Metabolic-associated fatty liver disease and hepatocellular carcinoma: a prospective study of characteristics and response to therapy.

BACKGROUND AND AIM: The rising incidence of hepatocellular carcinoma (HCC) in Australia is related to increasing rates of metabolic-associated fatty liver disease (MAFLD). This study aimed to prospectively characterize the metabolic profile, lifestyle, biometric features, and response to treatment of HCC patients in an Australian population. METHOD: Multicenter prospective cohort analysis of newly diagnosed HCC patients at six multidisciplinary team meetings over a 2-year period. RESULTS: Three hundred and thirteen (313) newly diagnosed HCC patients with MAFLD (n = 77), MAFLD plus other liver disease (n = 57) (the "mixed" group), and non-MAFLD (n = 179) were included in the study. Alcohol-associated liver disease (ALD) (43%) and MAFLD (43%) were the most common underlying liver diseases. MAFLD-HCC patients were older (73 years vs 67 years vs 63 years), more likely to be female (40% vs 14% vs 20%), less likely to have cirrhosis (69% vs 88% vs 85%), showed higher ECOG, and were less likely to be identified by screening (29% vs 53% vs 45%). Metabolic syndrome was more prevalent in the MAFLD and mixed groups. The severity of underlying liver disease and HCC characteristics were the same across groups. While the MAFLD population self-reported more sedentary lifestyles, reported dietary patterns were no different across the groups. Dyslipidemia was associated with tumor size, and those taking statins had a lower recurrence rate. CONCLUSION: Equal to ALD, MAFLD is now the most common underlying liver disease seen in HCC patients in Australia. Future HCC prevention screening and treatment strategies need to take this important group of patients into consideration.

The Graded Incomplete Letters Test (GILT): a rapid test to detect cortical visual loss, with UK Biobank implementation.

Impairments of object recognition are core features of neurodegenerative syndromes, in particular posterior cortical atrophy (PCA; the 'visual-variant Alzheimer's disease'). These impairments arise from damage to higher-level cortical visual regions and are often missed or misattributed to common ophthalmological conditions. Consequently, diagnosis can be delayed for years with considerable implications for patients. We report a new test for the rapid measurement of cortical visual loss - the Graded Incomplete Letters Test (GILT). The GILT is an optimised psychophysical variation of a test used to diagnose cortical visual impairment, which measures thresholds for recognising letters under levels of increasing visual degradation (decreasing "completeness") in a similar fashion to ophthalmic tests. The GILT was administered to UK Biobank participants (total n=2,359) and participants with neurodegenerative conditions characterised by initial cortical visual (PCA, n=18) or memory loss (typical Alzheimer's disease, n=9). UK Biobank participants, including both typical adults and those with ophthalmological conditions, were able to recognise letters under low levels of completeness. In contrast, participants with PCA consistently made errors with only modest decreases in completeness. GILT sensitivity to PCA was 83.3% for participants reaching the 80% accuracy cut-off, increasing to 88.9% using alternative cut-offs (60% or 100% accuracy). Specificity values were consistently over 94% when compared to UK Biobank participants without or with documented visual conditions, regardless of accuracy cut-off. These first-release UK Biobank and clinical verification data suggest the GILT has utility in both rapidly detecting visual perceptual losses following posterior cortical damage and differentiating perceptual losses from common eye-related conditions.

Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

PURPOSE: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway. METHODS: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary). RESULTS: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy. The chemotherapy group had poorer QoL; FACT-B total score mean differences were 8.53 (95% CI: 3.42 to 13.64), 5.38 (95% CI: 0.17 to 10.58) and 8.00 (95% CI: 2.76 to 13.24) at 6, 9 and 12 months, respectively. The odds of psychological morbidity (GHQ12 >4) were 5.5-fold greater for those treated with chemotherapy. Financial and caring burdens (PRRS) were worse for this group (mean difference in change at 9 months 3.25 (95% CI: 0.42 to 6.07)). GSE and GHQ-12 scores impacted FACT-B total scores, indicating QoL decline for those with high baseline psychological morbidity. Chemotherapy patients or those with high psychological morbidity or were unable to carry out normal activities had the highest service costs. Over the 12 months, 68.2% participants phoned/emailed breast care nurses, and 53.3% visited a hospital breast clinician. CONCLUSION: The data suggest that chemotherapy patients and/or those with heightened psychological morbidity might benefit from closer monitoring and/or supportive interventions whilst on the SSM/PIFU pathway. Reduced access due to COVID-19 could have affected service use.

Evidence for a left ear bias in incidence of Meniere's disease.

OBJECTIVE: To explore a side of lesion differences in Meniere's disease (MD). DESIGN: A retrospective review (2019-2021) was conducted of patients with definite MD, as defined by 2015 Bárány Society diagnostic criteria. Testing information included pure tone audiometry, tympanometry, and extra-tympanic electrocochleography (ECochG). Normative ECochG data from healthy subjects determined the 95% cut-off value for clinical abnormality. STUDY SAMPLE: 107 patients with definite MD were included in the study and 40 healthy controls. RESULTS: The review identified 75 patients with unilateral MD and 32 patients with bilateral MD according to their clinical histories. 79% of unilateral cases were found to have MD on the L ear. 94% of bilateral MD cases had L ears more affected than R ears. Objective ECochG testing indicated a greater incidence of elevated SP/AP area curve and amplitude ratios in L ears. On binomial testing, all results indicate a highly significant bias of MD to the L side. CONCLUSIONS: Unilateral MD appears more common on the L side than the R, suggesting that the disease process underlying MD is not symmetrical. MD also appears more common in females than males. It appears that there is a physiological asymmetry in the progression/cause of MD.

Solid amorphous formulations for enhancing solubility and inhibiting Erlotinib crystallization during gastric-to-intestinal transfer.

The objective of this study was to improve the solubility and inhibit the crystallisation during the gastric-to-intestinal transfer of Erlotinib (ERL), a small molecule kinase inhibitor (smKI) compound class, which is classified as class II drug in the Biopharmaceutical Classification System (BCS). A screening approach combining different parameters (solubility in aqueous media, inhibitory effect of drug crystallisation from supersaturated drug solutions) was applied to selected polymers for the development of solid amorphous dispersions of ERL. ERL solid amorphous dispersions formulations were then prepared with 3 different polymers (Soluplus®, HPMC-AS-L, HPMC-AS-H) at a fixed drug: polymer ratio (1:4) by two different production methods (spray drying and hot melt extrusion). The spray-dried particles and cryo-milled extrudates were characterized by thermal properties, shape and particle size, solubility and dissolution behavior in aqueous media. The influence of the manufacturing process on these solid characteristics was also identified during this study. Based on the obtained results, it is concluded that the cryo-milled extrudates of HPMC-AS-L displayed better performance (enhanced solubility, reduced ERL crystallization during the simulated gastric-to-intestinal transfer) and represents a promising amorphous solid dispersion formulation for oral administration of ERL.

Cross-sectional characteristics of pediatric-onset discoid lupus erythematosus: Results of a multicenter, retrospective cohort study.

BACKGROUND: The incidence of systemic lupus in children with discoid lupus is unknown. OBJECTIVE: This study assessed the baseline characteristics of patients with pediatric discoid lupus erythematosus (pDLE). METHODS: Medical records at 17 sites were reviewed for pediatric dermatology and rheumatology patients with discoid lupus erythematosus. The inclusion criteria were clinical and/or histopathologic diagnosis of discoid lupus erythematosus with an age at onset of <18 years. Baseline data were collected at the first documented visit. Outcomes included diagnosis of systemic lupus erythematosus (SLE) at the baseline visit using the 1997 American College of Rheumatology (primary) and the 2012 Systemic Lupus International Collaborating Clinics (secondary) criteria. RESULTS: Of the >1500 charts reviewed, 438 patients met the inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse. A diagnosis of SLE at the baseline visit (pDLE + SLE) was rendered in 162 (37%) patients using the American College of Rheumatology and in 181 (41%) patients using the Systemic Lupus International Collaborating Clinics criteria. Patients with pDLE + SLE were older at the time of rash onset (median, 12.9 vs 8.9 years; P < .001), with shorter time from discoid lupus erythematosus onset to diagnosis, compared with patients with pDLE-only (median, 2 vs 7 months; P < .001). Patients with pDLE + SLE were more likely to be female (P = .004), with generalized discoid lupus erythematosus and clinically aggressive disease, including end-organ involvement, positive serologies, and higher- titer levels of antinuclear antibodies (P < .001). LIMITATIONS: Retrospective study. CONCLUSION: A diagnosis of discoid lupus erythematosus in adolescence should prompt thorough screening for SLE.

Definitions of remission in psoriasis: a systematic literature review from the National Psoriasis Foundation.

Psoriasis studies increasingly employ outcomes that indicate complete disease resolution, yet remission and cure are poorly defined for psoriasis. We conducted a systematic literature review to identify definitions of psoriasis remission and cure reported in the literature. Medline, EMBASE, and The Cochrane Central Register of Controlled Trials databases were searched on July 22, 2020, for full-text studies providing definitions for psoriasis remission/cure. Definitions were analysed descriptively for endpoint, time-frame, on/off treatment, patient-reported outcomes, and disease domains. We identified 106 studies that provided 41 unique remission definitions. Most definitions included endpoints based on Psoriasis Area and Severity Index (PASI), such as PASI75 (n = 16 studies), PASI90 (n = 10), PASI100 (n = 10), and PASI of 0 (n = 3), and descriptive endpoints related to 'skin clearance' (n = 18). Few definitions specified time-frame, on/off treatment or other psoriasis-related disease domains. One small consensus-initiative defined drug-free remission for plaque psoriasis by BSA of 0 without any therapy for at least 12 months. While there is no cure for psoriasis, seven studies defined psoriasis cure using similar endpoints to those used to define remission. We identified a variety of definitions of psoriasis remission. These results will inform the development of consensus-based definitions for psoriasis remission to support efforts to improve research and clinical outcomes.

Transanal mesorectal excision: early outcomes in Australia and New Zealand.

BACKGROUND: Transanal total mesorectal excision (taTME) aims to overcome some of the technical challenges faced when operating on mid and low rectal cancers. Specimen quality has been confirmed previously, but recent concerns have been raised about oncological safety. This multicentre prospective study aimed to evaluate the safety of taTME among early adopters in Australia and New Zealand. METHODS: Data from all consecutive patients who had taTME for rectal cancer from July 2014 to February 2020 at six tertiary referral centres in Australasia were recorded and analysed. RESULTS: A total of 308 patients of median age of 64 years underwent taTME. Some 75.6 per cent of patients were men, and the median BMI was 26.8 kg/m2. The median distance of tumour from anal verge was 7 cm. Neoadjuvant chemoradiotherapy was administered to 57.8 per cent of patients. The anastomotic leak rate was 8.1 per cent and there was no mortality within 30 days of surgery. Pathological examination found a complete mesorectum in 295 patients (95.8 per cent), a near-complete mesorectum in seven patients (2.3 per cent), and an incomplete mesorectum in six patients (1.9 per cent). The circumferential resection margin and distal resection margin was involved in nine patients (2.9 per cent), and two patients (0.6 per cent) respectively. Over a median follow-up of 22 months, the local recurrence rate was 1.9 per cent and median time to local recurrence was 30.5 months. CONCLUSION: This study showed that, with appropriate training and supervision, skilled minimally invasive rectal cancer surgeons can perform taTME with similar pathological and oncological results to open and laparoscopic surgery.

A non-randomised single centre cohort study, comparing standard and modified bowel preparations, in adults with cystic fibrosis requiring colonoscopy.

BACKGROUND: Adults with cystic fibrosis (CF) have been reported to be at five to ten-fold risk (25 to 30 fold risk after solid organ transplant) of colorectal cancer (CRC) than the general population. Limited publications to date have reported on practical aspects of achieving adequate colonic cleanse producing good visualisation. In this study, we compared two bowel preparation regimens, standard bowel preparation and a modified CF bowel preparation. METHODS: A non-randomised study of adults with CF attending a single centre, requiring colonoscopy investigation were selected. Between 2001 and 2015, 485 adults with CF attended the clinic; 70 adults with CF had an initial colonoscopy procedure. After five exclusions, standard bowel preparation was prescribed for 27 patients, and modified CF bowel preparation for 38 patients. Demographic and clinical data were collected for all consenting patients. RESULTS: There was a significant difference between modified CF bowel preparation group and standard bowel preparation group in bowel visualisation outcomes, with the modified CF bowel preparation group having a higher proportion of "excellent/good" GI visualisation cleanse (50.0% versus 25.9%) and lower rates of "poor" visualisation cleanse (10.5% versus 44.5%) than standard bowel preparation (p = 0.006). Rates of "fair" GI cleanse visualisation were similar between the two groups (39.4% versus 29.6%) (Additional file 1: Table S1). Detection rates of adenomatous polyps at initial colonoscopy was higher in modified CF bowel preparation cohort than with standard preparation group (50.0% versus 18.5%, p < 0.01). Positive adenomatous polyp detection rate in patient's age > 40 years of age was higher (62.5%) than those < 40 years of age (24.3%) (p = 0.003). Colonic adenocarcinoma diagnosis was similar in both groups. CONCLUSION: This study primarily highlights that standard colonoscopy bowel preparation is often inadequate in patients with CF, and that colonic lavage using modified CF bowel preparation is required to obtain good colonic visualisation. A higher rate of polyps in patients over 40 years of age (versus less than 40 years) was evident. These results support adults with CF considered for colonoscopy screening at 40 years of age, or prior to this if symptomatic; which is earlier than CRC screening in the non-CF Australian population.

Measuring depth of anaesthesia using changes in directional connectivity: a comparison with auditory middle latency response and estimated bispectral index during propofol anaesthesia.

General anaesthesia is associated with changes in connectivity between different regions of the brain, the assessment of which has the potential to provide a novel marker of anaesthetic effect. We propose an index that quantifies the strength and direction of information flow in electroencephalographic signals collected across the scalp, assess its performance in discriminating 'wakefulness' from 'anaesthesia', and compare it with estimated bispectral index and the auditory middle latency response. We used a step-wise slow induction of anaesthesia in 10 patients to assess graded changes in electroencephalographic directional connectivity at propofol effect-site concentrations of 2 µg.ml-1 , 3 µg.ml-1 and 4 µg.ml-1 . For each stable effect-site concentration, connectivity was estimated from multichannel electroencephalograms using directed coherence, together with middle latency response and estimated bispectral index. We used a linear support vector machine classifier to compare the performance of the different electroencephalographic features in discriminating wakefulness from anaesthesia. We found a significant reduction in the strength of long-range connectivity (interelectrode distance > 10 cm) (p < 0.008), and a reversal of information flow from markedly postero-frontal to fronto-posterior (p < 0.006) between wakefulness and a propofol effect-site concentration of 2 µg.ml-1 . This then remained relatively constant as effect-site concentration increased, consistent with a step change in directed coherence with anaesthesia. This contrasted with the gradual change with increasing anaesthetic dose observed for estimated bispectral index and middle latency response. Directed coherence performed best in discriminating wakefulness from anaesthesia with an accuracy of 95%, indicating the potential of this new method (on its own or combined with others) for monitoring adequacy of anaesthesia.

Willingness to pay for policies to reduce future deaths from climate change: evidence from a British survey.

OBJECTIVES: Without urgent action, climate change will put the health of future populations at risk. Policies to reduce these risks require support from today's populations; however, there are few studies assessing public support for such policies. Willingness to pay (WtP), a measure of the maximum a person is prepared to pay for a defined benefit, is widely used to assess public support for policies. We used WtP to investigate whether there is public support to reduce future health risks from climate change and if individual and contextual factors affect WtP, including perceptions of the seriousness of the impacts of climate change. STUDY DESIGN: A cross-sectional British survey. METHODS: Questions about people's WtP for policies to reduce future climate change-related deaths and their perceptions of the seriousness of climate change impacts were included in a British survey of adults aged 16 years and over (n=1859). We used contingent valuation, a survey-based method for eliciting WtP for outcomes like health which do not have a direct market value. RESULTS: The majority (61%) were willing to pay to reduce future increases in climate change-related deaths in Britain. Those regarding climate change impacts as not at all serious were less willing to pay than those regarding the impacts as extremely serious (OR 0.04, 95% CI 0.02-0.09). Income was also related to WtP; the highest-income group were twice as likely to be willing to pay as the lowest-income group (OR 2.14, 95% CI 1.40-3.29). CONCLUSIONS: There was public support for policies to address future health impacts of climate change; the level of support varied with people's perceptions of the seriousness of these impacts and their financial circumstances. Our study adds to evidence that health, including the health of future populations, is an outcome that people value and suggests that framing climate change around such values may help to accelerate action.

A group sequential test for ABR detection.

Objective: To detect the auditory brainstem response (ABR) automatically using an innovative sequentially applied Hotelling's T 2 test, with the overall goal of optimising test time whilst controlling the false-positive rate (FPR). Design: The stage-wise critical decision boundaries for accepting or rejecting the null hypothesis were found using a new approach called the Convolutional Group Sequential Test (CGST). Specificity, sensitivity, and test time were evaluated using simulations and subject recorded data. Study sample: Data consists of click-evoked ABR threshold series from 12 normal hearing adults, and recordings of EEG background activity from 17 normal hearing adults. Results: Reductions in mean test time of up to 40-45% were observed for the sequential test, relative to a conventional "single shot" test where the statistical test is applied to the data just once. To obtain these results, it will occasionally be necessary to run the test to a higher number of stimuli, i.e. the maximum test time needs to be increased. Conclusions: The CGST can be used to control the specificity of a sequentially applied ABR detection method. Doing so can reduce test time, relative to the "single shot" test, when considered across a cohort of test subjects.

Pelvic fat volume reduction with preoperative very low energy diet (VLED): implications for rectal cancer surgery in the obese.

BACKGROUND: Obese patients have higher complication rates after pelvic surgery. Laparoscopic rectal surgery may not be possible in the obese individual due to mesorectal, total pelvic and general visceral fat volumes. Very low energy diets reduce visceral fat but the changes within the pelvis and mesorectum are unknown. The aim of the present study was to quantify the proportion of fat lost from total pelvic and mesorectal fat with a very low energy diet (VLED) and define simple, accessible measurements that correlate with expected volume reduction. METHODS: A study was conducted on proportion change in mesorectal and intrapelvic fat volumes in patients on a VLED prior to bariatric surgery at the Alfred Hospital in Melbourne. The VLED was a standardized 4-week meal replacement. Proportion change in mesorectal and intrapelvic fat volumes were measured. Patients had standardized pre-diet and post-diet magnetic resonance imaging (MRI) of the pelvis. Body mass index, weight and girth measures were obtained. Adipose quantification analysis was performed using Q-Fat. RESULTS: Nine patients were included in this study, who were preparing for bariatric (not colorectal) surgery (5 females, median age 42 years, range 27-59 years) pre-protocol body mass index was 55.8 (range 39.5-60.6 kg/m2); median weight was 163 kg. Median mesorectal fat reduction was 29.9% (range 11.6-66.6%). Linear regression showed a relationship between the amount of mesorectal fat reduction and two variables: patient height and the distance from S1 to the posterior aspect of the rectum on MRI. The relationship predicted response to the diet (R2 67%, p = 0.040). CONCLUSIONS: Very low energy diets result in a clinically significant reduction in mesorectal fat with a lesser change in total pelvic fat, suggesting that very low energy diets may be useful for preparation for pelvic surgery in the obese. The distance from S1 to the posterior rectum correlates well with mesorectal reduction, making this a valuable clinical tool when volumetric analysis is not possible. This analysis is limited to the quantification of the effect of the diet and cannot comment on the safety of this approach before pelvic cancer surgery.

Correction to: Pelvic fat volume reduction with preoperative very low energy diet (VLED): implications for rectal cancer surgery in the obese.

Due to substantial contributions by Dr. Phillip Malouf and Dr. Stephen Bell.

Surgical techniques in the management of rectal cancer: a modified Delphi method by colorectal surgeons in Australia and New Zealand.

BACKGROUND: Technological developments have allowed advances in minimally invasive techniques for total mesorectal excision such as laparoscopy, robotics, and transanal surgery. There remains an ongoing debate about the safety, benefits, and appropriate clinical scenarios for which each technique is employed. The aim of this study was to provide a panel of expert opinion on the role of each surgical technique currently available in the management of rectal cancer using a modified Delphi method. METHODS: Surveys were designed to explore the key patient- and tumor-related factors including clinical scenarios for determining a surgeon's choice of surgical technique. RESULTS: Open surgery was favoured in obese patients with an extra-peritoneal tumor and a positive circumferential resection margin (CRM) or T4 tumor when a restorative resection was planned. Laparoscopy was favoured in non-obese males and females, in both intra- and extra-peritoneal tumors with a clear CRM. Robotic surgery was most commonly offered to obese patients when the CRM was clear and if an abdominoperineal resection was planned. Transanal total mesorectal excision (taTME) was preferred in male patients with a mid or low rectal cancer, particularly when obese. Transanal endoscopic microsurgery/transanal minimally invasive surgery local excision was only offered to frail patients with small, early stage tumors. CONCLUSIONS: All surgical techniques for rectal cancer dissection have a role and may be considered appropriate. Some techniques have advantages over others in certain clinical situations, and the best outcomes may be achieved by considering all options before applying an individualised approach to each clinical situation.

The effect of increasing body mass index on laparoscopic surgery for colon and rectal cancer.

AIM: Obesity is common in Western countries and its prevalence is increasing. Colorectal cancer is common, and surgery for colorectal cancer is technically more challenging in obese patients. Laparoscopic surgery for colon cancer has been shown to be oncologically equivalent, with improved short- term outcomes. Laparoscopic surgery for rectal cancer has proven technically challenging, and recent results have raised concerns about oncological equivalence. Our aim was to evaluate the effect of body mass index (BMI) on the clinical and oncological outcomes of surgery for colorectal cancer, including the rate at which laparoscopic surgery is attempted and the rate at which laparoscopic surgery is converted to open surgery. METHOD: A retrospective analysis of prospectively collected data from two tertiary institutions was performed. Data were obtained from the Cabrini Monash University colorectal neoplasia database for patients having surgical resection for colon and rectal cancers between 1 January 2010 and 30 June 2015. Surgical and medical complications, tumour recurrence and overall survival and laparoscopic surgery and conversion rates were investigated. RESULTS: This large case series of 1464 patients undergoing elective surgery for colorectal cancer has demonstrated that an elevated BMI is associated with a lower likelihood of attempting laparoscopic surgery and a higher conversion rate to open surgery when laparoscopy is attempted. Conversion was 1.9 times more likely in obese patients with colon cancer and 4.1 times more likely in obese patients with rectal cancer. The critical BMI for colon cancer patients was > 35 kg/m2 , and for rectal cancer patients > 30 kg/m2 . Obesity is also associated with increased rates of surgical complications, including anastomotic leakage and wound complications. Pathological parameters, tumour recurrence and survival were not affected by elevated BMI. CONCLUSION: In the surgical management of colorectal cancer, obesity is associated with a lower likelihood of laparoscopic surgery being attempted, a higher likelihood of conversion to open surgery when laparoscopic surgery is attempted, and a higher rate of surgical complications.

An assessment of an Australasian pathway for the introduction of transanal total mesorectal excision (taTME).

AIM: To evaluate the use of a pathway for the introduction of transanal total mesorectal excision (taTME) into Australia and New Zealand. METHOD: A pathway for surgeons with an appropriate level of specialist training and baseline skill set was initiated amongst colorectal surgeons; it includes an intensive course, a series of proctored cases and ongoing contribution to audit. Data were collected for patients who had taTME, for benign and malignant conditions, undertaken by the initial adopters of the technique. RESULTS: A total of 133 taTME procedures were performed following the introduction of a training pathway in March 2015. The indication was rectal cancer in 84% of cases. There was one technique-specific visceral injury, which occurred prior to that surgeon completing the pathway. There were no cases of postoperative mortality; morbidity occurred in 27.1%. The distal resection margin was clear in all cases of rectal cancer, and the circumferential resection margin was positive in two cases. An intact or nearly intact total mesorectal excision was obtained in more than 98% of cases. CONCLUSION: This study demonstrates the safe and controlled introduction of a new surgical technique in a defined surgeon population with the use of a pathway for training. The authors recommend a similar pathway to facilitate the introduction of taTME to colorectal surgical practice.

Assessing skin disease and associated health-related quality of life in a rural Lao community.

BACKGROUND: Skin diseases are common and often have an impact on an individual's health-related quality of life. In rural communities where access to healthcare may be limited and individuals rely on farming for food and income, the impact of skin diseases may be greater. The objectives for this study were to perform an assessment of skin disease prevalence in a rural village in Laos and assess the associated impact of any skin disease found using the Dermatology Life Quality Index (DLQI). METHODS: A rural village was purposively selected and 340 participants examined by dermatologists over a four day period. Brief questionnaires were performed, followed by full body skin examinations and DLQI questionnaires completed were relevant. The data were analysed using chi square and Wilcoxon signed rank tests. RESULTS: One hundred and eighty-one participants were found to have a skin disease (53%). The six most common skin diseases were: eczema (22%), dermatophyte infections (19%), acne (10%), scabies infestation (9%), melasma (8%) and pityriasis versicolor (4%). Just over half of those with skin disease (51%) completed the DLQI, with scores ranging from 0 to 24. Those with skin problems on examination were significantly more likely to be farmers, have had a previous skin problem, be older or live in a smaller family. Conclusions This study represents the first formal documentation of skin disease prevalence in Laos and establishes the high rate of skin disease in the rural community and the associated impact these diseases have on health-related quality of life.

Objective measures for detecting the auditory brainstem response: comparisons of specificity, sensitivity and detection time.

OBJECTIVE: To evaluate and compare the specificity, sensitivity and detection time of various time-domain and multi-band frequency domain methods when detecting the auditory brainstem response (ABR). DESIGN: Simulations and subject recorded data were used to assess and compare the performance of the Hotelling's T2 test (applied in either time or frequency domain), two versions of the modified q-sample uniform scores test and both the Fsp and Fmp, which were evaluated using both conventional F-distributions with assumed degrees of freedom and a bootstrap approach. STUDY SAMPLE: Data consisted of click-evoked ABRs and recordings of EEG background activity from 12 to 17 normal hearing adults, respectively. RESULTS: An overall advantage in sensitivity and detection time was demonstrated for the Hotelling's T2 test. The false-positive rates (FPRs) of the Fsp and Fmp were also closer to the nominal alpha-level when evaluating statistical significance using the bootstrap approach, as opposed to using conventional F-distributions. The FPRs of the remaining methods were slightly higher than expected. CONCLUSIONS: In this work, Hotelling's T2 outperformed the alternative methods for automatically detecting ABRs. Its promise as a sensitive and efficient detection method should now be tested in a larger clinical study.

Ten-year alcohol consumption typologies and trajectories of C-reactive protein, interleukin-6 and interleukin-1 receptor antagonist over the following 12 years: a prospective cohort study.

BACKGROUND: Moderate alcohol consumption is thought to confer cardiometabolic protective effects. Inflammatory pathways are hypothesized to partly underlie this association. OBJECTIVES: The aim of this study was to examine the association between typologies of alcohol consumption and markers of inflammation, and their rate of change over time. METHODS: Data were collected from 8209 participants [69% men; mean age, 50 years (SD 6.1)] of the British Whitehall II study. Alcohol consumption typologies were defined using up to three measures during an approximately 10-year period spanning from 1985 to 1994 as (i) stable nondrinkers, (ii) stable moderate drinkers (referent), (iii) stable heavy drinkers, (iv) nonstable drinkers and (v) former drinkers. C-reactive protein (CRP), interleukin (IL)-6 and IL-1 receptor antagonist (IL-1 RA) were measured up to three times in the following 12 years. RESULTS: Stable moderate drinkers had lower levels of CRP than stable nondrinkers, stable heavy drinkers, former drinkers and nonstable drinkers, but there were no differences in the rate of change in CRP over time between groups. Stable nondrinkers had higher levels of IL-6 as did stable heavy drinkers; rates of change in IL-6 over time were also increased in the latter group. Stable nondrinkers also had higher levels of IL-1 RA. These associations were robust to adjustment for confounding factors. CONCLUSION: Our novel investigation of 10-year drinking typologies shows that stable moderate alcohol consumption is associated with a long-term inflammatory marker profile that is consistent with conferring a reduced risk of developing coronary heart disease.