, including the Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS). QoL was measured by the Parkinson's Disease Questionnaire-8. RESULTS: We identified 66 patients (50%) with tremor-dominant (TD) subtype, 47 (35.6%) with postural instability and gait disorder (PIGD) subtype and 19 (14.4%) with Intermediate subtype. By comparing NMSS scores, patients with the PIGD subtype had more severe sleep impairment and fatigue (domain 2 score: 5.64 vs. 2.52, P < 0.001), urinary symptoms (domain 7 score: 6.96 vs. 3.48, P = 0.005) and overall more severe non-motor symptoms (NMSS total score: 25.89 vs. 17.27, P = 0.031), compared with patients with the TD subtype. Validation using the PSQI and FSS again suggested that patients with the PIGD subtype had independently and significantly more severe sleep impairment (PSQI score: 5.57 vs. 4.29, P = 0.020) and fatigue (FSS score: 34.81 vs. 25.85, P = 0.003) compared with patients with the TD subtype. Several non-motor symptoms had significant associations with QoL, among which sleep impairment and fatigue (P < 0.0001, partial r2 = 0.273) explained the largest proportion of QoL variability in patients with PD. CONCLUSIONS: Patients with the PIGD subtype had more severe sleep impairment, fatigue and urinary disturbance compared with patients with the TD subtype. Sleep impairment and fatigue were the most important factors affecting QoL independent of motor subtypes. Prompt identification and treatment of these non-motor symptoms may improve patients' QoL.

Progression of subcortical atrophy in mild Parkinson's disease and its impact on cognition.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is associated with pronounced grey matter atrophy in various brain regions. However, the association between atrophy patterns and progression from no cognitive impairment (NCI) to Parkinson's disease (PD)-MCI is not clearly known. We investigated the pattern and progression of atrophy in subcortical structures and its impact on cognition in patients with mild PD. METHODS: Sixty-five patients with mild PD with baseline and longitudinal clinical and neuropsychological assessments, and structural magnetic resonance imaging scans were studied. Movement Disorder Society Task Force criteria were used to classify patients with PD into PD-NCI (n = 54) and PD-MCI (n = 11). Based on progression over time, those who remained without cognitive impairment were classified as PD-stable (n = 42) and those who converted to MCI over 18 months were classified as PD-converters (n = 12). FreeSurfer was used to measure cortical thickness and subcortical volumes at baseline and follow-up. RESULTS: Parkinson's disease-MCI showed baseline thalamus atrophy and progressive atrophy in the thalamus, caudate, presubiculum, cornu ammonis 1 and 2-3, and significant memory and executive dysfunction compared with PD-NCI. PD-converters had greater accumbens atrophy at baseline and progressive atrophy in the thalamus, caudate and accumbens with dysfunctions in memory and executive domains. CONCLUSIONS: Progression of cognitive impairment in non-demented PD is associated with a specific pattern of subcortical atrophy. Findings from this study will allow future studies to investigate in the role of subcortical structures as a biomarker for PD dementia.

AcuFocus Corneal Inlay to Correct Presbyopia Using Femto-LASIK. One Year Results of a Prospective Cohort Study.

PURPOSE: To evaluate the safety and efficacy of the AcuFocus small aperture corneal inlay (KAMRA) for the correction of presbyopia using femto-LASIK. PATIENTS AND METHODS: This is a prospective, non-randomised cohort study including 50 presbyopic patients with hyperopia, emmetropia or mild myopia. The intracorneal inlay was implanted in the non-dominant eye using a VisuMax femtosecond laser (Zeiss 500 kHz) to create a superior-hinged flap. The inlay was centred over the visual axis. Minimum postoperative follow-up was performed for a period of 12 months. RESULTS: Fifty intracorneal inlays were implanted. At one year follow-up, the median uncorrected near visual acuity significantly improved from Jaeger (J)8 to J2 (p < 0.001). 94 % of patients could read J3 or better. The median uncorrected distance visual acuity also improved from 20/32 to 20/22 (p < 0.001). 92 % of patients could see 20/32 or better. One implant had to be recentred at four weeks follow-up. One implant was removed six months after implantation due to insufficient uncorrected near and distance visual acuity as well as slight corneal haze, which resolved four weeks later under topical treatment with fluorometholone eye drops, without any loss of best corrected distance visual acuity. No other complications occurred during the postoperative follow-up period. CONCLUSION: AutoFocus Corneal Inlay (ACI), also known as KAMRA, can provide a safe, effective and, most importantly, reversible treatment for presbyopia in hyperopic, myopic and emmetropic patients.

Problems with cigarette smoking and attitudes towards the ban of smoking in Shantou, China.

OBJECTIVES: To investigate the extent of cigarette smoking, knowledge of health hazards and attitudes towards the ban of smoking in Shantou, China, as causes for failure to control smoking. STUDY DESIGN: Environmental monitoring and population survey. METHODS: Particulate matter (PM2.5) measurements were conducted in randomly selected public places (restaurants, non-alcoholic drink shops and internet bars) and exposure-related health hazards were evaluated. University students and adult citizens were randomly selected to determine their extent of cigarette smoking, knowledge of health hazards and attitude towards the ban of smoking in public places. The collected data were used to evaluate possible causes and solutions to the smoking problem. RESULTS: From PM2.5 measurements, the average indoor to outdoor concentrations in non-smoking restaurants were 33.4 vs. 30.6 µg/m(3), P > 0.05; average indoor of smoking restaurants was 350.0% higher, P < 0.05; internet bars was 395.7% higher, P < 0.05; and non-alcoholic drink shops was 650.2% higher, P > 0.001. From our survey of 1100 university students: 1) 17.5% and 7.5% were active male and female smokers, respectively; and 2) 57.5% of students would accept a smoke-ban policy. From 502 adult citizens: 1) 27.5% were active male smokers; 2) Approximately 40 and 60% had inadequate knowledge of health hazards from smoking and second-hand smoke exposure; and 3) >90% of them would accept a smoke-ban policy. CONCLUSIONS: Our data indicate that failure to ban smoking was not caused by resistance from smokers but inadequate (national and local) government effort to educate the public and to enforce existing policy. The data suggest that development of a citizen-based approach, in collaboration with willing officials, may be highly successful in the control of cigarette smoking in China.

Environmental and DNA repair risk factors for breast cancer in South China.

PURPOSE: The incidence of breast cancer (BC) in China has been rapidly increasing. We hypothesize that China-specific risk factors, both life-style and inherent ones, contribute to the problem. METHOD: We have conducted an epidemiology and functional DNA repair investigation to identify risk factors for the development of BC in Shantou, China. RESULTS: Our survey of 372 patients and 419 matched normal controls confirmed the significant risk from many universal factors: high BMI, low education level, low fruit intake and sedate lifestyle. Significant risk factors can be organized into endogenous ones (low education and cooking with lard instead of vegetable oil) and externally-introduced ones (sedate life-style and cigarette smoking). We also found highly significant risk from passive exposure to cigarette smoke. Using the Challenge-Comet assay and blood samples from 57 patients who did not inherit the tumor suppressor BRCA gene mutations and 62 matched normal controls; we showed that reduced functional DNA repair capacity was a significant risk factor. In addition, the reduced repair capacity was associated with lymph node metastasis, and with tumors that had negative ER receptor and over-expression of Her-2. CONCLUSION: Our study indicates that combined externally-introduced and endogenous life-style factors were involved with the increased incidence of BC in China. We also showed, for the first time, that inherent deficiency in DNA repair function was a significant risk factor for BC. The inherent deficiency can interact with other risk factors to significantly increase risk for BC. In addition, the reduced repair capacity was associated with certain clinical features that are indicative of poor prognosis. In this context, it is possible to integrate DNA repair capacity knowledge in promoting prevention of BC and in enhancing personalized therapeutic protocols.

Development of esophageal cancer in Chaoshan region, China: association with environmental, genetic and cultural factors.

Esophageal squamous cell carcinoma (ESCC) is the eighth most common cancer by incidence worldwide. Although the cancer is located at a readily recognizable and accessible site in the body, it is the sixth most common cause of cancer death. The 1- and 5-year survival rates in China are 50% and 15%, respectively. Furthermore, the cancer has distinct geographic and etiological risk factors in different locations around the world. Since ESCC is highly prevalent in the Chaoshan (Southeastern) region of China, this report will focus on a review of risk factors for the cancer in this area. From the review, it is clear that some important and traditional factors are involved, e.g. environmental mutagens, genetic predisposition. However, unique factors, e.g. the drinking of very hot tea, may play an important role. This review highlights the role of complex risk factors (environmental, genetic and cultural) which contribute to the multistage development of cancer: localized injury, inflammation, mitogenesis, mutagenesis, carcinogenesis and eventually mortality. The latter is contributed by unnecessary delay in seeking medical care which may be culturally related. The review emphasizes the need to identify causal mechanisms for the complex carcinogenic process which can provide opportunity for prevention and treatment of this potentially curable cancer.

Clinical evolution of Parkinson's disease and prognostic factors affecting motor progression: 9-year follow-up study.

BACKGROUND AND PURPOSE: There have been few long-term studies that have characterized and charted the clinical progression of Parkinson's disease (PD). This study was therefore undertaken to understand the natural clinical evolution of treated PD patients and to identify the variables that predict greater progression in these patients. METHODS: A longitudinal linear mixed model analysis of motor score progression was performed on 576 PD patients derived from the National Neuroscience Institute Movement Disorders Database. Clinical and demographic variables were taken at baseline and formed the subgroups for comparison (gender, age at diagnosis, subtype, Mini-Mental State Examination score and baseline motor score). Motor score progression was calculated at each patient follow-up time point as the difference between Unified Parkinson's Disease Rating Scale (UPDRS) motor score at baseline and follow-up scores. RESULTS: The overall annual motor score progression as measured by the change of UPDRS motor scores from baseline ranged from 0.62% to 3.67%. There are three distinct phases: improvement, stability, and steady progression. Patients returned to baseline score 2-2.5 years after diagnosis, with stability lasting to 7 years, followed by a period of steady progression. When analyzed longitudinally, male gender (P < 0.03), older age at diagnosis (P < 0.05), akinetic-rigid subtype (P < 0.04), cognitive impairment (P < 0.005) and lower baseline motor score (P < 0.04) were associated with greater progression of motor scores. CONCLUSIONS: Our results show that, when measured clinically, motor progression was non-linear and that it occurred in distinct phases, all of which were affected by baseline demographic and clinical variables such as gender, age at diagnosis, disease subtype, cognitive status and baseline motor score.

Oral arsenic trioxide-based regimen as salvage treatment for relapsed or refractory mantle cell lymphoma.

BACKGROUND: Mantle cell lymphoma (MCL) is aggressive, and relapsed/refractory disease has poor outcomes. PATIENTS AND METHODS: Thirty-nine patients (men = 34, women = 5) at 64 (41-82) years of age with relapsed/refractory MCL, ineligible for high-dose chemotherapy and had received 2 (1-5) prior regimens, were treated with a continuous oral regimen, comprising oral arsenic trioxide (oral-As2O3), chlorambucil and ascorbic acid. RESULTS: Overall response rate was 49% (complete response, CR = 28%; partial response, PR = 21%). Only grade 1/2 toxicities were observed (hematologic: 56%, hepatic: 8%). Response was maintained in 11 patients (CR = 8; PR = 3), after a median of 24 (2-108) months. Independent prognostic factors for response were increased lactate dehydrogenase (P = 0.04) and unfavorable MCL international prognostic index (P = 0.04). At a median follow-up of 21 (1-118) months, the median progression-free survival (PFS) was 16 months, and overall survival (OS) 38 months. Independent prognostic factors for PFS were female gender (P = 0.002), and Eastern Cooperative Oncology Group (ECOG) performance score of 2 (P = 0.009). Independent prognostic factors for OS were female gender (P < 0.001), ECOG performance score of 2 (P = 0.03), non-response (P < 0.001), and disease progression after initial response (P = 0.05). CONCLUSION: An oral regimen of oral-As2O3, chlorambucil and ascorbic acid was active with minimal toxicity in relapsed/refractory MCL, achieving durable responses in ∼30% of cases.

Clinico-genetic comparisons of paroxysmal kinesigenic dyskinesia patients with and without PRRT2 mutations.

BACKGROUND AND PURPOSE: Mutations in the PRRT2 gene have been identified in patients with paroxysmal kinesigenic dyskinesias (PKD); however, not many detailed clinico-genetic correlations have been performed. METHODS: To investigate PRRT2 mutations in a mixed Asian PKD population and perform clinico-genetic correlations, we recruited patients between 2002 and 2011 and administered a standardized questionnaire. RESULTS: Amongst 29 unrelated patients with PKD recruited, five PRRT2 mutations were present in 15 patients. Three mutations (c.649dupC, c.649delC, c.649C>T) were previous reported, while three were novel mutations (c.604delT; c.609_611delACC/p.Ser202Hisfs; c.697_698delAG/p.Ser233Trp fsX5). Clinico-genetic correlations revealed that a history of seizures was more common in patients with PRRT2 mutations, although this did not reach statistical significance (P= 0.08). A younger age of onset, non-Chinese, and the presence of premonitory sensations were significantly associated with PRRT2 mutations in the univariate analysis. Multivariate logistic regression analysis demonstrated that age of onset [odds ratio (OR) = 0.59, P = 0.025] and premonitory sensation (OR = 10.67, P = 0.028) were independently associated with positive PRRT2 mutation. CONCLUSIONS: PRRT2 mutations are common in patients with PKD, and a double PRRT2 mutation is reported for the first time. PRRT2 mutations are significantly associated with a younger age of onset and the presence of premonitory sensation in our population.

Are preoperative Kattan and Stephenson nomograms predicting biochemical recurrence after radical prostatectomy applicable in the Chinese population?

PURPOSE: Kattan and Stephenson nomograms are based on the outcomes of patients with prostate cancer recruited in the USA, but their applicability to Chinese patients is yet to be validated. We aim at studying the predictive accuracy of these nomograms in the Chinese population. PATIENTS AND METHODS: A total of 408 patients who underwent laparoscopic or open radical resection of prostate from 1995 to 2009 were recruited. The preoperative clinical parameters of these patients were collected, and they were followed up regularly with PSA monitored. Biochemical recurrence was defined as two or more consecutive PSA levels >0.4 ng/mL after radical resection of prostate or secondary cancer treatment. RESULTS: The overall observed 5-year and 10-year biochemical recurrence-free survival rates were 68.3% and 59.8%, which was similar to the predicted values by the Kattan and Stephenson nomograms, respectively. The results of our study achieved a good concordance with both nomograms (Kattan: 5-years, 0.64; Stephenson: 5-years, 0.62, 10-years, 0.71). CONCLUSIONS: The incidence of prostate cancer in Hong Kong is increasing together with the patients' awareness of this disease. Despite the fact that Kattan nomograms were derived from the western population, it has been validated in our study to be useful in Chinese patients as well.

Association of HLA locus variant in Parkinson's disease.

A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.

Estimating the lifetime economic burden of Parkinson's disease in Singapore.

BACKGROUND AND PURPOSE: We aimed to estimate the lifetime cost of Parkinson's disease (PD) from the societal perspective. METHODS: A convenience sample of English or Chinese-speaking patients with PD was recruited from a PD and Movement Disorders Centre in Singapore to complete a financial burden questionnaire. Sociodemographic and clinical data were retrieved from hospital databases. Markov cohort model analysis was performed (cycle length, 1-year; duration, death or reached 100 years old). Patients were assumed to progress from one Markov state to the next state or death without skipping states or regressing. All model parameters were based on published local data. RESULTS: In 195 patients with PD (median age: 68.9, male: 51.8%), the simulated lifetime cost of PD was Singapore Dollar (SGD) 60,487 (EUR purchasing power parity 56,253) per patient. Direct medical, non-medical and indirect cost accounted for 18.8%, 12.8% and 68.4% of total lifetime cost, respectively. The top three components of total lifetime cost were productivity losses (67.6%), pharmacotherapy (11.4%) and home care (8.7%). One-way sensitivity analysis and probabilistic sensitivity analyses revealed that estimates were sensitive to cost at H&Y stage 1, 2 and 2.5 and productivity losses. CONCLUSIONS: The lifetime cost of PD is evaluated for the first time. This cost is substantial and comparable to the lifetime cost of intracerebral haemorrhage in at least one study. Our study identified several priority areas for research and policy formulation: reducing productivity losses, reducing cost of pharmacotherapy, avoiding hospitalization and reducing home care cost.

Guide to surgical procedures on hollow viscera: part 1--Esophageal, gastric, and restrictive bariatric procedures.

OBJECTIVE: The objective of this article is to explore with a surgical perspective the key radiologic features after common esophageal, gastric, and bariatric procedures. CONCLUSION: An understanding of procedures on the hollow viscera is essential for radiologists at any level. The ability to quickly recognize postoperative anatomy is critical to accurately and efficiently interpret routine imaging studies and to diagnose postoperative complications.