Gestational diabetes mellitus: From consensus to action on screening and treatment

The 1998 consensus guidelines on the management of gestational diabetes mellitus from the Australasian Diabetes in Pregnancy Society emphasised that, “due to a lack of good quality randomised controlled clinical trials in the area of [gestational diabetes mellitus], these guidelines are based on what is a reasonable consensus of informed opinion in Australasia”.1 The clear benefits of treating women with gestational diabetes according to these guidelines have now been demonstrated by the Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS).2 This study randomised 1000 women with gestational diabetes to either routine antenatal care or to an intervention that comprised home glucose monitoring, review by a diabetes educator, dietitian and physician, and insulin therapy if glycaemic targets were not met. Serious adverse perinatal outcomes occurred in 1% of the intervention group versus 4% of the routine-care group (adjusted relative risk, 0.33 [95% CI, 0.14–0.75]). The percentage of infants who were large for gestational age was lower in the intervention group (13% v 22%), with no increase in those who were small for gestational age. Although induction of labour was more common in the intervention group (39% v 29%), rates of caesarean delivery were similar (around 31%). Measures of maternal quality of life were more favourable in the intervention group. To prevent one serious perinatal outcome, 34 women needed to be treated. The 1998 guidelines were equivocal in regard to screening for gestational diabetes, allowing either for universal screening or for selective screening based on clinical risk factors in relatively lowrisk populations. In the light of the findings of ACHOIS, we believe that universal screening should now be accepted and implemented.

Expression of the iron regulatory peptide hepcidin is reduced in patients with chronic liver disease

Disturbances in iron metabolism often accompany liver disease in humans and hepatic iron deposition is a frequent finding. Since the peptide hepcidin, a major regulator of body iron homeostasis, is synthesised in the liver, alterations in hepcidin expression could be responsible for these effects. To investigate this possibility, we studied hepcidin expression in liver biopsies from patients with hepatitis C virus (HCV) infection, non-alcoholic fatty liver disease (NAFLD) and hemochromatosis (HC). Total RNA was extracted from the liver tissue of 24 HCV, 17 NASH and 5 HC patients, and 17 liver transplant donors (controls). The levels of mRNA for hepcidin and several other molecules involved in iron metabolism (DMT1, Dcytb, hephaestin, ferroportin, TfR1, TfR2, HFE and HJV) were examined by ribonuclease protection assay and expressed relative to the housekeeping gene GAPDH. The expression of hepcidin was significantly decreased in HCV and NASH patients relative to control liver (109±16 and 200±44 versus 325±26 respectively; P=0.008 and 0.02). We have previously reported similar findings in patients with HC, and this was confirmed in the current analysis (176±21; P=0.003). In both HCV and NAFLD patients the expression of the iron reductase Dcytb and the transferrin binding regulatory molecule TfR2 was also decreased, while the cellular iron exporter ferroportin showed a significant increase. Levels of the mRNA for the iron oxidase hephaestin were lower in HCV patients alone, while expression of the major transferrin binding molecule TfR1 was decreased only in NAFLD patients. Of particular interest was the finding that the expression of HJV (which is mutated in patients with juvenile HC) was significantly increased in NAFLD patients. No changes were seen in the expression of the iron importer DMT1 or the regulatory molecule HFE. Decreased expression of hepcidin in patients with HCV and NAFLD provides an explanation why iron homeostasis could be perturbed in these disorders. Reduced hepcidin levels would increase intestinal iron absorption and iron release from macrophages, which could contribute to hepatic iron accumulation. This in turn could lead to alterations in the expression of various proteins involved in iron transport and its regulation. Indeed most of the changes in the expression of such molecules observed in this study are consistent with this. However, the mechanisms leading to changes in the expression of hepcidin in these diseases remain to be elucidated.

Long-Term Pharmacotherapy for Obesity in Elderly Patients A Retrospective Evaluation of Medical Records from a Specialized Obesity Outpatient Clinic

Background: Obesity is a serious chronic disease and the prevalence of this condition is increasing among the elderly. Although the benefits of weight loss to improve control of associated diseases are well known in young adults, they are not in older patients. The use of anti-obesity drugs to promote weight loss is widespread in Brazil and other countries, and obesity specialists frequently prescribe medicines in doses and for durations previously unreported in the literature. Sibutramine, orlistat and amfepramone (diethylpropion) have been evaluated in clinical trials of more than 2 years` duration in adults, demonstrating safety and efficacy, but long-term studies in obesity treatment are absent for other drugs. The efficacy and safety of obesity pharmacotherapy among the elderly is unknown. Objective: To describe the experience of obesity pharmacotherapy in the elderly in a specialized obesity care setting in Brazil, with a focus on efficacy and safety. Methods: A retrospective evaluation was conducted on medical charts from an outpatient clinic of a specialized tertiary centre for the treatment of obesity. We included patients who had had at least one consultation between January and December 2007, were aged >= 60 years at the beginning of the treatment, had had at least 6 months of follow-up and had received a prescription of at least one potential weight-loss drug. Diagnoses reported on medical records were documented. Age, weight, height and body mass index (BMI) were recorded at admission, after 6, 12, 18 and 24 months, and at the last available visit. The medicines prescribed, together with the dose, duration of use, adverse effects and reasons for discontinuation, were documented. Results: The group consisted of 44 women (86%) and 7 men (14%), with a mean +/- SD age of 65.2 +/- 4.5 years, weight of 95.3 +/- 12.5 kg and BMI of 38.5 +/- 4.3 kg/m(2). The mean +/- SD time of follow-up was 39.3 +/- 26.4 months, and the mean weight loss was 6.65 kg (p < 0.01). After the first 6 months, the mean +/- SD weight loss was 5.7 +/- 3.8 kg (p < 0.0001). A smaller weight loss was seen between the 6th and 12th months, with no statistically significant change in weight thereafter. A weight loss of >= 5% was achieved by 64.71%, 63.64%, 62.16% and 69.70% in the 6th, 12th, 18th and 24th months, respectively, and a weight loss of >= 10% was achieved by 17.65%, 34.09%, 32.43% and 39.39% in the 6th, 12th, 18th and 24th months, respectively. The medicines prescribed were sibutramine, orlistat, fluoxetine, sertraline, topiramate, fenproporex, mazindol and amfepramone, alone or in combinations, concomitantly or sequentially. The reasons for discontinuation were lack of response (n = 13), loss of response (development of tolerance) [n= 11], lack of adherence (n = 14) and adverse effects (n= 14). One episode of atrial flutter occurred in a patient taking fenproporex. The weight-loss medications were generally well tolerated, and only transient adverse events were reported. Conclusions: Long-term pharmacotherapy for obesity was effective and well tolerated by this group of elderly patients.

"Futuristic medical education"

The Australian National Medical Education Colloquium provided a productive forum for medical educators to meet and to discuss and debate important contemporary issues affecting Australian medical schools. None of us know what the future will hold, and some of the possibilities discussed at the Colloquium were futuristic indeed. We would be wise to keep an open mind, to focus very much on competence and fitness to practice, and to develop a strong evidence base, as we travel this important path.

Investigation on Brazilian Clinical Practices in Rheumatoid Arthritis The Brazilian Rheumatoid Arthritis Clinical Practices Investigation-BRACTICE

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease causing significant social, medical, and economic impact. Several therapeutic regimens are available within the medical arsenal. The rational and reasoned use of various medications approved for their treatment is imperative. This study aimed to evaluate how Brazilian rheumatologists use the drugs available to combat the disease. For this, 128 Brazilian rheumatologists from public and private health services responded to an 18-item questionnaire, sent over the Internet, about different situations of drug treatment of RA. The answers helped to confirm the trends among Brazilian rheumatologists in the drug treatment of RA. The study results have shown that most Brazilian rheumatologists follow the guidelines and consensus established by the Brazilian Society of Rheumatology for the treatment of RA. A small proportion, however, start the biologic therapy in early stages of the disease, including the very early stage, as the first treatment option. Most experts use corticosteroids in low doses early in the treatment. Conclusions: This study confirms that the majority but not all Brazilian rheumatologists follow, in their daily practice, established guidelines and consensus for the treatment of RA. However, it also shows that some few rheumatologists start with anti-tumor necrosis factor therapy in very early arthritis independently of disease severity or prognostic factors.

CR3 (CD11b/CD18) activation of nasal neutrophils: a measure of upper airway endotoxin exposure

Inhaled endotoxin (lipopolysaccharide, LPS) initiates an inflammatory response and leads to the expression of CR3 (CD11b/CD18) receptors on polymorphonuclear leukocytes (PMNs). We determined if PMN activation in nasal lavage fluid (NLF) is a possible biomarker of occupational endotoxin exposure. Seven subjects exposed to endotoxin provided NLF samples that were split into three aliquots (negative control - 1 M nicotinamide; sham; positive control - 11 eta g of exogenous LPS) and PMN activation was measured using a chemiluminometer. Differences in mean PMN activation were apparent, negative control: 548 +/- 15.65 RLU 100 mu l(-1); sham: 11469 +/- 2582 RLU 100 mu l(-1); positive control: 42026 +/- 16659 RLU 100 mu l (n = 7; p < 0.05). This technique shows promise as a diagnostic method for measuring upper airway LPS exposure.

The Society of Thoracic Surgeons Expert Consensus for the Surgical Treatment of Hyperhidrosis

Significant controversies surround the optimal treatment of primary hyperhidrosis of the hands, axillae, feet, and face. The world`s literature on hyperhidrosis from 1991 to 2009 was obtained through PubMed. There were 1,097 published articles, of which 102 were clinical trials. Twelve were randomized clinical trials and 90 were nonrandomized comparative studies. After review and discussion by task force members of The Society of Thoracic Surgeons` General Thoracic Workforce, expert consensus was reached from which specific treatment strategies are suggested. These studies suggest that primary hyperhidrosis of the extremities, axillae or face is best treated by endoscopic thoracic sympathectomy (ETS). Interruption of the sympathetic chain can be achieved either by electrocautery or clipping. An international nomenclature should be adopted that refers to the rib levels (R) instead of the vertebral level at which the nerve is interrupted, and how the chain is interrupted, along with systematic pre and postoperative assessments of sweating pattern, intensity and quality-of-life. The recent body of literature suggests that the highest success rates occur when interruption is performed at the top of R3 or the top of R4 for palmar-only hyperhidrosis. R4 may offer a lower incidence of compensatory hyperhidrosis but moister hands. For palmar and axillary, palmar, axillary and pedal and for axillary-only hyperhidrosis interruptions at R4 and R5 are recommended. The top of R3 is best for craniofacial hyperhidrosis. (Ann Thorac Surg 2011;91:1642-8) (C) 2011 by The Society of Thoracic Surgeons

Sex, Clinical Symptoms, and Angiographic Findings in Patients With Diabetes Mellitus and Coronary Artery Disease (from the Bypass Angioplasty Revascularization Investigation [BARI] 2 Diabetes Trial)

Previous studies have reported differences in presenting symptoms and angiographic characteristics between women and men undergoing evaluation for suspected coronary artery disease (CAD). We examined the relation between symptoms and extent of CAD in patients with type 2 diabetes mellitus and known CAD enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. Of 1,775 patients (533 women, 30%, and 1,242 men, 70%), women were more likely than men to have angina (65% vs 56%, p < 0.001) or an atypical angina/anginal equivalent (71% vs 58%, p < 0.001). More women reported unstable angina (17% vs 13%, p = 0.047) or were in a higher Canadian Cardiology Society class compared to men (Canadian Cardiology Society classes II to IV 78% vs 68%, p = 0.002). Fewer women than men had no symptoms (14% vs 22%, p < 0.001). Women had a lower mean myocardial jeopardy index (42.5 +/- 24.3 vs 47.9 +/- 24.3, p < 0.001), smaller number of total significant lesions (2.3 +/- 17 1.7 vs 2.7 +/- 1.8, p < 0.001), and fewer jeopardized left ventricular regions (p < 0.001 for distribution) or long-term occlusions (29% vs 42%, p < 0.001). After adjustment for relevant covariates, the odds of having CAD symptoms were still higher in women than men (odds ratio for angina 1.31, 95% confidence interval 1.02 to 1.69; odds ratio for atypical angina 1.52, 95% confidence interval 1.17 to 1.96). In conclusion, in a high-risk group of patients with known CAD and diabetes mellitus, women were more symptomatic than men but had less obstructive CAD. These data suggest that factors other than epicardial CAD severity influence symptom presentation in women in this population. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:980-985)

Increased Transactivation Associated with SOX3 Polyalanine Tract Deletion in a Patient with Hypopituitarism

Backgound and Aims: Correct gene dosage of SOX3 is critical for the development of the hypothalamo-pituitary axis. Both overdosage of SOX3, as a result of gene duplication, and loss of function resulting from expansion of the first polyalanine (PA) tract are associated with variable degrees of hypopituitarism, with or without mental retardation. The aim of this study was to further investigate the contribution of SOX3 in the etiology of hypopituitarism and the mechanisms involved in the phenotypic variability. Methods: We screened 154 patients with congenital hypopituitarism and an undescended posterior pituitary for mutations in SOX3 and variability in the length of the first PA tract. In addition, 300 patients with variable septooptic dysplasia were screened for variability of the PA tract. Results: We report a novel 18-base pair deletion (p.A243_A248del6, del6PA) in a female patient with hypopituitarism resulting in a 2-fold increase in transcriptional activation in vitro, compared with wild-type SOX3. We also identified a previously reported seven-alanine expansion (p.A240_A241ins7, +7PA) in two male siblings with isolated GH deficiency and a distinct phenotype, in addition to the nonsynonymous variant p.R5Q in an unrelated individual; this appears to have no functional effect on the protein. In contrast to +7PA, del6PA maintained its ability to repress beta-catenin mediated transcription in vitro. Conclusion: This is the first study to report that PA tract deletions associated with hypopituitarism have functional consequences in vitro, possibly due to increased activation of SOX3 target genes. In addition, we have expanded the phenotypic spectrum associated with PA tract expansion (+7PA) mutations to include panhypopituitarism or isolated GH deficiency, with or without mental retardation. (J Clin Endocrinol Metab 96: E685-E690, 2011)

Infection rate and risk factors associated with infections related to external ventricular drain

To describe incidence rates and risk factors associated with external ventricular drain (EVD)-related infections at a tertiary Brazilian teaching hospital. The patient cohort consisted of all patients at a major teaching hospital in Brazil with an EVD during the period 1 April 2007 to 30 June 2008 (15 months). Patients were followed up for 30 days after catheter removal. According to the Center for Diseases Control and Prevention criteria for meningitis/ventriculitis, all of the central nervous system (CNS) infections that occurred during this period could be considered to be meningitis or ventriculitis related to EVD placement. Infection rates were calculated using different denominators, such as (1) per patient (incidence), (2) per procedure, and (3) per 1,000 catheter-days (drain-associated infection rate). Patient demographic data, medical history of underlying diseases, antibiotic prophylaxis usage, American Society of Anesthesiologists Score classification, duration of surgery and hospitalization, length of time the EVD was in place, and overall mortality were evaluated during the study period. A logistic regression model was developed to identify factors associated with infection. A total of 119 patients, 130 EVD procedures, and 839 catheter-days were evaluated. The incidence of infection was 18.3%, the infection rate was 16.9% per procedure, and the drain-associated infection rate was 22.4 per 1,000 catheter-days; 77% of the infections were caused by Gram-negative micro-organisms. Only 75% of patients received antibiotic prophylaxis. The infection rate increased with length of the hospital stay. The length of time the catheter was in place was the only independent risk factor associated with infection (p = 0.0369). The incidence of EVD-related infections is high in our hospital, Gram-negative micro-organisms were the most frequent causal agents identified and length of time that the catheter was in place contributed to the infection rate.

DEVELOPING THE INTERNATIONAL SOCIETY OF PHYSICAL AND REHABILITATION MEDICINE (ISPRM): FOLLOWING THROUGH

In 2008 the International Society of Physical and Rehabilitation Medicine (ISPRM) started an initiative to systematically develop its capacity and its internal and external policy agenda. This paper sums up achievements that have been made with this ISPRM initiative as well as pending issues and strategies to address them. The paper treats the following: ISPRM`s policy agenda in collaboration with the World Health Organization (WHO), research capacity in functioning and rehabilitation, ISPRM world conferences, relationships with regional societies of Physical and Rehabilitation Medicine (PRM), and ISPRM`s membership and governance structure.