Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46,XY DSD and 48 with 46,XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46,XY DSD. In patients with 46,XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes.

OBJECTIVE: To study the MiniMed Advanced Hybrid Closed-Loop (AHCL) system, which includes an algorithm with individualized basal target set points, automated correction bolus function, and improved Auto Mode stability. RESEARCH DESIGN AND METHODS: This dual-center, randomized, open-label, two-sequence crossover study in automated-insulin-delivery–naive participants with type 1 diabetes (aged 7–80 years) compared AHCL to sensor-augmented pump therapy with predictive low glucose management (SAP + PLGM). Each study phase was 4 weeks, preceded by a 2- to 4-week run-in and separated by a 2-week washout. RESULTS: The study was completed by 59 of 60 people (mean age 23.3 ± 14.4 years). Time in target range (TIR) 3.9–10 mmol/L (70–180 mg/dL) favored AHCL over SAP + PLGM (70.4 ± 8.1% vs. 57.9 ± 11.7%) by 12.5 ± 8.5% (P < 0.001), with greater improvement overnight (18.8 ± 12.9%, P < 0.001). All age-groups (children [7–13 years], adolescents [14–21 years], and adults [>22 years]) demonstrated improvement, with adolescents showing the largest improvement (14.4 ± 8.4%). Mean sensor glucose (SG) at run-in was 9.3 ± 0.9 mmol/L (167 ± 16.2 mg/dL) and improved with AHCL (8.5 ± 0.7 mmol/L [153 ± 12.6 mg/dL], P < 0.001), but deteriorated during PLGM (9.5 ± 1.1 mmol/L [17 ± 19.8 mg/dL], P < 0.001). TIR was optimal when the algorithm set point was 5.6 mmol/L (100 mg/dL) compared with 6.7 mmol/L (120 mg/dL), 72.0 ± 7.9% vs. 64.6 ± 6.9%, respectively, with no additional hypoglycemia. Auto Mode was active 96.4 ± 4.0% of the time. The percentage of hypoglycemia at baseline (<3.9 mmol/L [70 mg/dL] and ≤3.0 mmol/L [54 mg/dL]) was 3.1 ± 2.1% and 0.5 ± 0.6%, respectively. During AHCL, the percentage time at <3.9 mmol/L (70 mg/dL) improved to 2.1 ± 1.4% (P = 0.034) and was statistically but not clinically reduced for ≤3.0 mmol/L (54 mg/dL) (0.5 ± 0.5%; P = 0.025). There was one episode of mild diabetic ketoacidosis attributed to an infusion set failure in combination with an intercurrent illness, which occurred during the SAP + PLGM arm. CONCLUSIONS: AHCL with automated correction bolus demonstrated significant improvement in glucose control compared with SAP + PLGM. A lower algorithm SG set point during AHCL resulted in greater TIR, with no increase in hypoglycemia.

Puréed foods are typically used as first foods for infants, with gradual exposure to more varied textures over time. Finger foods may be consumed but do not usually represent a large proportion of the diet until later in the complementary feeding period.^1-3 Baby-led weaning (BLW) is an alternative approach to introducing solid foods in which infants feed themselves all their food from the start of complementary feeding (approximately 6 months of age).^4,5 Proposed advantages include improved energy self-regulation (ability to respond appropriately to appetite and satiety cues),⁶ leading to improved body weight⁷ and reduced food fussiness.⁴ However, concerns have been raised that children may not eat enough, particularly if self-feeding skills are poor.^8-10

In 2002, the World Health Organization recommended that the age for starting complementary feeding should be changed from 4 to 6 months of age to 6 months. Although this change in age has generated substantial debate, surprisingly little attention has been paid to whether advice on how to introduce complementary foods should also be changed. It has been proposed that by 6 months of age most infants will have developed sufficient motor skills to be able to feed themselves rather than needing to be spoon-fed by an adult. This has the potential to predispose infants to better growth by fostering better energy self-regulation, however no randomised controlled trials have been conducted to determine the benefits and risks of such a “baby-led” approach to complementary feeding. This is of particular interest given the widespread use of “Baby-Led Weaning” by parents internationally. The Baby-Led Introduction to SolidS (BLISS) study aims to assess the efficacy and acceptability of a modified version of Baby-Led Weaning that has been altered to address potential concerns with iron status, choking and growth faltering. The BLISS study will recruit 200 families from Dunedin, New Zealand, who book into the region’s only maternity hospital. Parents will be randomised into an intervention (BLISS) or control group for a 12-month intervention with further follow-up at 24 months of age. Both groups will receive the standard Well Child care provided to all parents in New Zealand. The intervention group will receive additional parent contacts (n = 8) for support and education on BLISS from before birth to 12 months of age. Outcomes of interest include body mass index at 12 months of age (primary outcome), energy self-regulation, iron and zinc intake and status, diet quality, choking, growth faltering and acceptability to parents. This study is expected to provide insight into the feasibility of a baby-led approach to complementary feeding and the extent to which this method of feeding affects infant body weight, diet quality and iron and zinc status. Results of this study will provide important information for health care professionals, parents and health policy makers. Australian New Zealand Clinical Trials Registry ACTRN12612001133820 .

Aims: We aimed to conduct a systematic review and meta‐analysis of randomised controlled clinical trials (RCTs) assessing separately and together the effect of the three distinct categories of continuous glucose monitoring (CGM) systems (adjunctive, non‐adjunctive and intermittently‐scanned CGM [isCGM]), compared with traditional capillary glucose monitoring, on HbA1c and CGM metrics.Methods: PubMed, Web of Science, Scopus and Cochrane Central register of clinical trials were searched. Inclusion criteria were as follows: randomised controlled trials; participants with type 1 diabetes of any age and insulin regimen; investigating CGM and isCGM compared with traditional capillary glucose monitoring; and reporting glycaemic outcomes of HbA1c and/or time‐in‐range (TIR). Glycaemic outcomes were extracted post‐intervention and expressed as mean differences and 95%CIs between treatment and comparator groups. Results were pooled using a random‐effects meta‐analysis. Risk of bias was assessed using the Cochrane Rob2 tool.Results: This systematic review was conducted between January and April 2021; it included 22 RCTs (15 adjunctive, 5 non‐adjunctive, and 2 isCGM)). The overall analysis of the pooled three categories showed a statistically significant absolute improvement in HbA1c percentage points (mean difference (95% CI): −0.22% [−0.31 to −0.14], I² = 79%) for intervention compared with comparator and was strongest for adjunctive CGM (−0.26% [−0.36, −0.16]). Overall TIR (absolute change) increased by 5.4% (3.5 to 7.2), I² = 71% for CGM intervention compared with comparator and was strongest with non‐adjunctive CGM (6.0% [2.3, 9.7]).Conclusions: For individuals with T1D, use of CGM was beneficial for impacting glycaemic outcomes including HbA1c, TIR and time‐below‐range (TBR). Glycaemic improvement appeared greater for TIR for newer non‐adjunctive CGM technology.