Cost-effectiveness of multidisciplinary collaborative care versus usual care in the management of high-risk patients with diabetes in Singapore: Short-term results from a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: Economic evidence of multidisciplinary collaborative care on glycaemic improvement in uncontrolled diabetic patients is limited. Therefore, the primary objective of this study was to assess the cost-effectiveness of multidisciplinary collaborative care versus usual care and the secondary objective was to assess the cost-effectiveness of these two care approaches in relation to varying glycaemic control of patients. METHODS: An economic evaluation based on a six-month randomized controlled trial involving high-risk uncontrolled diabetic Asian patients with polypharmacy and multiple comorbidities was conducted from a healthcare institution perspective. The control arm received usual care, while the intervention arm received multidisciplinary care with regular clinical pharmacist follow-up in addition to usual care. The study outcomes included glycated haemoglobin (HbA1c) change and total direct outpatient medical costs for diabetes-related care. The cost-effectiveness analyses were conducted for both arms and those stratified according to baseline HbA1c (Group 1:HbA1c 7.1%-7.9%, Group 2:HbA1c ≥8.0%). The incremental cost per glycaemic improvement (HbA1c improvement of 0.1% and above) per patient was examined followed by uncertainty evaluation via probabilistic sensitivity analyses. A range of willingness-to-pay (WTP) thresholds (US$165.21 to US$5000.00 per glycaemic improvement) was used in analysis. RESULTS AND DISCUSSION: Overall, the intervention arm had greater improvement in HbA1c (I: mean -0.4% [95% CI -0.6 to -0.2] vs C: mean -0.1% [95% CI -0.2 to 0.1]; P = .014) and lower mean total direct outpatient medical costs per patient in comparison with the control arm (I: US$516.77 ± 222.10 vs C: US$607.78 ± 268.39; P < .001). The intervention arm was the dominant strategy across varying baseline HbA1c with higher probability of Group 2 being cost-effective at higher WTP threshold. WHAT IS NEW AND CONCLUSIONS: The multidisciplinary collaborative care arm was cost-effective in managing Asian patients with varying baseline HbA1c control. The multidisciplinary collaborative care also showed greater probability of being cost-effective among Asian patients with poorly uncontrolled glycaemia.

Mediators of medication adherence and glycaemic control and their implications for direct outpatient medical costs: a cross-sectional study.

AIMS: To investigate the effects of diabetes-related distress and perception of hyperglycaemia on self-reported medication adherence and glycaemic control, as measured by HbA1c , and to compare the cost outcomes in patients with sub-optimally vs uncontrolled Type 2 diabetes mellitus. METHODS: We conducted a retrospective cross-sectional study that involved the review of a chronic disease database in Singapore. Data on clinical characteristics, diabetes-related distress, perception of hyperglycaemia, self-reported medication adherence and costs were obtained from the database. Mediation analyses were conducted using a linear regression-based approach. A final path model was built to illustrate the sequential mediating effects of diabetes-related distress and perception on the association of medication adherence and HbA1c concentration. RESULTS: Diabetes-related distress and perception of hyperglycaemia were significantly associated with medication adherence and HbA1c concentration. Mediation analyses showed a significant indirect effect of diabetes-related distress and perception of hyperglycaemia on medication adherence and HbA1c concentration. People with uncontrolled diabetes were found to incur significantly higher total direct medical costs than those with sub-optimally controlled diabetes (P = 0.034), with medication cost as the main cost driver (66.6%). CONCLUSIONS: Identifying the influence of the sequential mediating effects of distress and perception was important in understanding the pathway between medication adherence and glycaemic control. This suggests the importance of a team-based approach to address these mediators and thus improve glycaemic control. Poor glycaemic control was also found to be associated with higher direct medical costs.

Impact of pharmacist-involved collaborative care on the clinical, humanistic and cost outcomes of high-risk patients with type 2 diabetes (IMPACT): a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: With the increasing prevalence of diabetes, the physician-centred model is challenged to deliver holistic care in Asia. Diabetes may be managed effectively within a multidisciplinary collaborative care model; however, evidence on its effectiveness in Asian patients is lacking. Therefore, the primary objective was to evaluate the clinical outcomes of multidisciplinary collaborative care vs physician-centred care in diabetes. The secondary objectives were to evaluate humanistic and economic outcomes among the two types of care. METHODS: This 6-month prospective, open-label, parallel-arm, randomized, controlled study was conducted at four outpatient healthcare institutions. High-risk patients aged ≥21 years with uncontrolled type 2 diabetes, polypharmacy and comorbidities were included. Patients with type 1 diabetes or those who were unable to communicate independently were excluded. The control arm received usual care with referrals to nurses and dietitians as needed. The intervention arm (multidisciplinary collaborative care) was followed up with pharmacists regularly, in addition to receiving the usual care. The primary outcomes included HbA1c, systolic blood pressure, low-density lipoprotein and triglycerides. The secondary outcomes included scores from the Problem Areas in Diabetes (PAID) and the Diabetes Treatment Satisfaction Questionnaires (DTSQ), and diabetes-related health service utilization rates and costs. RESULTS AND DISCUSSION: Of 411 eligible patients, 214 and 197 patients were randomized into the intervention and control arms, respectively. At 6 months, 141 patients in the intervention arm (65.9%) and 189 patients in the control arm (95.9%) completed the study. Mean HbA1c reduced from 8.6%±1.5% at baseline to 8.1%±1.3% at 6 months in the intervention arm (P=.04), with up to mean HbA1c improvement of 0.8% in patients with greater levels of uncontrolled glycemia. Whereas the mean HbA1c in the control arm remained unchanged (8.5%±1.4%) throughout the 6-month period. Improvements in PAID and DTSQ scores, reduction in physician workload and an average cost savings of US$91.01 per patient were observed in the intervention arm over 6 months. WHAT IS NEW AND CONCLUSIONS: The positive clinical, humanistic and economic outcomes highlighted the value of multidisciplinary collaborative care for Asian diabetic patients, thereby supporting the effectiveness of this approach in managing chronic diseases.

YM155 down-regulates survivin and XIAP, modulates autophagy and induces autophagy-dependent DNA damage in breast cancer cells.

BACKGROUND AND PURPOSE: The aim of this study was to determine the potency and molecular mechanism of action of YM155, a first-in-class survivin inhibitor that is currently under phase I/II clinical investigations, in various drug-resistant breast cancers including the oestrogen receptor positive (ER(+) ) tamoxifen-resistant breast cancer and the caspase-3-deficient breast cancer. EXPERIMENTAL APPROACH: The potency of YM155 in SK-BR-3, MDA-MB-231, MCF7 and its tamoxifen-resistant sublines, TamR6, TamR7, TamR8, TamC3 and TamC6, were determined by MTT assay. Western blot analysis, flow cytometric analysis, reverse transcription-PCR, fluorescent microscopy and comet assay were used to determine the molecular mechanism of action of YM155 in different breast cancer cell lines. KEY RESULTS: YM155 was equally potent towards the parental ER(+) /caspase-3-deficient MCF7 breast cancer cells and its tamoxifen-resistant sublines in vitro. The ER(-) /HER2(+) SK-BR-3 breast cancer cells and the triple-negative/caspase-3-expressing metastatic aggressive MDA-MB-231 breast cancer cells were also sensitive to YM155 with IC50 values in the low nanomolar range. Targeting survivin by YM155 modulated autophagy, induced autophagy-dependent caspase-7 activation and autophagy-dependent DNA damage in breast cancer cells. Interestingly, YM155 also induced XIAP degradation and the degradation of XIAP might play an important role in YM155-induced autophagy in breast cancer cells. CONCLUSIONS AND IMPLICATIONS: YM155 is a potent survivin inhibitor that has potential for the management of various breast cancer subtypes regardless of the expression of ER, HER2 and caspase-3. Importantly, this study provides new insights into YM155's molecular mechanism of action and therapeutic potential in the treatment of tamoxifen-resistant breast cancer.