Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

When and how to stop denosumab therapy in a patient with osteoporosis.

Denosumab is a human monoclonal antibody that competitively inhibits the receptor activator of nuclear factor kappa B ligand which regulates osteoclast activity. It is an effective treatment for osteoporosis with a reduced cumulative rate of vertebral fractures, hip and nonvertebral fractures as well as an increase in bone mineral density. The benefits have been shown to be maintained when treatment is continued up to and likely after 10 years of therapy, but the effects are lost rapidly if treatment is discontinued abruptly. There are rare medical indications for discontinuation of treatment. Discontinuation of denosumab is often driven by concern about complications such as osteonecrosis of the jaw, atypical femoral fractures and hypocalcaemia, which remain rare events. Further studies are required to confirm safety and efficacy beyond 10 years of treatment, but it is likely that patients will have ongoing benefits from therapy beyond this. We aim to present a personal perspective of why and how denosumab should be discontinued in patients with osteoporosis.

Pregnancy complications and later life women's health.

There has been increasing recognition of the association between various pregnancy complications and development of chronic disease in later life. Pregnancy has come to be regarded as a physiological stress test, as the strain it places on a woman's body may reveal underlying predispositions to disease that would otherwise remain hidden for many years. Despite the increasing body of data, there is a lack of awareness among healthcare providers surrounding these risks. We performed a narrative literature review and have summarized the associations between the common pregnancy complications including gestational hypertension, pre-eclampsia, gestational diabetes, placental abruption, spontaneous preterm birth, stillbirth and miscarriage and subsequent development of chronic disease. Hypertensive disorders of pregnancy, spontaneous preterm birth, gestational diabetes, pregnancy loss and placental abruption are all associated with increased risk of various forms of cardiovascular disease. Gestational diabetes, pre-eclampsia, early miscarriage and recurrent miscarriage are associated with increased risk of diabetes mellitus. Pre-eclampsia, stillbirth and recurrent miscarriage are associated with increased risk of venous thromboembolism. Pre-eclampsia, gestational diabetes and stillbirth are associated with increased risk of chronic kidney disease. Gestational diabetes is associated with postnatal depression, and also with increased risk of thyroid and stomach cancers. Stillbirth, miscarriage and recurrent miscarriage are associated with increased risk of mental health disorders including depression, anxiety and post-traumatic stress disorders. Counseling in the postnatal period following a complicated pregnancy, and advice regarding risk reduction should be available for all women. Further studies are required to establish optimal screening intervals for cardiovascular disease and diabetes following complicated pregnancy.

Efficacy of Burosumab in Adults with X-linked Hypophosphatemia (XLH): A Post Hoc Subgroup Analysis of a Randomized Double-Blind Placebo-Controlled Phase 3 Study.

The anti-fibroblast growth factor 23 monoclonal antibody burosumab corrects hypophosphatemia in adults with X-linked hypophosphatemia (XLH) and improves pain, stiffness, physical function, and fatigue. This post hoc subgroup analysis used data from the 24-week placebo-controlled period of a phase 3 study in 134 adults with XLH (ClinicalTrials.gov NCT02526160), to assess whether the benefits of burosumab are evident in 14 clinically relevant subgroups defined by baseline demographic and functional criteria, including sex, Brief Pain Inventory-short form (BPI-SF) Average And Worst Pain, region, race, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC®) Stiffness, Physical Function and Pain domains and total score, use of opioid/other pain medication, active fractures/pseudo-fractures, and 6-min walk test distance. There were no statistically significant interactions between any of the subgroups and treatment arm for any endpoint. Higher proportions of subjects achieved mean serum phosphate concentration above the lower limit of normal (the primary endpoint) with burosumab than with placebo in all subgroups. For the key secondary endpoints (WOMAC Stiffness and Physical Function; BPI-SF Worst Pain) individual subgroup categories showed improvements with burosumab relative to placebo. For additional efficacy endpoints, burosumab was favored in some subgroups but differences were not significant and confidence intervals were wide. For some endpoints the treatment effect is small at 24 weeks in all subjects. This subgroup analysis shows that burosumab was largely superior to placebo across endpoints in the 14 clinically relevant subgroup variables at 24 weeks and is likely to benefit all symptomatic adults with active XLH.

An mHealth-Supported antenatal lifestyle intervention may be associated with improved maternal sleep in pregnancy: Secondary analysis from the PEARS trial.

OBJECTIVE: To investigate the effect of an antenatal diet and exercise intervention during pregnancy on sleep duration. As a secondary objective, associations between sleep duration and gestational weight gain (GWG), maternal metabolic parameters and pregnancy outcomes were assessed. DESIGN: Secondary analysis. SETTING: Large tertiary Maternity Hospital in Dublin, Ireland. POPULATION: 326 women with overweight or obesity who participated in the Pregnancy Exercise And Nutrition Research Study (PEARS) randomised controlled trial between March 2013 and August 2016. METHODS: Secondary analysis of a randomised trial. MAIN OUTCOME MEASURES: Impact of the PEARS intervention on sleep duration, and association of sleep duration and maternal metabolic parameters, and pregnancy outcomes. RESULTS: Participants had a mean age of 32.5 ± 4.5 years and median (interquartile range [IQR]) body mass index of 28.3 (26.6-31.2) kg/m2 . The intervention group had a longer sleep duration in late pregnancy (mean difference 17.1 minutes (95% confidence interval [CI] 0.5-33.7) and a higher proportion achieving optimum sleep duration of 7-9 h (54.3 vs. 42.9%, relative risk [RR] 1.28 (95% CI 1.01-1.62). In late pregnancy, sleep duration of <6 h was associated with lower breastfeeding rates on discharge (RR 0.74, 95% CI 0.57-0.95) and higher triglyceride levels (mean difference 0.24, 95% CI 0.10-0.38). There were no significant associations between sleep and incidence of gestational diabetes mellitus or pre-eclampsia/toxaemia, or other metabolic parameters assessed (insulin, fasting glucose, HOMA-IR). CONCLUSION: A diet and exercise intervention from early pregnancy may promote longer and optimal sleep duration, with maternal benefits such as lower triglyceride levels and higher breastfeeding rates.

The effects of acute hyponatraemia on bone turnover in patients with subarachnoid haemorrhage: A preliminary report.

CONTEXT: Animal data and cross-sectional human studies have established that chronic hyponatraemia predisposes to osteoporosis; the effects of acute hyponatraemia on bone turnover have not been determined. Our objective was to test the hypothesis that acute hyponatraemia leads to dynamic effects on bone turnover. DESIGN: A prospective observational pilot study. METHODS: Bone turnover markers [C-terminal crosslinking telopeptide of type 1 collagen (CTX-1), N-propeptide of type 1 collagen (P1NP) and osteocalcin] were measured prospectively over one week in 22 eunatraemic patients with subarachnoid haemorrhage. Patients treated with glucocorticoids were excluded. RESULTS: Eight patients developed acute hyponatraemia, median nadir plasma sodium concentration 131 mmol/L (IQR 128-132), and 14 remained eunatraemic, nadir plasma sodium concentration 136 mmol/L (IQR 133-137). Significant main effects of hyponatraemia were found for P1NP (p = .02) and P1NP:CTX-1 ratio (p = .02), both fell in patients with acute hyponatraemia, with significant interaction between hyponatraemia and time from baseline for P1NP (p = .02). Significant main effects of time from baseline (p < .001) but not hyponatraemia (p = .07) were found for osteocalcin. For CTX-1, significant main effects of time from baseline (p = .001) but not hyponatraemia (p = .65) were found. There was a positive correlation between change in P1NP:CTX-1 ratio and nadir plasma sodium concentration, r = +.43, p = .04. Median serum cortisol (measured on days 1, 3 and 7) was higher in the hyponatraemia group than in those who remained eunatraemic, 545 nmol/L (IQR 373-778) versus 444 nmol/L (IQR 379-542) p = .03. CONCLUSION: These data suggest that acute mild hyponatraemia is associated with a reduction in bone formation activity.

Adherence with reporting of ethical standards in COVID-19 human studies: a rapid review.

BACKGROUND: Patients with COVID-19 may feel under pressure to participate in research during the pandemic. Safeguards to protect research participants include ethical guidelines [e.g. Declaration of Helsinki and good clinical practice (GCP)], legislation to protect participants' privacy, research ethics committees (RECs) and informed consent. The International Committee of Medical Journal Editors (ICMJE) advises researchers to document compliance with these safeguards. Adherence to publication guidelines has been suboptimal in other specialty fields. The aim of this rapid review was to determine whether COVID-19 human research publications report compliance with these ethical safeguards. METHODS: A rapid systematic literature review was conducted in MEDLINE using the search term 'COVID-19'. The search was performed in April 2020 with no start date and repeated to include articles published in November 2020. Filters were 'Full free text available' and 'English Language'. Two reviewers assessed article title, abstracts and full texts. Non-COVID-19 articles and non-clinical studies were excluded. Independent reviewers conducted a second assessment of a random 20% of articles. The outcomes included reporting of compliance with the Declaration of Helsinki and GCP, REC approval, informed consent and participant privacy. RESULTS: The searches yielded 1275 and 1942 articles of which 247 and 717 were deemed eligible, from the April  search and November respectively. The majority of journals had editorial policies which purported to comply with ICMJE ethical standards. Reporting of compliance with ethical guidelines was low across all study types but was higher in the November search for case series and observational studies. Reporting of informed consent for case studies and observational studies was higher in the November search, but similar for case series. Overall, participant confidentiality was maintained but some case studies included a combination of details which would have enabled participant identification. Reporting of REC approval was higher in the November search for observational studies. CONCLUSIONS: While the majority of journal's editorial policies purported to support the ethical safeguards, many COVID-19 clinical research publications identified in this rapid review lacked documentation of these important safeguards for research participants. In order to promote public trust, ethical declarations should be included consistently.

The impact of diet, body composition, and physical activity on child bone mineral density at five years of age-findings from the ROLO Kids Study.

Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD.Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.

Management of hypothalamic disease in patients with craniopharyngioma.

Patients with craniopharyngioma experience excess morbidity and mortality when compared with the background population and with other hypopituitary patients. Large, suprasellar tumours which form micropapillae into surrounding structures can cause hypothalamic damage before any therapeutic intervention; attempted gross total resection can lead to hypothalamic obesity, sleep disorders, thirst disorders and dysregulation of temperature as well as panhypopituitarism. The management of tumour bulk and the pathophysiology of hypothalamic complications have been reviewed extensively. We present a practical, clinical approach to management of hypothalamic disease in a patient with craniopharyngioma and highlight potential targets for future pharmacological or surgical intervention.

Blood pressure in pregnancy-A stress test for hypertension? Five-year, prospective, follow-up of the ROLO study.

OBJECTIVE: To investigate whether maternal blood pressure (BP) below the diagnostic criteria of hypertensive disorders of pregnancy (HDP) is associated with maternal BP 5 years later. DESIGN: Prospective, observational study. SETTING: Dublin, Ireland (2007-2011). SAMPLE: Three hundred twenty-nine women from the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet to prevent the recurrence of macrosomia). METHODS: Maternal BP measurements were taken during pregnancy (13, 28 and 34 weeks' gestation and day 1 postpartum) and at the 5-year follow-up. Systolic BP (SBP) and diastolic BP (DBP) were categorized as normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP 120-129 and DBP < 80 mm Hg), HTN stage 1 (SBP 130-139 or DBP 80-89 mm Hg) or HTN stage 2 (SBP ≥ 140 or DBP ≥ 90 mm Hg) at each timepoint. MAIN OUTCOME MEASURES: Maternal blood pressure at the 5-year follow-up. RESULTS: Women with elevated BP at 28 and 34 weeks' gestation had 2.68 (95% CI: 1.36-5.26) and 2.45-fold (95% CI: 1.22-4.95) increased odds of HTN stage 1 respectively, at the 5-year follow-up, compared to those with normal BP in pregnancy. CONCLUSION: Elevated BP at 28 and 34 weeks' gestation was associated with an increased risk of HTN stage 1 at 5 years later. Thus, raised BP, below the diagnostic criteria of HDP, could be flagged for follow-up postpartum.

Increased central adiposity and decreased subcutaneous adipose tissue 11ß-hydroxysteroid dehydrogenase type 1 are associated with deterioration in glucose tolerance-A longitudinal cohort study.

OBJECTIVE AND CONTEXT: Increasing adiposity, ageing and tissue-specific regeneration of cortisol through the activity of 11ß-hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance. DESIGN, PATIENTS, AND MEASUREMENTS: Sixty-five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated ("deteriorators") or improved ("improvers"). RESULTS: Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11ß-HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11ß-HSD1 expression. Global 11ß-HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow-up. CONCLUSION: Longitudinal deterioration in metabolic phenotype is not associated with increased 11ß-HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.

DIABETIC KETOACIDOSIS IN PATIENTS WITH TYPE 2 DIABETES RECENTLY COMMENCED ON SGLT-2 INHIBITORS: AN ONGOING CONCERN.

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly used as an adjunctive treatment for type 2 diabetes. We report the occurrence of diabetic ketoacidosis (DKA) in 3 patients with type 2 diabetes recently commenced on SGLT-2 inhibitors. METHODS: Clinical presentation, laboratory data, and treatment outcomes of all 3 cases are described. RESULTS: All 3 patients had documented history of longstanding type 2 diabetes. The presentation in all patients was that of hyperglycaemia, acidosis, and ketosis occurring within 4 weeks of commencing SGLT-2 inhibitors. The risk factors for developing DKA were infection, myocardial infarction, and alcohol excess. DKA resolved within 24 hours of initiating intravenous fluids and insulin in all cases. CONCLUSION: This case series illustrates the importance of careful patient selection, education, and monitoring when starting this group of antidiabetic medications. ABBREVIATIONS: DKA = diabetic ketoacidosis SGLT-2 = sodium-glucose cotransporter 2 T2D = type 2 diabetes.

Elevated PTH with normal serum calcium level: a structured approach.

Normocalcaemic hyperparathyroidism is a common biochemical finding, usually identified during an assessment of bone or renal health. Hypercalcaemia must be considered by calculation of adjusted calcium, and a careful history taken to assess dietary calcium intake and for the possibility of a malabsorption syndrome. 25-hydroxyvitamin D (25OHD) should be measured and replaced if indicated. The management plan for the patient is influenced by the context in which calcium and PTH were measured. In this brief review we describe the assessment of a patient with normocalcaemic hyperparathyroidism.

Symptoms of gonadal dysfunction are more predictive of hypopituitarism than nonspecific symptoms in screening for pituitary dysfunction following moderate or severe traumatic brain injury.

OBJECTIVE: The economic and logistic burden of screening for hypopituitarism following moderate/severe traumatic brain injury (TBI) is considerable. A key recommendation in published guidelines is to prioritize for screening those patients with symptoms suggestive of pituitary dysfunction. The purpose of this study was to evaluate the utility of targeted screening for hypopituitarism in long-term survivors after moderate/severe TBI using referrals on the basis of symptoms. DESIGN: In group 1 (G1), consecutive, unselected patients were screened from the Irish National Neurosurgery Centre, whereas in group 2 (G2) patients were targeted based on the presence of symptoms suggestive of pituitary dysfunction. PATIENTS: A total of 137 patients (113 male) were systematically screened (G1) and compared to 112 patients (77 male) referred for pituitary evaluation on the basis of suggestive symptoms (G2). MAIN OUTCOME MEASURES: The rate of GH, ACTH, gonadotrophin (GT), TSH and ADH deficiency was compared among groups. RESULTS: Patients referred with menstrual dysfunction had more GH (50% vs 11%, P = 0·001), ACTH (60% vs 14%, P < 0·0001), GT (90% vs 16%, P < 0·0001) deficiency and any pituitary hormone deficit (80% vs 33%, P = 0·003) than G1. Men with symptoms of hypogonadism had more GH (33% vs 11%, P = 0·003), GT (58% vs 16%, P < 0·0001) and TSH (16% vs 1%, P = 0·03) deficiency than G1. Patients with nonspecific symptoms were no more likely to have hypopituitarism than those consecutively screened. CONCLUSIONS: Symptoms of hypogonadism are sufficiently predictive of hypopituitarism to justify screening for hypopituitarism after moderate/severe TBI. Nonspecific symptoms of hypopituitarism are no more predictive than unselected screening.

Breastfeeding duration is associated with favorable body composition and lower glycoprotein acetyls in later life.

OBJECTIVE: The aim of the present study was to investigate associations between lifetime breastfeeding behaviors and cardiovascular risk in later reproductive years. METHOD: This was a prospective 10-year longitudinal cohort study of 168 parous women. Health, lifestyle and infant feeding questionnaires, blood samples, anthropometry and body composition were collected. Cardiovascular risk was estimated using QRISK®3 and hierarchical multiple linear regression analysis performed. RESULTS: Mean age was 42.4 years (SD 3.8; range 31-50) and 98.7% (n = 156/158) were premenopausal. Ever breastfeeding rates were 72.6% (n = 122/168) and 37.5% (n = 63/168) lifetime ≥12 months breastfeeding duration. Median durations were 5.5 weeks for exclusive breastfeeding (IQR 35.8; range 0-190) and 30.5 weeks for any breastfeeding (IQR 84.0; range 0-488). Breastfeeding duration was not associated with QRISK®3 scores in adjusted models. Lower glycoprotein acetyls were associated with ever breastfeeding (P = 0.03), and lifetime breastfeeding ≥12 months (P = 0.001). Lifetime breastfeeding ≥12 months and longer exclusive breastfeeding were associated with lower fat mass index (P = 0.03, P = 0.01), tissue percentage fat (P = 0.02, P = 0.009) and visceral adipose tissue volume (P = 0.04, P = 0.025) after correcting for confounders including body mass index. CONCLUSION: Longer breastfeeding is associated with favorable body composition and lower glycoprotein acetyls, a novel inflammatory biomarker associated with cardiometabolic risk. Breastfeeding is a low-cost, health promoting behavior for women and infants. Pregnant women, especially those at higher risk of cardiovascular disease, should be counseled about the potential benefits of exclusive and longer breastfeeding duration.

Associations of childhood physical activity and screen time with cardiometabolic health in preteens who were born to mothers with previous macrosomic delivery: Findings from the ROLO longitudinal birth cohort study.

BACKGROUND: Macrosomia (birthweight ≥4 kg) may alter the associations of physical activity (PA) and screen time (ST) throughout childhood with later cardiometabolic risk. OBJECTIVE: To investigate associations of PA and ST over a 4-6-year follow-up period with cardiometabolic outcomes in preteens (9-11-year-olds) who were born to mothers with previous macrosomic delivery. METHODS: This is an analysis of 402 preteens from the ROLO study, who were born to mothers that previously delivered an infant with macrosomia. Parental-reported measures of PA and ST were obtained in early childhood at 5-years of age. Preteen self-reported PA, parental-reported ST, anthropometry, dual-energy x-ray absorptiometry, blood pressure, heart rate, cardiorespiratory endurance, and blood biomarkers were obtained at 9-11-years. Crude and adjusted linear regression models explored associations and the interaction of birthweight was investigated in all models. RESULTS: Early childhood PA and ST at the 5-year follow-up were not related to preteen cardiometabolic outcomes. In adjusted models, higher preteen PA was associated with lower sum of skinfolds (B = -3.00, 95% CI -5.98, -0.02, p = 0.048) and higher cardiorespiratory endurance (B = 0.50, 95% CI 0.20, 0.80, p = 0.001) at the same time point. No strong evidence for modification by birthweight was found. CONCLUSION: Higher preteen PA may have potential benefits for cardiometabolic health, irrespective of birthweight.

Childhood Nutritional Factors and Cardiometabolic Outcomes at 9-11 y of Age: Findings from the ROLO Longitudinal Birth Cohort Study.

BACKGROUND: Childhood represents a critical period of nutritional risk in the programming of later chronic disease. Few longitudinal studies have explored repeated measures of nutrition throughout the first decade of life in relation to preteen cardiometabolic outcomes. OBJECTIVES: This research aimed to explore associations of early feeding practices (human milk exposure and duration and timing of introduction to solids) and childhood dietary quality and inflammatory scores (at 5 and 9-11 y and change during childhood) on preteen cardiometabolic outcomes. METHODS: This is an analysis of children from the ROLO longitudinal birth cohort study (n = 399). Information on early feeding practices were obtained at postnatal study visits. Food frequency questionnaires collected maternal-reported dietary intakes for each child at 5 and 9-11 y of age. Healthy Eating Index (HEI)-2015 and the Children's Dietary Inflammatory Index (C-DII) scores were calculated. Anthropometry, body composition, blood pressure, heart rate, cardiorespiratory endurance, and blood biomarkers were obtained at 9-11 y. Crude and adjusted linear regression models examined nutritional exposure associations with preteen cardiometabolic outcomes. RESULTS: In the adjusted model, any human milk exposure was associated with lower body fat (%) at 9-11 y (ß: -2.86; 95% confidence interval [CI]: -5.46, -0.27; P = 0.03), than never receiving human milk. At 5 y, diet scores were favorably associated with lean mass at 9-11 y (P < 0.05 for both). Higher preteen HEI-2015 scores were associated with lower preteen leptin levels (tertile 3 compared with tertile 1-ß: -2.92; 95% CI: -5.64, -0.21; P = 0.03). Diet quality significantly deteriorated (HEI-2015 score decreased) and became more proinflammatory (C-DII score increased) from 5 to 9-11 y of age. Diet quality/inflammation deterioration (compared with improvement) or overall change in dietary scores were not related to preteen cardiometabolic outcomes. CONCLUSIONS: Exposure to human milk in early life was associated with lower preteen adiposity, irrespective of duration. Diet quality/inflammatory potential deteriorated between early childhood and the preteen years, highlighting a potential period for intervention.

When would I use medical therapies for the treatment of primary hyperparathyroidism?

Although there may be controversy surrounding the indications for parathyroidectomy in primary hyperparathyroidism, it remains the only accepted definitive therapy. However, even if parathyroidectomy is indicated, some patients refuse surgery, are medically unfit or have residual or recurrent disease inaccessible to further surgery. Some of these patients may be suitable for long-term observation but others require intervention for management of symptomatic or moderate to severe hypercalcaemia, loss of bone mineral density or renal calculi. The selection of a suitable therapy for each patient should be individualized.