BACKGROUND:Neonatal hypoglycemia is common and associated with adverse neurodevelopmental outcomes, but it is unclear which glycemic measures best explain this association. METHODS:Blood glucose concentrations (BGC) from three prospective cohorts of late preterm and term babies born at risk of hypoglycemia, all screened and treated to maintain BGC ≥ 2.6 mmol/L, were used to derive both continuous (maximum, minimum, range, mean, median, standard deviation and variability metrics) and dichotomous glycemic measures (any, severe, recurrent and late hypoglycemic episodes). Generalized linear models adjusted for socioeconomic deprivation, site, primary risk of hypoglycemia and multiple birth related glycemic measures to outcomes at 2 years. RESULTS:We analyzed 18,947 BGCs from 2,894 babies. Higher gradient variability was associated with poorer neurodevelopment, but dichotomous indicators were more strongly predictive; e.g. 1 SD increase in gradient variability was associated with -0.9-point adjusted mean Bayley motor score (95% confidence interval -1.4, -0.3), compared to -3.1 (-4.8, -1.5) for severe and -2.1 (-3.6, -0.6) for recurrent hypoglycemia. Associations were similar for Bayley cognitive and language and Brief P global executive composite scores. CONCLUSIONS:Continuous glycemic measures derived from intermittent capillary sampling are not stronger predictors of neurodevelopment at 2 years than dichotomous measures, although glycemic variability warrants further investigation. IMPACT:Beyond simple dichotomous classifications (e.g., hypoglycemic or not), little is known about how blood glucose profiles derived from intermittent heel-prick measurements relate to later neurodevelopmental outcomes in infants at risk of neonatal hypoglycemia. Prespecified glycemic measures were related to neurodevelopmental outcomes at 2 years using data from three longitudinal studies of children born at risk of neonatal hypoglycemia. While the dichotomous indicators of severe (<2.0 mmol/L) and recurrent (≥3 episodes) hypoglycemia are most strongly related to neurodevelopmental outcome, measures of glycemic variability also relate to neurodevelopmental risk in infants at risk of neonatal hypoglycemia.

Introduction: There have been several prognostic tools proposed for determining spinal epidural abscess patient outcomes. One such method is the “mortality in spinal infection” scoring system. In this study, we aim to externally validate this score within the New Zealand population. Methods: We identified all patients who were admitted to a tertiary referral centre with a diagnosis of spinal epidural abscess between February 2009 and January 2022. The mortality in spinal infection score was calculated for all patients. We developed a receiver operating characteristic curve and a calibration plot to externally validate the score. Results: A total of 140 patients with spinal epidural abscesses met the criteria for inclusion in our study. Within the one-year follow-up period, 18 patients died while 122 survived. In total, 105 patients underwent surgical intervention, while 35 patients were managed nonoperatively. In total, 5/15 (33%) of patients with scores 11 died compared with 13/125 (10%) of those with scores <11 (odds ratio 4.3, 95% confidence interval [CI] 1.3-14.6, p=0.03). This threshold had high specificity (0.92) and negative predictive value (0.90) but lower sensitivity (0.28) and positive predictive value (0.33). The area under the curve of the receiver operating characteristics plot for mortality in spinal infection scoring and death (0.67, 95% CI 0.57-0.79) did not meet the prespecified criterion of an area under the curve >0.80 for acceptable prediction. Conclusions: In this cohort, the mortality in spinal infection-20 score demonstrated limited ability to discriminate between those patients who died vs those who survived at one year post follow-up. Prospective multicentre data collection may improve the development of predictive tools.

CONTEXT:We recently reported that zoledronate (zol) given once at baseline or twice (every 5 years) reduced fracture risk over 10 years. OBJECTIVE:We assessed whether the effects of zol differ over time or across important baseline variables, and how they relate to changes in bone mineral density (BMD) over time. METHODS:A 10-year, prospective, randomized, double-blind, placebo-controlled trial, was conducted at a clinical research center from 2012 to 2023. Participants included 1054 postmenopausal women, aged 50 to 60 years, with BMD T-score at the lumbar spine, femoral neck, or total hip between 0 and -2.5. Intervention included either 5-yearly 5-mg zol (zol-zol), 5-mg zol infusion at baseline and placebo at 5 years (zol-placebo), or 5-yearly placebo (placebo-placebo). Main outcome measures included morphometric vertebral fractures, major osteoporotic, and any fractures. RESULTS:Morphometric vertebral fractures were not reduced in the years 0 to 5 following zol but were reduced in years 5 to 10 by 58% (95% CI, 21%-77%) (zol-zol) and 57% (21%-77%) (zol-placebo). For any fracture and major osteoporotic fracture, similar temporal patterns were observed. There were no interactions between treatment effect and baseline variables (including age, body mass index, BMD, falls or fracture history, and estimated fracture risk) or between treatment effect and changes in BMD with zol. CONCLUSION:Fracture reductions with single-dose or 5-yearly zol appear greater during years 5 to 10 than years 0 to 5. The risk reductions are broadly consistent across this cohort and independent of baseline or change in BMD. This suggests that routine BMD monitoring may not be necessary for low-risk women considering the option of less frequent zol for long-term fracture risk reduction.

OBJECTIVE:Prior imaging studies have suggested that monosodium urate (MSU) crystal deposits in joints dissolve more rapidly than those in tendons during urate-lowering therapy (ULT) for gout. This study aimed to examine whether urate deposits visible on dual-energy computed tomography (DECT) reduce at different rates in joints and tendons during ULT. METHODS:Participants with gout from 2 clinical trials of oral ULT with the following criteria were included: paired DECT scans of the feet and ankles over 1-year of ULT, first DECT scan showing total urate volume ≥ 0.5 cm3, second DECT scan showing reduced total urate volume, and DECT deposition visible in at least 1 joint and 1 tendon on the first scan. DECT urate volumes in up to 3 index joints and up to 3 index tendons at baseline and year 1 were measured in known order. Data were analyzed using a general linear mixed analysis of covariance. RESULTS:In total, 125 joint deposits and 95 tendon deposits were analyzed from 50 participants. The least means change (95% CI) in DECT urate volumes of the joint deposits was -0.37 (-0.47 to -0.26) cm3 and of the tendon deposits was -0.39 (-0.50 to -0.27) cm3 (both P < 0.001). There was no difference in the change in DECT urate volumes between the joint and tendon deposits; least means difference was 0.02 (95% CI -0.09 to 0.13) cm3 (P = 0.73). CONCLUSION:This DECT study indicates that similar rates of MSU crystal dissolution occur at both joints and tendons during oral ULT.

AIM:The aim of this article was to assess agreement between verified self-reported fractures in a clinical trial with Accident Compensation Corporation (ACC) claim data. METHODS:In a 10-year randomised controlled trial of 1,054 women aged 50-60 years, participants self-reported fractures as they occurred or on routine 6-monthly questionnaires. Radiology imaging and reports were used to verify fractures, which were then compared with ACC claims data (ACC is the New Zealand no-fault accident claims organisation funded through levies). Initially, fracture claim data only were obtained, followed by all ACC claims for each participant for the study period. RESULTS:Three hundred and fifty-six self-reported fractures in 248 women were verified in the trial, whereas there were 328 ACC fracture claims from 238 women for the study period. Out of 356 trial fractures, 211 (59%) had a matching ACC fracture claim, and out of 328 ACC fracture claims 211 (64%) had a matching trial fracture. After obtaining all ACC claims, we identified a matching ACC claim for 340/356 (96%) trial fractures: 59% were fracture claims and 31% soft-tissue injury claims. CONCLUSIONS:Repurposing ACC fracture claims data for clinical trials has significant limitations and is likely to introduce false negative and false positive events. When tolerance for misclassification is higher (e.g., large non-randomised studies), ACC claims data may be useful because 60% of claims had a verified fracture, with higher proportions for major fracture types.

OBJECTIVE:To determine the impact of different feeding strategies in children born moderate-and-late preterm (MLPT) on later neurosensory impairment. STUDY DESIGN:Children born MLPT (320/7-356/7 weeks) recruited to the Different Approaches to Moderate & Late Preterm Nutrition: Determinants of Feed Intolerance, Body Composition, and Development (DIAMOND) factorial randomized trial from New Zealand neonatal units were randomized to intravenous amino acids vs intravenous dextrose, exclusive maternal breastmilk vs milk supplement, and taste/smell of milk before gastric tube feeds or not. Neurosensory impairment (blindness, deafness, cerebral palsy, or developmental delay [Bayley III composite cognitive/language/motor scores <85]) was assessed at 2 years of corrected age. Outcomes were compared using generalized linear mixed models. RESULTS:Of 529 eligible children, 425 were assessed at mean (SD) 25.6 (1.9) months. Rates of neurosensory impairment were similar in amino acids vs dextrose and in milk supplement vs maternal breastmilk only groups, but impairments were less frequent in children randomized to taste/smell of milk (43/203 [21%] vs 68/220 [31%]; adjusted risk ratio 0.7; 95% CI 0.5-0.9; P = .02). This difference was primarily attributable to mild developmental delay, particularly language delay (35/199 [18%] vs 61/218 [28%]; adjusted risk ratio 0.6; 95% CI 0.4-0.9; P = .01). Growth, general health, and behavior were similar between groups. CONCLUSIONS:Early parenteral and enteral nutrition strategies in children born MLPT did not alter outcomes at 2 years. However, exposure to taste/smell of milk before gastric tube feeds was associated with a lower risk of neurosensory impairment. TRIAL REGISTRATION:anzctr.org.au Identifier: ACTRN12616001199404 (https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371006&isReview=true).

Background: Given the paucity of evidence on diabetes and associated risk factors among Pasifika communities in Australia, this analysis aimed to estimate the prevalence of diabetes and associated risk factors in this population. Methods: A whole-of-community-based cross-sectional analysis was conducted using baseline health screening data from adults aged ≥18 years in the Pasifika Preventing Diabetes Programme, a stepped-wedge randomised controlled trial evaluating the effectiveness of a “through the church” behaviour change intervention on diabetes prevention and management in Pasifika communities in Greater Sydney. HbA1c, random blood glucose, blood pressure, and anthropometric measurements were collected alongside sociodemographic, health behaviour, diabetes knowledge, and quality-of-life questionnaire data. Diabetes was defined by HbA1c ≥ 6.5% or self-reported diagnosis. Multivariable binary logistic regression was conducted to identify significant factors associated with the odds of having diabetes. Results: Among 1161 participants, 33.9% (95% CI: 31.1–36.7) had diabetes, of whom 34.3% were previously undiagnosed. Only 2.5% met fruit and vegetable guidelines; 34.3% met minimum physical activity recommendations, 95.8% were obese/overweight, and 68.0% had high blood pressure. The adjusted odds ratio (AOR) of having diabetes increased with family history of diabetes (AOR, 2.23; 95% CI: 1.56–3.20), high blood pressure (AOR, 1.65; 95% CI: 1.15–2.38), and older age (AOR, 1.06; 95% CI: 1.05–1.07). A high level of physical activity was associated with a 41% lower odds of diabetes compared to a low level of physical activity (AOR, 0.59; 95% CI: 0.38–0.94). Conclusions: This study demonstrates a high burden of diabetes among Pasifika adults in Australia, including a substantial proportion of previously undiagnosed cases. Older age, family history of diabetes, and high blood pressure were associated with higher odds of diabetes, while high physical activity was associated with lower odds. These findings highlight the need for culturally safe, community-based approaches to strengthen diabetes screening, early diagnosis, and integrated prevention strategies in this underserved high-risk population.

OBJECTIVE:To determine if, after adjusting for potential confounders, child health outcomes differ between children exposed to maternal gestational diabetes mellitus (GDM) and their unexposed peers. STUDY DESIGN:Prospective cohort study. Recruitment took place between June 2022 and May 2024. The primary outcome was overweight or obesity. The secondary outcomes were other measures of size, eating behavior, behavioral and emotional problems, neurodevelopmental disorders, atopic disorders, and diabetes. Between-group differences were determined with generalized linear mixed models adjusted for gestational weight gain and socioeconomic status. RESULTS:Of the 699 children who participated at a mean age of 5.6 years, 295 (42.2%) were exposed to GDM. There was no difference in the risk of being overweight or obese in children exposed to GDM compared with those unexposed (adjusted relative risk [95% CI]: 0.69 [0.44, 1.08]). Children exposed to GDM had lower body mass index z scores (adjusted relative risk [95% CI]: -0.30 [-0.53, -0.60]), enjoyment of food scores (adjusted relative risk [95% CI]: -0.17 [-0.31, -.04]), and risk of abnormal hyperactivity scores (adjusted relative risk [95% CI]: 0.23 [0.06, 0.87])] Other outcomes were similar between exposure groups. CONCLUSIONS:After accounting for confounders, children exposed to treated GDM had a risk of being overweight or obese comparable with their unexposed peers. Our findings are reassuring for parents and health practitioners caring for women who experience GDM and their children.

OBJECTIVE:This study aims to describe the trends in remission rates over 6 years of follow-up among people with gout taking urate-lowering therapy (ULT) and to identify variables that predict remission. METHODS:A post hoc analysis was conducted using data from the Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout (CARES) trial, which enrolled people with gout and cardiovascular disease randomized to febuxostat or allopurinol. Gout remission over 6 years of follow-up was measured in participants with at least 1 year of follow-up data using the simplified gout remission definition, requiring the fulfillment of three domains: (1) no gout flares during the past year, (2) at least two serum urate measurements <0.36 mmol/L during the past year, and (3) no tophus. Logistic regression was used to identify baseline predictors of remission. RESULTS:Achievement of remission increased from 37.4% of participants (1,593/4,259) at year 1 to 63.1% (322/510) at year 6. Over the 6 years, 59.4% of participants achieved remission at least once. More participants receiving febuxostat achieved remission during the first 2 years, primarily because of a higher number achieving the serum urate remission domain. In multivariable analysis, baseline age, race, greater disease severity, presence of comorbidities, and febuxostat treatment were variables significantly associated with remission. CONCLUSION:On ULT, fulfillment of remission increases over time and remission can be achieved in most patients. Baseline predictors, including demographics, comorbidities, and disease severity, may be useful to identify people with gout who need more proactive management to achieve remission.

Importance Neonatal protein intake following very preterm birth has long lasting effects on brain development. However, it is uncertain whether these effects are associated with improved or impaired brain maturation. Objective To assess the association of neonatal protein intake following very preterm birth with brain structure at 7 years of age. Design, Setting, and Participants This cohort study involved children born very preterm before or after a change in neonatal intensive care unit nutritional protocol that increased protein intake at the National Women's Hospital in Auckland, New Zealand. The children completed magnetic resonance imaging (MRI) scanning at 7 years. There were 128 children who were initially eligible. MRI data were ineligible for analysis if excessive head motion or clinical brain abnormalities were present. Data were collected from July 2012 to January 2016, and data analysis took place from January 2017 to March 2024. Exposure Neonatal intensive care unit nutritional protocol. Those who were born before the protocol change took place (July 2005 to December 2006) were in the old protocol group, while those who were born after the protocol change (January 2007 to October 2008) were in the new protocol group. Observers were blind to participant grouping. Main Outcomes and Measures All actual enteral and parenteral intakes of protein, fat, energy, and breast milk for days 1 to 7 and days 1 to 14, and growth velocity to postnatal day 28 were calculated for each infant. Preplanned outcomes were group comparisons between regional brain volumes and diffusion parameters of major white matter tracts along with analyses with both groups combined exploring associations of nutrition with brain metrics. Results Data from 99 children were analyzed, including 42 in the old protocol group (26 female [55%]; mean [SD] gestational age at birth, 27 [2] weeks) and 57 in the new protocol group (27 female [47%]; mean [SD] gestational age at birth, 26 [2] weeks). Protein intake differed between the groups at both 7 days (old protocol: mean [SD] intake, 17 [2] g/kg(-1); new protocol: mean [SD] intake, 21 [2] g/kg(-1)) and 14 days after birth (old protocol: mean [SD] intake, 41 [6] g/kg(-1); new protocol: mean [SD] intake, 45 [7] g/kg(-1)). The new protocol group had smaller brain volume as a percentage of intercranial volume than the old protocol group (mean [SD], 80% [4%] vs 86% [7%]) but absolute brain volumes were similar. The new protocol group had significantly thinner lateral occipital and lateral parietal cortices than the old protocol group. With both groups combined, those with greater protein, fat, energy, and breast milk intake had more mature diffusion tensor metrics (higher fractional anisotropy and less diffusion) across multiple tracts, although this finding did not reach statistical significance for every tract. Conclusions and Relevance In this cohort of children born very preterm, children with greater neonatal protein intake had a more mature profile of brain metrics assessed with MRI at 7 years of age. These results contribute to the ongoing evaluation of optimal nutrition for infants born very preterm and suggest that the protein intake experienced by the new protocol group may promote brain maturation in a way that is still observable at 7 years of age.

Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero ( F 1 ) and in the second generation ( F 2 ). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation ( F 2 ) of Auckland Steroid Trial (AST) participants. In the AST, women ( F 0 ) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children ( F 1 ) were 50 years old, they and their children ( F 2 ) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F 2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F 2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean ( SD ) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

OBJECTIVES:This study compared the costs of tight with less tight glycemic targets in the management of gestational diabetes using data from the TARGET trial. METHODS:The TARGET trial included women with gestational diabetes from 10 District Health Boards in New Zealand. This economic evaluation assessed 2 glycemic control strategies: tight versus less tight targets. Data on healthcare resource use, including antenatal care, birth outcomes, and hospital stay, were collected and analyzed to identify cost differences. The analysis was conducted from the perspective of New Zealand's public healthcare system. The primary analysis adjusted for gestational age at the time of oral glucose tolerance test; additional analyses accounted for additional maternal and clinical factors. RESULTS:There were no significant differences in total healthcare costs between the 2 glycemic target groups. After adjusting for gestational age at the time of oral glucose tolerance test, the mean difference in combined maternal and infant costs was $203 (95% CI 1074 to 1479, P = .76). Further adjustment for additional confounders showed a cost difference of -$59 (95% CI: -1318 to 1200; P = .93). Although total combined costs were slightly lower in the tight glycemic group, patterns of resource use varied, particularly in antenatal care and birth outcomes. CONCLUSIONS:Tight glycemic control in gestational diabetes care does not result in higher healthcare costs. However, variations in resource use and birth outcomes warrant further investigation to optimize glycemic control strategies. Future research should explore the long-term impact of different glycemic targets and consider patient-centered outcomes to guide cost-effective policy decisions.

BACKGROUND:Punctate white matter injury on brain magnetic resonance imaging (MRI) is described in very preterm infants (< 32 weeks' gestation) and is predictive of poorer developmental outcomes. The reliability of scoring and the incidence and evolution of white matter injury in moderate-late preterm infants is unknown. OBJECTIVE:To assess inter-observer variability in white matter injury using a published scoring system (UCSF system), and to describe changes over time in moderate-late preterm infants. MATERIALS AND METHODS:Infants born between 32 + 0 and 36 + 6 weeks' gestation in the Auckland region underwent MRI scans as soon as clinically feasible after birth and again at term-equivalent age. De-identified scans were scored independently by two observers. White matter injury was graded as minimal (< 3 lesions measuring < 2 mm), moderate (> 3 lesions or lesions > 2 mm), or severe (> 5% hemispheric involvement). Scores were compared between reviewers using weighted and unweighted kappa statistics interpreted using Cohen's criteria. Incidences were compared between scans using generalised estimating equations. RESULTS:Scans of 101 infants were assessed. Inter-observer agreement was near perfect for the presence of white matter injury (k = 0.88 and 0.81 for the first and second scan respectively), and for the severity of white matter injury was near perfect at the first scan (k = 0.85) and substantial at the second scan (k = 0.80). The incidence of white matter injury detected by the two observers decreased between the first and second scans (30% to 22% and 29% to 19%), and severity also decreased. CONCLUSIONS:This scoring system can be reliably applied in moderate-late preterm infants. White matter injury is common in moderate-late preterm infants but may be underestimated when MRI is performed close to term-equivalent age.

BackgroundFor the follow-up of participants in randomised trials, data linkage is thought a more cost-efficient method for assessing outcomes. However, researchers often encounter technical and budgetary challenges. Data requests often require a significant amount of information from researchers, and can take several years to process. This study aimed to determine the feasibility, direct costs and the total time required to access administrative datasets for assessment of outcomes in a follow-up study of two randomised trials.MethodsWe applied to access administrative datasets from New Zealand government agencies. All actions of study team members, along with their corresponding dates, were recorded prospectively for accessing data from each agency. Team members estimated the average time they spent on each action, and invoices from agencies were recorded. Additionally, we compared the estimated costs and time required for data linkage with those for obtaining self-reported questionnaires and conducting in-person assessments.ResultsEight agencies were approached to supply data, of which seven gave approval. The time from first enquiry to receiving an initial dataset ranged from 96 to 854 days. For 859 participants, the estimated time required to obtain outcome data from agencies was 1,530 min; to obtain completed self-reported questionnaires was 11,025 min; and to complete in-person assessments was 77,310 min. The estimated total costs were 20,827 NZD for data linkage, 11,735 NZD for self-reported questionnaires, and 116,085 NZD for in-person assessments. Using this data, we estimate that for a cohort of 100 participants, the costs would be similar for data linkage and in-person assessments. For a cohort of 5,000 participants, we estimate that costs would be similar for data linkage and questionnaires, but ten-fold higher for in-person assessments.ConclusionsObtaining administrative datasets demands a substantial amount of time and effort. However, data linkage is a feasible method for outcome ascertainment in follow-up studies in New Zealand. For large cohorts, data linkage is likely to be less costly, whereas for small cohorts, in-person assessment has similar costs but is likely to be faster and allows direct assessment of outcomes.

BACKGROUND Zoledronate prevents fractures in older women when administered every 12 to 18 months, but its effects on bone density and bone turnover persist beyond 5 years. Whether infrequent zoledronate administration would prevent vertebral fractures in early postmenopausal women is unknown. METHODS We conducted a 10-year, prospective, double-blind, randomized, placebo-controlled trial involving early postmenopausal women (50 to 60 years of age) with bone mineral density T scores lower than 0 and higher than -2.5 (scores of -1 or higher typically indicate normal bone mineral density) at the lumbar spine, femoral neck, or hip. Participants were randomly assigned to receive an infusion of zoledronate at a dose of 5 mg at baseline and at 5 years (zoledronate-zoledronate group), zoledronate at a dose of 5 mg at baseline and placebo at 5 years (zoledronate-placebo group), or placebo at both baseline and 5 years (placebo-placebo group). Spinal radiographs were obtained at baseline, 5 years, and 10 years. The primary end point was morphometric vertebral fracture, which was assessed semiquantitatively and defined as at least a 20% change in vertebral height from that seen on the baseline radiograph. Secondary end points were fragility fracture, any fracture, and major osteoporotic fracture. RESULTS Of 1054 women with a mean age of 56.0 years at baseline, 1003 (95.2%) completed 10 years of follow-up. A new morphometric fracture occurred in 22 women (6.3%) in the zoledronate-zoledronate group, in 23 women (6.6%) in the zoledronate-placebo group, and in 39 women (11.1%) in the placebo-placebo group (relative risk, zoledronate-zoledronate vs. placebo-placebo, 0.56 [95% confidence interval {CI}, 0.34 to 0.92; P=0.04]; and zoledronate-placebo vs. placebo-placebo, 0.59 [95% CI, 0.36 to 0.97; P=0.08]). The relative risk of fragility fracture, any fracture, and major osteoporotic fracture was 0.72 (95% CI, 0.55 to 0.93), 0.70 (95% CI, 0.56 to 0.88), and 0.60 (95% CI, 0.42 to 0.86), respectively, when zoledronate-zoledronate was compared with placebo-placebo and 0.79 (95% CI, 0.61 to 1.02), 0.77 (95% CI, 0.62 to 0.97), and 0.71 (95% CI, 0.51 to 0.99), respectively, when zoledronate-placebo was compared with placebo-placebo. CONCLUSIONS Ten years after trial initiation, zoledronate administered at baseline and 5 years was effective in preventing morphometric vertebral fracture in early postmenopausal women.

There is limited high-quality evidence about perinatal mental health among women with gestational diabetes. We aimed to assess the risks and longitudinal changes in anxiety, depression, and health-related quality of life comparing women with gestational diabetes and those without among a contemporary cohort of pregnant women. Prospective cohort study of participants in the GEMS Trial. Women with a singleton pregnancy were eligible if they had a 75-g diagnostic oral glucose-tolerance test between 24 and 32 weeks’ gestation, provided written informed consent, and completed questionnaires about anxiety, depression, and health-related quality of life at the study time points. There were no differences in risk for anxiety (RR 1.13, 95

Background: Ensuring clinical trial participants are representative of the target population is important for the generalizability of trial findings. This study aimed to determine if phase 3 clinical trials of gout medications approved by the US Food and Drug Administration (FDA) included participants representative of the US general population with gout. Methods: Gout therapeutics were identified by searching the FDA and CenterWatch websites. Data from phase 3 clinical trials of FDA approved gout medications between 2009 and 2023 were analyzed. Demographic variables (sex, age, and ethnicity) and comorbidities (hypertension, myocardial infarction, heart failure, nephrolithiasis, chronic kidney disease, BMI >= 30 kg/m2, and diabetes) were extracted and compared with published data from the 2007-2008 and 2015-2016 US National Health and Nutrition Examination Survey (NHANES). Data were pooled using a random effects model and presented as a percentage with a 95 % confidence interval. Results: Twelve phase 3 clinical trials were included, covering febuxostat, colchicine, pegloticase, lesinurad, and canakinumab. Compared to the NHANES gout population, clinical trials over-represented men, younger individuals, and White ethnicity participants. Under-representation was observed for clinical trial participants with hypertension, prior myocardial infarction, nephrolithiasis, and diabetes, while those with a BMI >= 30 kg/m2 were over-represented. Conclusions: FDA approved gout medication trials since 2009 have not enrolled a study population that is representative of the US general population with gout, particularly regarding age, ethnicity, and cardiometabolic comorbidities. For broader applicability, future phase 3 trials should ensure the greater inclusion of women, older individuals, diverse ethnicities, and those with common gout-associated comorbid conditions.

OBJECTIVES:In gout, MSU crystal deposition occurs preferentially within certain joints, particularly the first MTP joint. The aim of this study was to map the distribution of MSU crystals within the MTP joints in people with tophaceous gout. METHODS:Bilateral foot dual-energy CT (DECT) scans of 119 people with tophaceous gout were analysed. Each quadrant (dorsal, plantar, medial and lateral) of the metatarsal head and phalangeal base was scored independently by two trained readers for MSU crystal deposition (9696 sites scored). MSU crystal deposition was considered present if crystals were in contact with or directly adjacent (within 1 mm) to bone or cartilage. Data were analysed using general estimating equations. RESULTS:MSU crystal deposition was most frequent at the medial quadrant of the first metatarsal head (60%) followed by the plantar quadrants of the first and second metatarsal heads and medial quadrant of the first phalangeal base (all >30%). The phalangeal bases of the third and fourth MTP joints were rarely affected, particularly the lateral quadrants (1%). Across all joints, there was more MSU crystal deposition at the first MTP joint compared with other joints, at the metatarsal head compared with the phalangeal base, and at the plantar and medial quadrants compared with other quadrants (P < 0.0001 for all comparisons). CONCLUSION:In people with tophaceous gout, MSU crystal deposition is unevenly distributed. There is marked variation in sites of deposition not only between different MTP joints, but also within these joints.