Functional recovery with peripheral nerve block versus general anesthesia for upper limb surgery: a systematic review.

BACKGROUND: Peripheral nerve block is a common anesthetic technique used during orthopedic upper limb surgery. Injection of local anesthetics around the target nerve inhibits the action of voltage-dependent sodium channels, inhibiting neurotransmission of pain impulses and providing motor immobility. Compared to general anesthesia, it could improve functional recovery by inhibiting nociceptive impulses and inflammation, thus reducing postoperative pain and immobilization and improving postoperative rehabilitation. This systematic review evaluates the impact of peripheral nerve block versus general anesthesia on postoperative functional recovery following orthopedic upper limb surgery. METHODS: We searched CENTRAL, MEDLINE, CINHAL, EMBASE, and Scopus trial databases from inception until September 2021 for studies comparing peripheral nerve block to general anesthesia. We collected data on functional recovery, range of motion, patient satisfaction, quality of life, and return to work. We pooled studies using a random-effects model and summarized the quality of evidence with the GRADE approach. RESULTS: We assessed 373 citations and 19 full-text articles for eligibility, and included six studies. Six studies reported on functional recovery, but failed to detect a significant superiority of peripheral nerve block over general anesthesia (3 RCT studies, N = 160; SMD -0.15; CI at 95% -0.60-0.3; I2 = 45%; p = 0.07; low quality of evidence and 3 observational studies, N = 377; SMD -0.35; CI at 95% -0.71-0.01; I2 = 64%; p = 0.06; very low quality of evidence). CONCLUSIONS: Current literature is limited and fails to identify the benefit of peripheral nerve block on functional recovery. More studies are needed to assess the impact on long-term recovery. Considering the potential impact on clinical practice and training, a prospective study on functional recovery is ongoing (NCT04541745). TRIAL REGISTRATION: PROSPERO ID CRD42018116298. Registered on December 4, 2018.

Functional recovery of wrist surgery with regional versus general anesthesia: a prospective observational study.

PURPOSE: Regional anesthesia may favour postoperative rehabilitation by inhibiting peripheral sensitization and secondary hyperalgesia. The literature on this subject is limited. In the present FUNCTION study, we sought to compare the functional recovery post orthopedic wrist surgery with regional versus general anesthesia. METHODS: We conducted a single-centre prospective observational cohort study in adult patients with a distal radial fracture. Functional recovery was assessed with validated psychometrics questionnaires (Quick Disabilities of Arm, Shoulder and Hand [QuickDASH] and Patient-Rated Wrist Evaluation [PRWE]), range of motion, and grip strength. We used a linear mixed regression model to assess the impact of the anesthesia technique on functional recovery. Postoperative pain and patient satisfaction were evaluated using a visual analog scale. RESULTS: We recruited 76 patients. At 12 weeks post surgery, there was no difference between the type of anesthesia and functional recovery with the QuickDASH (higher scores worse; regional anesthesia [RA], 22.7 vs general anesthesia [GA], 19.3; adjusted mean difference [aMD], -0.3; 95% confidence interval [CI], -9.6 to 9.0; P = 0.9) and PRWE (higher scores worse; RA group, 21.0 vs GA group, 20.5; aMD, -3.3; 95% CI, -12.1 to 5.6; P = 0.93) questionnaires. Range of motion, satisfaction, and postoperative pain were similar between groups. Right-hand grip strength was higher in the GA group. CONCLUSION: Regional anesthesia was not associated with improved functional recovery compared with general anesthesia. The dominance of the operated limb was a confusion factor in all evaluation modalities. Further research taking into account the dominance of the hand is necessary to establish the effects of regional anesthesia on functional recovery. STUDY REGISTRATION: ClinicalTrials.gov (NCT04541745); registered 9 September 2020.

RéSUMé: OBJECTIF: L'anesthésie régionale pourrait favoriser la rééducation postopératoire en inhibant la sensibilisation périphérique et l'hyperalgésie secondaire. La littérature à ce sujet est limitée. Dans la présente étude nommée FUNCTION, nous avons cherché à comparer la récupération fonctionnelle après une chirurgie orthopédique du poignet réalisée sous anesthésie régionale vs sous anesthésie générale. MéTHODE: Nous avons réalisé une étude de cohorte observationnelle prospective monocentrique auprès de patient·es adultes présentant une fracture radiale distale. La récupération fonctionnelle a été évaluée à l'aide de questionnaires psychométriques validés (questionnaires QuickDASH [Quick Disabilities of Arm, Shoulder and Hand] et PRWE [Patient-Rated Wrist Evaluation]), de l'amplitude des mouvements et de la force de préhension. Nous avons utilisé un modèle de régression linéaire mixte pour évaluer l'impact de la technique d'anesthésie sur la récupération fonctionnelle. La douleur postopératoire et la satisfaction des patient·es ont été évaluées à l'aide d'une échelle visuelle analogique. RéSULTATS: Nous avons recruté 76 personnes. Douze semaines après la chirurgie, il n'y avait aucune différence entre le type d'anesthésie et la récupération fonctionnelle selon le questionnaire QuickDASH (scores plus élevés les pires; anesthésie régionale [AR], 22,7 vs anesthésie générale [AG], 19,3; différence moyenne ajustée [DMa], −0,3; intervalle de confiance [IC] à 95 %, −9,6 à 9,0; P = 0,9) et PRWE (scores plus élevés les pires; groupe AR, 21,0 vs groupe AG, 20,5; DMa, −3,3; IC 95 %, −12,1 à 5,6; P = 0,93). L'amplitude des mouvements, la satisfaction et la douleur postopératoire étaient similaires entre les groupes. La force de préhension de la main droite était plus élevée dans le groupe AG. CONCLUSION: L'anesthésie régionale n'a pas été associée à une amélioration de la récupération fonctionnelle par rapport à l'anesthésie générale. La prédominance du membre opéré était un facteur de confusion dans toutes les modalités d'évaluation. D'autres recherches tenant compte du côté dominant au niveau des mains sont nécessaires pour déterminer les effets de l'anesthésie régionale sur la récupération fonctionnelle. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT04541745); enregistrée le 9 septembre 2020.

Impact of an educational intervention combining clinical obesity preceptorship with electronic networking tools on primary care professionals: a prospective study.

BACKGROUND: Primary care providers' (PCPs) attitude toward obesity is often negative, and their confidence level for helping patients manage their weight is low. Continuing professional development (CPD) on the subject of obesity is often based on a single activity using a traditional passive approach such as lectures known to have little effect on performance or patient outcomes. The aim of this study was to evaluate the impact of an educational intervention for obesity management on PCPs' attitude, self-efficacy, practice changes and patient-related outcomes. METHODS: Prospective interventional study with 12 months follow-up. A two-day clinical obesity preceptorship was offered where participants were actively involved in competence building using real-life situations, in addition to electronic networking tools, including a discussion forum and interactive monthly webinars. Thirty-five participants (12 nurses and 23 physicians) from seven Family medicine groups were enrolled. Questionnaires were used to evaluate the impact on primary care nurses' and physicians' attitudes and self-efficacy for obesity management. Practice changes and patient outcomes were evaluated using clinical vignettes, de-identified electronic patient records and qualitative analyses from group interviews. RESULTS: Physicians' general attitude towards patients with obesity was improved (61 ± 22 mm vs 85 ± 17 mm, p <  0.001). Self-efficacy for obesity management and lifestyle counselling were also improved immediately and 1 year after the intervention (all Ps <  0.05). De-identified patient records and clinical vignettes both showed improvement in recording of weight, waist circumference and evaluation of readiness to change lifestyle (all Ps <  0.05) that was confirmed by group interviews. Also, 15% of patients who were prospectively registered for weight management had lost more than 5% of their initial weight at the time of their last visit (P <  0.0001, median follow-up of 152 days). CONCLUSION: A multimodal educational intervention for obesity management can improve PCPs'attitude and self-efficacy for obesity management and lifestyle counselling. This translates into beneficial practice changes and patient-related outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01385397 . Retrospectively registered, 28 June 2011.

Physical activity assessment and counseling in Quebec family medicine groups.

OBJECTIVE: To determine how often primary health care providers (PHCPs) in family medicine groups (FMGs) assess physical activity (PA) levels, provide PA counseling (PAC), and refer patients to exercise professionals; to describe patients' PA levels, physical fitness, and satisfaction regarding their PA management in FMGs; to describe available PA materials in FMGs and PHCPs' PAC self-efficacy and PA knowledge; and to identify characteristics of patients and PHCPs that determine the assessment of PA and PAC provided by PHCPs. DESIGN: Cross-sectional study using questionnaires and a medical chart audit. SETTING: Ten FMGs within the Integrated University Health Network of the Centre hospitalier universitaire de Sherbrooke in Quebec. PARTICIPANTS: Forty FPs, 24 nurses, and 439 patients. MAIN OUTCOME MEASURES: Assessment of PA level and PAC provided by PHCPs. RESULTS: Overall, 51.9% of the patients had had their PA level assessed during the past 18 months, but only 21.6% received PAC from at least 1 of the PHCPs. Similar percentages were found among the inactive (n = 244) and more active (n = 195) patients. The median PAC self-efficacy score of PHCPs was 70.2% (interquartile range 52.0% to 84.7%) and the median PA knowledge score was 45.8% (interquartile range 41.7% to 54.2%), with no significant differences between nurses and FPs. In multivariate analysis, 34% of the variance in PAC provided was explained by assessment of PA level, overweight or obese status, type 2 diabetes or prediabetes, less FP experience, lower patient annual family income, more nurse encounters, and a higher patient physical component summary of quality of life. CONCLUSION: The rates of assessment of PA and provision of PAC in Quebec FMGs were low, even though most of the patients were inactive. Initiatives to support PHCPs and more resources to assess PA levels and provide PAC should be implemented.

Evolution of metabolic alterations 5 Years after early puberty in a cohort of girls predisposed to polycystic ovary syndrome.

BACKGROUND: We and others have observed that young girls predisposed to polycystic ovary syndrome (PCOS) display defective insulin sensitivity, beta-cell function and non-esterified fatty acids (NEFA) suppressibility during early pubertal years, compared to controls. Our objective is to assess whether these differences in glucose and NEFA metabolisms persist after 5 years in late/post-puberty. METHODS: We conducted a prospective cohort study between 2007 and 2015 with 4-6 years of follow-up in an academic institution research center. We compared 8 daughters and sisters of PCOS women (PCOSr) to 8 age-matched girls unrelated to PCOS (±1.5 years). Girls were assessed initially at 8-14 years old and re-assessed after a median follow-up of 5.4 years, at 13-21 years old. Our main measures were a frequently sampled intravenous glucose tolerance test (FSivGTT)-derived insulin sensitivity (IS) and beta-cell function (disposition index, DIFSivGTT); and indices of NEFA suppression during FSivGTT (logn-linear slope of NEFA and T50 of NEFA suppression). RESULTS: At follow-up, both PCOSr and controls had similar results: IS = 3.2 vs 3.4 (p = 0.88), DIFSivGTT = 1926 vs 1380 (p = 0.44), logn-linear slope = -0.032 vs -0.032 (p = 0.88) and T50NEFA = 18.1 vs 20.8 min (p = 0.57). IS, DIFSivGTT and NEFA suppressibility were stable in PCOSr after 5 years, but decreased significantly in controls (all p < 0.05). CONCLUSIONS: Impaired metabolism observed during early puberty in girls predisposed to PCOS remains stable after 5 years whereas control girls deteriorated their metabolic parameters. Therefore, both groups become comparable in late/post-puberty. Early puberty may thus represent a window during which metabolic alterations are transiently apparent in girls at risk of PCOS.

Regulation of blood flow in adipose tissue: involvement of the cholinergic system.

Acetylcholine (Ach) has vasodilatory actions. However, data are conflicting about the role of Ach in regulating blood flow in subcutaneous adipose tissue (ATBF). This may be related to inaccurate ATBF recording or to the responder/nonresponder (R/NR) phenomenon. We showed previously that healthy individuals are R (ATBF increases postprandially by >50% of baseline BF) or NR (ATBF increases ≤50% postprandially). Our objective was to assess the role of the cholinergic system on ATBF in R and NR subjects. ATBF was manipulated by in situ microinfusion of vasoactive agents (VA) in AT and monitored by the (133)Xenon washout technique (both recognized methods) at the VA site and at the control site. We tested incrementally increasing doses of Ach (10(-5), 10(-3), and 10(-1) mol/l; n = 15) and Ach receptor antagonists (Ra) before and after oral administration of 75-g glucose using atropine (muscarinic Ra; 10(-4) mol/l, n = 13; 10(-5) mol/l, n = 22) and mecamylamine (nicotinic Ra; 10(-3) mol/l, n = 15; 10(-4) mol/l, n = 10). Compared with baseline [2.41 (1.36-2.83) ml·100 g(-1)·min(-1)], Ach increased ATBF dose dependently [3.32 (2.80-5.09), 6.46 (4.36-9.51), and 10.31 (7.98-11.52), P < 0.0001], with no difference between R and NR. Compared with control side, atropine (both concentrations) had no effect on fasting ATBF; only atropine 10(-4) mol/l decreased post-glucose ATBF [iAUC: 1.25 (0.32-2.91) vs. 1.98 (0.64-2.94); P = 0.04]. This effect was further apparent in R. Mecamylamine had no impact on fasting and postglucose ATBF in R and NR. Our results suggest that the cholinergic system is implicated in ATBF regulation, although it has no role in the blunting of ATBF response in NR.

PCOS in adolescence and type 2 diabetes.

Polycystic ovary syndrome is a frequent disorder in women of reproductive age that consists of a heterogeneous combination of hyperandrogenism, chronic anovulation, and polycystic ovaries. Hyperandrogenism and anovulation are clearly linked to insulin resistance and compensatory hyperinsulinism, with an ovarian androgenic hyperresponsiveness to circulating insulin. Evidence is increasing that suggests that lipotoxicity, which is a key mechanism in the development of insulin resistance and type 2 diabetes, could also explain the androgen overproduction. During adolescence, diagnosis of polycystic ovarian syndrome (PCOS) may be difficult but is of importance because PCOS increases future risk of type 2 diabetes and metabolic complications. Metabolic perturbations begin early in adolescence and also exist in adolescent relatives of women with PCOS, even before clinical signs of PCOS. Screening for impaired glucose tolerance or type 2 diabetes is also important in this population, and treatment should focus on PCOS clinical manifestations as well as long-term metabolic risk.

The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and ß-cell function.

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (ß-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m(2) were divided based on weight loss at 1 year: < 5% (non-responders, n 56) and ≥ 5% (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9.5% of their weight when compared with non-responders who lost only 0.8% of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P = 0.0003) and disposition index (P = 0.02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8.9 (SD 12.5) v. 3.6 (SD 10.7) nmol/l, P = 0.05). However, it had not been associated with amelioration of insulin sensitivity and ß-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or ß-cell function.

Improved cardiac function and dietary fatty acid metabolism after modest weight loss in subjects with impaired glucose tolerance.

Using a novel positron emission tomography (PET) method with oral administration of 14(R,S)-[¹8F]-fluoro-6-thia-heptadecanoic acid (¹8FTHA), we recently demonstrated that subjects with impaired glucose tolerance (IGT) display an impairment in cardiac function associated with increased myocardial uptake of dietary fatty acids. Here, we determined whether modest weight loss induced by lifestyle changes might improve these cardiac metabolic and functional abnormalities. Nine participants with IGT, enrolled in a one-year lifestyle intervention trial, were invited to undergo determination of organ-specific postprandial dietary fatty acids partition using the oral ¹8FTHA method, and cardiac function and oxidative metabolic index using PET [¹¹C]acetate kinetics with ECG-gated PET ventriculography before and after the intervention. The intervention resulted in significant weight loss and reduction of waist circumference, with reduced postprandial plasma glucose, insulin, and triglycerides excursion. We observed a significant increase in stroke volume, cardiac output, and left ventricular ejection fraction associated with reduced myocardial oxidative metabolic index and fractional dietary fatty acid uptake. Modest weight loss corrects the exaggerated myocardial channeling of dietary fatty acids and improves myocardial energy substrate metabolism and function in IGT subjects.

Dietary conjugated α-linolenic acid did not improve glucose tolerance in a neonatal pig model.

PURPOSE: There is an increased interest in the benefits of conjugated α-linolenic acid (CLNA) on obesity-related complications such as insulin resistance and diabetes. The aim of the study was to investigate whether a 1% dietary supplementation of mono-CLNA isomers (c9-t11-c15-18:3 + c9-t13-c15-18:3) improved glucose and lipid metabolism in neonatal pigs. METHODS: Since mono-CLNA isomers combine one conjugated two-double-bond system with an n-3 polyunsaturated fatty acid (PUFA) structure, the experimental protocol was designed to isolate the dietary structural characteristics of the molecules by comparing a CLNA diet with three other dietary fats: (1) conjugated linoleic acid (c9-t11-18:2 + t10-c12-18:2; CLA), (2) non-conjugated n-3 PUFA, and (3) n-6 PUFA. Thirty-two piglets weaned at 3 weeks of age were distributed among the four dietary groups. Diets were isoenergetic and food intake was controlled by a gastric tube. After 2 weeks of supplementation, gastro-enteral (OGTT) and parenteral (IVGTT) glucose tolerance tests were conducted. RESULTS: Dietary supplementation with mono-CLNA did not modify body weight/fat or blood lipid profiles (p > 0.82 and p > 0.57, respectively) compared with other dietary groups. Plasma glucose, insulin, and C-peptide responses to OGTT and IVGTT in the CLNA group were not different from the three other dietary groups (p > 0.18 and p > 0.15, respectively). Compared to the non-conjugated n-3 PUFA diet, CLNA-fed animals had decreased liver composition in three n-3 fatty acids (18:3n-3; 20:3n-3; 22:5n-3; p < 0.001). CONCLUSIONS: These results suggest that providing 1% mono-CLNA is not effective in improving insulin sensitivity in neonatal pigs.

Angiotensin II type 2 receptor promotes adipocyte differentiation and restores adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats.

This study was aimed at establishing whether specific activation of angiotensin II (ANG II) type 2 receptor (AT2R) modulates adipocyte differentiation and function. In primary cultures of subcutaneous (SC) and retroperitoneal (RET) preadipocytes, both AT2R and AT1R were expressed at the mRNA and protein level. Cells were stimulated with ANG II or the AT2R agonist C21/M24, alone or in the presence of the AT1R antagonist losartan or the AT2R antagonist PD123,319. During differentiation, C21/M24 increased PPARγ expression in both RET and SC preadipocytes while the number of small lipid droplets and lipid accumulation solely increased in SC preadipocytes. In mature adipocytes, C21/M24 decreased the mean size of large lipid droplets. Upon abolishment of AT2R expression using AT2R-targeted shRNAs, expressions of AT2R, aP2, and PPARγ remained very low, and cells were unable to differentiate. In Wistar rats fed a 6-wk high-fat/high-fructose (HFHF) diet, a significant shift toward larger adipocytes was observed in RET and SC adipose tissue depots. C21/M24 treatments for 6 wk restored normal adipocyte size distribution in both these tissue depots. Moreover, C21/M24 and losartan decreased hyperinsulinemia and improved insulin sensitivity impaired by HFHF diet. A strong correlation between adipocyte size area and glucose infusion rate during euglycemic-hyperinsulinemic clamp was observed. These results indicate that AT2R is involved in early adipocyte differentiation, while in mature adipocytes and in a model of insulin resistance AT2R activation restores normal adipocyte morphology and improves insulin sensitivity.

Association of Cumulative Lifetime Exposure to Female Hormones With Cerebral Small Vessel Disease in Postmenopausal Women in the UK Biobank.

BACKGROUND AND OBJECTIVES: Rates of cerebrovascular disease increase after menopause, which is often attributed to the absence of hormones. It remains unknown whether the cumulative exposure to hormones across a female person's premenopausal life extends the window of cerebrovascular protection to the postmenopausal period. To investigate this, we examined the relationship between lifetime hormone exposure (LHE) and cerebral small vessel disease in more than 9,000 postmenopausal women in the UK-Biobank. METHODS: The cohort consisted of women (aged 40-69 years) who attended one of 22 research centers across the United Kingdom between 2006 and 2010. Women were excluded if they were premenopausal when scanned, had missing reproductive history data, self-reported neurologic disorders, brain cancer, cerebral vascular incidents, head or neurologic injury, and nervous system infection. Endogenous LHE (LHEEndo) was estimated by summing the number of years pregnant (LHEParity) with the duration of the reproductive period (LHECycle = age menopause - age menarche). Exogenous LHE (LHEExo) was estimated by summing the number of years on oral contraceptives and hormone replacement therapy. Cerebral small vessel disease was determined by estimating white matter hyperintensity volume (WMHV) from T2-fluid-attenuated inversion recovery brain MRI (acquired between 2014 and 2021), normalized to intracranial volume and log-transformed. Multiple linear regressions were used to assess the relationship between LHEEndo on WMHV adjusted for age, cardiovascular risk factors, sociodemographics, and LHEExo. RESULTS: A total of 9,163 postmenopausal women (age 64.21 ± 6.81 years) were retained for analysis. Average LHEEndo was 39.77 ± 3.59 years. Women with higher LHEEndo showed smaller WMHV (adj-R 2 = 0.307, LHEEndo ß = -0.007 [-0.012 to -0.002], p < 0.01). LHEParity and LHECycle were independent contributors to WMHV (adj-R 2 = 0.308, p << 0.001; LHEParity ß = -0.022 [-0.042 to -0.002], p < 0.05; LHECycle ß = -0.006 [-0.011 to -0.001], p < 0.05). LHEExo was not significantly related to WMHV (LHEExo ß = 0.001 [-0.001 to 0.002], p > 0.05). DISCUSSION: Women with more prolonged exposure to endogenous hormones show relatively smaller burden of cerebral small vessel disease independent of the history of oral contraceptive use or hormone replacement therapy. Our results highlight the critical role endogenous hormones play in female brain health and provide real-world evidence of the protective effects premenopausal endogenous hormone exposure plays on postmenopausal cerebrovascular health.

An intergenerational life-course approach to address early childhood obesity and adiposity: the Healthy Life Trajectories Initiative (HeLTI).

BACKGROUND: Interactions between genes and early-life exposures during conception, fetal life, infancy, and early childhood have been shown to affect an individual's health later in life. Maternal undernutrition and obesity, gestational diabetes, and impaired growth in utero and in early life are associated with adiposity and overweight and obesity in childhood, which are risk factors for poor health trajectories and non-communicable diseases. In Canada, China, India, and South Africa, 10-30% of children aged 5-16 years are overweight or obese. METHODS: The application of developmental origins of health and disease principles offers a novel approach to prevention of overweight and obesity and reduction of adiposity by delivering integrated interventions across the life course, starting before conception and continuing through early childhood. The Healthy Life Trajectories Initiative (HeLTI) was established in 2017 through a unique collaboration between national funding agencies in Canada, China, India, South Africa, and WHO. The aim of HeLTI is to evaluate the effect of an integrated four-phase intervention starting preconceptionally and continuing through pregnancy, infancy, and early childhood on reducing childhood adiposity (fat mass index) and overweight and obesity, and optimising early child development, nutrition, and other healthy behaviours. FINDINGS: Approximately 22 000 women are being recruited in Shanghai (China), Mysore (India), Soweto (South Africa), and across various provinces of Canada. Women who conceive (an expected 10 000) and their children will be followed up until the child reaches the age of 5 years. INTERPRETATION: HeLTI has harmonised the intervention, measures, tools, biospecimen collection, and analysis plans for the trial to be run across four countries. HeLTI will help establish whether an intervention aimed at addressing maternal health behaviours, nutrition, and weight; providing psychosocial support to reduce maternal stress and prevent mental illness; optimising infant nutrition, physical activity, and sleep; and promoting parenting skills can reduce the intergenerational risk of excess childhood adiposity and overweight and obesity across diverse settings. FUNDING: Canadian Institutes of Health Research; National Science Foundation of China; Department of Biotechnology, India; and South African Medical Research Council.

SmartMoms Canada: An evaluation of a mobile app intervention to support a healthy pregnancy.

BACKGROUND: There is a lack of cost-effective and readily available access to evidence-based information to manage healthy behaviours for pregnant individuals. Mobile health (mHealth) tools offer a cost-effective, interactive, personalized option that can be delivered anywhere at a time most convenient for the user. This study protocol was primarily developed to, i) assess the feasibility of the SmartMoms Canada intervention in supporting participants to achieve gestational weight gain (GWG) guidelines. The secondary objectives are to, ii) assess user experience with the app, measured by adherence to the program via app software metrics and frequency of use, iii) determine the impact of SmartMoms Canada app usage on the adoption of healthful behaviours related to nutrition, physical activity and sleep habits, improvements in health-related quality of life, pregnancy-related complications, and symptoms of depression, and iv) investigate the potential extended effects of the app on postpartum health-related outcomes. METHODS: This is a feasibility trial. Pregnant individuals aged 18-40 years with pre-gravid body mass index between 18.5 and 39.9 kg/m2, carrying a singleton fetus, having Wi-Fi access, and at ≤20 weeks' gestation will be recruited. Eligible people will be followed from recruitment until 12 months postpartum. DISCUSSION: SmartMoms Canada is the first bilingual Canadian-centric app designed for pregnant people. This mHealth intervention, with its ability to supply frequent interactions, provides pregnancy- related health knowledge to users, potentially leading to an improvement in pregnancy-related outcomes and behaviours, and, ultimately a reduction in the present economic burden related to in-person interventions. TRIAL REGISTRATION: ISRCTN, ISRCTN16254958. Registered 20 December 2019, http://www.isrctn.com/ ISRCTN16254958.

Promoting healthy eating in early pregnancy in individuals at risk of gestational diabetes mellitus: does it improve glucose homeostasis? A study protocol for a randomized control trial.

Background: Healthy eating during pregnancy has favorable effects on glycemic control and is associated with a lower risk of gestational diabetes mellitus (GDM). According to Diabetes Canada, there is a need for an effective and acceptable intervention that could improve glucose homeostasis and support pregnant individuals at risk for GDM. Aims: This unicentric randomized controlled trial (RCT) aims to evaluate the effects of a nutritional intervention initiated early in pregnancy, on glucose homeostasis in 150 pregnant individuals at risk for GDM, compared to usual care. Methods: Population: 150 pregnant individuals ≥18 years old, at ≤14 weeks of pregnancy, and presenting ≥1 risk factor for GDM according to Diabetes Canada guidelines. Intervention: The nutritional intervention initiated in the first trimester is based on the health behavior change theory during pregnancy and on Canada's Food Guide recommendations. It includes (1) four individual counseling sessions with a registered dietitian using motivational interviewing (12, 18, 24, and 30 weeks), with post-interview phone call follow-ups, aiming to develop and achieve S.M.A.R.T. nutritional objectives (specific, measurable, attainable, relevant, and time-bound); (2) 10 informative video clips on healthy eating during pregnancy developed by our team and based on national guidelines, and (3) a virtual support community via a Facebook group. Control: Usual prenatal care. Protocol: This RCT includes three on-site visits (10-14, 24-26, and 34-36 weeks) during which a 2-h oral glucose tolerance test is done and blood samples are taken. At each trimester and 3 months postpartum, participants complete web-based questionnaires, including three validated 24-h dietary recalls to assess their diet quality using the Healthy Eating Food Index 2019. Primary outcome: Difference in the change in fasting blood glucose (from the first to the third trimester) between groups. This study has been approved by the Ethics Committee of the Centre de recherche du CHU de Québec-Université Laval. Discussion: This RCT will determine whether a nutritional intervention initiated early in pregnancy can improve glucose homeostasis in individuals at risk for GDM and inform Canadian stakeholders on improving care trajectories and policies for pregnant individuals at risk for GDM. Clinical trial registration: https://clinicaltrials.gov/study/NCT05299502, NCT05299502.

Age differences in expectations and readiness regarding lifestyle modifications in individuals at high risk of diabetes.

OBJECTIVE: The main objective of this study was to determine whether expectations and readiness to modify eating habits and physical activity (PA) level are different between young and older individuals with prediabetes who agreed to participate in a lifestyle modification program. DESIGN: Cross-sectional analysis. SETTING: Primary care or referral center. PARTICIPANTS: Adults between ages 27 and 78 years (N=74) were tested before starting a 12-month lifestyle intervention. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The visual analog scale questionnaire was used to assess expectations and readiness (ie, intentions, conviction, and self-confidence) to modify the PA level and eating habits. The PA level was assessed with a pedometer and eating habits with a questionnaire. Analyses were stratified by the age group: <60 years old versus ≥60 years old. RESULTS: Body mass loss expectations in terms of goal (-22.9% vs -17.9% of the current body mass; P=.04), acceptable (-15.6% vs -9.4%; P=.01), and failure (-7.6% vs -3.8%; P=.05) in future body mass loss were all greater for the younger group. Despite no significant age group difference in the initial PA level and eating habits, the youngest group had a greater intention to increase the PA level (89% vs 81%; P=.004) and to eat healthier (90% vs 85%; P=.001). Finally, the PA level and the consumption of fruits and vegetables, but not body mass, were associated with intentions or self-confidence to make some lifestyle modifications within age groups. CONCLUSIONS: In individuals at high risk for diabetes, increasing age is associated with lower expectations and reduced readiness with regard to lifestyle modifications. Thus, age should be considered when planning a lifestyle modification program.

Protocol of the Fit-For-Fertility study: a multicentre randomised controlled trial assessing a lifestyle programme targeting women with obesity and infertility.

INTRODUCTION: Women with obesity are at a higher risk of infertility as well as gestational and neonatal complications. Lifestyle changes are universally recommended for women with obesity seeking fertility treatments, but such intervention has only been assessed in very few robust studies. This study's objectives are therefore to assess the clinical outcomes and cost-effectiveness of an interdisciplinary lifestyle intervention (the Fit-For-Fertility Programme; FFFP) targeting women with obesity and subfertility in a diverse population. METHODS AND ANALYSIS: This pragmatic multicentre randomised controlled trial (RCT) will include 616 women with obesity (body mass index ≥30 kg/m2 or ≥27 kg/m2 with polycystic ovary syndrome or at-risk ethnicities) who are evaluated at a Canadian fertility clinic for subfertility. Women will be randomised either to (1) the FFFP (experimental arm) alone for 6 months, and then in combination with usual care for infertility if not pregnant; or (2) directly to usual fertility care (control arm). Women in the intervention group benefit from the programme up to 18 months or, if pregnant, up to 24 months or the end of the pregnancy (whichever comes first). Women from both groups are evaluated every 6 months for a maximum of 18 months. The primary outcome is live birth rate at 24 months. Secondary outcomes include fertility, pregnancy and neonatal outcomes; lifestyle and anthropometric measures; and cost-effectiveness. Qualitative data collected from focus groups of participants and professionals will also be analysed. ETHICS AND DISSEMINATION: This research study has been approved by the Research Ethics Board (REB) of Centre intégré universtaire de santé et des services sociaux de l'Estrie-CHUS (research coordinating centre) on 10 December 2018 and has been or will be approved successively by each participating centres' REB. This pragmatic RCT will inform decision-makers on improving care trajectories and policies regarding fertility treatments for women with obesity and subfertility. TRIAL REGISTRATION NUMBER: NCT03908099. PROTOCOL VERSION: 1.1, 13 April 2019.

Profile of Daughters and Sisters of Women With Polycystic Ovary Syndrome: The Role of Proband's Glucose Tolerance.

CONTEXT: First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the PCOS proband confers a more severe metabolic predisposition on their first-degree relatives. OBJECTIVE: To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters. DESIGN: Cross-sectional study. SETTING: Seven academic centers in North America, South America, and Europe. PATIENTS: Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT). MAIN OUTCOME MEASURES: Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels. RESULTS: Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040). CONCLUSIONS: Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.

Dietary and/or physical activity interventions in women with overweight or obesity prior to fertility treatment: protocol for a systematic review and individual participant data meta-analysis.

INTRODUCTION: Dietary and/or physical activity interventions are often recommended for women with overweight or obesity as the first step prior to fertility treatment. However, randomised controlled trials (RCTs) so far have shown inconsistent results. Therefore, we propose this individual participant data meta-analysis (IPDMA) to evaluate the effectiveness and safety of dietary and/or physical activity interventions in women with infertility and overweight or obesity on reproductive, maternal and perinatal outcomes and to explore if there are subgroup(s) of women who benefit from each specific intervention or their combination (treatment-covariate interactions). METHODS AND ANALYSIS: We will include RCTs with dietary and/or physical activity interventions as core interventions prior to fertility treatment in women with infertility and overweight or obesity. The primary outcome will be live birth. We will search MEDLINE, Embase, Cochrane Central Register of Controlled Trials and trial registries to identify eligible studies. We will approach authors of eligible trials to contribute individual participant data (IPD). We will perform risk of bias assessments according to the Risk of Bias 2 tool and a random-effects IPDMA. We will then explore treatment-covariate interactions for important participant-level characteristics. ETHICS AND DISSEMINATION: Formal ethical approval for the project (Venus-IPD) was exempted by the medical ethics committee of the University Medical Center Groningen (METc code: 2021/563, date: 17 November 2021). Data transfer agreement will be obtained from each participating institute/hospital. Outcomes will be disseminated internationally through the collaborative group, conference presentations and peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42021266201.