Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses.

Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p = .0002 for both). Anti-spike IgG correlated with lymphocyte count (r = .63; p = .002), and time from treatment (r = .56; p = .007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p = .03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p = .0008) and HC (p < .0001). Anti-spike IgG correlated with neutralization of the delta variant (r = .62, p < .0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p < .0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p = .004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant.

Pfizer/BioNtech BNT162b2: adverse events and insights from an Australian mass vaccination clinic for COVID-19.

The Pfizer/BioNtech BNT162b2 is a major vaccine used in the Australian COVID-19 immunisation programme. We report on BNT162b2 safety in the observation period in a dedicated vaccination clinic linked to a quaternary teaching hospital. We performed a retrospective review of medical records for 57 842 vaccinations, and describe the model of care and adverse event rate at the clinic during its first 2 months of operation. A total of 243 adverse events following immunisation (0.42% of total vaccine doses) were recorded in the immediate observation period post-vaccination, which were predominantly immunisation stress-related responses. Of the 110 patients who experienced an adverse event with their first dose of the vaccine, 90% returned for their second dose of the vaccine, with 87% not reporting any further adverse reaction with the subsequent dose. Nineteen (0.03% of total doses) people were reviewed for an allergic reaction, of which 10 (53%) reported a history of prior allergies. A female predominance was present in both total adverse reactions (70%) and allergic vaccine reactions (79%). Only two patients experienced anaphylaxis (0.003% of total doses), in keeping with low rates of adverse reactions to the BNT162b2 vaccine in the current literature. Overall, the present study reinforces the safety of BNT162b2 in the Australian population, describes vaccination completion rates after adverse events and identifies predisposing factors for rare allergic reactions to the vaccine.

Degree of adiposity and obesity severity is associated with cutaneous microvascular dysfunction in type 2 diabetes.

BACKGROUNDS AND AIMS: Obesity and diabetes independently contribute to cutaneous microvascular dysfunction via pathological processes that are not fully understood. We sought to determine if obesity severity is associated with cutaneous microvascular dysfunction and measures of peripheral arterial disease in adults with type 2 diabetes in cross-sectional observational study design. METHODS AND RESULTS: Primary outcomes were post-occlusive reactive hyperaemia as determined by laser-Doppler fluxmetry (peak flux post-occlusion, time to peak flux post-occlusion, peak as a percentage of baseline, and area under the curve [AuC] index post-occlusion to pre-occlusion). Secondary outcomes were ankle- and toe-brachial indices (ABI and TBI) and systolic toe pressure. Thirty-six participants (20 men, 16 women) with mean age 55 ± 8 years, BMI of 36 ± 5 kg/m2 and duration of diabetes 8 ± 6 years underwent measurements. After adjusting for age and duration of diabetes, SAT and total percentage body fat were able to explain 29% (p = 0.001) and 20% (p = 0.01) of variance of AuC index models, as well as 29% (p = 0.02) and 18% (p = 0.02) of peak as a percentage of baseline models, respectively. Though TBI demonstrated moderate, significant correlations with SAT (r:0.37, p = 0.04) and total percentage body fat (r:0.39, p = 0.03), these were not upheld by regression analyses. Neither ABI nor systolic toe pressure significantly correlated with any measure of adiposity or obesity. CONCLUSION: These findings demonstrate impairment in cutaneous microvascular function related to adiposity and obesity severity in adults with type 2 diabetes, suggesting that obesity may pathologically effect cutaneous microvascular function in the absence of overt macrovascular disease, warranting further investigation.

Influence of maternal and placental factors on newborn body composition.

AIM: The objective of this study was to assess whether maternal characteristics, placental size or histological chorioamnionitis was associated with newborn body composition. Furthermore, we sought to determine whether placental weight may mediate the association between maternal pre-pregnancy weight and age with newborn body composition. METHODS: A cross-sectional study was conducted at Royal Prince Alfred Hospital, Sydney, Australia. This study included 136 healthy, singleton, term-born newborns. Recruitment was stratified by newborn body fat percentiles (gender and gestational adjusted). Body fat was assessed by air displacement plethysmography. Placental examination was conducted by an anatomical pathologist. Maternal (chorioamnionitis) and fetal (chorionic and umbilical vasculitis, funisitis) inflammatory responses were classified according to Redline criteria. RESULTS: Maternal pre-pregnancy weight, parity, labour, placental weight and surface area were associated with newborn fat mass and fat-free mass. Gestational diabetes and maternal age were associated with newborn fat mass but not fat-free mass. There was no association between histological chorioamnionitis and newborn body composition; however, spontaneous onset of labour was strongly associated with the presence of histological chorioamnionitis. Only 25-31% of the association of maternal weight and age with newborn fat mass was mediated via the placenta. CONCLUSIONS: Maternal factors associated with newborn fat mass and fat-free mass differed, indicating that different mechanisms control fat mass and fat-free mass. Our mediation analysis suggests that placental weight partly mediates the association of maternal factors with newborn body composition. Histological chorioamnionitis was not associated with newborn body composition.

The relationship between obesity and tertiary education outcomes: a systematic review.

Previous reviews have documented an overall weak or uncertain association between obesity and school-based educational attainment in children and young people. However, up to half of young adults will go on to further college or university education by age 30. The study aim was to systematically review evidence on the association between obesity and tertiary education outcomes in young men and women. A search of multiple databases, including Embase, Global Health, ERIC, Medline, PsycInfo, and Science Citation Index was conducted in March 2018. Cross-sectional and longitudinal studies were included that reported on young people aged 16+, an association between obesity and academic achievement, and a comparison to healthy weight students. Risk of bias was assessed using criteria from the STROBE checklist. From 1297 records, 16 studies met all inclusion criteria. All six cross-sectional studies and 8/10 longitudinal studies reported lower educational achievement by students with obesity. All longitudinal studies were at low risk of bias but four cross-sectional studies were at medium risk and two at high risk of bias. Three of four studies showed reduced enrolment, in 6/8 graduation was less likely, and all 6 studies reporting on performance showed this was lower in those with obesity. Five of nine studies reported that obesity had a greater impact on educational achievement for women. Overall, there is compelling evidence of weight bias in that students with obesity do less well in tertiary education than their healthy weight peers. It is likely that university/college attainment is less impacted by socio-economic factors than school-based achievement. A better understanding of the processes that underpin this weight bias is needed, including stakeholder (student, staff) experiences of weight stigma, perceived or enacted. Responsive actions could mirror those to address disability or gender bias, or in health promotion in tertiary education settings.

Gaps to bridge: Misalignment between perception, reality and actions in obesity.

AIMS: Despite increased recognition as a chronic disease, obesity remains greatly underdiagnosed and undertreated. We aimed to identify international perceptions, attitudes, behaviours and barriers to effective obesity care in people with obesity (PwO) and healthcare professionals (HCPs). MATERIALS AND METHODS: An online survey was conducted in 11 countries. Participants were adults with obesity and HCPs who were primarily concerned with direct patient care. RESULTS: A total of 14 502 PwO and 2785 HCPs completed the survey. Most PwO (68%) and HCPs (88%) agreed that obesity is a disease. However, 81% of PwO assumed complete responsibility for their own weight loss and only 44% of HCPs agreed that genetics were a barrier. There was a median of three (mean, six) years between the time PwO began struggling with excess weight or obesity and when they first discussed their weight with an HCP. Many PwO were concerned about the impact of excess weight on health (46%) and were motivated to lose weight (48%). Most PwO (68%) would like their HCP to initiate a conversation about weight and only 3% were offended by such a conversation. Among HCPs, belief that patients have little interest in or motivation for weight management may constitute a barrier for weight management conversations. When discussed, HCPs typically recommended lifestyle changes; however, more referrals and follow-up appointments are required. CONCLUSIONS: Our international dataset reveals a need to increase understanding of obesity and improve education concerning its physiological basis and clinical management. Realization that PwO are motivated to lose weight offers an opportunity for HCPs to initiate earlier weight management conversations.

Greater improvements in diet quality among overweight participants following a group-based commercial weight loss programme than those receiving support to lose weight in primary care.

BACKGROUND: Relatively little is known about dietary changes and their relationships with weight change during behavioural weight loss interventions. In a secondary analysis of data from a multicentre RCT, we investigated whether greater improvements in diet would be achieved by overweight adults following a 12 month group-based commercial weight loss programme (CP) than those receiving standard care (SC) in primary practice, and if these dietary changes were associated with greater weight loss. METHODS: Adults with a BMI 27-35 kg/m2 and >1 risk factor for obesity-related disorders were recruited in study centres in Australia and the UK during 2007-2008. Dietary intake and body weight were measured at baseline, 6 and 12 months. Linear mixed effects models compared mean changes in dietary macronutrient intake, fibre density and energy density over time between groups, and their relationships with weight loss. RESULTS: The CP group demonstrated greater mean weight loss than the SC group at 6 months (3.3 kg, 95% CI: 2.2, 4.4) and 12 months (3.3 kg, 95% CI: 2.1, 4.5). Diet quality improved in both intervention groups at 6 and 12 months. However, the CP group (n = 228) achieved significantly greater mean reductions in energy intake (mean difference; 95% CI: - 503 kJ/d; - 913, - 93), dietary energy density (- 0.48 MJ/g; - 0.81, - 0.16), total fat (- 6.9 g/d; - 11.9, - 1.8), saturated fat (- 3.3 g/d; - 5.4, - 1.1), and significantly greater mean increases in fibre density (0.30 g/MJ; 0.15, 0.44) at 6 months than the SC group (n = 239). Similar differences persisted at 12 months and the CP group showed greater mean increases in protein density (0.65 g/MJ). In both groups, weight loss was associated with increased fibre density (0.68 kg per g/MJ, 95% CI: 0.08, 1.27) and protein density (0.26 kg per g/MJ, 95% CI: 0.10, 0.41). CONCLUSIONS: Following a group-based commercial program led to greater improvements in diet quality than standard care. Increases in dietary protein and fibre density were independently associated with weight loss in both behavioural weight loss interventions. Greater increases in protein and fibre density in the commercial program likely contributed to their greater weight loss. TRIAL REGISTRATION: ISRCTN: ISRCTN85485463 Registered 03/08/2007 Retrospectively Registered.

Are large dinners associated with excess weight, and does eating a smaller dinner achieve greater weight loss? A systematic review and meta-analysis.

There are suggestions that large evening meals are associated with greater BMI. This study reviewed systematically the association between evening energy intake and weight in adults and aimed to determine whether reducing evening intake achieves weight loss. Databases searched were MEDLINE, PubMed, Cinahl, Web of Science, Cochrane Library of Clinical Trials, EMBASE and SCOPUS. Eligible observational studies investigated the relationship between BMI and evening energy intake. Eligible intervention trials compared weight change between groups where the proportion of evening intake was manipulated. Evening intake was defined as energy consumed during a certain time - for example 18.00-21.00 hours - or self-defined meal slots - that is 'dinner'. The search yielded 121 full texts that were reviewed for eligibility by two independent reviewers. In all, ten observational studies and eight clinical trials were included in the systematic review with four and five included in the meta-analyses, respectively. Four observational studies showed a positive association between large evening intake and BMI, five showed no association and one showed an inverse relationship. The meta-analysis of observational studies showed a non-significant trend between BMI and evening intake (P=0·06). The meta-analysis of intervention trials showed no difference in weight change between small and large dinner groups (-0·89 kg; 95 % CI -2·52, 0·75, P=0·29). This analysis was limited by significant heterogeneity, and many trials had an unknown or high risk of bias. Recommendations to reduce evening intake for weight loss cannot be substantiated by clinical evidence, and more well-controlled intervention trials are needed.

Effect of resistance training on liver fat and visceral adiposity in adults with obesity: A randomized controlled trial.

AIM: Regular aerobic exercise reduces visceral adipose tissue (VAT) and liver fat, however, not all individuals are able to adopt and adhere to such programs. Progressive resistance training (PRT) may be an alternative therapy, but there is limited available evidence. We examined the efficacy of PRT as per current exercise guidelines, compared with sham exercise placebo on liver fat and VAT. METHODS: Twenty-nine inactive and overweight/obese (body mass index ≥25 kg/m2 ) adults (age 29-59) were randomized to receive 8 weeks of PRT (n = 15, 10 exercises per session, 8-12 repetitions, 2-3 sets per exercise at 80-85% of one-repetition maximum, 3 days per week) or a sham exercise placebo control (CON) (n = 14). Change in liver fat, VAT, and abdominal s.c. adipose tissue (SAT) were assessed by magnetic resonance spectroscopy and imaging). RESULTS: There were no significant group by time interactions for change in liver fat in PRT versus CON groups (-0.07 ± 0.31% vs. 0.55 ± 0.77%, respectively, P = 0.19), VAT (-175 ± 85 cm3 vs. 10 ± 64 cm3 , respectively, P = 0.11), or abdominal SAT (-436 ± 245 cm3 vs. 127.29 ± 182 cm3 , respectively, P = 0.10) despite a significant increase in muscle volume (55 ± 78 cm3 vs. -0.04 ± 8 cm3 , respectively, P = 0.03). CONCLUSION: Traditional PRT is not effective for reducing liver fat in overweight/obese adults compared with placebo control. Although PRT has known metabolic benefits, an adequate volume of aerobic exercise should be promoted if liver fat is the therapeutic target.

Approaches to obesity management.

This review will provide an overview of the currently available approaches to obesity management available in Australia, including the various approaches to lifestyle intervention, in addition to evaluating the safety and efficacy of adjuvant therapies, including pharmacotherapy and bariatric surgery.

Effect of aerobic exercise training dose on liver fat and visceral adiposity.

BACKGROUND & AIMS: Aerobic exercise reduces liver fat and visceral adipose tissue (VAT). However, there is limited data from randomized trials to inform exercise programming recommendations. This study examined the efficacy of commonly prescribed exercise doses for reducing liver fat and VAT using a randomized placebo-controlled design. METHODS: Inactive and overweight/obese adults received 8 weeks of either; i) low to moderate intensity, high volume aerobic exercise (LO:HI, 50% VO 2peak, 60 min, 4d/week); ii) high intensity, low volume aerobic exercise (HI:LO, 70% VO 2peak, 45 min, 3d/week); iii) low to moderate intensity, low volume aerobic exercise (LO:LO, 50% VO 2peak, 45 min, 3d/week); or iv) placebo (PLA). Liver fat (spectroscopy) and VAT (magnetic resonance imaging) were measured before and after intervention. RESULTS: Forty-seven of the 48 (n = 12 in each group) participants completed the trial. There were no serious adverse events. There was a significant change in group × time interaction in liver fat, which reduced in HI:LO by 2.38 ± 0.73%, in LO:HI by 2.62 ± 1.00%, and in LO:LO by 0.84 ± 0.47% but not in PLA (increase of 1.10 ± 0.62%) (p = 0.04). There was a significant reduction in VAT in HI:LO (-258.38 ± 87.78 cm(3)), in LO:HI (-386.80 ± 119.5 cm(3)), and in LO:LO (-212.96 ± 105.54 cm(3)), but not in PLA (92.64 ± 83.46 cm(3)) (p = 0.03). There were no significant differences between the dose or intensity of the exercise regimen and reductions in liver fat or VAT (p > 0.05). CONCLUSION: The study found no difference in efficacy of liver fat reduction by either aerobic exercise dose or intensity. All of the aerobic exercise regimens employed reduced liver fat and VAT by a small amount without clinically significant weight loss.

Efficacy of the Omega-3 Index in predicting non-alcoholic fatty liver disease in overweight and obese adults: a pilot study.

Non-alcoholic fatty liver disease (NAFLD) is an independent predictor of CVD in otherwise healthy individuals. Low n-3 PUFA intake has been associated with the presence of NAFLD; however, the relationship between a biomarker of n-3 status - the Omega-3 Index - and liver fat is yet to be elucidated. A total of eighty overweight adults (fifty-six men) completed the anthropometric and biochemical measurements, including the Omega-3 Index, and underwent proton magnetic resonance spectroscopy assessment of liver fat. Bivariate correlations and multiple regression analyses were performed with reference to prediction of liver fat percentage. The mean Omega-3 Index was high in both NAFLD (intrahepatic lipid concentration≥5·5 %) and non-NAFLD groups. The Omega-3 Index, BMI, waist circumference, glucose, insulin, TAG, high-sensitive C-reactive protein (hsCRP) and alanine aminotransferase (ALT) were positively correlated, and HDL and erythrocyte n-6:n-3 ratio negatively correlated with liver fat concentration. Regression analysis found that simple anthropometric and demographic variables (waist, age) accounted for 31 % of the variance in liver fat and the addition of traditional cardiometabolic blood markers (TAG, HDL, hsCRP and ALT) increased the predictive power to 43 %. The addition of the novel erythrocyte fatty acid variable (Omega-3 Index) to the model only accounted for a further 3 % of the variance (P=0·049). In conclusion, the Omega-3 Index was associated with liver fat concentration but did not improve the overall capacity of demographic, anthropometric and blood markers to predict NAFLD.

Analysis of factors influencing general practitioners' decision to refer obese patients in Australia: a qualitative study.

BACKGROUND: Referral for both lifestyle and surgical interventions are recommended as part of the clinical management of obesity in general practice. However, current practice falls short of this. This qualitative study aimed to describe the factors influencing general practitioners' (GPs) referral intentions for their obese patients. METHODS: Semi-structured qualitative interviews were conducted with 24 GPs from four geographically different areas in New South Wales, Australia about the management of their obese patients. A qualitative analysis was applied using inductive thematic analysis. RESULTS: The predominant factors influencing GPs' referral were their own attitudes and experience, and their patient's motivation. Lifestyle intervention Referrals were usually initiated by GPs and influenced by their patients and the local health system. Referrals to conduct bariatric surgery were frequently initiated by the patient and influenced by GPs' limited previous experience, patients' expectations and ability to pay, as well as professional and legal issues. There was no strong link between referral and the remoteness of areas or the availability of surgical referral services. CONCLUSION: There were differences between GPs reported referral behaviour for lifestyle and surgical interventions. GPs' attitudes to referral were often formed by their limited case experience rather than by a review of more systematic evidence, especially for surgical interventions. These patterns may be improved by educating and better communicating with GPs about the outcomes for their patients when they are referred.

The efficacy of bariatric surgery performed in the public sector for obese patients with comorbid conditions.

OBJECTIVE: To determine the efficacy of bariatric surgery in the public sector for the treatment of complicated obesity. DESIGN, SETTING AND PARTICIPANTS: A longitudinal observational study of obese participants with comorbid conditions, aged 21-73 years, who underwent publicly funded bariatric surgery. Data were extracted from clinical databases (1 October 2009 to 1 September 2013) and recorded at seven time points. Participants are from an ongoing public obesity program. MAIN OUTCOME MEASURES: Postoperative weight loss and partial or full resolution of: type 2 diabetes mellitus (T2DM), hypertension (HTN), dyslipidaemia and obstructive sleep apnoea (OSA). RESULTS: The 65 participants in the cohort lost a mean weight of 22.6 kg (SD, 9.5 kg) by 3 months, 34.2.kg (SD, 20.1 kg) by 12 months and 39.9 kg (SD, 31.4 kg) by 24 months (P < 0.001). Body mass index (BMI) decreased from a preoperative mean of 48.2 kg/m(2) (SD, 9.5 kg/m(2)) to 35.7 kg/m(2) (SD, 7.7 kg/m(2)) by 24 months (P < 0.001). Full resolution of comorbid conditions by 18 months (P < 0.001) was achieved by almost half of those with baseline T2DM, nearly two-thirds with HTN and three-quarters of those with OSA, with continued improvements beyond 24 months. CONCLUSIONS: Bariatric surgery performed in the public sector is efficacious in the treatment of obese patients with comorbid conditions. Our findings parallel similar studies suggesting that there is equal benefit in publicly funded and privately performed procedures. This study highlights that obese patients reliant on public health care maintain sufficient intrinsic motivation in the absence of payment and supposed value-driven incentive. Improved access to bariatric surgery in the public sector can justifiably reduce the health inequities for those most in need.

Young children's choices and thoughts about pro-social behaviour towards others with overweight.

OBJECTIVES: This study aimed to investigate weight bias within young children's pro-social choices between characters who differed in body size. METHODS: Seventy-six children aged 4-6 years read stories asking them to choose who they would first help, share with, comfort, and steal from, between a healthy weight and child with overweight. They also selected the one character they would most like to play with. Children's reasoning for these choices was recorded and analysed. RESULTS: The character with overweight was helped first in only a third of the choices made. Children chose the characters with overweight more often as the target for anti-social action. In friendship selections, children overwhelmingly rejected the characters with overweight. However, weight bias was not prominent in the reasons children gave for the choices. Most children were not negative about body shape, weight or appearance. Similarly, in friendship choices, these were mostly expressed positively to the character chosen. Only a small minority of children were explicitly negative about the character with overweight. CONCLUSIONS: A better understanding of weight bias acquisition and variation between children will benefit those working in health care and educational settings. Future research should link with developmental theory, such as on social categorization and theory of mind.

Cost-effectiveness analysis of recruitment strategies in a large diabetes prevention trial conducted across two sites in Sydney, Australia.

BACKGROUND: Diabetes prevention trials require large samples and community-based recruitment, which can be protracted and expensive. We analysed the cost-effectiveness of recruitment strategies used in a randomised placebo-controlled supplement trial in adults with prediabetes and overweight or obesity conducted in Sydney, Australia. METHODS: Recruitment strategies included advertising through local radio stations and newspapers, television news coverage, online advertising and editorials, advertising in and referral from primary care settings, university- and hospital-based advertising, and attending or hosting local events. For each strategy, the number of expressions of interest, screenings booked, and randomised participants were collated. The percentage contribution from each strategy, overall cost, and cost per participant were calculated. RESULTS: Of 4498 expressions of interest, 551 (12%) were eligible for onsite screening and 401 (9%) were randomised. Recruitment costs totalled AU$218,501, averaging AU$545 per participant. The recruitment strategy was recorded for 49% who expressed interest in the trial, and for 75% randomised into the trial. From these data, advertising on local radio stations was the most cost-effective strategy, contributing 46% of participants at AU$286 per participant, then advertising in and referral from primary care settings (57 participants [19%], AU$1438 per participant). The least cost-effective strategy was television news coverage, which was not targeted to the Sydney-based audience, contributing only six participants (AU$10,000 per participant). CONCLUSION: Radio advertising and recruitment through healthcare were the most effective recruitment strategies in this trial. Recruitment strategies should be location-specific and appropriate for the target population, prioritising low-effort high-yield strategies. Trial investigators should seek opportunities for free advertising.

Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.

BACKGROUND: The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. METHODS: We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events. All the subjects received sibutramine in addition to participating in a weight-management program during a 6-week, single-blind, lead-in period, after which 9804 subjects underwent random assignment in a double-blind fashion to sibutramine (4906 subjects) or placebo (4898 subjects). The primary end point was the time from randomization to the first occurrence of a primary outcome event (nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death). RESULTS: The mean duration of treatment was 3.4 years. The mean weight loss during the lead-in period was 2.6 kg; after randomization, the subjects in the sibutramine group achieved and maintained further weight reduction (mean, 1.7 kg). The mean blood pressure decreased in both groups, with greater reductions in the placebo group than in the sibutramine group (mean difference, 1.2/1.4 mm Hg). The risk of a primary outcome event was 11.4% in the sibutramine group as compared with 10.0% in the placebo group (hazard ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.31; P=0.02). The rates of nonfatal myocardial infarction and nonfatal stroke were 4.1% and 2.6% in the sibutramine group and 3.2% and 1.9% in the placebo group, respectively (hazard ratio for nonfatal myocardial infarction, 1.28; 95% CI, 1.04 to 1.57; P=0.02; hazard ratio for nonfatal stroke, 1.36; 95% CI, 1.04 to 1.77; P=0.03). The rates of cardiovascular death and death from any cause were not increased. CONCLUSIONS: Subjects with preexisting cardiovascular conditions who were receiving long-term sibutramine treatment had an increased risk of nonfatal myocardial infarction and nonfatal stroke but not of cardiovascular death or death from any cause. (Funded by Abbott; ClinicalTrials.gov number, NCT00234832.)

Barriers to progression through Australian obesity management pathways: Survey data from the ACTION-IO study.

BACKGROUND AND OBJECTIVES: Our previous work uncovered a nine-year delay, from when Australian people with obesity (PwO) first began struggling with excess weight and first discussed weight with a healthcare professional (HCP). In this study we explore barriers to having an obesity consultation, making and discussing the diagnosis of obesity and arranging a management plan, including a follow-up appointment. METHOD: Australian PwO (n = 1000) and HCPs (n = 200; 50% general practitioners [GPs]), completed the Awareness, Care & Treatment In Obesity Management - An International Observation (ACTION-IO) online survey. RESULTS: Of Australian PwO, 53% had discussed weight with an HCP in the past five years, 25% were informed of their obesity diagnosis and 15% had weight-related follow-up appointments scheduled. Fewer GPs than other specialists reported recording obesity diagnoses, but GPs scheduled more follow-up appointments. Receiving formal obesity training was reported by 22% of GPs and 44% of other specialists. DISCUSSION: Barriers to obesity care in Australia include unrealistic expectations from both PwO and HCPs, lack of evidence-based strategies and insufficient training. Further exploration of barriers is required.

Changes in Prediabetes Status Among Adults During a 6-Month Randomized Placebo-controlled Supplement Trial With Nutrition and Lifestyle Counselling and 6-Month Follow-up.

OBJECTIVES: In this work, we present an exploratory within-trial analysis of the changing prevalence of prediabetes in response to nutrition and lifestyle counselling provided as part of a randomized placebo-controlled supplement trial with follow-up. We aimed to identify factors associated with changing glycemia status. METHODS: Participants (n=401) in this clinical trial were adults with a body mass index (BMI) of ≥25 kg/m2 and prediabetes (defined by the American Diabetes Association as a fasting plasma glucose [FPG] of 5.6 to 6.9 mmol/L or a glycated hemoglobin [A1C] of 5.7% to 6.4%) within 6 months before trial entry. The trial consisted of a 6-month randomized intervention with 2 dietary supplements and/or placebo. At the same time, all participants received nutrition and lifestyle counselling. This was followed by a 6-month follow-up. Glycemia status was assessed at baseline and at 6 and 12 months. RESULTS: At baseline, 226 participants (56%) met a threshold for prediabetes, including 167 (42%) with elevated FPG and 155 (39%) with elevated A1C. After the 6-month intervention, the prevalence of prediabetes decreased to 46%, driven by a reduction in prevalence of elevated FPG to 29%. The prevalence of prediabetes then increased to 51% after follow-up. Risk of prediabetes was associated with older age (odds ratio [OR], 1.05; p<0.01), BMI (OR, 1.06; p<0.05), and male sex (OR, 1.81; p=0.01). Participants who reverted to normoglycemia had greater weight loss and lower baseline glycemia. CONCLUSIONS: Glycemia status can fluctuate over time and improvements can be gained from lifestyle interventions, with certain factors associated with a higher likelihood of reverting to normoglycemia.

Incidence of adverse mental health outcomes after sleeve gastrectomy compared with gastric bypass and restrictive bariatric procedures: a retrospective cohort study.

OBJECTIVE: This study examined rates of suicide and hospitalization with psychiatric diagnoses after sleeve gastrectomy compared with gastric bypass and restrictive procedures (gastric banding/gastroplasty). METHODS: This was a longitudinal retrospective cohort study comprising all patients who underwent primary bariatric surgery in New South Wales or Queensland, Australia, between July 2001 and December 2020. Hospital admission records, death registration, and cause of death records (if applicable) within these dates were extracted and linked. Primary outcome was death by suicide. Secondary outcomes were admissions with self-harm; substance-use disorder, schizophrenia, mood, anxiety, behavioral, and personality disorders; any of these; and psychiatric inpatient admission. RESULTS: A total of 121,203 patients were included, with median follow-up of 4.5 years per patient. There were 77 suicides, with no evidence of difference in rates by surgery type (rates [95% CI] per 100,000 person years: 9.6 [5.0-18.4] restrictive, 10.8 [8.4-13.9] sleeve gastrectomy, 20.4 [9.7-42.8] gastric bypass; p = 0.18). Rates of admission with self-harm declined after restrictive and sleeve procedures. Admission with anxiety disorders, any psychiatric diagnosis, and as a psychiatric inpatient increased after sleeve gastrectomy and gastric bypass, but not restrictive procedures. Admissions with substance-use disorder increased after all surgery types. CONCLUSIONS: Variable associations between bariatric surgeries and hospitalization with psychiatric diagnoses might indicate distinct vulnerabilities among patient cohorts or that differing anatomical and/or functional changes may contribute to effects on mental health.