Sustaining better diabetes care in remote indigenous Australian communities*

Problem: Inhabitants of Torres Strait Islands have the highest prevalence of diabetes in Australia and many preventable complications. In 1999, a one year randomised cluster trial showed improved diabetes care processes and reduced admissions to hospital when local indigenous health workers used registers, recall and reminder systems, and basic diabetes care plans, supported by a specialist outreach service. This study looked at whether those improvements were sustained two years after the end of the trial.

Design: Three year follow up clinical audit of 21 primary healthcare centres, and review of admissions to hospital in the previous 12 months.

Background and Setting: Remote indigenous communities in far north east Australia, population about 9600, including 921 people with diabetes.

Key Measures for Improvement: Number of people on registers, care processes (regular measures of weight, blood pressure, haemoglobin A1c, urinary protein concentration, and concentrations of serum lipids and creatinine), appropriate clinical interventions (drug treatment and vaccinations), and intermediate patient outcome measures (weight, blood pressure, and glycaemic control). Admissions to hospital.

Strategies for Change: Audit and feedback to clinicians and managers; provision of clinical guidelines and a clear management structure; workshops and training.

Effects of Change: The number of people on registers increased from 555 in 1999 to 921 in 2002. Most care processes and clinical interventions improved. The proportion of people with good glycaemic control (haemoglobin A1c 7%) increased from 18% to 25% in line with increased use of insulin (from 7% to 16%). The proportion of those with well controlled hypertension (< 140/90) increased from 40% to 64%. The proportion admitted to hospital with a diabetes related condition fell from 25% to 20%. Mean weight increased from 87 kg to 91 kg.

Lessons Learnt: In remote settings, appropriate management structures and clinical support for people with diabetes can lead to improvements in care processes, control of blood pressure, and preventable complications that result in admission to hospital. Control of weight and glycaemia are more difficult and requires more active community engagement. Priorities now include increasing the availability and affordability of good food, achieving weight loss, and increasing appropriate use of hypoglycaemic agents, including insulin.

     

An amazing case of working wrist watch in the esophagus

Foreign bodies in the esophagus are commonly seen in otolaryngologic practice. We report the successful removal of a working wrist watch dial lodged for one month in the esophagus of an adult schizophrenic patient, which is a rare incident.     

Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers

Although the effects of alcohol on brain-derived neurotrophic factor (BDNF) have been extensively studied in rodents, BDNF levels have rarely been measured in abstinent, alcohol-dependent (AD) individuals. Interpretation of reported group comparisons of serum BDNF levels is difficult due to limited information regarding analytical variance, biological variability, and the relative contribution of platelet and plasma pools to serum BDNF. Analytical variance (intra- and inter-assay coefficients of variation) of the enzyme-linked immunosorbent assay (ELISA) was characterized. Within- and between-subject variability, and group differences in serum and plasma BDNF, was assessed on three separate days in 16, 4-week abstinent AD individuals (7M/9F) and 16 social drinkers (SDs; 8M/8F). Significantly higher mean (±sd) serum BDNF levels were observed for the AD group compared to the SD (p = 0.003). No significant difference in mean baseline plasma BDNF levels was observed between AD and SD groups. The low analytical variance, high day-to-day within-individual stability and the high degree of individuality demonstrates the potential clinical utility of measuring serum BDNF levels. The low correlations that we observed between plasma and serum levels are congruent with their representing separate pools of BDNF. The observation of higher basal serum BDNF in the AD group without a concomitant elevation in plasma BDNF levels indicates that the elevated serum BDNF in AD patients is not due to greater BDNF exposure. Further research is warranted to fully elucidate mechanisms underlying this alteration and determine the utility of serum BDNF as a predictor or surrogate marker of chronic alcohol abuse.     

Adaptive optics imaging of the retina

Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) meetings. In total, 261 relevant publications and 389 conference abstracts were identified.     

Frequent Alterations of MCPH1 and ATM are Associated with Primary Breast Carcinoma: Clinical and Prognostic Implications

Background

MCPH1 is a proximal regulator of DNA damage response pathway that is involved in recruitment of phosphorylated ATM to double-stranded DNA breaks.

Methods

To understand the importance of MCPH1 and ATM in deregulation of DNA damage response pathway in breast carcinoma, we studied m-RNA expression and genetic/epigenetic alterations of these genes in primary breast carcinoma samples.

Results

Our study revealed reduced expression (mRNA/protein) and high alterations (deletion/methylation) (96 %, 121 of 126) of MCPH1 and ATM. Mutation was, however, rare in inactivation of MCPH1. In immunohistochemical analysis, reduced protein expression of MCPH1, ATM and p-ATM were concordant with their molecular alterations (P = 0.03–0.01). Alterations of MCPH1 and deletion of ATM were significantly high in estrogen/progesterone receptor–negative than estrogen/progesterone receptor–positive breast carcinoma samples compared to early or late age of onset tumors, indicating differences in pathogenesis of the molecular subtypes (P = 0.004–0.01). These genes also showed differential association with tumor stage, grade and lymph node status in different subtypes of breast carcinoma (P = 0.00001–0.01). Their coalterations showed significant association with tumor progression and prognosis (P = 0.003–0.05). Interestingly, patients with alterations of these genes or MCPH1 alone had poor outcome after treatment with DNA-interacting drugs and/or radiation (P = 0.01–0.05).

Conclusions

Inactivation of MCPH1-ATM-associated DNA damage response pathway might have an important role in the development of breast carcinoma with diagnostic, prognostic and therapeutic implications.