Identifying eating disorders at the earliest opportunity: Testing the reliability of an online eating disorder screener (IOI-S) in primary care and youth mental health settings.

AIM: Eating disorders (EDs) are associated with significant disease burden and unacceptably high mortality rates. Early intervention significantly improves prognosis and can prevent chronic suffering; however, large numbers of people with the illness are not being identified or managed in primary healthcare. The current study aimed to test the reliability of the face-to-face, clinician delivery of a previously validated, co-designed, online screening tool for eating disorders. METHODS: Individuals aged 14 and over who read, English were recruited from the community in either primary care (general practice) settings or headspace youth mental health centres. They completed the InsideOut Institute Screener (IOI-S) face-to-face, delivered verbally by the study researcher clinician and then online by self-report. The primary outcome was test-retest reliability as measured by two-way mixed effects model Intraclass Correlation Coefficient (ICC) with absolute agreement. RESULTS: A total of 83 participants aged 14-81 (M 36.2) completed the study in New South Wales and the Northern Territory, Australia, between April and November 2022. The ICC between successive iterations of the test was significantly positive (0.980), demonstrating strong internal validity and test-retest reliability of the scale. CONCLUSIONS: The IOI-S is an adaptive 6-item screening tool designed to 'start a conversation' and determine risk using gentle language conceived by individuals with lived experience. Originally designed for online use, the current study broadens its versatility to clinical settings. The screener performs equally well when delivered face-to-face in clinical practice. In conjunction with increased practitioner education and improved treatment referral pathways, broad implementation of the screener in early healthcare settings can support timely identification and intervention for those with EDs.

Study protocol for an open labelled randomised controlled trial of perioperative oral nutrition supplement in breast and colorectal cancer patients undergoing elective surgery.

BACKGROUND: While it is well established that perioperative use of oral nutrition supplement (ONS) improves nutrition status among severely malnourished surgical cancer patients, the evidence requires further substantiation for non-severely malnourished patients with cancer. This protocol paper presents the rationale and design of a randomised controlled trial to evaluate the effectiveness of preoperative as well as an extended 90-day postoperative use of ONS on nutritional and clinical outcomes among patients undergoing elective surgery for breast and colorectal cancer. METHODS: Patients with primary breast and colorectal cancer undergoing elective surgery are recruited from two tertiary hospitals. Eligible patients are assigned into one of the three intervention arms: (i) Group SS will receive ONS in addition to their normal diet up to 14 days preoperatively and postoperatively up to discharge; (ii) Group SS-E will receive ONS in addition to their normal diet up to 14 days preoperatively, postoperatively up to discharge and for an extended 90 days after discharge; and (iii) Group DS will receive ONS in addition to their normal diet postoperatively up to discharge from the hospital. The ONS is a standard formula fortified with lactium to aid in sleep for recovery. The primary endpoints include changes in weight, body mass index (BMI), serum albumin and prealbumin levels, while secondary endpoints are body composition (muscle and fat mass), muscle strength (handgrip strength), energy and protein intake, sleep quality, haemoglobin, inflammatory markers (transferrin, high sensitivity C-reactive protein, interleukin-6), stress marker (saliva cortisol), length of hospital stay and postoperative complication rate. DISCUSSION: This trial is expected to provide evidence on whether perioperative supplementation in breast and colorectal cancer patients presenting with high BMI and not severely malnourished but undergoing the stress of surgery would be beneficial in terms of nutritional and clinical outcomes. TRIAL REGISTRATION: ClinicalTrial.gov NCT04400552. Registered on 22 May 2020, retrospectively registered.

Mutant clones in normal epithelium outcompete and eliminate emerging tumours.

Human epithelial tissues accumulate cancer-driver mutations with age1-9, yet tumour formation remains rare. The positive selection of these mutations suggests that they alter the behaviour and fitness of proliferating cells10-12. Thus, normal adult tissues become a patchwork of mutant clones competing for space and survival, with the fittest clones expanding by eliminating their less competitive neighbours11-14. However, little is known about how such dynamic competition in normal epithelia influences early tumorigenesis. Here we show that the majority of newly formed oesophageal tumours are eliminated through competition with mutant clones in the adjacent normal epithelium. We followed the fate of nascent, microscopic, pre-malignant tumours in a mouse model of oesophageal carcinogenesis and found that most were rapidly lost with no indication of tumour cell death, decreased proliferation or an anti-tumour immune response. However, deep sequencing of ten-day-old and one-year-old tumours showed evidence of selection on the surviving neoplasms. Induction of highly competitive clones in transgenic mice increased early tumour removal, whereas pharmacological inhibition of clonal competition reduced tumour loss. These results support a model in which survival of early neoplasms depends on their competitive fitness relative to that of mutant clones in the surrounding normal tissue. Mutant clones in normal epithelium have an unexpected anti-tumorigenic role in purging early tumours through cell competition, thereby preserving tissue integrity.

Comparison of amlodipine/valsartan/hydrochlorothiazide single pill combination and free combination: adherence, persistence, healthcare utilization and costs.

OBJECTIVES: To determine whether amlodipine/valsartan/hydrochlorothiazide single pill combination (SPC) is associated with improved persistence, adherence and reduced healthcare utilization and costs compared to the corresponding free combination (FC). METHODS: Adult (≥18 years) patients covered by commercial and Medicare Supplemental insurance in the Truven MarketScan database with hypertension (HTN) diagnosis between October 2009 and December 2011 were included. At least two filled prescriptions for the SPC cohort or two periods of minimum 15 days of concurrent use of amlodipine, valsartan and hydrochlorothiazide (HCT) for the FC cohort were required. Cohorts were propensity score matched (PSM) to balance on important confounders. Outcomes included: 1) adherence (proportion of days covered [PDC] and medication possession ratio [MPR]); 2) persistence (treatment gap >30 days); 3) all-cause and HTN-specific healthcare utilization and costs at 12 months. RESULTS: After cohort matching with PSM, patients taking SPC (N = 9221) exhibited better outcomes than FC (N = 1884): higher mean adherence (85.7% vs. 77.0%), mean PDC (73.8% vs. 60.6%) and persistence (46.8% vs. 23.6%) (all p < 0.0001). Patients taking SPC were associated with higher odds of persistence (OR: 3.51; 95% CI: 3.08-4.02), MPR ≥80% (OR: 2.72; 95% CI: 2.40-3.08) and PDC ≥80% (OR: 2.88; 95% CI: 2.55-3.26). After PSM, the SPC cohort exhibited statistically significantly lower mean number of resource utilization events compared to FC. Patients in the SPC cohort also had a statistically significantly (p < 0.05) lower percentage of patients with ≥1 all-cause hospitalization (15.0% vs. 18.2%), ≥1 all-cause emergency room (ER) visits (25.7 vs. 31.4%), and ≥1 ER HTN-specific visits (9.7% vs. 14.1%). The costs incurred by SPC cohort patients were 2.8% to 41.7% numerically lower than the FC cohort, statistically significant for all-cause ER costs ($430.6 vs. $549.5, p < 0.05). CONCLUSIONS: Real-world data indicate an association of the amlodipine/valsartan/HCT SPC with improved adherence and persistence vs. FC with no difference in overall healthcare or hypertension specific costs between the cohorts.

An incremental approach to pigmented skin lesion segmentation with classification refinements in uncertain regions.

Skin lesion segmentation in dermatoscopic images is difficult because there are large inter variations in shape, size, color, and texture between lesions and skin types. Hence, computational features learned from a training set of lesion images may not be applicable to other lesion images. In this paper, we propose an incremental method for lesion segmentation. It leverages the Expectation-Maximization algorithm to find an initial segmentation. A new adaptive method is proposed to define two types of segmented regions: the high-confident and the low-confident. We train a support vector machine, using computational features from the high-confident regions, to further refine segmentation and, hence, achieve improved results for the low-confident regions. Validation experiments of our proposed method are performed on 319 dermatoscopy images and we have achieved good results with precision and recall to be 0.864 and 0.875 respectively.

Transradial percutaneous coronary intervention in acute ST elevation myocardial infarction and high-risk patients: experience in a single centre without cardiothoracic surgical backup.

INTRODUCTION: Primary transradial percutaneous coronary intervention (TRI) is shown to be efficacious in stable patients with acute coronary syndrome. We aimed to evaluate the application of primary TRI for acute ST elevation myocardial infarction (STEMI), including among high-risk patients from our registry. METHODS: This was a single-centre case series comprising 138 patients who underwent primary TRI for STEMI between May 2007 and June 2008. TRI was attempted with a 6-Fr guiding catheter in all patients regardless of Killip class status. Outcome measures were success rates of primary TRI, door-to-balloon time, procedure duration and volume of contrast used. All patients were followed up for major adverse cardiac events in-hospital, at 30 days and six months. RESULTS: A total of 138 patients had primary TRI attempted for STEMI. Four patients failed primary TRI and required a femoral approach. The remaining 134 patients underwent primary TRI. The mean patient age was 56.4 years. Most patients with acute STEMI presented in Killip class I and II (91.8 percent). Only 8.2 percent were in Killip class III or IV on admission. 50 percent of patients presented with anterior STEMI. The median door-to-balloon time for this group was 92 (interquartile range [IQR] 77-121) minutes, with a median procedure time of 39 (IQR 29-51) minutes. The success rate of primary TRI was 97.1 percent. CONCLUSION: Success rate, procedural and radiation time for TRI are comparable to those achieved via the femoral approach. Primary TRI is therefore a feasible and effective approach for acute STEMI, even in high-risk patients.

Integrating spatial fuzzy clustering with level set methods for automated medical image segmentation.

The performance of the level set segmentation is subject to appropriate initialization and optimal configuration of controlling parameters, which require substantial manual intervention. A new fuzzy level set algorithm is proposed in this paper to facilitate medical image segmentation. It is able to directly evolve from the initial segmentation by spatial fuzzy clustering. The controlling parameters of level set evolution are also estimated from the results of fuzzy clustering. Moreover the fuzzy level set algorithm is enhanced with locally regularized evolution. Such improvements facilitate level set manipulation and lead to more robust segmentation. Performance evaluation of the proposed algorithm was carried on medical images from different modalities. The results confirm its effectiveness for medical image segmentation.

Effects on blood pressure and cardiovascular risk of variations in patients' adherence to prescribed antihypertensive drugs: role of duration of drug action.

AIM: To determine the effects of imperfect adherence (i.e. occasionally missing prescribed doses), and the influence of rate of loss of antihypertensive effect during treatment interruption, on the predicted clinical effectiveness of antihypertensive drugs in reducing mean systolic blood pressure (SBP) and cardiovascular disease (CVD) risk. METHOD: The effects of imperfect adherence to antihypertensive treatment regimens were estimated using published patterns of missed doses, and taking into account the rate of loss of antihypertensive effect when doses are missed (loss of BP reduction in mmHg/day; the off-rate), which varies between drugs. Outcome measures were the predicted mean SBP reduction and CVD risk, determined from the Framingham Risk Equation for CVD. RESULTS: In patients taking 75% of prescribed doses (typical of clinical practice), only long-acting drugs with an off-rate of ∼1 mmHg/day were predicted to maintain almost the full mean SBP-lowering effect throughout the modelled period. In such patients, using shorter-acting drugs (e.g. an off-rate of ∼5-6 mmHg/day) was predicted to lead to a clinically relevant loss of mean SBP reduction of > 2 mmHg. This change also influenced the predicted CVD risk reduction; in patients with a baseline 10-year CVD risk of 27.0% and who were taking 75% of prescribed doses, a difference in off-rate from 1 to 5 mmHg/day led to a predicted 0.5% absolute increase in 10-year CVD risk. CONCLUSIONS: In patients who occasionally miss doses of antihypertensives, modest differences in the rate of loss of antihypertensive effect following treatment interruption may have a clinically relevant impact on SBP reduction and CVD risk. While clinicians must make every effort to counsel and encourage each of their patients to adhere to their prescribed medication, it may also be prudent to prescribe drugs with a low off-rate to mitigate the potential consequences of missing doses.

ST segment elevation myocardial infarction following elective direct current synchronised cardioversion for atrial fibrillation.

Atrial fibrillation is the most common arrhythmia in clinical practice. There is no difference in mortality, incidence of stroke or quality of life regardless of whether the rhythm control or rate control strategy is used. However, in certain circumstances, such as when rate control is inadequate, rhythm control is a viable option. We present a 74-year-old Eurasian man with a history of hypertension who presented with new-onset atrial fibrillation and sustained an ST segment elevation myocardial infarction following elective direct current cardioversion.

Accurate measurement of bone mineral density using clinical CT imaging with single energy beam spectral intensity correction.

Although dual-energy X-ray absorptiometry (DXA) offers an effective measurement of bone mineral density, it only provides a 2-D projected measurement of the bone mineral density. Clinical computed tomography (CT) imaging will have to be employed for measurement of 3-D bone mineral density. The typical dual energy process requires precise measurement of the beam spectral intensity at the 80 kVp and 120 kVp settings. However, this is not used clinically because of the extra radiation dosage and sophisticated hardware setup. We propose an accurate and fast approach to measure bone material properties with single energy scans. Beam hardening artifacts are eliminated by incorporating the polychromatic characteristics of the X-ray beam into the reconstruction process. Bone mineral measurement from single energy CT correction is compared with that of dual energy correction and the commonly used DXA. Experimental results show that single energy correction is compatible with dual energy CT correction in eliminating beam hardening artifacts and producing an accurate measurement of bone mineral density. We can then estimate Young's modulus, yield stress, yield strain and ultimate tensile stress of the bone, which are important data for patient specific therapy planning.

Fast segmentation of bone in CT images using 3D adaptive thresholding.

Fast bone segmentation is often important in computer-aided medical systems. Thresholding-based techniques have been widely used to identify the object of interest (bone) against dark backgrounds. However, the darker areas that are often present in bone tissue may adversely affect the results obtained using existing thresholding-based segmentation methods. We propose an automatic, fast, robust and accurate method for the segmentation of bone using 3D adaptive thresholding. An initial segmentation is first performed to partition the image into bone and non-bone classes, followed by an iterative process of 3D correlation to update voxel classification. This iterative process significantly improves the thresholding performance. A post-processing step of 3D region growing is used to extract the required bone region. The proposed algorithm can achieve sub-voxel accuracy very rapidly. In our experiments, the segmentation of a CT image set required on average less than 10s per slice. This execution time can be further reduced by optimizing the iterative convergence process.

Stonefish envenomation presenting to a Singapore hospital.

INTRODUCTION: Stonefish, belonging to the genus Synanceia and classified under the Synanceiidae family, are commonly found in the shallow waters of the Indo-Pacific region and are considered the most dangerous and venomous of this family. The aim of the study was to describe the presenting features, clinical course and current management of this series of patients with stonefish envenomation presenting to a tertiary general hospital in Singapore. METHODS: Data involving stonefish stings was retrospectively retrieved from the Singapore General Hospital Accident & Emergency Emerge Version 3.7.6 database from October 2004 to September 2006. Information, such as the patients' demographics, date and location of the incident, identity of the fish, local or systemic effects, pain score (upon arrival and after treatment), investigations and treatment as well as the outcome of the patients, were evaluated. RESULTS: 30 cases were identified. The median age of the patients was 28 years. The majority of patients were male (80 percent) and 47 percent of cases were foreign nationals. Most incidences occurred on weekends/public holidays (77 percent), with November having the highest number of cases (seven cases). The majority of cases (80 percent) arrived at the hospital within two hours of envenomation. Symptoms included extreme pain, swelling and redness of the affected limbs. 24 (80 percent) patients received hot water soak treatment and 27 (90 percent) patients received either intramuscular pethidine or diclofenac for analgesia, where nine patients (33 percent) required additional analgesics after a period of observation. 17 patients (58 percent) were treated and discharged, eight (26 percent) were referred to a specialist for follow-up and five (16 percent) were admitted for an average of three days. 13 out of 25 patients (52 percent) were discharged with antibiotics. One case complained of persistent pain and hyperalgesia five months post-envenomation. One patient required surgical intervention. No deaths and systemic symptoms were reported. CONCLUSION: Cases of stonefish envenomation that presented to our hospital showed that the majority of patients were young male adults. Stonefish envenomation, though it rarely kills, can cause extreme pain, swelling and erythema, which can be managed with symptomatic treatment.

Quantitative analysis of human masticatory muscles using magnetic resonance imaging.

OBJECTIVES: The objective of this study was to quantitatively evaluate the correlation between left and right masticatory muscle volumes in normal subjects. METHODS: Contiguous 1 mm MR scans were obtained of 12 normal adult subjects aged 20-25 years using a Siemens 1.5 T MR scanner. The volumes of the human masticatory muscles (masseter, lateral and medial pterygoid) were measured from the scans using our previously proposed method. To test for inter- and intraobserver reproducibility, measurements were performed by two users on two separate occasions, with a span of 2 weeks between them and with the previous results blinded. Good inter- and intraobserver reproducibility was achieved in our study. RESULTS: The mean volumes for left and right masseters, and lateral and medial pterygoids were 29.54 cm3, 29.65 cm3, 9.47 cm3, 10.23 cm3, 8.69 cm3 and 8.92 cm3, respectively. The Pearson correlation coefficients between the volumes of the left and right masseters, lateral and medial pterygoids are 0.969, 0.906 and 0.924, respectively. CONCLUSIONS: The computed volumes of the masticatory muscles show a strong correlation between the volumes of the left and right masseters, and lateral and medial pterygoids for normal adult subjects. The total masticatory muscle volume on the left and right sides of normal subjects is similar.

Issues in blood pressure control and the potential role of single-pill combination therapies.

Hypertension (HTN) is a major risk factor for cardiovascular mortality, yet only a small proportion of hypertensive individuals receive appropriate therapy and achieve target blood pressure (BP) values. Factors influencing the success of antihypertensive therapy include physicians' acceptance of guideline BP targets, the efficacy and tolerability of the drug regimen, and patient compliance and persistence with therapy. It is now well recognised that most hypertensive patients require at least two antihypertensive agents to achieve their target BP. However, complicated treatment regimens are a major contributory factor to poor patient compliance. The use of combination therapy for HTN offers a number of advantages over the use of monotherapy, including improved efficacy, as drug combinations with a synergistic mechanism of action can be used. This additive effect means that lower doses of the individual components can be used, which may translate into a decreased likelihood of adverse events. The use of single-pill combination therapy, in which two or more agents are combined in a single dosage form, offers all the benefits of free combination therapy (improved efficacy and tolerability over monotherapy) together with the added benefit of improved patient compliance because of the simplified treatment regimen. The use of single-pill combination therapy may also be associated with cost savings compared with the use of free combinations for reasons of cheaper drug costs, fewer physician visits and fewer hospitalisations for uncontrolled HTN and cardiovascular events. Thus, the use of single-pill combination therapy for HTN should help improve BP goal attainment through improved patient compliance, leading to reduced costs for cardiovascular-related care.

3D segmentation and quantification of a masticatory muscle from MR data using patient-specific models and matching distributions.

A method is proposed for 3D segmentation and quantification of the masseter muscle from magnetic resonance (MR) images, which is often performed in pre-surgical planning and diagnosis. Because of a lack of suitable automatic techniques, a common practice is for clinicians to manually trace out all relevant regions from the image slices which is extremely time-consuming. The proposed method allows significant time savings. In the proposed method, a patient-specific masseter model is built from a test dataset after determining the dominant slices that represent the salient features of the 3D muscle shape from training datasets. Segmentation is carried out only on these slices in the test dataset, with shape-based interpolation then applied to build the patient-specific model, which serves as a coarse segmentation of the masseter. This is first refined by matching the intensity distribution within the masseter volume against the distribution estimated from the segmentations in the dominant slices, and further refined through boundary analysis where the homogeneity of the intensities of the boundary pixels is analyzed and outliers removed. It was observed that the left and right masseter muscles' volumes in young adults (28.54 and 27.72 cm(3)) are higher than those of older (ethnic group removed) adults (23.16 and 22.13 cm(3)). Evaluation indicates good agreement between the segmentations and manual tracings, with average overlap indexes for the left and right masseters at 86.6% and 87.5% respectively.

Generalized negative binomial distribution: a promising statistical distribution for Oncomelania hupensis in the lake- and marsh-land regions of China.

A new generalization of the negative binomial distribution (GNBD) is introduced and fitted to counts of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, made, in areas of Chinese lakeland and marshland, early in the winter of 2005 and late in the spring of 2006. The GNBD was found to fit the snail data better than the standard negative binomial distribution (NBD) that has previously been widely used to model the distribution of O. hupensis. With two more parameters than the NBD, the GNBD can integrate many discrete distributions and is more flexible than the NBD in modelling O. hupensis. It also provides a better theoretical distribution for the quantitative study of O. hupensis, especially in building an accurate prediction model of snail density. The justification for adopting the GNBD is discussed. The GNBD allows researchers to broaden the field in the quantitative study not only of O. hupensis and schistosomiasis japonica but also of other environment-related helminthiases and family-clustered diseases that have, traditionally, been modelled using the NBD.

Spectrogram denoising and automated extraction of the fundamental frequency variation of dolphin whistles.

Marine mammal vocalizations are often analyzed using time-frequency representations (TFRs) which highlight their nonstationarities. One commonly used TFR is the spectrogram. The characteristic spectrogram time-frequency (TF) contours of marine mammal vocalizations play a significant role in whistle classification and individual or group identification. A major hurdle in the robust automated extraction of TF contours from spectrograms is underwater noise. An image-based algorithm has been developed for denoising and extraction of TF contours from noisy underwater recordings. An objective procedure for measuring the accuracy of extracted spectrogram contours is also proposed. This method is shown to perform well when dealing with the challenging problem of denoising broadband transients commonly encountered in warm shallow waters inhabited by snapping shrimp. Furthermore, it would also be useful with other types of broadband transient noise.