Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 151
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Nano Lett ; 23(3): 872-879, 2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36662599

ABSTRACT

The kagome metal CsV3Sb5 features an unusual competition between the charge-density-wave (CDW) order and superconductivity. Evidence for time reversal symmetry breaking (TRSB) inside the CDW phase has been accumulating. Hence, the superconductivity in CsV3Sb5 emerges from a TRSB normal state, potentially resulting in an exotic superconducting state. To reveal the pairing symmetry, we first investigate the effect of nonmagnetic impurity. Our results show that the superconducting critical temperature is insensitive to disorder, pointing to conventional s-wave superconductivity. Moreover, our measurements of the self-field critical current (Ic,sf), which is related to the London penetration depth, also confirm conventional s-wave superconductivity with strong coupling. Finally, we measure Ic,sf where the CDW order is removed by pressure and superconductivity emerges from the pristine normal state. Our results show that s-wave gap symmetry is retained, providing strong evidence for the presence of conventional s-wave superconductivity in CsV3Sb5 irrespective of the presence of the TRSB.

2.
J Neurol Neurosurg Psychiatry ; 94(11): 893-903, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37399287

ABSTRACT

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

3.
Article in English | MEDLINE | ID: mdl-37803887

ABSTRACT

BACKGROUND: Previous study has shown that a brief cognitive-behavioral prevention insomnia program could reduce 71% risk of developing insomnia among at-risk adolescents. This study aimed to evaluate the differential response to insomnia prevention in subgroups of at-risk adolescents. METHODS: Adolescents with a family history of insomnia and subthreshold insomnia symptoms were randomly assigned to a 4-week insomnia prevention program or nonactive control group. Assessments were conducted at baseline, 1 week, and 6- and 12-month after the intervention. Baseline sleep, daytime, and mood profiles were used to determine different subgroups by using latent class analysis (LCA). Analyses were conducted based on the intention-to-treat approach. RESULTS: LCA identified three subgroups: (a) insomnia symptoms only, (b) insomnia symptoms with daytime sleepiness and mild anxiety, and (c) insomnia symptoms with daytime sleepiness, mild anxiety, and depression. The incidence rate of insomnia disorder over the 12-month follow-up was significantly reduced for adolescents receiving intervention in subgroup 3 compared with the controls (hazard ratio [HR] = 0.37; 95% confidence interval [CI]: 0.13-0.99; p = .049) and marginally for subgroup 2 (HR = 0.14; 95% CI: 0.02-1.08; p = .059). In addition, adolescents who received intervention in subgroups 2 and 3 had a reduced risk of excessive daytime sleepiness (subgroup 2: adjusted OR [AdjOR] = 0.45, 95% CI: 0.23-0.87; subgroup 3: AdjOR = 0.32, 95% CI: 0.13-0.76) and possible anxiety (subgroup 2: AdjOR = 0.47, 95% CI: 0.27-0.82; subgroup 3: AdjOR = 0.33, 95% CI: 0.14-0.78) compared with the controls over the 12-month follow-up. CONCLUSIONS: Adolescents at risk for insomnia can be classified into different subgroups according to their psychological profiles, which were associated with differential responses to the insomnia prevention program. These findings indicate the need for further phenotyping and subgrouping at-risk adolescents to develop personalized insomnia prevention.

4.
J Neurol Neurosurg Psychiatry ; 93(9): 1010-1017, 2022 09.
Article in English | MEDLINE | ID: mdl-34764151

ABSTRACT

OBJECTIVE: To investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD). METHODS: This is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen-negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson's disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria. RESULTS: A total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD. CONCLUSIONS: Almost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration.


Subject(s)
Depressive Disorder, Major , Parkinson Disease , REM Sleep Behavior Disorder , Depressive Disorder, Major/complications , Depressive Disorder, Major/epidemiology , Female , Humans , Male , Parkinson Disease/complications , Parkinson Disease/epidemiology , Polysomnography , Prevalence , REM Sleep Behavior Disorder/diagnosis
5.
Dig Endosc ; 34(1): 43-62, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34115407

ABSTRACT

Recent advancement in endoscopic closure techniques have revolutionized the treatment of gastrointestinal perforations, leaks and fistulas. Traditionally, these have been managed surgically. The treatment strategy depends on the size and location of the defect, degree of contamination, presence of healthy surrounding tissues, patients' condition and the availability of expertise. One of the basic principles of management includes providing a barricade to the flow of luminal contents across the defect. This can be achieved with a wide range of endoscopic techniques. These include endoclips, stenting, suturing, tissue adhesives and glue, and endoscopic vacuum therapy. Each method has their distinct indications and shortcomings. Often, a combination of these techniques is required. Apart from endoscopic closure, drainage procedures by the interventional radiologist and surgical management also play an important role. In this review article, the outcomes of each of these endoscopic closure techniques in the literature is provided in tables, and practical management algorithms are being proposed.


Subject(s)
Fistula , Upper Gastrointestinal Tract , Anastomotic Leak/surgery , Endoscopy , Humans , Stents , Treatment Outcome
6.
Gene Ther ; 28(6): 351-372, 2021 06.
Article in English | MEDLINE | ID: mdl-33531684

ABSTRACT

Small and cell-type restricted promoters are important tools for basic and preclinical research, and clinical delivery of gene therapies. In clinical gene therapy, ophthalmic trials have been leading the field, with over 50% of ocular clinical trials using promoters that restrict expression based on cell type. Here, 19 human DNA MiniPromoters were bioinformatically designed for rAAV, tested by neonatal intravenous delivery in mouse, and successful MiniPromoters went on to be tested by intravitreal, subretinal, intrastromal, and/or intravenous delivery in adult mouse. We present promoter development as an overview for each cell type, but only show results in detail for the recommended MiniPromoters: Ple265 and Ple341 (PCP2) ON bipolar, Ple349 (PDE6H) cone, Ple253 (PITX3) corneal stroma, Ple32 (CLDN5) endothelial cells of the blood-retina barrier, Ple316 (NR2E1) Müller glia, and Ple331 (PAX6) PAX6 positive. Overall, we present a resource of new, redesigned, and improved MiniPromoters for ocular gene therapy that range in size from 784 to 2484 bp, and from weaker, equal, or stronger in strength relative to the ubiquitous control promoter smCBA. All MiniPromoters will be useful for therapies involving small regulatory RNA and DNA, and proteins ranging from 517 to 1084 amino acids, representing 62.9-90.2% of human proteins.


Subject(s)
Endothelial Cells , Animals , Humans , Mice , Neuroglia , PAX6 Transcription Factor/genetics , Promoter Regions, Genetic , Retina , Retinal Cone Photoreceptor Cells
7.
Arch Womens Ment Health ; 24(3): 463-471, 2021 06.
Article in English | MEDLINE | ID: mdl-33094351

ABSTRACT

Given that the perinatal period is a time of increased risk for pregnant women to manifest mental health problems, the identification of antenatal hypomanic symptoms is particularly important. However, data on antenatal hypomanic symptoms is lacking. The present study was aimed at filling this research gap by investigating the prevalence of hypomanic symptoms, including the "active-elated" and "irritable/risk-taking" sides of hypomanic symptoms at the first trimester, and examining their associations with anxiety and depressive symptoms at the following time points: the first trimester, the second trimester, and up to 6-week postpartum. A prospective longitudinal design with a quantitative approach was adopted. A consecutive sample of 229 pregnant Chinese women in Hong Kong was assessed. Hypomanic symptoms were assessed with the Hypomania Checklist-32 (HCL-32). Of the sample, 43.6% had elevated levels of hypomanic symptoms in the first trimester. Multiple regression analysis showed that after adjusting for potential confounding factors, irritable/risk-taking symptoms were independently associated with higher anxiety symptoms in the first and second trimesters and in the 6-week postpartum period. Primary healthcare practitioners should be made aware of antenatal hypomanic symptoms in pregnant women to facilitate early identification and intervention for anxiety and depression to improve the well-being of both mothers and infants.


Subject(s)
Depression, Postpartum , Pregnancy Complications , Anxiety/diagnosis , Anxiety/epidemiology , Depression/diagnosis , Depression/epidemiology , Female , Humans , Postpartum Period , Pregnancy , Pregnancy Complications/diagnosis , Pregnancy Complications/epidemiology , Prevalence , Prospective Studies , Risk Factors
8.
Ann Neurol ; 85(4): 582-592, 2019 04.
Article in English | MEDLINE | ID: mdl-30761606

ABSTRACT

OBJECTIVE: To determine the familial aggregation of idiopathic rapid eye movement sleep behavior disorder (iRBD), neurodegenerative diseases, and related biomarkers. METHODS: A total of 404 and 387 first-degree relatives of 102 patients with iRBD and of 89 controls were recruited, respectively. Among them, 204 and 208 relatives of patients and controls underwent face-to-face clinical assessment, whereas 97 and 75 relatives underwent further video-polysomnographic assessment, respectively. RESULTS: Compared with relatives of controls, relatives of patients demonstrated higher levels of RBD features, including chin tonic electromyography activity (mean = 1.5 ± 7.5 vs 0.3 ± 1.0, p = 0.04) and behavioral events (n [weighted %] = 12 [11.3] vs 2 [1.9], adjusted hazard ratio [aHR] = 7.69, 95% confidence interval [CI] = 1.54-33.33, p = 0.009) during rapid eye movement sleep, probable diagnosis (n [%] = 57 [14.9] vs 20 [4.9], aHR = 3.45, 95% CI = 1.96-6.25, p < 0.001), and definite diagnosis (n [weighted %] = 10 [8.4] vs 2 [1.4], aHR = 5.56, 95% CI = 1.16-25.00, p = 0.03). They also had higher risks of Parkinson disease (3.1% vs 0.5%, aHR = 5.88, 95% CI = 1.37-25.00, p = 0.02), dementia (6.9% vs 2.6%, aHR = 2.44, 95% CI = 1.15-5.26, p = 0.02), constipation (8.3% vs 2.4%, adjusted odds ratio = 4.21, 95% CI = 1.34-13.17, p = 0.01), and motor dysfunction (Movement Disorders Society Unified Parkinson's Disease Rating Scale part III motor score, mean = 1.9 ± 3.2 vs 0.9 ± 2.3, p = 0.002). The unaffected relatives of patients demonstrated a higher likelihood ratio of prodromal Parkinson disease (median [interquartile range] = 0.27 [1.19] vs 0.22 [0.51], p = 0.03). INTERPRETATION: iRBD is familially aggregated from isolated features to full-blown sleep disorder. Relatives of patients carry a higher risk of alpha-synucleinopathy in terms of neurodegenerative diseases and prodromal markers, suggesting a familial aggregation and staging pathology of alpha-synucleinopathy. Ann Neurol 2019;85:582-592.


Subject(s)
Neurodegenerative Diseases/epidemiology , Neurodegenerative Diseases/genetics , REM Sleep Behavior Disorder/epidemiology , REM Sleep Behavior Disorder/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Cohort Studies , Female , Hong Kong/epidemiology , Humans , Male , Middle Aged , Neurodegenerative Diseases/diagnosis , REM Sleep Behavior Disorder/diagnosis
9.
Cardiovasc Diabetol ; 19(1): 197, 2020 11 24.
Article in English | MEDLINE | ID: mdl-33234149

ABSTRACT

BACKGROUND: The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. METHODS: Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. RESULTS: The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e' (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (ß = 0.89, P < 0.01) and worsening of average E/e' (ß = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16-6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. CONCLUSION: Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.


Subject(s)
Diabetes Mellitus, Type 2/complications , Echocardiography, Doppler, Pulsed , Fatty Acid-Binding Proteins/blood , Hypertrophy, Left Ventricular/etiology , Ventricular Dysfunction, Left/etiology , Ventricular Function, Left , Ventricular Remodeling , Aged , Biomarkers/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diastole , Female , Humans , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Time Factors , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
10.
J Sleep Res ; 29(4): e13049, 2020 08.
Article in English | MEDLINE | ID: mdl-32394606

ABSTRACT

Sleep quantity and quality are both important for optimal development and functioning during youth. Yet few studies have examined the effects of insomnia symptoms and objective short sleep duration on memory performance among adolescents and young adults. One-hundred and ninety participants (female: 61.6%) aged from 12 to 24 years completed this study. All participants underwent a clinical interview, a 7-day actigraphic assessment, a battery of self-report questionnaires and cognitive tests to assess working memory and episodic memory. Insomnia symptoms were defined as a score ≥ 9 on the Insomnia Severity Index, and objective short sleep duration was defined as average total sleep time less than 7 hr for those aged 12-17 years, and 6 hr for those aged 18 years and above as assessed by actigraphy. Insomnia symptoms were significantly associated with worse self-perceived memory (p < .05) and poorer performance on the digit span task (p < .01), but not the dual N-back task and verbal learning task. There was no significant difference in any of the memory measures between participants with objective short sleep duration and their counterparts. No interaction effect was found between insomnia and short sleep duration on any of the objective memory outcomes. Insomnia symptoms, but not objective short sleep duration, were associated with poorer subjective memory and objective working memory performance in youths. Further studies are needed to investigate the underlying mechanisms linking insomnia and memory impairments, and to delineate the long-term impacts of insomnia on other aspects of neurocognitive functioning in youth.


Subject(s)
Memory, Short-Term/physiology , Polysomnography/methods , Sleep Initiation and Maintenance Disorders/complications , Adolescent , Adult , Child , Female , Humans , Male , Young Adult
11.
Gut ; 68(7): 1169-1179, 2019 07.
Article in English | MEDLINE | ID: mdl-30842211

ABSTRACT

OBJECTIVE: The pathogenesis of UC relates to gut microbiota dysbiosis. We postulate that alterations in the viral community populating the intestinal mucosa play an important role in UC pathogenesis. This study aims to characterise the mucosal virome and their functions in health and UC. DESIGN: Deep metagenomics sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on the rectal mucosa of 167 subjects from three different geographical regions in China (UC=91; healthy controls=76). Virome and bacteriome alterations in UC mucosa were assessed and correlated with patient metadata. We applied partition around medoids clustering algorithm and classified mucosa viral communities into two clusters, referred to as mucosal virome metacommunities 1 and 2. RESULTS: In UC, there was an expansion of mucosa viruses, particularly Caudovirales bacteriophages, and a decrease in mucosa Caudovirales diversity, richness and evenness compared with healthy controls. Altered mucosal virome correlated with intestinal inflammation. Interindividual dissimilarity between mucosal viromes was higher in UC than controls. Escherichia phage and Enterobacteria phage were more abundant in the mucosa of UC than controls. Compared with metacommunity 1, metacommunity 2 was predominated by UC subjects and displayed a significant loss of various viral species. Patients with UC showed substantial abrogation of diverse viral functions, whereas multiple viral functions, particularly functions of bacteriophages associated with host bacteria fitness and pathogenicity, were markedly enriched in UC mucosa. Intensive transkingdom correlations between mucosa viruses and bacteria were significantly depleted in UC. CONCLUSION: We demonstrated for the first time that UC is characterised by substantial alterations of the mucosa virobiota with functional distortion. Enrichment of Caudovirales bacteriophages, increased phage/bacteria virulence functions and loss of viral-bacterial correlations in the UC mucosa highlight that mucosal virome may play an important role in UC pathogenesis.


Subject(s)
Colitis, Ulcerative/virology , Dysbiosis/virology , Gastrointestinal Microbiome , Intestinal Mucosa/virology , Rectum/virology , Adult , Case-Control Studies , China , Colitis, Ulcerative/pathology , Dysbiosis/pathology , Female , Humans , Male , Rectum/pathology
13.
Int J Eat Disord ; 52(6): 652-658, 2019 06.
Article in English | MEDLINE | ID: mdl-30821851

ABSTRACT

OBJECTIVE: Although eating disorders in pregnancy have been studied extensively, little research attention has been given to disordered eating. The objectives of the present study were to determine the prevalence and levels of disordered eating in the perinatal period, and to identify risk factors and adverse outcomes of disordered eating during pregnancy. METHOD: A prospective longitudinal design with a quantitative approach was adopted. A consecutive sample of 1,470 Chinese pregnant women from hospitals in Hong Kong was assessed using standardized instruments at five time points from the first trimester to 6 months postpartum. RESULTS: The levels of disordered eating changed significantly across trimesters. Higher levels of disordered eating in pregnancy were significantly associated with higher levels of disordered eating at 6 weeks and 6 months postpartum, greater anxiety and depressive symptoms, lower 1-min Apgar scores, and abnormal birth weight. DISCUSSION: The present study pointed to the need for more research and clinical attention to antenatal disordered eating given that it is associated with anxiety, depression, postpartum disordered eating and obstetric outcomes.


Subject(s)
Feeding and Eating Disorders/complications , Feeding and Eating Disorders/psychology , Pregnancy Complications/epidemiology , Adult , Female , Humans , Longitudinal Studies , Pregnancy , Prospective Studies , Risk Factors
14.
Pharmacol Res ; 128: 122-129, 2018 02.
Article in English | MEDLINE | ID: mdl-28827188

ABSTRACT

We examined whether genetic polymorphisms (SNPs) in the capecitabine activation pathway and CDA enzymatic activity were associated with prognosis, benefit from capecitabine-containing treatment or capecitabine-related toxicities. The study population comprised 188 metastatic breast cancer patients of the ATX trial (EudraCT 2006-006058-83) randomized for first-line paclitaxel and bevacizumab with (ATX) or without capecitabine (AT). Cumulative capecitabine dose until grade ≥2 hand-foot syndrome or until first dose reduction were toxicity endpoints. We genotyped CDA c.-451C>T (rs532545), CDA c.-33delC (rs3215400) and CES2 c.-806C>G (rs11075646). CDA activity in baseline serum was measured with a spectrophotometric assay and values were analyzed using a median cut-off or as continuous variable. CDA c.-33delC was prognostic for overall survival (OS) independent of hormone receptor status. For the predictive analysis, progression-free survival benefit from ATX over AT was observed in patients with a CDA c.-33del/del or del/insC genotype, a CDA c.-451CC or CT genotype, and a CES2 c.-806CC genotype compared with their counterparts. There was a higher response rate for ATX over AT in patients with a CDA c.-451CT or TT genotype. Patients with high CDA enzymatic activity had more benefit from capecitabine, while this was marginally observed in the CDA low group. Toxicity endpoints were not associated with any candidate markers. In conclusion, CDA c.-33delC was associated with OS. Since particular SNPs in CDA and CES2 were associated with benefit from the addition of capecitabine to AT, their predictive value should be explored in a higher number of patients.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Breast Neoplasms/genetics , Capecitabine/therapeutic use , Carboxylesterase/genetics , Cytidine Deaminase/genetics , Adult , Aged , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Cytidine Deaminase/metabolism , Female , Humans , Middle Aged , Polymorphism, Single Nucleotide , Treatment Outcome
16.
Br J Cancer ; 115(11): 1335-1342, 2016 Nov 22.
Article in English | MEDLINE | ID: mdl-27736846

ABSTRACT

BACKGROUND: The purpose of this study was to evaluate single-nucleotide polymorphisms (SNPs) in genes encoding key metabolising enzymes or involved in pharmacodynamics for possible associations with paclitaxel-induced peripheral neuropathy. METHODS: The study population consists of 188 women from the multicenter, randomised, phase II ATX trial (BOOG2006-06; EudraCT number 2006-006058-83) that received paclitaxel and bevacizumab without or with capecitabine as first-line palliative therapy of HER2-negative metastatic breast cancer. Genotyping of CYP2C8*3 (c.416G>A), CYP3A4*22 (c.522-191C>T), TUBB2A (c.-101T>C), FGD4 (c.2044-236G>A) and EPHA5 (c.2895G>A) was performed by real-time PCR. Toxicity endpoints were cumulative dose (1) until first onset of grade ⩾1 peripheral neuropathy and (2) until first paclitaxel dose reduction from related toxicity (NCI-CTCAE version 3.0). SNPs were evaluated using the Kaplan-Meier method, the Gehan-Breslow-Wilcoxon test and the multivariate Cox regression analysis. RESULTS: The rate of grade ⩾1 peripheral neuropathy was 67% (n=126). The rate of dose reduction was 46% (n=87). Age ⩾65 years was a risk factor for peripheral neuropathy (HR=1.87, P<0.008), but not for dose reduction. When adjusted for age, body surface area and total cumulative paclitaxel dose, CYP2C8*3 carriers had an increased risk of peripheral neuropathy (HR=1.59, P=0.045). FGD4 c.2044-236 A-allele carriers had an increased risk of paclitaxel dose reduction (HR per A-allele=1.38, P=0.036) when adjusted for total cumulative paclitaxel dose. CONCLUSIONS: These findings may point towards clinically useful indicators of early toxicity, but warrant further investigation.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Breast Neoplasms/drug therapy , Cytochrome P-450 CYP2C8/genetics , Genotype , Microfilament Proteins/genetics , Paclitaxel/therapeutic use , Peripheral Nervous System Diseases/genetics , Adult , Aged , Breast Neoplasms/genetics , Female , Gene Frequency , Humans , Middle Aged , Polymorphism, Single Nucleotide
17.
Br J Cancer ; 115(8): 940-948, 2016 10 11.
Article in English | MEDLINE | ID: mdl-27575850

ABSTRACT

BACKGROUND: Only a small proportion of patients respond to anti-VEGF therapy, pressing the need for a reliable biomarker that can identify patients who will benefit. We studied the biological activity of anti-VEGF antibodies in patients' blood during anti-VEGF therapy by using the Ba/F3-VEGFR2 cell line, which is dependent on VEGF for its growth. METHODS: Serum samples from 22 patients with cancer before and during treatment with bevacizumab were tested for their effect on proliferation of Ba/F3-VEGFR2 cells. Vascular endothelial growth factor as well as bevacizumab concentrations in serum samples from these patients were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: The hVEGF-driven cell proliferation was effectively blocked by bevacizumab (IC50 3.7 µg ml-1; 95% CI 1.7-8.3 µg ml-1). Cell proliferation was significantly reduced when patients' serum during treatment with bevacizumab was added (22-103% inhibition compared with pre-treatment). Although bevacizumab levels were not related, on-treatment serum VEGF levels were correlated with Ba/F3-VEGFR2 cell proliferation. CONCLUSIONS: We found that the neutralising effect of anti-VEGF antibody therapy on the biological activity of circulating VEGF can be accurately determined with a Ba/F3-VEGFR2 bioassay. The value of this bioassay to predict clinical benefit of anti-VEGF antibody therapy needs further clinical evaluation in a larger randomised cohort.


Subject(s)
Angiogenesis Inhibitors/blood , B-Lymphocytes/drug effects , Bevacizumab/blood , Biological Assay , Enzyme-Linked Immunosorbent Assay , Neoplasms/blood , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Angiogenesis Inhibitors/pharmacology , Angiogenesis Inhibitors/therapeutic use , Animals , Bevacizumab/pharmacology , Bevacizumab/therapeutic use , Cell Division , Cell Line , Interleukin-3/pharmacology , Mice , Neoplasms/drug therapy , Receptors, Erythropoietin/genetics , Receptors, Interleukin-3/physiology , Recombinant Fusion Proteins/drug effects , Recombinant Fusion Proteins/genetics , Reproducibility of Results , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/pharmacology , Vascular Endothelial Growth Factor Receptor-2/genetics , Vascular Endothelial Growth Factor Receptor-2/immunology
18.
Endoscopy ; 48(8): 717-22, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27275859

ABSTRACT

BACKGROUND AND STUDY AIM: Previous studies have shown that both scheduled second-look endoscopy and high-dose continuous omeprazole infusion are effective in preventing peptic ulcer rebleeding. The aim of this noninferiority trial was to compare the efficacy of these two strategies for the prevention of rebleeding following primary endoscopic hemostasis. PATIENTS AND METHODS: Consecutive patients who received endoscopic treatment for bleeding peptic ulcers (actively bleeding, with nonbleeding visible vessels) were randomized to two treatment groups following hemostasis. One group (second-look endoscopy group) received the proton pump inhibitor (PPI) omeprazole as an intravenous bolus every 12 hours for 72 hours and a second endoscopy within 16 - 24 hours with retreatment for persistent stigmata of bleeding. The other group (PPI infusion group) received continuous high-dose omeprazole infusion for 72 hours. Patients who developed rebleeding underwent surgery if repeat endoscopic therapy failed. The primary outcome was the rebleeding rate within 30 days after initial hemostasis. The margin for noninferiority was set at 5 %. RESULTS: A total of 153 patients were randomized to the PPI infusion group and 152 to the second-look endoscopy group. Rebleeding occurred within 30 days in 10 patients (6.5 %) in the PPI infusion group and in 12 patients (7.9 %) in the second-look endoscopy group (P = 0.646). Surgery was required for rebleeding in six patients from the PPI infusion group and three patients in the second-look endoscopy group (P = 0.32). Intensive care unit stay, transfusion requirements, and mortality were not different between the groups. Patients in the second-look endoscopy group were discharged 1 day earlier than those in the PPI infusion group (P < 0.001). CONCLUSIONS: After endoscopic hemostasis, high-dose PPI infusion was not inferior to second-look endoscopy with bolus PPI in preventing peptic ulcer rebleeding. TRIAL REGISTRATION: ClinicalTrials.gov (NCT: 00164931).


Subject(s)
Hemostasis, Endoscopic , Omeprazole/administration & dosage , Peptic Ulcer Hemorrhage/prevention & control , Proton Pump Inhibitors/administration & dosage , Second-Look Surgery , Secondary Prevention/methods , Aged , Female , Humans , Infusions, Intravenous , Length of Stay , Male , Peptic Ulcer Hemorrhage/therapy , Prospective Studies
19.
Epilepsy Behav ; 63: 118-122, 2016 10.
Article in English | MEDLINE | ID: mdl-27636142

ABSTRACT

PURPOSE: This study evaluated self-esteem in adolescents with epilepsy and its association with psychosocial and disease-related variables. METHODS: This was a cross-sectional study with patients enrolled between January and June 2010. Culture-Free Self-Esteem Inventory for Children (CFSEI-2) was administered to 140 children with epilepsy and 50 children with asthma, aged 10-18years attending mainstream schools. RESULTS: Adolescents with epilepsy had a significantly lower overall self-esteem score when compared with those with asthma, 17±5.21 versus 19.4±3.83, respectively (P=0.005). Thirty-one (22.1%) children with epilepsy compared with 4 (8.3%) with asthma had overall self-esteem score below the cutoff (P=0.034). There was a significant correlation between overall self-esteem score and duration of epilepsy, Hospital Anxiety and Depression Scale (HADS) anxiety score, HADS depression score, and Strengths and Weaknesses of ADHD symptoms and Normal-Behaviors (SWAN) rating combined score. The impact of various correlates on individual domains was not identical. Independent factors associated with low overall self-esteem were HADS depression score (OR: 1.62; 95% CI: 1.2, 2.2; P=0.002), duration of epilepsy (OR: 1.4; 95% CI: 1.04, 1.88; P=0.024), and father employment status economically inactive (OR: 11.9; 95% CI: 1.07, 125; P=0.044). Seizure-free ≥12months was a favorable factor that was less likely to be associated with low self-esteem (OR: 0.14; 95% CI: 0.02, 0.81; P=0.028). CONCLUSION: Self-esteem was compromised in adolescents with epilepsy. A significant correlation between self-esteem and psychological comorbidities was demonstrated. Enhancing social support and education programs may improve the self-esteem and, ultimately, the lives of adolescents living with epilepsy.


Subject(s)
Epilepsy/psychology , Seizures/psychology , Self Concept , Social Support , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Male
20.
BMC Psychiatry ; 15: 198, 2015 Aug 18.
Article in English | MEDLINE | ID: mdl-26281832

ABSTRACT

BACKGROUND: The validity of the 20-item Center for Epidemiological Studies Depression (CES-D) scale for depression screening in Hong Kong Chinese patients with type 2 diabetes remains unknown. We aimed to validate CES-D, compare its psychometric properties with the 9-item Patient Health Questionnaire (PHQ-9), and explore whether one of the two is more suitable for depression screening in Chinese patients with type 2 diabetes. METHODS: Between June 2010 and July 2011, 545 consecutive Chinese patients with type 2 diabetes who underwent structured comprehensive assessments completed the CES-D and PHQ-9. Forty patients were retested within 2-4 weeks by telephone interview and 97 patients were randomly selected to undergo the Mini International Neuropsychiatric Interview (MINI) by psychiatrists for clinical diagnosis of depression. RESULTS: The internal consistency (Cronbach's α) of CES-D was 0.85, with a test-retest correlation coefficient of 0.64. The area under the curve for CES-D compared to the clinical diagnosis of major depression was 0.85. A cut-off score of ≥21 for CES-D provided the optimal balance between sensitivity (78.3 %) and specificity (74.3 %) and identified 17.8 % (n = 97) of patients with depression. CES-D and PHQ-9 showed moderate agreement in depression screening (Cohen's Kappa: 0.45). Compared to non-depressed patients, those who screened positive by PHQ-9 had a higher HbA1c whereas the glycemic differences were not significant when using CES-D. CONCLUSION: The CES-D is a valid screening tool for depression in Chinese type 2 diabetic patients although the PHQ-9 was more discriminative in identifying those with suboptimal glycemic control.


Subject(s)
Asian People/psychology , Depression/complications , Depression/diagnosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/psychology , Psychiatric Status Rating Scales , Adult , Aged , China , Female , Humans , Male , Middle Aged , Psychometrics , Reproducibility of Results
SELECTION OF CITATIONS
SEARCH DETAIL