Gestational Diabetes, Infant Feeding Practices, and Early Indicators of Obesity Risk in a Sample of Mother-Infant Dyads in the U.S.

Research suggests that the trajectory to obesity and its associated metabolic disorders begins early in life. Prenatal exposure to maternal gestational diabetes mellitus (GDM) is associated with increased risk, while breastfeeding is associated with reduced risk. Breastfeeding may influence obesity risk by preventing rapid postnatal weight gain. Mothers with gestational diabetes may not breastfeed as intensely as healthy mothers, potentially exacerbating the risk to their infants. We conducted three distinct investigations related to gestational diabetes, breastfeeding, and infant weight gain. All used data from the U.S. Infant Feeding Practices Study II. Multivariate logistic regression was used to estimate associations between predictor and outcome variables. In the first study (N=1,225), we found that compared to 100% breast milk feeds, likelihood of rapid weight gain was increased two-to-three-fold for infants fed any other way. In the second study, which used prenatal (N=3,244) and postpartum (N=2,051) data, GDM was associated with a 46% reduced odds of ever EBF. Intention to breastfeed was similar in both groups. Infants of GDM mothers were 78% more likely to receive formula in the hospital. Duration of breastfeeding was similar in both groups. The third study included 3,010 and 1,733 women in prenatal and postnatal analyses, respectively. During pregnancy, GDM women were nearly 40% less likely to report breastfeeding as optimal feeding and 74-78% more likely to indicate formula or mixed feeding as the preferred feeding by the infant’s father. They were nearly three times more likely than NDM women to say their physician preferred formula, and were 30% less likely to report being comfortable breastfeeding in front of women friends. There were no differences in knowledge of breastfeeding benefits or recommendations. Following delivery, infants of GDM women were 45% less likely to room-in with their mother. GDM women were 66% more likely to indicate problems with sucking and twice as likely to say the infant was not interested in breastfeeding. The results of these studies suggest that high-intensity breastfeeding in early infancy may be necessary to prevent rapid infant weight gain, and that women with GDM may especially need support and encouragement to achieve optimal breastfeeding outcomes

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Omega-3 index, cardiorespiratory fitness, and cognitive function in mid-age and older adults

Higher levels of omega-3 fatty acids in red blood cell membranes (omega-3 index or O3I) and cardiorespiratory fitness (CRF) are each associated with reduced cognitive impairment, but little research has examined the relationship between O3I and cognitive function while accounting for CRF. We analyzed cross-sectional data from 5,464 healthy men and women aged 55–85 years who had preventive medical examinations between 2009 and 2023. Primary exposures included O3I (<4.0%, 4.0–7.9%, or ≥ 8.0%) and age- and sex-based CRF quintile (1 = low, 2–3 = moderate, 4–5 = high). Cognitive impairment was defined as a Montreal Cognitive Assessment score of ≤ 25. We used Poisson regression to estimate relative risks (RR) of cognitive impairment, controlling for covariates. O3I < 4% was associated with increased cognitive impairment relative to ≥ 8.0% (RR, 1.21; 95% CI, 1.01–1.44) in a partially adjusted model. This association did not remain statistically significant in the fully adjusted model which included CRF. Low versus high CRF was associated with cognitive impairment (RR, 1.28; 95% CI, 1.07–1.53), independent of O3I and clinical biomarkers. The interaction between CRF and O3I was not significant (P = 0.8). In joint association analysis, risk of cognitive impairment was elevated with lower omega-3 index or CRF or both. Additional research is needed to fully understand the association between O3I and cognitive function at varying CRF levels