INTRODUCTION: Psychiatric comorbidity is common in patients with functional dyspepsia (FD) but a good screening tool for psychiatric disorders in gastrointestinal clinical practice is lacking. Aims: 1) Evaluate the performance and optimal cut-off of 12-item General Health Questionnaire (GHQ-12) as a screening tool for psychiatric disorders in FD patients; 2) Compare health-related quality of life (HRQoL) in FD patients with and without psychiatric comorbidities. METHODS: Consecutive patients fulfilling Rome III criteria for FD without medical co-morbidities and gastroesophageal reflux disease were recruited in a gastroenterology clinic. The followings were conducted at 4 weeks after index oesophagogastroduodenoscopy: self-administrated questionnaires on socio-demographics, dyspeptic symptom severity (4-point Likert scale), GHQ-12, and 36-item short-form health survey (SF-36). Psychiatric disorders were diagnosed with Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) by a trained psychiatrist, which served as reference standard. RESULTS: 55 patients underwent psychiatrist-conducted interview and questionnaire assessment. 27 (49.1%) had current psychiatric disorders as determined by SCID (anxiety disorders: 38.2%, depressive disorders: 16.4%). Receiver operating characteristic curve analysis of GHQ-12 revealed an area under curve of 0.825 (95%CI: 0.698-0.914). Cut-off of GHQ-12 at > or =3 gave a sensitivity of 63.0% (95%CI = 42.4-80.6%) and specificity of 92.9% (95%CI = 76.5%-98.9%). Subjects with co-existing psychiatric disorders scored significantly lower in multiple domains of SF-36 (mental component summary, general health, vitality and mental health). By multivariate linear regression analysis, current psychiatric morbidities (Beta = -0.396, p = 0.002) and family history of psychiatric illness (Beta = -0.299, p = 0.015) were independent risk factors for poorer mental component summary in SF-36, while dyspepsia severity was the only independent risk factor for poorer physical component summary (Beta = -0.332, p = 0.027). CONCLUSIONS: Concomitant psychiatric disorders adversely affect HRQoL in FD patients. The use of GHQ-12 as a reliable screening tool for psychiatric disorders allows early intervention and may improve clinical outcomes of these patients.
Area Under Curve ; Axis, Cervical Vertebra ; Comorbidity ; Diagnostic and Statistical Manual of Mental Disorders ; Dyspepsia ; Early Intervention (Education) ; Gastroenterology ; Gastroesophageal Reflux ; Health Surveys ; Humans ; Linear Models ; Mass Screening ; Mental Disorders ; Psychiatry ; Quality of Life ; Surveys and Questionnaires ; Risk Factors ; ROC Curve ; Rome ; Sensitivity and Specificity

INTRODUCTIONAwake craniotomy allows accurate localisation of the eloquent brain, which is crucial during brain tumour resection in order to minimise risk of neurologic injury. The role of the anaesthesiologist is to provide adequate analgesia and sedation while maintaining ventilation and haemodynamic stability in an awake patient who needs to be cooperative during neurological testing. We reviewed the anaesthetic management of patients undergoing an awake craniotomy procedure.

MATERIALS AND METHODSThe records of all the patients who had an awake craniotomy at our institution from July 2004 till June 2006 were reviewed. The anaesthesia techniques and management were examined. The perioperative complications and the outcome of the patients were noted.

RESULTSThere were 17 procedures carried out during the study period. Local anaesthesia with moderate to deep sedation was the technique used in all the patients. Respiratory complications occurred in 24% of the patients. Hypertension was observed in 24% of the patients. All the complications were transient and easily treated. During cortical stimulation, motor function was assessed in 16 patients (94%). Three patients (16%) had lesions in the temporal-parietal region and speech was assessed intraoperatively. Postoperative motor weakness was seen in 1 patient despite uneventful intraoperative testing. No patient required intensive care unit stay. The median length of stay in the high dependency unit was 1 day and the median length of hospital stay was 9 days. There was no in-hospital mortality.

CONCLUSIONAwake craniotomy for brain tumour excision can be successfully performed under good anaesthetic conditions with careful titration of sedation. Our series showed it to be a well-tolerated procedure with a low rate of complications. The benefits of maximal tumour excision can be achieved, leading to potentially better patient outcome.

Adult ; Aged ; Anesthesia, Local ; methods ; Anesthetics, Local ; administration & dosage ; Brain Neoplasms ; surgery ; Conscious Sedation ; Craniotomy ; Female ; Humans ; Male ; Medical Audit ; Middle Aged ; Outcome Assessment (Health Care) ; Perioperative Care ; Singapore

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.