Reappraisal of endometrial thickness for the detection of endometrial cancer in postmenopausal bleeding: a retrospective cohort study.

OBJECTIVE: To estimate the accuracy of transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in postmenopausal women with vaginal bleeding (PMB). DESIGN: Retrospective cohort study. SETTING: One-stop PMB clinic in a Hong Kong teaching hospital. POPULATION: A cohort of 4383 women with PMB. METHODS: Transvaginal ultrasonic measurement of ET and endometrial biopsies were obtained in women presenting with PMB between 2002 and 2013. Endometrial histology was used as the reference standard to calculate accuracy estimates. MAIN OUTCOME MEASURES: Accuracy data for TVS ET presented as sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. RESULTS: Endometrial cancer was diagnosed in 3.8% of women. The median ET in those with endometrial cancer was significantly higher than those with benign conditions (15.7 versus 3.2 mm, P < 0.001). The area under the ROC curve was 0.92 (95% CI 0.89-0.94). The sensitivity for the detection of endometrial cancer at 3-, 4-, and 5-mm cut-offs were 97.0% (95% CI 94.5-99.6%), 94.1% (95% CI 90.5-97.6%), and 93.5% (95% CI 89.7-97.2%), respectively. The corresponding estimates of specificity at these thresholds were 45.3% (95% CI 43.8-46.8%), 66.8% (65.4-68.2%), and 74.0% (72.7-75.4%). CONCLUSIONS: Transvaginal ultrasound using a 3-mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy.

PubMed-supported clinical term weighting approach for improving inter-patient similarity measure in diagnosis prediction.

BACKGROUND: Similarity-based retrieval of Electronic Health Records (EHRs) from large clinical information systems provides physicians the evidence support in making diagnoses or referring examinations for the suspected cases. Clinical Terms in EHRs represent high-level conceptual information and the similarity measure established based on these terms reflects the chance of inter-patient disease co-occurrence. The assumption that clinical terms are equally relevant to a disease is unrealistic, reducing the prediction accuracy. Here we propose a term weighting approach supported by PubMed search engine to address this issue. METHODS: We collected and studied 112 abdominal computed tomography imaging examination reports from four hospitals in Hong Kong. Clinical terms, which are the image findings related to hepatocellular carcinoma (HCC), were extracted from the reports. Through two systematic PubMed search methods, the generic and specific term weightings were established by estimating the conditional probabilities of clinical terms given HCC. Each report was characterized by an ontological feature vector and there were totally 6216 vector pairs. We optimized the modified direction cosine (mDC) with respect to a regularization constant embedded into the feature vector. Equal, generic and specific term weighting approaches were applied to measure the similarity of each pair and their performances for predicting inter-patient co-occurrence of HCC diagnoses were compared by using Receiver Operating Characteristics (ROC) analysis. RESULTS: The Areas under the curves (AUROCs) of similarity scores based on equal, generic and specific term weighting approaches were 0.735, 0.728 and 0.743 respectively (p < 0.01). In comparison with equal term weighting, the performance was significantly improved by specific term weighting (p < 0.01) but not by generic term weighting. The clinical terms "Dysplastic nodule", "nodule of liver" and "equal density (isodense) lesion" were found the top three image findings associated with HCC in PubMed. CONCLUSIONS: Our findings suggest that the optimized similarity measure with specific term weighting to EHRs can improve significantly the accuracy for predicting the inter-patient co-occurrence of diagnosis when compared with equal and generic term weighting approaches.

Reliability and validity of the Severity of Dependence Scale in a Chinese sample of treatment-seeking ketamine users.

OBJECTIVE: Despite growing popularity of ketamine misuse in Asia, there is a lack of a validated instrument to measure the severity of ketamine dependence. Psychometric properties of Chinese Severity of Dependence Scale for ketamine (C-SDS-K) were examined in a sample of treatment-seeking ketamine users in Hong Kong. METHODS: A total of 80 treatment-seeking ketamine users were recruited from 3 treatment centres. The C-SDS-K was administered to assess their severity of dependence on ketamine in the previous month. The diagnosis of their ketamine misuse as per the DSM-IV criteria, and the count of dependence criteria fulfilled in the previous month were determined by the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). RESULTS: The C-SDS-K showed high internal consistency (α = 0.74) and test-retest reliability (intraclass correlation coefficient = 0.95). Total score of C-SDS-K correlated positively with frequency (rs = 0.73, p < 0.001) and dose (rs = 0.89, p < 0.001) of ketamine use per week in the previous month, duration of regular ketamine use (rs = 0.28, p = 0.01), and the count of DSM-IV ketamine dependence criteria met in the previous month (rs = 0.84, p < 0.001). All items loaded strongly on a single factor (factor loading ≥ 0.60) in principal component analysis. CONCLUSION: The findings support SDS as a reliable and valid tool for measuring the severity of dependence in the treatment-seeking population of Chinese ketamine users.

Spontaneous carotid cavernous fistula complicating pregnancy.

Carotid cavernous fistula is a well-documented but rare condition in pregnancy, about which there are a limited number of reports in the literature. We report such a case in a 41-year-old woman presenting with right-sided headache, proptosis, and diplopia at 37 weeks of gestation. She was subsequently diagnosed to have carotid cavernous fistula based on angiography. Embolisation was performed in the postpartum period. Carotid cavernous fistula has the potential of serious morbidity including visual loss and intracranial haemorrhage. It can be treated effectively by endovascular embolisation, which confers a good prognosis. Although headache is a common complaint during pregnancy, obstetrician should be aware of this condition if the clinical presentation is suspicious.

Predicting patient arrivals to an accident and emergency department.

OBJECTIVES: To characterise and forecast daily patient arrivals into an accident and emergency (A&E) department based on previous arrivals data. METHODS: Arrivals between 1 April 2002 and 31 March 2007 to a busy case study A&E department were allocated to one of two arrival streams (walk-in or ambulance) by mode of arrival and then aggregated by day. Using the first 4 years of patient arrival data as a "training" set, a structural time series (ST) model was fitted to characterise each arrival stream. These models were used to forecast walk-in and ambulance arrivals for 1-7 days ahead and then compared with the observed arrivals given by the remaining 1 year of "unseen" data. RESULTS: Walk-in arrivals exhibited a strong 7-day (weekly) seasonality, with ambulance arrivals showing a distinct but much weaker 7-day seasonality. The model forecasts for walk-in arrivals showed reasonable predictive power (r = 0.6205). However, the ambulance arrivals were harder to characterise (r = 0.2951). CONCLUSIONS: The two separate arrival streams exhibit different statistical characteristics and so require separate time series models. It was only possible to accurately characterise and forecast walk-in arrivals; however, these model forecasts will still assist hospital managers at the case study hospital to best use the resources available and anticipate periods of high demand since walk-in arrivals account for the majority of arrivals into the A&E department.

Use of plasma DNA to predict mortality and need for intensive care in patients with abdominal pain.

BACKGROUND: We investigated the value of plasma deoxyribonucleic acid concentrations in patients presenting with acute abdominal pain to predict need for intensive care or mortality. METHODS: Plasma deoxyribonucleic acid taken from patients with acute abdominal pain was analyzed for the beta-globin gene using the quantitative polymerase chain reaction. The primary outcome measure was the combined 28-day mortality or admission to the intensive care unit. RESULTS: Of 287 consecutive patients with acute abdominal pain recruited, 12 patients were admitted to the intensive care unit and/or died. Median plasma DNA concentrations were higher in patients with cancer and major organ inflammation. Mean plasma DNA concentrations were three-fold higher in patients with systemic inflammatory response syndrome, five-fold higher in patients who died within 28 days, and eight-fold higher in patients admitted to the intensive care unit. The area under the receiver operator curve for plasma DNA concentrations and intensive care unit admission/mortality was 0.804. At a cut-off of 1100 GE/ml, the sensitivity was 67% (95%CI 35-90) and specificity was 89% (95%CI 84-92). At a cut-off of 175 GE/ml, the sensitivity was 100% (95%CI 73-100) and specificity was 30% (95%CI 25-36). Plasma DNA concentration predicted need for intensive care unit admission or death (adjusted odds ratio 1.4; P<0.0001). CONCLUSIONS: Plasma DNA may have a role in patients with acute abdominal pain as a marker for inflammation and cancer, and a predictor of intensive care unit admission/mortality.

Quantitative analysis of circulating methylated DNA as a biomarker for hepatocellular carcinoma.

BACKGROUND: Hypermethylation of the RASSF1A [Ras association (RalGDS/AF-6) domain family member 1A] gene is frequently observed in hepatocellular carcinoma (HCC). We evaluated the analysis of circulating hypermethylated RASSF1A for detecting HCC and assessing its prognosis. METHODS: In module 1, we studied 63 pairs of HCC patients and age- and sex-matched chronic hepatitis B virus (HBV) carriers, as well as 50 healthy volunteers. In module 2, we studied 22 HCC patients with cancer detected through a surveillance program. The concentrations of circulating hypermethylated RASSF1A sequences were measured by real-time PCR after digestion with a methylation-sensitive restriction enzyme. RESULTS: We detected hypermethylated RASSF1A sequences in the sera of 93% of HCC patients, 58% of HBV carriers, and 8% of the healthy volunteers. The median RASSF1A concentrations for the HCC patients and HBV carriers were 7.70 x 10(5) copies/L and 1.18 x 10(5) copies/L, respectively (P < 0.01). The detection of low concentrations in HBV carriers is consistent with previous findings that RASSF1A hypermethylation is an early event in HCC pathogenesis and can be found in premalignant liver tissues. Use of a marker cutoff value of 1 x 10(6) copies/L also identifies 50% of alpha-fetoprotein-negative HCC cases. Patients with higher RASSF1A concentrations at diagnosis or 1 year after tumor resection showed poorer disease-free survival (P < 0.01). For the HBV carriers who underwent HCC surveillance and subsequently developed HCC, the circulating concentration of RASSF1A increased significantly from the time of enrollment to cancer diagnosis (P = 0.014). CONCLUSIONS: Detection and quantification of circulating methylated RASSF1A sequences are useful for HCC screening, detection, and prognostication.

Engraftment of human lymphocytes and thyroid tissue into scid and rag2-deficient mice: absent progression of lymphocytic infiltration.

To study human autoimmune thyroid disease in an animal model we have investigated the in vivo survival of human thyroid tissues and functionality of human lymphocytes in severe combined immunodeficient (scid) mice and recombination-activating gene (rag2) knockout mice. We found successful engraftment of human thyroid tissues in both scid and rag2-deficient mice. However, when peripheral blood mononuclear cells were transplanted ip, human immunoglobulin production was poor in rag2-deficient mice compared to that in scid mice (mean human immunoglobulin G levels at 6 weeks, 0.2 +/- 0.2 microgram/mL in two of eight rag2-deficient mice compared to 20.8 +/- 7.0 micrograms/mL in seven of nine scid mice; P < 0.05). We, therefore, only pursued the further use of scid mice and transplanted them with thyroid tissue from patients with either Graves' disease (four patients) or Hashimoto's thyroiditis (one patient). At the functional level, we observed transiently increased thyroid hormone levels (T4 peaking at 5.4 +/- 0.2 microgram/dL compared to a normal level of 2.6 +/- 0.2 microgram/dL); human autoantibodies to human thyroglobulin, human thyroid peroxidase, and the human TSH receptor were also detected in thyroid-transplanted mice. In contrast to recent reports, histological examination of the thyroid explants showed no increase in the lymphocytic infiltrate compared to the original donor tissue, nor was there any thyroid follicular destruction observed. In fact, many of the transplants demonstrated a marked diminution in the infiltrates over time, with an absence of HLA-DR antigen expression by both T-cells and thyrocytes. Cotransplanted allogeneic thyroid tissues were unremarkable in terms of lymphocytic infiltrates and showed intact morphology. Taken together, these data point to a relative degree of T-cell inactivity within the thyroid explants from the scid mouse. Hence, a factor(s) present in the patient with autoimmune thyroid disease that activates their thyroid-specific T-cells may be absent in this murine model as presently constructed.