ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine.

Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment. These polymorphisms influenced baseline BMI in males (p=0.009 and 0.054, B1 and C1, respectively), changes in BMI in males after 3 (p=0.026, ABCB1) and 12 months (p=0.022, ABCC1) of CZ treatment, and level of diastolic pressure (p=0.002 and 0.051, respectively). The combination of ABCB1 + ABCC1 homozygote SNPs was associated with increased CZ and norclozapine serum levels (p=0.054 and 0.010, respectively). ABC transporter SNPs could be potential biomarkers for CZ-induced weight gain and cardiovascular complications. Further pharmacogenetic research is warranted to help clinicians with their treatment decision, including concomitant use of drugs and prevention of side effects.

Coordinated care versus standard care in hospital admissions of people with chronic illness: a randomised controlled trial.

OBJECTIVE: To determine whether Care Navigation (CN), a nurse-led hospital-based coordinated care intervention, reduced the use of hospital services and improved quality of life for patients with chronic illness. DESIGN: Randomised controlled trial; participants were allocated to CN or standard care. PARTICIPANTS AND SETTING: Patients with chronic illness presenting to the emergency department of Nepean Hospital, Sydney, New South Wales. High-risk status for an unplanned admission was defined as i) three or more unplanned hospital admissions in 12 months for patients aged ≥ 70 or at least one admission for cardiac or respiratory disease in patients aged 16-69 years; or ii) judged by a CN nurse to be high risk and likely to benefit. MAIN OUTCOME MEASURES: Numbers of re-presentations or readmissions, quality of life, time to re-presentation, readmission or death, length of stay, and access to hospital and community health services. RESULTS: 500 participants were randomised between May 2010 and February 2011; 359 by previous unplanned admission and 141 by clinical impression. The CN group received more community health services (rate ratio, 1.94; 95% CI, 1.35-2.81; P < 0.001) than participants receiving standard care; however, this did not result in statistically significant differences in number of re-presentations (rate ratio, 0.83; 95% CI, 0.68-1.01; P = 0.07), number of readmissions (rate ratio, 0.85; 95% CI, 0.70-1.04; P = 0.11), quality of life at 24 months (mean difference, 0; 95% CI, - 0.10 to 0.09, P = 0.93), or other measures. CONCLUSIONS: CN did not improve quality of life or reduce unplanned hospital presentations or admissions despite community health services almost doubling. Future service development should explore potential benefits of linking navigated intrahospital care to ongoing, proactive care planning and delivery in the community. TRIAL REGISTRATION: ACTRN12609000554268.

Effect of prehospital triage on revascularization times, left ventricular function, and survival in patients with ST-elevation myocardial infarction.

Shorter reperfusion times lead to better outcomes in patients with ST-elevation myocardial infarction (STEMI). We assessed the efficacy of prehospital triage with bypass of community hospitals and early activation of the cardiac catheterization team on revascularization times, left ventricular (LV) ejection fraction, and survival. Patients with STEMI (624) were divided into 3 groups determined by site of triage: ambulance field triage (163), interventional center emergency department (202), and 3 community hospital emergency departments (259). Compared with community hospital and interventional center triages, ambulance field triage resulted in a significant median decrease in door-to-balloon times of 68 and 27 minutes, respectively (p <0.001). LV ejection fraction was highest in the field triage group (52 +/- 13%) compared with the interventional center (49 +/- 12%) and community hospital (48 +/- 12%, p = 0.017) groups. Thirty-day mortality was lowest in the ambulance field group (3%) compared with the interventional facility (11%) and community hospital (4%, p = 0.007) groups. There was a significant difference in long-term survival with up to 30-month follow-up among the 3 triage groups (p = 0.041). With time-dependent Cox regression modeling the difference in survival was significant only during the first week after STEMI (p = 0.020). Every extra minute of symptom onset to reperfusion time was associated with a relative risk of long-term mortality of 1.003 (95% confidence interval 1.000 to 1.006, p = 0.027). In conclusion, field triage of patient with STEMI decreased revascularization times, which preserved LV function, and improved early survival.

Implementing and sustaining transformational change in health care: lessons learnt about clinical process redesign.

*Clinical process redesign has enabled significant improvements in the delivery of health care services in emergency departments and elective surgery programs in New South Wales and at Flinders Medical Centre in South Australia, with tangible benefits for patients and staff. *The principles used in clinical process redesign are not new; they have been applied in other industries with significant gains for many years, but have only recently been introduced into health care systems. *Through experience with clinical process redesign, we have learnt much about the factors critical to the success of implementing and sustaining this process in the health care setting. *The key elements for success are leadership by senior executives, clinical leadership, team-based problem solving, a focus on the patient journey, access to data, ambitious targets, strong performance management, and a process for maintaining improvement.

Iodine status in pregnant women and their newborns: are our babies at risk of iodine deficiency?

OBJECTIVES: To determine whether pregnant women and their newborns show evidence of iodine deficiency, and to examine the correlation between maternal urine iodine concentration (UIC) and newborn thyroid-stimulating hormone (TSH) level. DESIGN: A cross-sectional study. SETTING: Hospital antenatal care services (March-May 2004) and private obstetrician clinics (June 2004) in the Central Coast area of New South Wales. PARTICIPANTS: 815 pregnant women (> or = 28 weeks' gestation) and 824 newborns. MAIN OUTCOME MEASURES: World Health Organization/International Council for the Control of Iodine Deficiency Disorders criteria for assessing severity of iodine deficiency (recommended levels: < 20% of urine samples in a population with UIC < 50 microg/L; and < 3% of newborns with whole-blood TSH level > 5 mIU/L). RESULTS: The median UIC for pregnant women was 85 microg/L, indicating mild iodine deficiency. Almost 17% of pregnant women had a UIC < 50 microg/L, and 18 newborns (2.2%) had TSH values > 5 mIU/L. There was no statistically significant linear correlation between neonatal whole-blood TSH level and maternal UIC (r = - 0.03; P = 0.4). Mothers with a UIC < 50 microg/L were 2.6 times (relative risk = 2.65; 95% CI, 1.49-4.73; P = 0.01) more likely to have a baby with a TSH level > 5 mIU/L. CONCLUSION: The pregnant women surveyed were mildly iodine deficient. TSH values for their newborns were mostly within acceptable limits. Ongoing surveillance of the iodine status of NSW communities to establish trends over time is recommended.

Hyperglycemia: still an important predictor of adverse outcomes following AMI in the reperfusion era.

Hyperglycemia in patients admitted to hospital with myocardial infarction has been associated with adverse outcomes. However, with the improvements in survival seen in the reperfusion era, the glycometabolic state of patients presenting with acute myocardial infarction (AMI) is often given a low priority. The aim of this study was to determine if hyperglycemia remains a significant predictor of cardiac mortality and morbidity in the reperfusion era. We conducted a retrospective review of 158 patients presenting with AMI to our institution, where reperfusion therapy is routinely administered. The glucose level on admission and other risk factors were correlated against adverse cardiac outcomes. From multi-variate logistic regression analysis, admission glucose level was a consistent predictor of mortality and morbidity for all AMI patients as well as those who were reperfused. The odds ratios (OR) of in-hospital and 6-month mortality for each 1 mmol/l increment of glucose level were 1.14 (P = 0.002) and 1.18 (P < 0.001) respectively. For patients who underwent reperfusion therapy, the OR of in-hospital and 6-month mortality for each 1 mmol/l increment of glucose level were 1.27 (P = 0.001) and 1.36 (P = 0.001), respectively. We conclude that in the reperfusion era, hyperglycemia is still associated with adverse cardiac outcomes, although it is unclear whether treatment of hyperglycemia will lead to improved outcomes.