Folate Supplementation in Women with Pre-Existing Diabetes.

Folate supplementation in the periconceptual period is the standard of care for the prevention of neural tube defects. To support dietary folate intake, some countries have introduced mandatory folic acid fortification of food products. Robust evidence supports the additional use of a low-dose folic acid supplement (0.4 mg/day) in all women from 2-3 months preconception until the end of the 12th week of gestation. For women with pre-existing diabetes, high-dose folic acid supplementation (5 mg/day) is recommended in some, but not all international guidelines. The recommendation is made based on consensus opinion and reflects the increased risk of neural tube defects in pregnant women with pre-existing diabetes. However, there is limited evidence to clarify the high-risk groups that benefit from high-dose folic acid versus those that do not. There are also some data to suggest that high-dose folic acid may be harmful to mothers and offspring, although this issue remains controversial. This narrative review explores the evidence that supports the recommendation for women with pre-existing diabetes to take high-dose folic acid in the periconceptual period. It explores the potential benefits of high-dose supplemental folate beyond the prevention of neural tube defects, and also the potential adverse impacts of high-dose folate use. These topics are considered with a specific focus on the issues that are pertinent to women with pre-existing diabetes. Based on the available evidence, a pragmatic approach to the use of folic acid supplements in women with pre-existing diabetes during the periconception period is suggested. The need for comprehensive preconception care that optimises glycaemic control and addresses other modifiable risk factors before pregnancy is emphasized.

Diabetes IN hospital - Glucose and Outcomes in the COVID-19 pandemic (DINGO COVID-19): the 2020 Melbourne hospital experience prior to novel variants and vaccinations.

BACKGROUND AND AIMS: A relationship between diabetes, glucose and COVID-19 outcomes has been reported in international cohorts. This study aimed to assess the relationship between diabetes, hyperglycaemia and patient outcomes in those hospitalised with COVID-19 during the first year of the Victorian pandemic prior to novel variants and vaccinations. DESIGN, SETTING: Retrospective cohort study from March to November 2020 across five public health services in Melbourne, Australia. PARTICIPANTS: All consecutive adult patients admitted to acute wards of participating institutions during the study period with a diagnosis of COVID-19, comprising a large proportion of patients from residential care facilities and following dexamethasone becoming standard-of-care. Admissions in patients without known diabetes and without inpatient glucose testing were excluded. RESULTS: The DINGO COVID-19 cohort comprised 840 admissions. In 438 admissions (52%), there was no known diabetes or in-hospital hyperglycaemia, in 298 (35%) patients had known diabetes, and in 104 (12%) patients had hyperglycaemia without known diabetes. ICU admission was more common in those with diabetes (20%) and hyperglycaemia without diabetes (49%) than those with neither (11%, P < 0.001 for all comparisons). Mortality was higher in those with diabetes (24%) than those without diabetes or hyperglycaemia (16%, P = 0.02) but no difference between those with in-hospital hyperglycaemia and either of the other groups. On multivariable analysis, hyperglycaemia was associated with increased ICU admission (adjusted odds ratio (aOR) 6.7, 95% confidence interval (95% CI) 4.0-12, P < 0.001) and longer length of stay (aOR 173, 95% CI 11-2793, P < 0.001), while diabetes was associated with reduced ICU admission (aOR 0.55, 95% CI 0.33-0.94, P = 0.03). Neither diabetes nor hyperglycaemia was independently associated with in-hospital mortality. CONCLUSIONS: During the first year of the COVID-19 pandemic, in-hospital hyperglycaemia and known diabetes were not associated with in-hospital mortality, contrasting with published international experiences. This likely mainly relates to hyperglycaemia indicating receipt of mortality-reducing dexamethasone therapy. These differences in published experiences underscore the importance of understanding population and clinical treatment factors affecting glycaemia and COVID-19 morbidity within both local and global contexts.

Practising refraction in ophthalmology: instructive or outdated? A prospective study and literature review.

CLINICAL RELEVANCE: Many ophthalmologists preform clinical refactions, although little is known of the perceptions and practise of refraction by ophthalmologists and key barriers preventing this aspect of ophthalmic practice. BACKGROUND: Although there are numerous studies on visual acuity in ophthalmology, there is no study to date on the practice of refraction by ophthalmologists. This study evaluates the practice patterns of ophthalmologists in current practice. It specifically addresses perceptions of ophthalmologists about (a) the importance of refraction in clinical practice, and (b) barriers to performing refraction. The methodology and frequency of performing refraction by ophthalmologists is also assessed. METHODS: This cross-sectional study was conducted at the Annual Scientific Congress of the Royal Australian and New Zealand College of ophthalmologists in 2017, held in Perth, Australia. All attending ophthalmologists and ophthalmology trainees were invited to participate. Participants completed a 17-variable questionnaire on the perceptions of practitioners about refraction and their practice of it. Data were analysed using Microsoft Excel and IBM SPSS Version 24. RESULTS: At this Congress, 213 attendees completed the survey, with most being consultant general ophthalmologists (85%). Twenty-six percent of participants either 'really loved' or 'liked' refracting patients. Those who reported feeling competent with refraction were more likely to perform it themselves (p = 0.001). Individuals most commonly reported taking 3-5 minutes to refract a patient (38%). Participants under the age of 65, and participants practising paediatric ophthalmology, were more likely to perform a refraction. CONCLUSIONS: The literature indicates that this is the first study to describe the practice patterns of refraction by ophthalmologists. Although ophthalmologists found refraction important, the majority preferred patients to be refracted by others. Key barriers to ophthalmologists performing refraction included the time required to perform the refraction, a busy clinic, and the availability of alternative providers.

Prescribing Trends of Topical Glaucoma Medications in Australia From 2001 to 2017.

PRECIS: As new glaucoma treatments arise, including minimally invasive glaucoma surgeries and new classes of glaucoma medications, it is important to examine the prescription trends of current topical glaucoma medications and how they may change. PURPOSE: To determine the prescribing trends of topical glaucoma medications in Australia from 2001 to 2017. METHODS AND ANALYSIS: Pharmaceutical Benefits Scheme (PBS) item numbers were used to determine glaucoma medication prescribing rates from 2001 to 2017. All data were adjusted for population (/100,000) as per the Australian Bureau of Statistics (ABS) population data. RESULTS: Overall prescription rates for glaucoma medications ranged between 67,904 and 86,936 per 100,000 from 2001 to 2017. An upward trend was noted from 2001 to 2015, with the exception of a notable decline in 2013 by 14.7%, before then increasing by 13.7% in 2014. After 2015, prescribing rates were seen to decrease over the subsequent years in the study period. Latanoprost remained the most prescribed medication and prostaglandin the most prescribed class. Prescribing rates of single-agent beta-blockers were noted to decrease during the 17-year period, particularly with the introduction of combination agents, which note an upward trend. Brinzolamide/brimonidine has increased by 50.0% from 2016 to 2017. CONCLUSIONS: Total rates of prescriptions have remained relatively stable from 2001 to 2017. The number of medications prescribed when considering combination agents separately was seen to be increasing from 2001 to 2015. From 2015 to 2017, a downward trend was noted in the number of medications prescribed. Prostaglandins remain the most prescribed class throughout the study period.

When 'glaucomatous fields' are not glaucoma: bilateral calcarine fissure strokes masquerading as glaucoma in a normal tension glaucoma suspect.

A 78-year-old man with vascular risk factors and a family history of glaucoma presents with bilateral superior arcuate visual field loss. MRI brain was reported normal. Intraocular pressure (IOP) and optical coherence tomography of the retinal nerve fibre layer (RNFL) were within normal limits. A tentative diagnosis of normal tension glaucoma was made. Over the next 5 years, IOP remained stable without treatment, serial visual fields noted repeatable bilateral superior depressions with normal RNFL. Referral to a glaucoma subspecialist and subsequently neuro-ophthalmologist prompted repeat MRIs, which demonstrated mild small vessel ischaemia. Standard visual evoked potentials (VEPs) were normal. Multifocal VEPs identified poor response across the entire visual field in both eyes. The combination of visual defects, unremarkable RNFL and reduced multifocal VEPs raised suspicion of bilateral inferior calcarine fissure change. Retrospective review of MRI's in a multidisciplinary meeting confirmed extensive microvascular changes with bilateral inferior calcarine fissure ischaemia.

An immunohistochemical analysis of the effects of androgen receptor knock out on gubernacular differentiation in the mouse.

AIM: Cryptorchidism affects 2%-4% of newborn boys and causes infertility and cancer. While normal androgen function is required for successful inguinoscrotal descent, its exact role on gubernacular morphology remains unidentified. We aimed to decipher the effect of androgen blockade on the gubernaculum and surrounding structures. METHODS: Genetically modified mice with androgen receptor knock out (ARKO) were sectioned at ages E17, D0, and D2 for immunohistochemical analysis and D4 for morphological analysis (with ethical approval; A644). Mutants and control littermates were labeled with Ki67, Desmin, and Pax7 to identify the degree of gubernaculuar eversion and the composition of the growth center in the gubernaculum, using light or confocal microscopy. RESULTS: Androgen blockade prevented gubernacular eversion in all animals aged between E17 and D2 when compared to wild types. Furthermore, a growth center was visible, as indicated by a 'swirl' of immature fibroblasts, in D2 animals but was absent in ARKO mice. Moreover, the gubernacular cord was seen to increase in ARKO mice when compared to wild types and increased in size with age. There were no labeling differences in the antibodies tested for gubernacular differentiation. CONCLUSION: Gubernacular eversion in rodents prior to inguinoscrotal migration was androgen dependent, as well as maintenance of gubernacular cord length. This study shows that androgen blockade causes cryptorchidism in mice by preventing gubernacular eversion and possibly by preventing shortening of the gubernacular cord. Altering the morphology of the gubernaculum in response to androgen clearly contributes to the clinical problem of cryptorchidism.

Incidental prostate cancer in transurethral resection of prostate specimens in men aged up to 65 years.

BACKGROUND: The identification of prostate cancer (PC) is important in men aged ≤ 65 years. We examined complete transurethral resection of prostate (TURP) specimens to quantify the incidence and nature of PC in men aged ≤ 65 years. METHODS: A prospective multi-institutional database included TURP specimens. The cohort was stratified into two groups according to age. For men aged ≤ 65 years, the entire specimen was submitted for histological analysis, while the TURP specimens from men aged > 65 years were sampled following standard guidelines. RESULTS: A total of 923 men were included, with 224 in the younger group. PC was identified in 13.4% in men aged ≤ 65 years, compared with 28.7% the older group. The younger group had a lower proportion of Gleason score ≥ 7 (30% compared with 40%) and higher rates of pT1a (57% compared with 43%). In men aged ≤ 65 years with cancer, tumor was identified in one block in 15 of 30 cases (50%). Following diagnosis, 4/30 underwent radical prostatectomy, 5/30 underwent curative radiotherapy, 10/30 androgen deprivation, and 1/30 received palliative radiotherapy. CONCLUSION: Incidental PC in men aged ≤ 65 years is not uncommon. Our results suggest that TURP specimens in men aged ≤ 65 years should be completely assessed. Underidentification of cancer may occur as a result of increasing use of laser prostatectomy and the consequent loss of tissue for pathological examination.

Estimating glomerular filtration rate: Performance of the CKD-EPI equation over time in patients with type 2 diabetes.

AIMS: To assess the performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation at baseline and longitudinally in people with type 2 diabetes. METHODS: Adults with type 2 diabetes attending Austin Health, Melbourne, with≥3 prospective GFR measurements were included in this retrospective study. Plasma disappearance rate of DTPA (diethylene-triamine-penta-acetic acid) was used to calculate measured GFR (mGFR) and compared to estimated GFR (eGFR). The agreement between mGFR and eGFR was estimated using Intraclass Correlation Coefficient (ICC). RESULTS: 152 patients had a median of 4 (IQR: 3, 5) mGFR measurements over a period of 11years (IQR: 9, 12). The difference between mGFR and eGFR increased proportionally to the magnitude of the GFR, increasing by 0.2ml/min/1.73m(2) for every 1ml/min/1.73m(2) increase in mGFR, indicative of proportional bias. At lower mGFR levels, eGFR overestimated mGFR, and at higher mGFR levels, eGFR underestimated mGFR. There was a significant association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR. CONCLUSIONS: The CKD-EPI formula underestimates mGFR and the rate of decline of mGFR in patients with type 2 diabetes with an mGFR greater than 60ml/min/1.73m(2). The association between LDL cholesterol, triglycerides, HbA1c, diastolic blood pressure and the difference between mGFR and eGFR warrants further study.