It starts from the womb: maximizing bone health.

The foundation of bone health is established in utero. Bone accrual starts from the developing fetus and continues throughout childhood and adolescence. This process is crucial to achieve peak bone mass. Understanding factors that influence bone accrual before attainment of peak bone mass is thus critical to improve bone health and prevent osteoporosis, thereby reducing the burden of osteoporotic fractures in older women. In this review, we broadly outline factors influencing peak bone mass from pregnancy to infancy, childhood and adolescence with potential diseases and medications that may affect the optimum trajectory to maximizing bone health. It is estimated that a 10% increase in peak bone mass will delay the onset of osteoporosis by 13 years in a woman.

A pilot screening study for low bone mass in Singaporean women using years since menopause and BMI.

OBJECTIVE: Current risk assessment tools for osteoporosis have inconsistent performance across different cohorts, making them difficult for clinical practice. This study aimed to evaluate a simple screening index comprising years since menopause (YSM) and body mass index (BMI) that identifies postmenopausal Singaporean women with a greater likelihood of low bone mass. METHODS: The study used data from 188 treatment-naïve postmenopausal women. The associations between low bone mass and different demographic variables, including age, YSM and BMI, were assessed using multivariable logistic regression. Diagnostic performance of the calculated screening index was compared to the Osteoporosis Self-Assessment Tool for Asians (OSTA) and the Fracture Risk Assessment Tool (FRAX®). RESULTS: YSM and BMI were significantly associated with low bone mass. The area under the receiver operating characteristic curves was 0.803 for the screening index, 0.759 for the OSTA, 0.683 for the FRAX® (major osteoporotic fracture probability [MOFP]) and 0.647 for the FRAX® (hip fracture probability [HFP]). Non-parametric Spearman's correlation between the screening index and the other models was 0.857 with the OSTA score, 0.694 with the FRAX® (HFP) and 0.565 with the FRAX® (MOFP) (p < 0.0005). CONCLUSIONS: The diagnostic performance of the screening index comprising YSM and BMI was equivalent to the OSTA and the FRAX®. A risk chart was developed for clinicians to identify and recommend subjects for a further dual-energy X-ray absorptiometry scan. Validation of this model in larger and more diverse cohorts is required.

Increased risk of strontium ranelate-related SJS/TEN is associated with HLA.

UNLABELLED: Severe adverse drug reactions (ADR) of Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) in some patients receiving strontium ranelate have been reported, but the risk factors are unclear. We show that HLA-A*33:03 and B*58:01 are significantly associated with patients who developed SJS/TEN; and provide the first evidence that genetic risk factors are involved in strontium ranelate-associated SJS/TEN. INTRODUCTION: In this study, HLA as a genetic risk factor was assessed among osteoporotic patients prescribed with strontium ranelate that developed severe cutaneous adverse drug reactions (SCARs) compared with those who were tolerant. METHODS: Genomic DNA isolated from peripheral blood mononuclear cells (PBMCs) of patients was HLA typed using sequencing-based typing method to determine their HLA profiles. RESULTS: Osteoporotic patients who are currently on strontium ranelate were enrolled in the study (n = 76). Tolerant controls were defined as patients who received strontium ranelate for a minimum of 3 months (range 3 months to 8 years) with no reports of any cutaneous reactions as these reactions usually occur within the first 12 weeks after starting treatment. Retrospective cases of SJS/TEN were also identified (n = 5). The majority of the accrued samples were of Han Chinese descent: controls (n = 72) and cases (n = 4). All cases and controls were genotyped at four HLA genes, namely HLA-A, HLA-B, HLA-C, and HLA-DRB1. In comparing the samples of Han Chinese descent (72 controls and 4 cases), we found significant associations with HLA-A*33:03 (p = 0.002) and HLA-B*58:01 (p = 0.023). There was no significant association with any HLA-C or HLA-DRB1 alleles. CONCLUSIONS: This study reveals that the occurrence of SJS/TEN in Han Chinese patients receiving strontium ranelate is HLA associated. This has important clinical implications for understanding the underlying mechanisms for this ADR as well as evaluating the potential role of genetic pre-screening for osteoporotic patients who may be prescribed strontium ranelate.

Use of emollients in atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder that has strong financial and psychosocial impacts. Its pathogenesis is related to increased transepidermal water loss due to a defective skin epidermal barrier. Emollients serve as first-line therapy during both acute flares and remission. However, their use is poorly characterized, posing therapeutic challenges to clinicians and patients. In this article, we review available evidence to provide recommendations, aiming to standardize and optimize the use of emollients in AD. Literature search was performed using Pubmed and Google. All articles were retrieved using Pubmed. Recommendations were graded based on the British Medical Journal's Grading of Recommendations Assessment, Development and Evaluation system and the American Academy of Family Physicians' Strength of Recommendation Taxonomy. Emollients should be applied post-bathing. However, the need for immediate application is debatable. The optimal frequency for application is still undetermined, but multiple applications daily are encouraged. Ideally, a balance should be achieved between patient's compliance and clinical efficacy. Emollients hold the potential to act as steroid-sparing agents, but more well-designed studies are pertinent for a definite conclusion. At present, it is recommended that 250-500 g of emollients be applied every week. Finally, primary prevention of AD by regular application of emollients in high-risk infants cannot yet be recommended.

Ministry of Health Clinical Practice Guidelines: Diabetes Mellitus.

The Ministry of Health (MOH) have updated the clinical practice guidelines on Diabetes Mellitus to provide doctors and patients in Singapore with evidence-based treatment for diabetes mellitus. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Diabetes Mellitus, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Experience with the use of the Codonics Safe Label System(™) to improve labelling compliance of anaesthesia drugs.

The Codonics Safe Labeling System(™) (http://www.codonics.com/Products/SLS/flash/) is a piece of equipment that is able to barcode scan medications, read aloud the medication and the concentration and print a label of the appropriate concentration in the appropriate colour code. We decided to test this system in our facility to identify risks, benefits and usability. Our project comprised a baseline survey (25 anaesthesia cases during which 212 syringes were prepared from 223 drugs), an observational study (47 cases with 330 syringes prepared) and a user acceptability survey. The baseline compliance with all labelling requirements was 58%. In the observational study the compliance using the Codonics system was 98.6% versus 63.8% with conventional labelling. In the user acceptability survey the majority agreed the Codonics machine was easy to use, more legible and adhered with better security than the conventional preprinted label. However, most were neutral when asked about the likelihood of flexibility and customisation and were dissatisfied with the increased workload. Our findings suggest that the Codonics labelling machine is user-friendly and it improved syringe labelling compliance in our study. However, staff need to be willing to follow proper labelling workflow rather than batch label during preparation. Future syringe labelling equipment developers need to concentrate on user interface issues to reduce human factor and workflow problems. Support logistics are also an important consideration prior to implementation of any new labelling system.

The effect of propofol on human gastric and colonic muscle contractions.

UNLABELLED: Although propofol is widely used for sedation in the intensive care unit, there are limited data on its effects on gastrointestinal motility. For that reason, we studied the in vitro effects of propofol on human gastric and colonic smooth muscle. Grossly normal human gastric and colonic muscle strips were mounted in an organ bath set-up for isometric contraction and stimulated by acetylcholine (Ach), using a cumulative dose schedule in the absence or presence of different concentrations of propofol [1.7 x 10(-6) M (0.3 microg/mL) to 4.4 x 10(-4) M (78 microg/mL)]. Ach led to concentration-dependent contraction of both gastric and colonic muscle strips, whereas propofol, at a concentration 6.7 x 10(-6) M (1.2 microg/mL) and above, significantly depressed Ach-induced contraction in a concentration-dependent manner for both smooth muscle preparations. In addition, propofol, at a concentration 2.7 x 10(-5)M (4.8 microg/mL) and above, depressed spontaneous contractile activity of both smooth muscle preparations. Fat emulsion 10% (Intralipid), the solvent for propofol, had no effect on either the spontaneous activity or the Ach-induced contraction of gastric and colonic smooth muscles. IMPLICATIONS: The success of enteral feeding requires a normal gastrointestinal motility. We found that, at clinically relevant concentrations, propofol impaired gastrointestinal contractile activity. Further investigations are required to determine the clinical significance of this change.

Anaesthesia for transmyocardial laser revascularization--initial experience with seven patients.

The introduction of transmyocardial laser revascularization for ischaemic heart disease has brought with it new challenges for anaesthetists. These include acute deterioration of cardiac function, the need for emergency cardiopulmonary bypass and difficulty weaning from haemodynamic support. Recurrent arrhythmias can occur despite amiodarone prophylaxis. We describe our initial experience and the problems we encountered.

Specific 3H-cimetidine binding to receptors in the submandibular gland of the rat.

Recent studies indicate that the secretagogue action of histamine on the salivary gland is mediated via H2-receptors. In this study we attempt to characterize the histamine H2-receptors in the submandibular gland of the rat. The results show the presence of a specific 3H-cimetidine binding site in the gland. However, the binding constants of this site are not fully characteristic of the specific 3H-cimetidine-H2-receptor binding. They tend to indicate that the binding of 3H-cimetidine to the gland membrane is similar to the well-characterized 3H-cimetidine-imidazole-recognition-receptor binding found in the membrane of the brain, gastric mucosae and atrium of various mammalian species.