Association between body composition and mortality in patients requiring extracorporeal membrane oxygenation support.

AIM: To ascertain the association between body composition, including muscle mass and adiposity, and patient mortality in those requiring extracorporeal membrane oxygenation (ECMO) for acute respiratory failure. MATERIALS AND METHODS: A retrospective study was undertaken of all patients with acute respiratory failure requiring veno-venous (VV) ECMO between January 2015 and December 2019. Automated image segmentation software was used to quantify the cross-sectional area and average radiodensity (in Hounsfield units) of different muscle and fat compartments at the L3 level of whole-body computed tomography (CT) images taken within 48 h of initiation of ECMO support. The primary endpoint was 30-day post-ECMO initiation all-cause mortality. Logistic regression was used to analyse the correlation between CT measurements, co-morbidities, and 30-day survival. RESULTS: The study included 189 patients (age = 43.8 ± 14.6, sex = 42.3% female). There was no significant association between 30-day survival status and cross-sectional area of muscle or fat. Muscle attenuation (psoas, long spine, and abdominal muscles respectively) at the L3 level were significantly lower in those who died within 30 days of ECMO cannulation (p<0.05). On multivariable analysis including age, sex, and pre-existing respiratory comorbidities, psoas muscle attenuation was an independent predictor of survival at 30 days (OR 0.97; 95% CI 0.94 to 1.00; p=0.047). CONCLUSIONS: Reduced psoas muscle attenuation is associated with poorer survival outcomes at 30 days post-ECMO cannulation in patients who received VV ECMO support for respiratory failure. Cross-sectional areas of muscle and fat compartments did not correlate with survival outcomes at 30 days even when corrected for height and sex.

Routine whole-body CT identifies clinically significant findings in patients supported with veno-venous extracorporeal membrane oxygenation.

AIM: To determine the yield of routine whole-body computed tomography (CT) following extracorporeal membrane oxygenation (ECMO) initiation and to assess the association of these findings with prognosis. MATERIALS AND METHODS: One hundred and ninety-eight consecutive patients with acute respiratory failure admitted for ECMO support between January 2015 and December 2019 who underwent whole-body CT performed within 48 h of ECMO initiation were examined in this single-institution retrospective study. CT findings were divided into three categories: clinically significant findings that may affect immediate management strategy or short-term outcomes; findings not related to hospital stay or outcome but require further workup; and benign findings that do not require further investigation. Logistic regression analysis was used to assess the association of CT findings with 7- and 30-day survival. RESULTS: Clinically significant findings were present in 147 (74%) patients, findings requiring further workup were found in 82 (41%) patients, and benign findings were identified in 180 (90%) of the patients. Patients with clinically significant neurological findings had an elevated risk of death at 7 days (odds ratio [OR] 3.58; 95% confidence interval [CI] 1.29; 9.93; p=0.01), but not 30 days. Increasing numbers of clinically significant findings were associated with greater odds of mortality at 7 days (OR 1.70; 95% CI 1.08; 2.67; p=0.02) and 30 days (OR 1.41; 95% CI 1.02; 1.96; p=0.04). CONCLUSIONS: Imaging patients at the point of admission for VV-ECMO with CT frequently identified clinically significant abnormalities with prognostic implications of these. These findings provide support for the use of more routine CT at the point of treatment escalation with prospective studies now required.

A meta-epidemiological study of bias in randomized clinical trials of open and laparoscopic surgery.

BACKGROUND: Blinding, random sequence generation, and allocation concealment are established strategies to minimize bias in RCTs. Meta-epidemiological studies of drug trials have demonstrated exaggerated treatment effects in RCTs where such methods were not employed. As blinding is more difficult in surgical trials it is important to determine whether this applies to them. The study aimed to investigate this using systematic meta-epidemiological methods. METHOD: The Cochrane Database of Systematic Reviews was searched for systematic reviews of RCTs that compared laparoscopic and open abdominal surgical procedures. Each review was then scrutinized to determine whether at least one of the included trials was blinded. Eligible reviews were updated and individual RCTs retrieved. Extracted data included the primary outcomes of interest (length of stay and complications), secondary outcomes and a risk of bias assessment. A multistep meta-regression analysis was then performed to obtain an overall difference in the reported outcome differences between trials that employed each bias-minimization strategy, and those that did not. RESULTS: Some 316 RCTs were included, reporting on eight different procedures. Patient-blinded RCTs reported a smaller difference in length of stay between laparoscopic and open groups (difference of standardized mean differences -0·36 (95 per cent c.i. -0·73 to 0·00)) and complications (ratio of odds ratios 0·76 (95 per cent c.i. 0·61 to 0·93)). Blinding of postoperative carers and outcome assessors had similar effects. CONCLUSION: Lack of blinding significantly altered the treatment effect estimates of RCTs comparing laparoscopic and open surgery. Blinding should be implemented in surgical RCTs where possible to avoid systematic bias.

Impact of solitary pulmonary nodule size on qualitative and quantitative assessment using 18F-fluorodeoxyglucose PET/CT: the SPUTNIK trial.

PURPOSE: To compare qualitative and semi-quantitative PET/CT criteria, and the impact of nodule size on the diagnosis of solitary pulmonary nodules in a prospective multicentre trial. METHODS: Patients with an SPN on CT ≥ 8 and ≤ 30 mm were recruited to the SPUTNIK trial at 16 sites accredited by the UK PET Core Lab. Qualitative assessment used a five-point ordinal PET-grade compared to the mediastinal blood pool, and a combined PET/CT grade using the CT features. Semi-quantitative measures included SUVmax of the nodule, and as an uptake ratio to the mediastinal blood pool (SURBLOOD) or liver (SURLIVER). The endpoints were diagnosis of lung cancer via biopsy/histology or completion of 2-year follow-up. Impact of nodule size was analysed by comparison between nodule size tertiles. RESULTS: Three hundred fifty-five participants completed PET/CT and 2-year follow-up, with 59% (209/355) malignant nodules. The AUCs of the three techniques were SUVmax 0.87 (95% CI 0.83;0.91); SURBLOOD 0.87 (95% CI 0.83; 0.91, p = 0.30 versus SUVmax); and SURLIVER 0.87 (95% CI 0.83; 0.91, p = 0.09 vs. SUVmax). The AUCs for all techniques remained stable across size tertiles (p > 0.1 for difference), although the optimal diagnostic threshold varied by size. For nodules < 12 mm, an SUVmax of 1.75 or visual uptake equal to the mediastinum yielded the highest accuracy. For nodules > 16 mm, an SUVmax ≥ 3.6 or visual PET uptake greater than the mediastinum was the most accurate. CONCLUSION: In this multicentre trial, SUVmax was the most accurate technique for the diagnosis of solitary pulmonary nodules. Diagnostic thresholds should be altered according to nodule size. TRIAL REGISTRATION: ISRCTN - ISRCTN30784948. ClinicalTrials.gov - NCT02013063.

CT in planning transcatheter aortic valve implantation procedures and risk assessment.

For surgical aortic valve replacement, the Society of Thoracic Surgeons score (STSS) is the reference standard for the prediction of operative risk. In transcatheter aortic valve implantation (TAVI) though, where the procedure itself is minimally invasive, the traditional risk assessment is supplemented by CTA. Through a consistent approach to the acquisition of high-quality images and the standardised reporting of annular measurements and adverse root and vascular features, patients at risk of complications can be identified. In turn, this may allow for a personalised procedural approach and treatment strategies devised to potentially reduce or mitigate this risk. This article provides a systematic and standardised approach to pre-procedural work-up with computed tomography angiography (CTA) and explores the current state of evidence and future areas of development in this rapidly developing field.

Whole-body magnetic resonance angiography.

Vascular disease, whether it be atherosclerosis, inflammatory, or hereditary vasculitide, is a systemic disorder with disease in one territory predictive of disease in another. Despite this, current approaches focus on single-territory assessment ignoring the global burden of disease. Advances in MRI have enabled us to surmount previous limitations and expand our approach to such conditions with the ability to simultaneously assess the entirety of the arterial tree in a single examination, allowing a staging examination as it were, of the vascular health in its totality. This review will cover the acquisition technique, reporting, clinical utility, and current evidence base for such an approach.

Network meta-analysis of surgical management of gastro-oesophageal reflux disease in adults.

BACKGROUND: Proton pump inhibitors are the mainstay of treatment for gastro-oesophageal reflux disease, but are associated with ongoing costs and side-effects. Antireflux surgery is cost-effective and is preferred by many patients. A total (360o or Nissen) fundoplication is the traditional procedure, but other variations including partial fundoplications are also commonly performed, with the aim of achieving durable reflux control with minimal dysphagia. Many RCTs and some pairwise meta-analyses have compared some of these procedures but there is still uncertainty about which, if any, is superior. Network meta-analysis allows multiple simultaneous comparisons and robust synthesis of the available evidence in these situations. A network meta-analysis comparing all antireflux procedures was performed to identify which has the most favourable outcomes at short-term (3-12 months), medium-term (1-5 years) and long-term (10 years and more than 10 years) follow-up. METHODS: Article databases were searched systematically for all eligible RCTs. Primary outcomes were quality-of-life measures and dysphagia. Secondary outcomes included reflux symptoms, pH studies and complications. RESULTS: Fifty-one RCTs were included, involving 5357 patients and 14 different treatments. Posterior partial fundoplication ranked best in terms of reflux symptoms, and caused less dysphagia than most other interventions including Nissen fundoplication. This was consistent across all time points and outcome measures. CONCLUSION: Posterior partial fundoplication provides the best balance of long-term, durable reflux control with less dysphagia, compared with other treatments.

Network meta-analysis of the effect of preoperative carbohydrate loading on recovery after elective surgery.

BACKGROUND: Three meta-analyses have summarized the effects of preoperative carbohydrate administration on postoperative outcomes in adult patients undergoing elective surgery. However, these studies could not account for the different doses of carbohydrate administered and the different controls used. Multiple-treatments meta-analysis allows robust synthesis of all available evidence in these situations. METHODS: Article databases were searched systematically for RCTs comparing preoperative carbohydrate administration with water, a placebo drink, or fasting. A four-treatment multiple-treatments meta-analysis was performed comparing two carbohydrate dose groups (low, 10-44 g; high, 45 g or more) with two control groups (fasting; water or placebo). Primary outcomes were length of hospital stay and postoperative complication rate. Secondary outcomes included postoperative insulin resistance, vomiting and fatigue. RESULTS: Some 43 trials involving 3110 participants were included. Compared with fasting, preoperative low-dose and high-dose carbohydrate administration decreased postoperative length of stay by 0·4 (95 per cent c.i. 0·03 to 0·7) and 0·2 (0·04 to 0·4) days respectively. There was no significant decrease in length of stay compared with water or placebo. There was no statistically significant difference in the postoperative complication rate, or in most of the secondary outcomes, between carbohydrate and control groups. CONCLUSION: Carbohydrate loading before elective surgery conferred a small reduction in length of postoperative hospital stay compared with fasting, and no benefit in comparison with water or placebo.

Evidence-based anatomical review areas derived from systematic analysis of cases from a radiological departmental discrepancy meeting.

AIM: To produce short checklists of specific anatomical review sites for different regions of the body based on the frequency of radiological errors reviewed at radiology discrepancy meetings, thereby creating "evidence-based" review areas for radiology reporting. MATERIALS AND METHODS: A single centre discrepancy database was retrospectively reviewed from a 5-year period. All errors were classified by type, modality, body system, and specific anatomical location. Errors were assigned to one of four body regions: chest, abdominopelvic, central nervous system (CNS), and musculoskeletal (MSK). Frequencies of errors in anatomical locations were then analysed. RESULTS: There were 561 errors in 477 examinations; 290 (46%) errors occurred in the abdomen/pelvis, 99 (15.7%) in the chest, 117 (18.5%) in the CNS, and 125 (19.9%) in the MSK system. In each body system, the five most common location were chest: lung bases on computed tomography (CT), apices on radiography, pulmonary vasculature, bones, and mediastinum; abdominopelvic: vasculature, colon, kidneys, liver, and pancreas; CNS: intracranial vasculature, peripheral cerebral grey matter, bone, parafalcine, and the frontotemporal lobes surrounding the Sylvian fissure; and MSK: calvarium, sacrum, pelvis, chest, and spine. CONCLUSION: The five listed locations accounted for >50% of all perceptual errors suggesting an avenue for focused review at the end of reporting.

Acute pancreatitis: a comparison of intervention rates precipitated by early vs guideline CT scan timing.

AIM: To assess whether computed tomography (CT) examination earlier in acute pancreatitis (AP) precipitates any surgical or radiological intervention. MATERIALS AND METHODS: A single-centre retrospective cohort study comparing intervention rates in AP precipitated by early (<6 day of admission, n=100) and UK guideline (≥6 day of admission, n=103) CT examinations. RESULTS: No intervention was precipitated by performing CT before the sixth day of admission in AP. A statistically significant larger number of interventions were precipitated when CT was performed on the sixth day or later (p<0.05). Of note, this study was conducted using day of admission, rather than day of symptom onset. Six patients underwent repeat CT examination in the same admission after an early CT examination. CONCLUSION: Performing CT before the sixth day of admission does not lead to earlier intervention. Such early examinations waste resources and may offer false reassurance to clinicians.

Imaging of cardiovascular risk in patients with Turner's syndrome.

Turner's syndrome is a disorder defined by an absent or structurally abnormal second X chromosome and affects around 1 in 2000 newborn females. The standardised mortality ratio in Turner's syndrome is around three-times higher than in the general female population, mainly as a result of cardiovascular disorders. Most striking is the early age at which Turner's syndrome patients develop the life-threatening complications of cardiovascular disorders compared to the general population. The cardiovascular risk stratification in Turner's syndrome is challenging and imaging is not systematically used. The aim of this article is to review cardiovascular risks in this group of patients and discuss a systematic imaging approach for early identification of cardiovascular disorders in these patients.

Technical assessment of whole body angiography and cardiac function within a single MRI examination.

AIM: To evaluate a combined protocol for simultaneous cardiac MRI (CMR) and contrast-enhanced (CE) whole-body MR angiography (WB-MRA) techniques within a single examination. MATERIALS AND METHODS: Asymptomatic volunteers (n = 48) with low-moderate risk of cardiovascular disease (CVD) were recruited. The protocol was divided into four sections: (1) CMR of left ventricle (LV) structure and function; (2) CE-MRA of the head, neck, and thorax followed by the distal lower limbs; (3) CMR LV "late gadolinium enhancement" assessment; and (4) CE-MRA of the abdomen and pelvis followed by the proximal lower limbs. Multiple observers undertook the image analysis. RESULTS: For CMR, the mean ejection fraction (EF) was 67.3 ± 4.8% and mean left ventricular mass (LVM) was 100.3 ± 22.8 g. The intra-observer repeatability for EF ranged from 2.1-4.7% and from 9-12 g for LVM. Interobserver repeatability was 8.1% for EF and 19.1 g for LVM. No LV delayed myocardial enhancement was observed. For WB-MRA, some degree of luminal narrowing or stenosis was seen at 3.6% of the vessel segments (involving n = 29 of 48 volunteers) and interobserver radiological opinion was consistent in 96.7% of 1488 vessel segments assessed. CONCLUSION: Combined assessment of WB-MRA and CMR can be undertaken within a single examination on a clinical MRI system. The associated analysis techniques are repeatable and may be suitable for larger-scale cardiovascular MRI studies.

Contrast-enhanced magnetic resonance lymphography in the assessment of lower limb lymphoedema.

Chronic lower limb lymphoedema is a debilitating condition that may occur as a primary disorder or secondary to other conditions. Satisfactory visualization of the lymphatic vessels to aid diagnosis and surgical planning has been problematic. Historically, direct lymphography was used to visualize lymphatic vessels, although the significant surgical risks involved led to this being largely abandoned as a technique. Technetium-99m lymphoscintigraphy has been the mainstay of diagnosis for over two decades, but is hampered by inherently poor temporal and spatial resolution and limited anatomical detail. Contrast-enhanced magnetic resonance lymphography (MRL) is a relatively new technique that shows early promise in the evaluation of chronic lymphoedema. This article provides the procedural technique for lower limb MRL at both 1.5 and 3 T, discusses pathophysiology and classifications of lymphoedema, provides an overview of relevant lower limb lymphatic anatomy using MRL imaging, compares the various techniques used in the diagnosis of lower limb lymphoedema, shows common pathological MRL imaging findings, and describes alternative uses of MRL. Utilization of this technique will allow more accurate diagnosis and classification of patients suffering from lymphoedema.

D2MOPSO: MOPSO based on decomposition and dominance with archiving using crowding distance in objective and solution spaces.

This paper improves a recently developed multi-objective particle swarm optimizer (D2MOPSO) that incorporates dominance with decomposition used in the context of multi-objective optimization. Decomposition simplifies a multi-objective problem (MOP) by transforming it to a set of aggregation problems, whereas dominance plays a major role in building the leaders' archive. D2MOPSO introduces a new archiving technique that facilitates attaining better diversity and coverage in both objective and solution spaces. The improved method is evaluated on standard benchmarks including both constrained and unconstrained test problems, by comparing it with three state of the art multi-objective evolutionary algorithms: MOEA/D, OMOPSO, and dMOPSO. The comparison and analysis of the experimental results, supported by statistical tests, indicate that the proposed algorithm is highly competitive, efficient, and applicable to a wide range of multi-objective optimization problems.

Prescribed safer supply during dual public health emergencies: a qualitative study examining service providers perspectives on early implementation.

BACKGROUND: Within North America and worldwide, drug related overdoses have increased dramatically over the past decade. COVID-19 escalated the need for a safer supply to replace unregulated substances and to reduce toxicity and overdoses. Service providers play an integral role in the delivery of safer supply but there is little empirical evidence that conceptualizes effective safer supply from their perspectives. This study explored early implementation and impacts of a safer supply program, capturing the perspectives of an interdisciplinary team of service providers on tensions and issues encountered in the development of the SAFER program. METHODS: Using a community-based participatory approach, we conducted individual interviews with program providers (n = 9). The research team was composed of researchers from a local drug user organization, a local harm reduction organization, and academic researchers. The Consolidated Framework for Implementation Research (CFIR) informed the interview guide. Data was analyzed using thematic analysis. RESULTS: There are six themes describing early implementation: (1) risk mitigation prescribing as context for early implementation; (2) developing SAFER specific clinical protocols; (3) accessibility challenges and program innovations; (4) interdisciplinary team and wraparound care; (5) program tensions between addiction medicine and harm reduction; (6) the successes of safer supply and future visions. CONCLUSION: Early implementation issues and tensions included prescriber concerns about safer supply prescribing in a highly politicized environment, accessibility challenges for service users such as stigma, encampment displacement, OAT requirements, program capacity and costs, and tensions between addiction medicine and harm reduction. Navigating these tensions included development of clinical protocols, innovations to reduce accessibility challenges such as outreach, wraparound care, program coverage of medication costs and prescribing safer supply with/without OAT. These findings contribute important insights for the development of prescribed safer supply programs.

Primary hepatocellular neoplasms in a MODY3 family with a novel HNF1A germline mutation.

Maturity onset diabetes of the young type 3 (MODY3) and hepatocellular adenomas (HCAs) are associated with mutations in the HNF1A gene. HNF1A codes for the transcription factor HNF1α, which interacts with DNA as a homodimer or a heterodimer with HNF1ß, to regulate multiple cellular functions including glucidic metabolism, lipidic transport, and detoxication. We report three members of one family with a novel germline in-frame deletion of HNF1A exons 2-3 identified initially using array CGH and direct sequence analysis. All three family members have MODY3 in association with primary liver cell tumours (HCA, liver adenomatosis (LA), and hepatocellular carcinoma (HCC)). Additionally, a high rate of infant mortality was observed in the family. The described family demonstrates a novel HNF1A mutation associated with both benign and malignant primary liver cell tumours and MODY3.

Dirofilariasis mouse models for heartworm preclinical research.

Introduction: Dirofilariasis, including heartworm disease, is a major emergent veterinary parasitic infection and a human zoonosis. Currently, experimental infections of cats and dogs are used in veterinary heartworm preclinical drug research. Methods: As a refined alternative in vivo heartworm preventative drug screen, we assessed lymphopenic mouse strains with ablation of the interleukin-2/7 common gamma chain (γc) as susceptible to the larval development phase of Dirofilaria immitis. Results: Non-obese diabetic (NOD) severe combined immunodeficiency (SCID)γc-/- (NSG and NXG) and recombination-activating gene (RAG)2-/-γc-/- mouse strains yielded viable D. immitis larvae at 2-4 weeks post-infection, including the use of different batches of D. immitis infectious larvae, different D. immitis isolates, and at different laboratories. Mice did not display any clinical signs associated with infection for up to 4 weeks. Developing larvae were found in subcutaneous and muscle fascia tissues, which is the natural site of this stage of heartworm in dogs. Compared with in vitro-propagated larvae at day 14, in vivo-derived larvae had completed the L4 molt, were significantly larger, and contained expanded Wolbachia endobacteria titres. We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%-90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%-88% reduction in L4 larvae at 14-28 days. Discussion: Future adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use.

Evaluation of an electromagnetic 3D navigation system to facilitate endovascular tasks: a feasibility study.

INTRODUCTION: We describe a novel approach to arterial cannulation using the StealthStation(®) Guidance System (Medtronic, USA). This uses electromagnetic technology to track the guidewire, displaying a 3D image of the vessel and guidewire. METHODS: The study was performed on a 'bench top' simulation model called the Cannulation Suite comprising of a silicone aortic arch model and simulated fluoroscopy. The accuracy of the StealthStation(®) was assessed. 16 participants of varying experience in performing endovascular procedures (novices: 6 participants, ≤5 procedures performed; intermediate: 5 participants, 6-50 procedures performed; experts: 5 participants, >50 procedures performed) underwent a standardised training session in cannulating the left subclavian artery on the model with the conventional method (i.e. with fluoroscopy) and with the StealthStation(®). Each participant was then assessed on cannulating the left subclavian artery using the conventional method and with the StealthStation(®). Performance was video-recorded. The subjects then completed a structured questionnaire assessing the StealthStation(®). RESULTS: The StealthStation(®) was accurate to less than 1 mm [mean (SD) target registration error 0.56 mm (0.91)]. Every participant was able to complete the cannulation task with a significantly lower use of fluoroscopy with the navigation system compared with the conventional method [median 0 s (IQR 0-2) vs median 14 s (IQR 10-19), respectively; p = <0.001]. There was no significant difference between the StealthStation(®) and conventional method for: total procedure time [median 17 s (IQR 9-53) vs median 21 s (IQR 11-32), respectively; p=0.53]; total guidewire hits to the vessel wall [median 0 (IQR 0-1) vs median 0 (IQR 0-1), respectively; p=0.86]; catheter hits to the vessel wall [median 0.5 (IQR 0-2) vs median 0.5 (IQR 0-1), respectively; p=0.13]; and cannulation performance on the global rating scale [median score, 39/40 (IQR 28-39) vs 38/40 (IQR 33-40), respectively; p=0.40]. The intra-class correlation coefficient for agreement between video-assessors for all scores was 0.99. 88% strongly agreed that the StealthStation(®) can potentially decrease exposure of the patient to contrast and radiation. CONCLUSION: Arterial cannulation is feasible with the StealthStation(®).

A concept mapping study of service user design of safer supply as an alternative to the illicit drug market.

BACKGROUND: Within North America and worldwide, drug-related overdoses have increased dramatically over the past decade. COVID-19 escalated the need for a safer supply of illicit substances to reduce overdoses with hopes of replacing substances obtained from the illicit drug market. Drug users1 should be at the centre of program and policy decisions related to the development and implementation of safer supply. Yet, there is little empirical research that conceptualizes effective safer supply from their perspectives. METHOD: Within a community based participatory approach to research, we conducted a concept mapping study to foreground the perspectives of drug users and develop a conceptual model of effective safer supply. Our team was composed of researchers from a local drug user organization, a local harm reduction organization, and academic researchers. The focused prompt developed by the team was: "Safe supply would work well if…" Sixty-three drug users participated in three rounds of focus groups as part of the concept mapping process, involving brainstorming, sorting, rating and naming of themes. RESULTS: The concept mapping process resulted in six clusters of statements: 1) Right dose and right drugs for me; 2) Safe, positive and welcoming spaces; 3) Safer supply and other services are accessible to me; 4) I am treated with respect; 5) I can easily get my safer supply; and 6) Helps me function and improves my quality of life (as defined by me). The statements within each cluster describe key components central to an effective model of safer supply as defined by drug users. CONCLUSION: The results of this study provide insights into key components of effective safer supply to inform planning and evaluation of future safer supply programs informed by drug user perspectives.

Negative appendicectomy and perforation rates in patients undergoing laparoscopic surgery for suspected appendicitis.

BACKGROUND: Despite widespread use of imaging technologies including ultrasonography and computed tomography, rates of negative appendicectomy and perforated appendicitis remain high. This trend analysis examined whether rates of negative appendicectomy and perforated appendicitis have decreased over time, and sought to evaluate clinical predictors associated with negative appendicectomy and perforated appendicitis. METHODS: This analysis was based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery (SALTS). All patients aged 12 years and over undergoing emergency laparoscopic appendicectomy between 1995 and 2006 were included. Unadjusted and risk-adjusted logistic regression analyses were performed. RESULTS: A total of 7964 patients underwent laparoscopic appendicectomy, of whom 7452 (93.6 per cent) had acute appendicitis and 512 (6.4 per cent) had a macroscopically normal appendix. Perforation occurred in 1230 (16.5 per cent) of those with appendicitis. In multivariable analysis, younger age (12-18 years), female sex, absence of local or generalized peritonitis and an early point during the study period were significant predictors of negative appendicectomy. For perforated appendicitis, significant predictors included age over 36 years, presence of localized or generalized peritonitis, and high American Society of Anesthesiologists grade. The rate of negative appendicectomy decreased from 12.7 per cent in 1995 to 2.8 per cent in 2006, there being a significant reduction in both unadjusted and risk-adjusted analyses (P < 0.001 for trend). In adjusted analyses, the rate of perforated appendicitis did not increase significantly over time. CONCLUSION: The rate of negative appendicectomy decreased over time, without an accompanying increase in perforated appendicitis. The risk of having a negative appendicectomy was highest in girls aged 12-18 years without local or generalized peritonitis during the early study period, whereas perforation was associated with age over 36 years, presence of localized or generalized peritonitis, and greater co-morbidity. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.