Regression From Early GDM to Normal Glucose Tolerance and Adverse Pregnancy Outcomes in the Treatment of Booking Gestational Diabetes Mellitus Study.

OBJECTIVE: To compare pregnancy outcomes among women with a normal oral glucose tolerance test (OGTT) before 20 weeks' gestation (early) and at 24-28 weeks' gestation (late) (no gestational diabetes mellitus, or No-GDM), those with early GDM randomized to observation with a subsequent normal OGTT (GDM-Regression), and those with GDM on both occasions (GDM-Maintained). RESEARCH DESIGN AND METHODS: Women at <20 weeks' gestation with GDM risk factors who were recruited for a randomized controlled early GDM treatment trial were included. Women with treated early GDM and late GDM (according to the World Health Organization's 2013 criteria) were excluded from this analysis. Logistic regression compared pregnancy outcomes. RESULTS: GDM-Regression (n = 121) group risk factor profiles and OGTT results generally fell between the No-GDM (n = 2,218) and GDM-Maintained (n = 254) groups, with adjusted incidences of pregnancy complications similar between the GDM-Regression and No-GDM groups. CONCLUSIONS: Women with early GDM but normal OGTT at 24-28 weeks' gestation had pregnancy outcomes that were similar to those of individuals without GDM. Identifying early GDM likely to regress would allow treatment to be avoided.

Perinatal Outcomes in Early and Late Gestational Diabetes Mellitus After Treatment From 24-28 Weeks' Gestation: A TOBOGM Secondary Analysis.

OBJECTIVE: In most gestational diabetes mellitus (GDM) studies, cohorts have included women combined into study populations without regard to whether hyperglycemia was present earlier in pregnancy. In this study we sought to compare perinatal outcomes between groups: women with early GDM (EGDM group: diagnosis before 20 weeks but no treatment until 24-28 weeks if GDM still present), with late GDM (LGDM group: present only at 24-28 weeks), and with normoglycemia at 24-28 weeks (control subjects). RESEARCH DESIGN AND METHODS: This is a secondary analysis of a randomized controlled treatment trial where we studied, among women with risk factors, early (<20 weeks' gestation) GDM defined according to World Health Organization 2013 criteria. Those receiving early treatment for GDM treatment were excluded. GDM was treated if present at 24-28 weeks. The primary outcome was a composite of birth before 37 weeks' gestation, birth weight ≥4,500 g, birth trauma, neonatal respiratory distress, phototherapy, stillbirth/neonatal death, and shoulder dystocia. Comparisons included adjustment for age, ethnicity, BMI, site, smoking, primigravity, and education. RESULTS: Women with EGDM (n = 254) and LGDM (n = 467) had shorter pregnancy duration than control subjects (n = 2,339). BMI was lowest with LGDM. The composite was increased with EGDM (odds ratio [OR] 1.59, 95% CI 1.18-2.12)) but not LGDM (OR 1.19, 95% CI 0.94-1.50). Induction of labor was higher in both GDM groups. In comparisons with control subjects there were higher birth centile, higher preterm birth rate, and higher rate of neonatal jaundice for the EGDM group (but not the LGDM group). The greatest need for insulin and/or metformin was with EGDM. CONCLUSIONS: Adverse perinatal outcomes were increased with EGDM despite treatment from 24-28 weeks' gestation, suggesting the need to initiate treatment early, and more aggressively, to reduce the effects of exposure to the more severe maternal hyperglycemia from early pregnancy.

PsyNBIOsis: Investigating the Association between Maternal Gestational Diabetes, Mental Health, Diet and Childhood Obesity Risk: Protocol for a Prospective, Longitudinal, Observational Study.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with poorer maternal mental health (depression and anxiety). Maternal mental health and GDM are likely to influence diet, which in turn impacts the course of GDM. Maternal diet may also be directly or indirectly associated with changes in infant anthropometry. The aims of this study are to (1) examine the associations between maternal GDM, mental health and diet, and (2) evaluate the associations between these maternal factors, breastmilk composition and infant anthropometry. METHODS: This prospective, observational, longitudinal cohort study compares a cohort of women with and without GDM. Maternal mental health and diet are assessed using validated questionnaires. Breastmilk composition is measured with the Human Milk Analyzer, and infant body composition is measured with air displacement plethysmography. SIGNIFICANCE AND IMPACT: Once data have been collected, PsyNBIOsis will provide evidence for the associations between maternal mental health, GDM status and diet, and their impact on breastmilk composition and early infant growth. The results may inform the Developmental Origins of Health and Disease framework and provide data on which to build cost-effective interventions to prevent both the development of mental health issues in mothers and adverse growth patterns in infants.

Maternal diabetes independent of BMI is associated with altered accretion of adipose tissue in large for gestational age fetuses.

AIM: To analyse the effects of maternal diabetes mellitus (DM) and body mass Index (BMI) on central and peripheral fat accretion of large for gestational age (LGA) offspring. METHODS: This retrospective study included LGA fetuses (n = 595) with ultrasound scans at early (19.23 ± 0.68 weeks), mid (28.98 ± 1.62 weeks) and late (36.20 ± 1.59 weeks) stages of adipogenesis and measured abdominal (AFT) and mid-thigh (TFT) fat as surrogates for central and peripheral adiposity. Women were categorised according to BMI and DM status [pre-gestational (P-DM; n = 59), insulin managed (I-GDM; n = 132) and diet managed gestational diabetes (D-GDM; n = 29)]. Analysis of variance and linear regressions were applied. RESULTS: AFT and TFT did not differ significantly between BMI categories (normal, overweight and obese). In contrast, AFT was significantly higher in pregnancies affected by D-GDM compared to non-DM pregnancies from mid stage (0.44 mm difference, p = 0.002) and for all DM categories in late stage of adipogenesis (≥ 0.49 mm difference, p < 0.008). Late stage TFT accretion was higher than controls for P-DM and I-GDM but not for D-GDM (0.67 mm difference, p < 0.001; 0.49 mm difference, p = 0.001, 0.56 mm difference, p = 0.22 respectively). In comparison to the early non-DM group with an AFT to TFT ratio of 1.07, the I-GDM group ratio was 1.25 (p < 0.001), which normalised by 28 weeks becoming similar to control ratios. CONCLUSIONS: DM, independent of BMI, was associated with higher abdominal and mid-thigh fat accretion in fetuses. Use of insulin improved central to peripheral fat ratios in fetuses of GDM mothers.

Hyperglycaemia in early pregnancy: the Treatment of Booking Gestational diabetes Mellitus (TOBOGM) study. A randomised controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) causes adverse pregnancy outcomes that can be averted by treatment from 24-28 weeks' gestation. Assessing and treating women for overt diabetes in pregnancy (ODIP) at the first antenatal clinic booking is now recommended in international guidelines. As a consequence, women with milder hyperglycaemia are being diagnosed and treated for early GDM, but randomised controlled trial (RCTs) assessing the benefits and harms of such treatment have not been undertaken. The Treatment Of Booking Gestational diabetes Mellitus (TOBOGM) study is a multi-centre RCT examining whether diagnosing and treating GDM diagnosed at booking improves pregnancy outcomes. Methods and analysis: 4000 adult pregnant women (< 20 weeks' gestation) at risk of ODIP will be recruited from 12 hospital antenatal booking clinics and referred for an oral glucose tolerance test (OGTT). 800 women with hyperglycaemia (ie, booking GDM) according to the 2014 Australasian Diabetes-in-Pregnancy Society criteria for pregnant women at 24-28 weeks' gestation will be randomised to immediate treatment for GDM (intervention) or to no treatment (control), pending the results of a second OGTT at 24-28 weeks' gestation. Antenatal and GDM care will otherwise follow local guidelines. Randomisation will be stratified by site and OGTT glycaemic risk strata. The primary pregnancy outcome is a composite of respiratory distress, phototherapy, birth trauma, birth before 37 weeks' gestation, stillbirth or death, shoulder dystocia, and birthweight ≥ 4.5 kg. The primary neonatal outcome is neonatal lean body mass. The primary maternal outcome is pre-eclampsia. Ethics approval: South Western Sydney Local Health District Research and Ethics Office (reference, 15/LPOOL/551). Dissemination of results: Peer-reviewed publications, scientific meetings, collaboration with research groups undertaking comparable studies, discussions with guideline groups and policy makers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000924459.

Preconception care and contraceptive use among Australian women with diabetes mellitus

Background and objective: Effective contraception is important for pregnancy planning and reducing adverse pregnancy outcomes in women with diabetes mellitus (DM). The aim of this study was to explore preconception care practices and contraception use among women with DM. Methods: The study used a cross-sectional structured questionnaire to survey women with DM aged 16­49 years in Nepean Blue Mountains Local Health District (NBMLHD), a Western Sydney tertiary referral centre. Results: A total of 107 of 215 (49.7%) women completed the questionnaire. While 80.4% were aware of DM-related pregnancy risks, preconception advice was reported by only 46.8% of the 47 previously or currently pregnant women. Most women had used condoms (87.2%) and/or the combined oral contraceptive pill (74.4%). Many did not know if intrauterine contraception (61.7%) or contraceptive implants (43.7%) were safe in DM. Discussion: Despite being aware of the risks of DM in pregnancy, less than half of the women had sought preconception care, and many had poor knowledge of the most reliable contraceptive methods.

Single nucleotide polymorphism 1623 A/G (rs180195) in the promoter of the Thyroglobulin gene is associated with autoimmune thyroid disease but not with thyroid ophthalmopathy.

BACKGROUND: Our studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves' ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored. METHODS: We identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of TG gene associated with autoimmune thyroid disorders. We genotyped the TG SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls. RESULTS: We showed that variant 1623 A/G SNP (rs180195) in the promoter of TG gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto's thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of TG gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity. CONCLUSION: rs180195 SNP was previously identified by Stefan et al independently of us, who showed that this TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, "Graves' disease" or "Hashimoto's disease", but separate autoimmune disorders.

Stimulants for the Control of Hedonic Appetite.

The focus of this paper is treatment of obesity in relation to the management of hedonic appetite. Obesity is a complex condition which may be potentiated by excessive reward seeking in combination with executive functioning deficits that impair cognitive control of behavior. Stimulant medications address both reward deficiency and enhance motivation, as well as suppressing appetite. They have long been recognized to be effective for treating obesity. However, stimulants can be abused for their euphoric effect. They induce euphoria via the same neural pathway that underlies their therapeutic effect in obesity. For this reason they have generally not been endorsed for use in obesity. Among the stimulants, only phentermine (either alone or in combination with topiramate) and bupropion (which has stimulant-like properties and is used in combination with naltrexone), are approved by the United States Food and Drug Administration (FDA) for obesity, although dexamphetamine and methylpenidate are approved and widely used for treating attention deficit hyperactivity disorder (ADHD) in adults and children. Experience gained over many years in the treatment of ADHD demonstrates that with careful dose titration, stimulants can be used safely. In obesity, improvement in mood and executive functioning could assist with the lifestyle changes necessary for weight control, acting synergistically with appetite suppression. The obesity crisis has reached the stage that strong consideration should be given to adequate utilization of this effective and inexpensive class of drug.

General practitioner understanding of abbreviations used in hospital discharge letters.

OBJECTIVES: To determine the incidence of abbreviation use in electronic hospital discharge letters (eDLs) and general practitioner understanding of abbreviations used in eDLsDesign, setting and participants: Retrospective audit of abbreviation use in 200 sequential eDLs was conducted at Nepean Hospital, Sydney, a tertiary referral centre, from 18 December to 31 December 2012. The 15 most commonly used abbreviations and five clinically important abbreviations were identified from the audit. A survey questionnaire using these abbreviations in context was then mailed to 240 GPs in the area covered by the Nepean Blue Mountains Local Health District to determine their understanding of these abbreviations. MAIN OUTCOME MEASURES: Number of abbreviations and frequency of their use in eDLs, and GPs' understanding of abbreviations used in the survey. RESULTS: 321 abbreviations were identified in the eDL audit; 48.6% were used only once. Fifty five per cent of GPs (132) responded to the survey. No individual abbreviation was correctly interpreted by all GPs. Six abbreviations were misinterpreted by more than a quarter of GPs. These were SNT (soft non-tender), TTE (transthoracic echocardiogram), EST (exercise stress test), NKDA (no known drug allergies), CTPA (computed tomography pulmonary angiogram), ORIF (open reduction and internal fixation). These abbreviations were interpreted incorrectly by 47.0% (62), 33.3% (44), 33.3% (44) 32.6% (43), 31.1% (41) and 28.0% (37) of GPs, respectively. CONCLUSION: Abbreviations used in hospital eDLs are not well understood by the GPs who receive them. This has potential to adversely affect patient care in the transition from hospital to community care.

Piloting a new approach to the treatment of obesity using dexamphetamine.

BACKGROUND AND AIMS: There is a clear need for a new approach to the treatment of obesity, which is inexpensive and is effective for establishing lifestyle change. We conducted a pilot study to evaluate whether dexamphetamine can be used safely, combined with diet and exercise, for treating obesity. Our ultimate aim is to develop a 6-month treatment program for establishing the lifestyle changes necessary for weight control, utilizing dexamphetamine for its psychotropic effect on motivation. We viewed the anorexigenic effect as an additional advantage for promoting initial weight loss. METHODS: Obese adults were treated with dexamphetamine for 6 months (maximum of 30 mg twice daily), diet, and exercise. Weight, electrocardiogram, echocardiogram, and blood pressure were monitored. RESULTS: Twelve out of 14 completed 6 months treatment. Weight loss by intention to treat was 10.6 kg (95% CI 5.8-15.5, p < 0.001). The mean weight gain in the 6 months after ceasing dexamphetamine was 4.5 kg (95% CI 1.9-7.2, p = 0.003), leaving a mean weight loss at 12 months from baseline of 7.0 kg (95% CI -13.4 to -0.6, p = 0.03). All reported favorable increases in energy and alertness. Dose-limiting symptoms were mood changes (2) and insomnia (2). None had drug craving on ceasing dexamphetamine, and there were no cardiac complications. Among the seven women, there was a significant correlation for those who lost most weight on treatment to have the least regain in the following 6 months (r = 0.88, p = 0.009). CONCLUSION: Our treatment with dexamphetamine, diet, and exercise was well tolerated and effective for initial weight loss. Future research will focus on identifying baseline predictive variables associated with long-term weight control.

Relationship between Clinical and Immunological Features of Thyroid Autoimmunity and Ophthalmopathy during Pregnancy.

Problem. Clinical features of Graves' hyperthyroidism (GH) generally improve during pregnancy and rebound in the postpartum period. It is unclear whether the ophthalmopathy that is associated with GH and, less often, Hashimoto's thyroiditis (HT) changes in parallel with the thyroid associated antibody reactions and clinical features or runs a different course. Method of Study. We retrospectively studied 19 patients with autoimmune thyroid disease over 22 pregnancies: 9 pregnancies with GH and 13 with HT. Ophthalmopathy was defined by NOSPECS class. Results. Thyroid peroxidase (TPO) and thyroglobulin (Tg) antibody titres decreased during pregnancy and rose in the postpartum period. During pregnancy, 5 patients with GH and 4 patients with HT developed mild ophthalmopathy and two patients with GH and HT developed new upper eyelid retraction (UER). In the postpartum period, eye scores improved in 3 patients with GH and 3 with HT, remained stable in two and 5 patients, respectively, and worsened in 2 patients with GH and one with HT. Conclusions. In patients with mild to moderate eye signs associated with GH and HT, the orbital and thyroid reactions ran different courses during pregnancy. Since no patient had severe ophthalmopathy, we cannot draw definitive conclusions from this preliminary study.

A randomized controlled pilot trial comparing the impact of access to clinical endocrinology video demonstrations with access to usual revision resources on medical student performance of clinical endocrinology skills.

BACKGROUND: Demonstrating competence in clinical skills is key to course completion for medical students. Methods of providing clinical instruction that foster immediate learning and potentially serve as longer-term repositories for on-demand revision, such as online videos demonstrating competent performance of clinical skills, are increasingly being used. However, their impact on learning has been little studied. The aim of this study was to determine the value of adjunctive on-demand video-based training for clinical skills acquisition by medical students in endocrinology. METHODS: Following an endocrinology clinical tutorial program, 2nd year medical students in the pre-assessment revision period were recruited and randomized to either a set of bespoke on-line clinical skills training videos (TV), or to revision as usual (RAU). The skills demonstrated on video were history taking in diabetes mellitus (DMH), examination for diabetes lower limb complications (LLE), and examination for signs of thyroid disease (TE). Students were assessed on these clinical skills in an observed structured clinical examination two weeks after randomization. Assessors were blinded to student randomization status. RESULTS: For both diabetes related clinical skills assessment tasks, students in the TV group performed significantly better than those in the RAU group. There were no between group differences in thyroid examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to the video were rated globally as competent at the skill compared with 40% (n = 4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n = 10/12) of students randomized to the video were rated globally as competent at the skill compared with 20% (n = 2/10) of students not randomized to the video (p = 0.007). CONCLUSION: Exposure to high quality videos demonstrating clinical skills can significantly improve medical student skill performance in an observed structured clinical examination of these skills, when used as an adjunct to clinical skills face-to-face tutorials and deliberate practice of skills in a blended learning format. Video demonstrations can provide an enduring, on-demand, portable resource for revision, which can even be used at the bedside by learners. Such resources are cost-effectively scalable for large numbers of learners.

Clinical skills in junior medical officers: a comparison of self-reported confidence and observed competence.

BACKGROUND: The intern year is a key time for the acquisition of clinical skills, both procedural and cognitive. We have previously described self-reported confidence and experience for a number of clinical skills, finding high levels of confidence among Australian junior doctors. This has never been correlated with an objective measure of competence. AIMS AND HYPOTHESIS: We aimed to determine the relationship between self-reported confidence and observed competence for a number of routine, procedural clinical skills. METHODS: A group of 30 junior medical officers in their first postgraduate year (PGY1) was studied. All subjects completed a questionnaire concerning their confidence and experience in the performance of clinical skills. A competency-based assessment instrument concerning 7 common, practical, clinical skills was developed, piloted and refined. All 30 PGY1s then completed an assessment using this instrument. Comparisons were then made between the PGY1s' self-reported levels of confidence and tutors' assessments of their competence. RESULTS: A broad range of competence levels was revealed by the clinical skills assessments. There was no correlation between the PGY1s' self-ratings of confidence and their measured competencies. CONCLUSIONS: Junior medical officers in PGY1 demonstrate a broad range of competence levels for several common, practical, clinical skills, with some performing at an inadequate level. There is no relationship between their self-reported level of confidence and their formally assessed performance. This observation raises important caveats about the use of self-assessment in this group.