Optimising plasma clozapine levels to improve treatment response: an individual patient data meta-analysis and receiver operating characteristic curve analysis.

BACKGROUND: Although clozapine is the most efficacious medication for treatment-refractory schizophrenia, not all patients will have an adequate response. Optimising clozapine dose using therapeutic drug monitoring could therefore maximise response. AIMS: Using individual patient data, we undertook a receiver operating characteristic (ROC) curve analysis to determine an optimal therapeutic range for clozapine levels to guide clinical practice. METHOD: We conducted a systematic review of PubMed, PsycINFO and Embase for studies that provided individual participant level data on clozapine levels and response. These data were analysed using ROC curves to determine the prediction performance of plasma clozapine levels for treatment response. RESULTS: We included data on 294 individual participants from nine studies. ROC analysis yielded an area under the curve of 0.612. The clozapine level at the point of optimal diagnostic benefit was 372 ng/mL; at this level, the response sensitivity was 57.3%, and specificity 65.7%. The interquartile range for treatment response was 223-558 ng/mL. There was no improvement in ROC performance with mixed models including patient gender, age or length of trial. Clozapine dose and clozapine concentration to dose ratio did not provide significantly meaningful prediction of response to clozapine. CONCLUSIONS: Clozapine dose should be optimised based on clozapine therapeutic levels. We found that a range between 250 and 550 ng/mL could be recommended, while noting that a level of >350 ng/mL is the most optimal for response. Although some patients may not respond without clozapine levels >550 ng/mL, the benefits should be weighed against the increased risk of adverse drug reactions.

Analysis of rare disruptive germline mutations in 2135 enriched BRCA-negative breast cancers excludes additional high-impact susceptibility genes.

BACKGROUND: Breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. PATIENTS AND METHODS: We included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. ELIGIBILITY CRITERIA: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (<30 years), and (iv) concomitant ovarian cancer. We undertook exome sequencing of cases and carried out gene-level burden testing of rare damaging variants against those from 51 377 ethnicity-matched population controls from gnomAD. RESULTS: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10-5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10-4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. CONCLUSIONS: This is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

Mental health treatment experiences of commonwealth veterans from diverse ethnic backgrounds who have served in the UK military.

INTRODUCTION: Research has shown that the likelihood of ex-military personnel developing mental health problems following service is around one in five. Little is known about the barriers to accessing mental health in veterans from diverse ethnic backgrounds. This study aims to explore mental health treatment experiences of veterans from commonwealth countries and therefore diverse ethnic backgrounds. METHODS: Semi-structured interviews were conducted over the telephone with veterans from commonwealth countries. Veterans were recruited from a mental health charity and were at various stages of treatment. RESULTS: We interviewed six veterans who were from a diverse range of commonwealth countries including St Lucia, Gambia, Ghana, Fiji and South Africa. All had served in the UK army in combat roles. Our findings consisted of key themes: (1) feeling that they are treated differently, (2) they felt as though they were unheard when reaching out for help, (3) systemic pressures such as financial difficulties, missed opportunities and lack of insight about mental health and (4) the importance of involving the wider community in care. CONCLUSION: Our findings highlight some distinct barriers to mental health treatment that commonwealth veterans experience. The themes reported by the participants appear to suggest they had experience signs of institutional racism. Suggesting the importance of highlighting these issues, and to help overcome these potential barriers to accessing services. Given that commonwealth veterans involvement in the UK military is significant and increasing, the findings in this study should be used to support this population by implementing service provision and policy.

Low speech rate but high gesture rate during conversational interaction in people with Cornelia de Lange syndrome.

BACKGROUND: Cornelia de Lange syndrsome (CdLS) is a rare genetic syndrome with notable impaired expressive communication characterised by reduced spoken language. We examined gesture use to refine the description of expressive communication impairments in CdLS. METHODS: During conversations, we compared gesture use in people with CdLS to peers with Down syndrome (DS) matched for receptive language and adaptive ability, and typically developing (TD) individuals of similar chronological age. RESULTS: As anticipated the DS and CdLS groups used fewer words during conversation than TD peers (P < .001). However, the CdLS group used twice the number of gestures per 100 words compared with the DS and TD groups (P = .003). CONCLUSIONS: Individuals with CdLS have a significantly higher gesture rate than expected given their level of intellectual disability and chronological age. This result indicates the cause of reduced use of spoken language does not extend to all forms of expressive communication.

A systematic review of the behaviours associated with depression in people with severe-profound intellectual disability.

The assessment of depression in people with severe to profound intellectual disability (severe-profound ID) is challenging, primarily due to inability to report internal states such as mood, feelings of worthlessness and suicidal ideation. This group also commonly presents with challenging behaviours (e.g. aggression and self-injury) with debate about whether these behaviours should be considered 'depressive equivalents' or are sensitive for, but not specific to, depression in severe-profound ID. We conducted a systematic review exploring behaviours associated with depression and low mood in individuals with severe-profound ID. The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (2009) guidelines. Three electronic databases were searched (Embase, PsycINFO and Ovid MEDLINE), and 13 studies were included and rated for quality. Few studies were rated as having high methodological quality. Behaviours captured by standard diagnostic schemes for depression (e.g. Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases) showed a relationship with depression in severe-profound ID, including the two core symptoms (depressed affect and anhedonia), as well as irritability, sleep disturbance, psychomotor agitation, reduced appetite and fatigue. Challenging behaviours such as aggression, self-injury, temper tantrums, screaming and disruptive behaviour were associated with depression. Challenging behaviours show a robust relationship with depression. Whilst these behaviours may suggest an underlying depression, study limitations warrant caution in labelling them as 'depressive equivalents'. These limitations include not controlling for potential confounds (autism, other affective disorders and pain) and bias associated with comparing depressed/non-depressed groups on the same behavioural criteria used to initially diagnose and separate these groups. Future studies that use depressive measures designed for ID populations, which control for confounds and which explore low mood irrespective of psychiatric diagnosis, are warranted to better delineate the behaviours associated with depression in this population (PROSPERO 2018: CRD42018103244).

Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: An IMI-DIRECT study.

AIM: To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration. METHODS: We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI-DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven-point oral glucose tolerance test at baseline and follow-up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months. RESULTS: At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1-4. Participants in Subgroups 2-4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (ß = 0.36, 95% CI 0.13-0.58), Subgroup 3 (ß = 0.30; 95% CI 0.10-0.50) and Subgroup 2 (ß = 0.18; 95% CI 0.04-0.32), compared to Subgroup 1. The same was observed for C-peptide and insulin. Five subgroups were identified at follow-up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months. CONCLUSIONS: Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified.

Quantifying the hygroscopic properties of cyclodextrin containing aerosol for drug delivery to the lungs.

Aerosol dynamics is important to quantify in drug delivery to the lungs with the aim of delivering therapeutics to a target location and optimising drug efficacy. The macrocycle (2-hydroxypropyl)-ß-cyclodextrin (2-HP-ß-CD) is thought to alleviate symptoms associated with neurodegenerative diseases when inhaled but the hygroscopic response is not well understood. Here we measure the hygroscopic growth of individual aqueous aerosol containing 2-HP-ß-CD in optical tweezers through analysis of morphology-dependent resonances arising in Raman spectra. Droplets are analysed in the size range of 3-5 µm in radius. The evolving radius and refractive index of each droplet are measured in response to change in relative humidity from 98-20% to determine mass and radius based hygroscopic growth factors, and compared with dynamic vapour sorption measurements. Bulk solution refractive index and density measurements were used in accordance with the self-consistent Lorenz-Lorentz rule to determine melt solute and droplet properties. The refractive index of 2-HP-ß-CD was determined to be 1.520 ± 0.002 with a density of 1.389 ± 0.005 g cm-3. To our knowledge, we show the first aerosol measurements of 2-HP-ß-CD and determine hygroscopicity. By quantifying the hygroscopic growth and physicochemical properties of 2-HP-ß-CD, the impact of aerosol dynamics can be accounted for in tailoring drug formulations and informing models used to predict drug deposition patterns within the respiratory system.

Renal artery embolization in a child with delayed hemodynamic instability from penetrating knife wound.

Penetrating laceration injury in the pediatric population may present as an acute or delayed life-threatening injury. Although emergent intra-arterial embolization is commonly utilized in adults, few cases have been reported for children. Surgical treatment for severe renal laceration injuries may require complete nephrectomy; an unfortunate outcome for a pediatric patient if a renal-preserving alternative is feasible. We present a case of penetrating renal laceration in a 10-year-old boy treated with intra-arterial embolization of the lacerated dominant renal artery and subsequent renal perfusion by an uninjured accessory renal artery allowing for renal preservation.

Exploring the perspectives of 10-, 11-, and 12-year-old primary school students on physical activity engagement-"'Cause you can't just be sitting at a desk all the time!"

BACKGROUND: Research indicates that 91% of Canadian children are not engaging in enough physical activity (PA) to achieve health benefits. Physical education (PE) classes have been identified as a way to improve child health by facilitating engagement in movement-based activities. The daily physical activity (DPA) initiative was created with similar intentions and requires that students participate in at least 20 min of PA daily via PE classes and/or during instructional time for other subjects. Despite recommendations that 150 min of exercise/play be incurred weekly through either avenue, nearly half of Canadian schools fail to achieve this goal. The disconnect between PA-related school policies and low reported participation rates suggests that additional research is warranted. The purpose of this study was to explore the perspectives of primary students regarding the facilitators, barriers, and recommendations for PA engagement at their schools. METHODS: Researchers conducted nine group interviews with 53 children aged 10-12, representing six primary schools in Northwestern Ontario using a semi-structured interview format. Sessions were analysed using inductive content analysis. RESULTS: Participants discussed several facilitators of PA including enjoying activities (alleviating boredom and participating with others), accomplishment (skill building and enhanced self-image), and benefits in the classroom (thinking clearly and enhanced readiness to learn). Barriers to PA participation included school rules and culture (PA/PE restrictions, heavy workload, and "no work, no PA"), personal struggles (physical challenges and varied skill levels), and technology (being addictive and a replacement for being active). Recommendations for enhancing engagement that were outlined by the children centred around PE and daily physical activity (increase opportunities and involve students in planning/delivery) and recess-based themes (decrease focus on safety and make equipment more available). CONCLUSION: These student perspectives and related recommendations may be beneficial for administrators and teachers in similar contexts who are seeking to enhance PA engagement among students with the goal of improving child health.

Characteristics of people with high visit-to-visit glycaemic variability in Type 2 diabetes.

AIMS: Increased visit-to-visit glycaemic variability is independently associated with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient characteristics associated with raised visit-to-visit glycaemic variability in people with Type 2 diabetes. METHODS: A case-control study was conducted to establish associations between HbA1c variability and clinical covariates in 10 130 people with Type 2 diabetes. Variability was calculated by two metrics [sd and coefficient of variation (CV)] from a minimum of four HbA1c readings obtained over a 4-year period. High and low variability groups were defined as the top and bottom tertile of the sd or CV, and used in logistic regression analyses including a number of clinical and biochemical covariates. The analyses were stratified into low mean (< 53 mmol/mol; 7%) and high mean (≥ 53 mmol/mol; 7%) HbA1c groups. RESULTS: Findings were consistent across both HbA1c groups and variability metrics. Treatment, independent of other factors, was the most strongly associated covariate for the risk of high HbA1c variability. A six-fold increased risk was observed in the low HbA1c group, between the most and least intense treatment regimens (P < 0.001). Similar findings were present in the high HbA1c group with a three-fold increase in risk (P < 0.001). In addition, male gender, younger age, reduced HDL-cholesterol and increased BMI were all found to be independently associated with raised visit-to-visit glycaemic variability. CONCLUSIONS: Intensive treatment resulting in low mean HbA1c was associated with marked increase in HbA1c variability. Irrespective of diabetes control, the greatest visit-to-visit variability was observed in young, insulin resistant men.

Interventions for cancer-related fatigue: a scoping review.

Cancer-related fatigue (CRF) is common and can be distressing for some survivors. There is increasing interest in measuring levels of CRF, highlighting its impact on quality of life. This review describes the nature and scope of evidence relating to interventions for CRF. Scoping review methodology was used to identify studies, extract data, collate and summarise results. Data were collated according to cancer tumour streams, stage of illness and the types of trial interventions. A total of 447 trials and 37 systematic reviews met the inclusion criteria. Nine papers reported longitudinal results. Populations studied were predominantly of mixed cancer diagnoses and breast cancer. The most frequent interventions were exercise, pharmacological, psycho-education and mind-body interventions. Fatigue was identified as a primary outcome measure (OM) in 58% of studies, with 58 different fatigue measures reported. Emerging evidence exists for the effectiveness of fatigue interventions for some cancer types. More research on interventions with participants with the same cancer type and illness phase is needed. Measurement of severity and impact of CRF using fewer, robust OMs will permit comparisons across studies.

The Clinical Utility of Next Generation Sequencing Results in a Community-Based Hereditary Cancer Risk Program.

Since the 2013 Supreme Court ruling on BRCA1/BRCA2 patenting, hereditary cancer gene panels now include BRCA1 and BRCA2, making these panels an option for first-tier testing. However, questions remain about the clinical utility and implications of these panels for medical management with inclusion of genes of unknown to moderate penetrance. To better understand how use of these panels affected our practice, we reviewed patients who underwent testing in our clinic from July 1, 2013 through May 23, 2014. Indications for testing included personal and/or family history of breast and/or ovarian cancer. A total of 136 patients underwent panel testing via a single commercial laboratory; 12 (8.8 %) patients were positive for a pathogenic or likely pathogenic mutation (four BRCA2 mutations, two TP53 mutations, one CDH1 mutation, two ATM mutations, and one patient each with a CHEK2, NBN, or PALB2 mutation). Of these positive patients, 100 % met the National Comprehensive Cancer Network (NCCN) guidelines for Hereditary Breast and Ovarian Cancer genetic testing (2.2014). Mutations in seven of twelve (58 %) patients led to changes in medical management; three of seven (43 %) had a non-BRCA1 or BRCA2 gene mutation. Our findings suggest that there is clinical utility of panels that include genes of unknown to moderate penetrance.

Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.

Therapeutic response to metformin, a first-line drug for type 2 diabetes (T2D), is highly variable, in part likely due to genetic factors. To date, metformin pharmacogenetic studies have mainly focused on the impact of variants in metformin transporter genes, with inconsistent results. To clarify the significance of these variants in glycemic response to metformin in T2D, we performed a large-scale meta-analysis across the cohorts of the Metformin Genetics Consortium (MetGen). Nine candidate polymorphisms in five transporter genes (organic cation transporter [OCT]1, OCT2, multidrug and toxin extrusion transporter [MATE]1, MATE2-K, and OCTN1) were analyzed in up to 7,968 individuals. None of the variants showed a significant effect on metformin response in the primary analysis, or in the exploratory secondary analyses, when patients were stratified according to possible confounding genotypes or prescribed a daily dose of metformin. Our results suggest that candidate transporter gene variants have little contribution to variability in glycemic response to metformin in T2D.

Personalized medicine in diabetes: the role of 'omics' and biomarkers.

Personalized medicine, otherwise called stratified or precision medicine, aims to better target intervention to the individual to maximize benefit and minimize harm. This review discusses how diabetes aetiology, pathophysiology and patient genotype influence response to or side effects of the commonly used diabetes treatments. C-peptide is a useful biomarker that is underused to guide treatment choice, severe insulin deficiency predicts non-response to glucagon-like peptide-1 receptor agonists, and thiazolidinediones are more effective in insulin-resistant patients. The field of pharmacogenetics is now yielding clinically important results, with three examples outlined: sulphonylurea sensitivity in patients with HNF1A maturity-onset diabetes of the young; sulphonylurea sensitivity in patients with Type 2 diabetes with reduced function alleles at CYP2C9, resulting in reduced metabolism of sulphonylureas; and severe metformin intolerance associated with reduced function organic cation transporter 1 (OCT1) variants, exacerbated by drugs that also inhibit OCT1. Genome-wide approaches and the potential of other 'omics', including metagenomics and metabolomics, are then outlined, highlighting the complex interacting networks that we need to understand before we can truly personalize diabetes treatments.

Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance.

AIM: To investigate glucose and insulin metabolism in participants with ataxia telangiectasia in the absence of a diagnosis of diabetes. METHODS: A standard oral glucose tolerance test was performed in participants with ataxia telangiectasia (n = 10) and in a control cohort (n = 10). Serial glucose and insulin measurements were taken to permit cohort comparisons of glucose-insulin homeostasis and indices of insulin secretion and sensitivity. RESULTS: During the oral glucose tolerance test, the 2-h glucose (6.75 vs 4.93 mmol/l; P = 0.029), insulin concentrations (285.6 vs 148.5 pmol/l; P = 0.043), incremental area under the curve for glucose (314 vs 161 mmol/l/min; P = 0.036) and incremental area under the curve for insulin (37,720 vs 18,080 pmol/l/min; P = 0.03) were higher in participants with ataxia telangiectasia than in the controls. There were no significant differences between groups in fasting glucose, insulin concentrations or insulinogenic index measurement (0.94 vs 0.95; P = 0.95). The Matsuda index, reflecting whole-body insulin sensitivity, was lower in participants with ataxia telangiectasia (5.96 vs 11.03; P = 0.019) than in control subjects. CONCLUSIONS: Mutations in Ataxia Telangiectasia Mutated (ATM) that cause ataxia telangiectasia are associated with elevated glycaemia and low insulin sensitivity in participants without diabetes. This indicates a role of ATM in glucose and insulin metabolic pathways.

Organic cation transporter 1 variants and gastrointestinal side effects of metformin in patients with Type 2 diabetes.

AIMS: Metformin is the most widely used oral anti-diabetes agent and has considerable benefits over other therapies, yet 20-30% of people develop gastrointestinal side effects, and 5% are unable to tolerate metformin due to the severity of these side effects. The mechanism for gastrointestinal side effects and their considerable inter-individual variability is unclear. We have recently shown the association between organic cation transporter 1 (OCT1) variants and severe intolerance to metformin in people with Type 2 diabetes. The aim of this study was to explore the association of OCT1 reduced-function polymorphisms with common metformin-induced gastrointestinal side effects in Type 2 diabetes. METHODS: This prospective observational cohort study included 92 patients with newly diagnosed Type 2 diabetes, incident users of metformin. Patients were genotyped for two common loss-of-function variants in the OCT1 gene (SLC22A1): R61C (rs12208357) and M420del (rs72552763). The association of OCT1 reduced-function alleles with gastrointestinal side effects was analysed using logistic regression. RESULTS: Forty-three patients (47%) experienced gastrointestinal adverse effects in the first 6 months of metformin treatment. Interestingly, the number of OCT1 reduced-function alleles was significantly associated with over two-fold higher odds of the common metformin-induced gastrointestinal side effects (odds ratio = 2.31, 95% confidence interval 1.07-5.01, P = 0.034). CONCLUSIONS: In conclusion, we showed for the first time the association between OCT1 variants and common metformin-induced gastrointestinal side effects. These results confirm recent findings related to the role of OCT1 in severe metformin intolerance, and suggest that high inter-individual variability in mild/moderate and severe gastrointestinal intolerance share a common underlying mechanism. These data could contribute to more personalized and safer metformin treatment.

tRNA methyltransferase homologue gene TRMT10A mutation in young adult-onset diabetes with intellectual disability, microcephaly and epilepsy.

BACKGROUND: A syndrome of young-onset diabetes mellitus associated with microcephaly, epilepsy and intellectual disability caused by mutations in the tRNA methyltransferase 10 homologue A (TRMT10A) gene has recently been described. CASE REPORT: We report two siblings from the fourth family reported to have diabetes mellitus as a result of a TRMT10A mutation. A homozygous nonsense mutation p.Glu27Ter in TRMT10A was identified using targeted next-generation sequencing and confirmed by PCR/Sanger sequencing. Diabetes was diagnosed while the subjects were in their 20s and was characterized by insulin resistance. Epilepsy and intellectual disability were features in common. Mild microcephaly was present at birth but their final head circumferences were normal. CONCLUSION: Our report provides independent confirmation of the role of TRMT10A mutations in this syndrome and expands its phenotypic description. TRMT10A sequencing should be considered in children or adults with young-onset diabetes who have a history of intellectual disability, microcephaly and epilepsy. This report also shows the advantages of using a targeted panel to identify previously unsuspected monogenic diabetes among young-onset non-insulin-dependent diabetes in the absence of obesity and autoimmunity.

Interventional oncology for liver and lung metastases from colorectal cancer: The current state of the art.

Interventional oncology is developing rapidly as a result of advances in imaging and medical devices. Although the treatments offered are recent and not yet fully validated in the guidelines, they allow non-invasive curative treatments to be offered to a growing number of patients. When it is used in a highly selected patients with less than three metastases under 2-3cm in size, percutaneous tumor ablation offers local efficacy similar to excision surgery with considerable sparing of the parenchyma, both for lung and liver metastases. Hepatic intra-arterial therapies (chemotherapy, radioembolization, and chemoembolization) are now "salvage" methods after chemotherapy has failed and are being assessed in earlier lines of treatment.

Survey of patient satisfaction after Doppler-guided transanal hemorrhoidal dearterialization performed in ambulatory settings.

BACKGROUND: Transanal hemorrhoidal dearterialization (THD) is a recently developed procedure to minimize postoperative pain from hemorrhoidectomy. This technique utilizes Doppler signals to aid ligation of hemorrhoidal arteries followed by mucopexy of redundant mucosa if needed. The aim of the present study was to assess patient satisfaction after THD. METHODS: This is a retrospective cohort study of patients who underwent THD at three different sites from April 2007 through October 2010. All procedures were performed in ambulatory settings according to protocol. Telephone surveys were conducted after a minimum of 1-month follow-up to assess patients' satisfaction on a scale of 1-10. Patients were asked whether the procedure had alleviated their symptoms. Patients were asked to recall duration of pain and time from surgery to return to work. RESULTS: Between April 2007 and October 2010, 216 patients with grade III-IV hemorrhoids underwent THD. There were 165 males and 61 females. Average age was 52.2 ± 14.2 years. All patients were discharged the same day after meeting ambulatory surgery center discharge criteria. Postoperative difficulty urinating occurred in 37 (17 %) patients, and six of them required temporary urinary catheterization. Transitory postoperative bleeding was reported by 38 (18 %) patients. Transitory incontinence to stool and flatus occurred in 18 (9 %) and 16 patients (8 %), respectively. Pelvic muscle spasms occurred in 21 (10 %) patients. Median follow-up was 23 months (range 1-42 months) with 143 (66 %) having at least 9 months between procedure and interview. Mean patient satisfaction was 8.5 ± 0.7 (on a scale of 1-10 with 10 being the best), and 91.5 % of patients felt the procedure had "helped" them. Average number of days with discomfort was 6.7 ± 2.1. Patients returned to work after an average of 10.3 ± 3.2 days. Our study is limited by lack of long-term follow-up and by retrospective complication assessment. CONCLUSIONS: Patient satisfaction with THD performed in ambulatory settings is high. Our data support performance of this procedure in an ambulatory setting.

Factors influencing the occurrence of a T2-STIR hypersignal in the lumbosacral adipose tissue.

PURPOSE: The purpose of our study is to determine whether there is a relation between overweight, age, sex, "hospitalised/outpatient" status and a non-inflammatory hypersignal of the subcutaneous lumbosacral adipose tissue in T2 Short-Tau Inversion-Recovery (T2-STIR) MR imaging sequences. PATIENTS AND METHODS: One hundred and six lumbar MRI, including a T2-STIR and T1 Fluid Attenuated Inversion-Recovery (FLAIR) weighted sagittal sequences, were retrospectively taken from the picture archiving and communication system (PACS) of our hospital and then made anonymous and analysed. The presence or absence of a T2-STIR hypersignal within subcutaneous adipose tissue behind the paraspinal muscle aponeurosis was determined. In addition, the weight, thickness of the fat tissue, the administrative status of the patient, the age, sex, time of the examination and, when present, the height of this hypersignal were noted. A uni- and multivariate analysis by logistic regression was carried out in order to examine the relationship between the data gathered. RESULTS: In the examinations selected, 25.5% (n=27) demonstrated a T2-STIR hypersignal in the subcutaneous tissue. We identified the weight (P<0.023), thickness of the fat tissue (P<0.001), the age of the patient (P<0.017) and the "hospitalised" status (P<0.009) as significant variables associated with this T2-STIR hypersignal. The mean height of the hypersignal was 109.5mm. Five of the 27 patients had an injection of gadolinium chelate and no enhancement was found at this level. CONCLUSION: We found a significant link between overweight, age and "hospitalised" status and the non-inflammatory infiltration of lumbar adipose tissue. This phenomenon seems to correspond with an interstitial oedema, related to subcutaneous stasis. This anomaly should not be confused with a local inflammation.