Evaluation of Aintree LOSS, a community-based, multidisciplinary weight management service: outcomes and predictors of engagement.

Aintree LOSS is a community-based, multidisciplinary weight management programme for patients with severe and complex obesity, focusing on a flexible and individualized service with follow-up for up to 2 years. We evaluated all 2472 patients referred to the service between October 2009 and 2013. Demographic data were recorded at baseline, with the Index of Multiple Deprivation (IMD) used to measure socioeconomic deprivation. Weight was recorded at each visit. Mean body mass index at baseline was 45.6 (standard deviation 6.8), and 58.9% of patients lived in areas in the most deprived decile nationally. Of 2315 appropriate referrals, 1249 (55.1%) attended >2 visits; mean final weight loss was 3.50 ± 8.55 kg, and 24.1% achieved ≥5% weight loss. Of the patients, 754 (33.3%) attended for over 6 months; mean final weight loss was 4.94 ± 10 kg, and 34% achieved 5% weight loss. Multivariate logistic regression analysis showed increasing age, residence in a less deprived area and sleep apnoea to be independently associated with attendance for >6 months, and there was a linear relationship between 6-month attendance and deprivation quintile. Year-on-year analyses showed improvement in engagement over time, coinciding with efforts to improve access to the service. This work shows a multidisciplinary, community-based weight loss programme prioritizing a fully flexible and individualized approach functioning effectively in real-world practice. Maintaining engagement remains a challenge in weight loss programmes, and our results suggest younger patients living in areas with greater deprivation should be a target for efforts to improve engagement.

Screening methods for obstructive sleep apnoea in severely obese pregnant women.

Obstructive sleep apnoea (OSA) is an often-overlooked diagnosis, more prevalent in the obese population. Screening method accuracy, uptake and hence diagnosis is variable. There is limited data available regarding the obese pregnant population; however, many studies highlight potential risks of apnoeic episodes to mother and foetus, including hypertension, diabetes and preeclampsia. A total of 162 women with a body mass index (BMI) ≥ 35 were recruited from a tertiary referral hospital in the northwest of England. They were invited to attend three research antenatal clinics, completing an Epworth Sleepiness Scale (ESS) questionnaire at each visit. A monitor measuring the apnoea hypopnoea index (AHI) was offered at the second visit. Data taken from consent forms, hospital notes and hospital computer records were collated and anonymized prior to statistical analysis. A total of 12.1% of women had an ESS score of >10, suggesting possible OSA. Rates increased throughout pregnancy, although unfortunately, the attrition rate was high; 29.0% of women used the RUSleeping (RUS) meter, and only one (2.1%) met pre-specified criteria for OSA (AHI ≥ 15). This individual had OSA categorized as severe and underwent investigations for preeclampsia, eventually delivering by emergency caesarean section due to foetal distress. The accuracy of the ESS questionnaire, particularly the RUS monitor, to screen for OSA in the pregnant population remains unclear. Further research on a larger sample size using more user-friendly technology to confidently measure AHI would be beneficial. There are currently no guidelines regarding screening for OSA in the obese pregnant population, yet risks to both mother and foetus are well researched.

Fit for Birth - the effect of weight changes in obese pregnant women on maternal and neonatal outcomes: a pilot prospective cohort study.

UNLABELLED: The 'Fit for Birth' study aimed to explore patterns of gestational weight gain and their relationship with pregnancy outcomes. The study had three aims: 1. To explore the feasibility of conducting a large cohort study in this setting. 2. To describe patterns of weight gain through pregnancy in obese women. 3. To explore associations of weight change during pregnancy with outcomes. STUDY POPULATION: Pregnant women with a BMI ≥ 30 kg m(-2) at first antenatal clinic visit. METHODS: This was a single centre pilot observational study based at the Liverpool Women's Hospital, a large UK maternity hospital.Women were recruited into the study at their antenatal booking visit and had weights measured throughout pregnancy. Patterns of weight gain were described and related to maternal and neonatal outcomes. MAIN OUTCOME MEASURE: The primary outcome was a composite measure consisting of any of 12 adverse maternal and foetal outcomes. This was compared by categorized pregnancy weight gain (<0 kg, 0-5 kg, 5.1-9 kg and >9 kg). RESULTS: Eight hundred and twenty four women consented to participation between June 2009 and June 2010. Weight data were collected on 756 women. Only 385 women had weights measured in all three study assessment periods (6-20 weeks, 20 + 1 to 32 weeks and >32 weeks gestation) while 427 women had weights measured in period 3. Individual patterns of weight gain varied widely and missing data were common and non-random. There was a significant association between increased weight gain during pregnancy and poor maternal and foetal outcome. CONCLUSIONS: Weight gain in obese women during pregnancy can be highly variable. Our study supports an association between increased weight gain in pregnancy and adverse perinatal outcomes.

Non-directed aromatic C-H amination: catalytic and mechanistic studies enabled by Pd catalyst and reagent design.

This manuscript describes the systematic development of pyridine-type ligands, which promote the Pd catalyzed, non-directed amination of benzene in combination with novel, hydroxylamine-based electrophilic amination reagents. DFT calculations and mechanistic experiments provide insights into the factors influencing the arene C-H amination protocol.

Socioeconomic deprivation independently predicts painful diabetic neuropathy in type 2 diabetes.

OBJECTIVE: Painful peripheral neuropathy in people with type 2 diabetes is a disabling complication. We explored associations of this condition with socioeconomic deprivation. RESEARCH DESIGN AND METHODS: The Townsend index of socioeconomic deprivation was examined in the pseudonymised GP records of 15388 (44.1% female) individuals with type 2 diabetes in the Cheshire county of England, and related to prevalence of drug treated painful diabetic neuropathy. We also analysed prescription trends with respect to pharmacotherapy for neuropathy pain relief. RESULTS: Treatment for neuropathic pain was initiated in 3 266 (21.2%) of patients. Those on treatment were older [68.2 (95% CI 67.8-68.7) vs. 66.6 (66.4-66.8) years] than those not on treatment. There was no difference in HbA1c (7%, 55 mmol/mol).There were significant differences between the groups for the Townsend deprivation index, with a greater proportion (30.6% vs. 22.8% of patients with treated neuropathic pain) having a score of ≥1 (Χ(2)=83.9, p<0.0001).Multivariate logistic regression analyses indicated that each unit increment in the Townsend index was associated with an 6% increased odds of requiring neuropathic pain treatment [odds ratio (95%CI) 1.06 (1.05-1.08), p<0.0001] independent of 5 year age band, BMI, gender, systolic BP, eGFR, HbA1C and total cholesterol. CONCLUSIONS: In this study using pseudonymised clinical records, a higher level of socioeconomic deprivation seemingly may predispose to severe neuropathic pain in diabetes requiring pharmacological intervention. Targeted allocation of healthcare resources to this group may offer clinical benefits.

IGF2 gene polymorphisms and IGF-II concentration are determinants of longitudinal weight trends in type 2 diabetes.

The hypothesis of the study was that IGF2 gene polymorphisms were associated with longitudinal trends in weight through modification of IGF-II concentration.Observational study that explored associations of the IGF2 gene and baseline circulating IGF-II concentration with 'real-world' longitudinal trends in body-mass index in a type 2 diabetes population.26 haplotype tagging single nucleotide polymorphisms (SNPs) from the IGF2 and H19 genes were studied in 485 Caucasian individuals in the Salford Longitudinal Diabetes Cohort. A generalised-estimating equation (GEE) model was used to separately study the association of SNPs and IGF-II concentration with 8-year longitudinal trends in body-mass index.High serum IGF-II concentration at baseline was associated with weight loss over the study period (ß=-0.006, 95% CI -0.009 to -0.002, p<0.001). 8 SNPs were associated with longitudinal body-mass index trends, of which 4 retained significance after multiple -testing correction. 2 SNPs rs10770063 and rs3842767 were associated with both IGF-II concentration as well as longitudinal weight changes.We report novel associations between polymorphisms in the IGF2 gene, with concentration of circulating IGF-II and also with longitudinal weight change in type 2 diabetes. Our data indicate that the IGF2 gene and its gene product may be important determinants of longitudinal weight trends in type 2 diabetes.

Interactions of the IGF System with Diabetes and its Vascular Complications.

The insulin-like growth factor (IGF) system is an evolutionarily conserved group of important proteins that are fundamental to life. Indeed, insulin can be viewed as simply a specialized arm of the IGF system that has evolved to regulate primarily metabolic functions. The main purpose of the IGF system is to form a highly refined mechanism for the control of cellular growth, metabolism and survival. Dysregulation of such a system can have serious consequences. In this review we have focussed on the IGF system and its relation to diabetes and the development of cardiometabolic disorders.

HOMA-S is associated with greater HbA1c reduction with a GLP-1 analogue in patients with type 2 diabetes.

Exenatide, a glucagon-like peptide-1 (GLP-1) analogue, is an effective glucoregulator for treating overweight individuals, not at target HbA1 c. This prospective study aimed to determine whether estimates of beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) predict response to Exenatide treatment.Prospective data on 43 type 2 diabetes patients were collected for up to 2.8 years in UK primary care. HOMA-B and HOMA-S were estimated prior to initiating Exenatide, with monitoring of cardio-metabolic risk factors.Mean (SD) age and BMI pre-treatment were 54.1±10.5 years and 35.7±7.5 kg/m2 respectively. HbA1c decreased (mean reduction 0.9%, p=0.04; p for trend=0.01) in 61% of patients. In univariate analyses, HOMA-S as a measure of insulin sensitivity was inversely (ß=- 0.41, p 0.009) related to change in HbA1c, with no relation for HOMA-B.In a random effects regression model that included age at baseline, weight, LDL-C, HDL-C and triglycerides, change in HbA1c (ß= - 0.14, p<0.001) and HDL-C (ß= - 0.52, p=0.011) were independently associated with increasing insulin sensitivity (r2=0.52). Thus patients with greater measured insulin sensitivity achieved greater reduction in HbA1c independent of the factors described above.In logistic regression those in the highest tertile of log-HOMA-S were 45% more likely to have a fall in HbA1c with an odds ratio (OR) of 0.55 (95% CI 0.47-0.66) p<0.0001 (log likelihood ratio for the model χ2=71.6, p<0.0001).Patients with greater measured insulin sensitivity achieve greater reduction in HbA1c with Exenatide. Determination of insulin sensitivity may assist in guiding outcome expectation in overweight patients treated with GLP-1 analogues.

Hypogonadism secondary to hyperprolactinaemia: successful treatment but adverse consequences.

It is accepted that care must be taken in initiating testosterone replacement in hypogonadal individuals with historically low androgen levels. However less is reported about the influence of restoration of normal endogenous testosterone production on behaviour.Here we report how the adverse sequelae of successful treatment of hypogonadism secondary to hyperprolactinaemia, manifesting as irritability and low threshold to aggression, were managed through a joint approach between psychiatrist and physician.

Catalase-negative listeria monocytogenes causing meningitis in an adult. Clinical and laboratory features.

A 63-year-old previously healthy woman presented with acute meningitis. Cultures of the cerebrospinal fluid yielded a serotype 1/2a isolate of Listeria monocytogenes that was biochemically typical in all respects, other than the reproducible lack of catalase production. During therapy, the patient developed oculomotor dysfunction that was attributed to an abscess in the internal capsule. This case report documents the existence of catalase-negative L. monocytogenes indicating that catalase production should not be a strict criterion for identification of Listeria. Furthermore, this clinical experience extends in vitro and experimental animal studies indicating that catalase production is not a necessary virulence factor for invasion by Listeria.