Feeding \u3ci\u3eDrosophila\u3c/i\u3e a biotin-deficient diet for multiple generations increases stress resistance and lifespan and alters gene expression and histone biotinylation patterns

Caloric restriction increases stress resistance and lifespan in Drosophila melanogaster and other species. The roles of individual nutrients in stress resistance and longevity are largely unknown. The vitamin biotin is a potential candidate for mediating these effects, given its known roles in stress signaling and gene regulation by epigenetic mechanisms, i.e., biotinylation of histones. Here, we tested the hypothesis that prolonged culture of Drosophila on biotin-deficient medium increases stress resistance and lifespan. Flies were fed a biotin-deficient diet for multiple generations; controls were fed a biotin-normal diet. In some experiments, a third group of flies was fed a biotin-deficient diet for 12 generations and then switched to control diets for two generations to eliminate potential effects of short-term biotin deficiency. Flies fed a biotin-deficient diet exhibited a 30% increase in lifespan. This increase was associated with enhanced resistance to the DNA-damaging agent hydroxyurea and heat stress. Also, fertility increased significantly compared with biotin-normal controls. Biotinylation of histones was barely detectable in biotin-deprived flies, suggesting that epigenetic events might have contributed to effects of biotin deprivation

Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist decision- making on reimbursement

Abstract Background: XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid + oxaliplatin) have shown similar improvements in survival in patients with metastatic colorectal cancer (MCRC). A US cost-minimization study found that the two regimens had similar costs from a healthcare provider perspective but XELOX had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost-effectiveness study found XELOX had superior cost-effectiveness. This study compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in two oncology departments in Hong Kong. Methods: Cost data were collected from the medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4) from two hospitals. Drug costs, outpatient visits, hospital days and investigations were recorded and expressed as cost per patient from the healthcare provider perspective. Estimated travel and time costs were included in a societal perspective analysis. All costs were classed as either scheduled (associated with planned chemotherapy and follow-up) or unscheduled (unplanned visits or admissions and associated tests and medicines). Costs were based on government and hospital sources and expressed in US dollars (US$). Results: XELOX patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles) and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The scheduled cost per patient per cycle was$2,046 for XELOX and $2,152 for FOLFOX4, while the unscheduled cost was$240 and $421, respectively. Total treatment cost per patient was$16,609 for XELOX and $23,672 for FOLFOX4; the total cost for FOLFOX4 was 37$17,836 for XELOX and $27,455 for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4 when using full drug regimen costs, incorporating data from a US model with costs and adverse event data from their clinical trial and with the removal of oxaliplatin from both treatment arms. Capecitabine would have to cost around four times its present price in Hong Kong for the total resource cost of treatment with XELOX to equal that of FOLFOX4

Cost-analysis of XELOX and FOLFOX4 for treatment of colorectal cancer to assist decision-making on reimbursement

<p>Abstract</p> <p>Background</p> <p>XELOX (capecitabine + oxaliplatin) and FOLFOX 4 (5-FU + folinic acid + oxaliplatin) have shown similar improvements in survival in patients with metastatic colorectal cancer (MCRC). A US cost-minimization study found that the two regimens had similar costs from a healthcare provider perspective but XELOX had lower costs than FOLFOX4 from a societal perspective, while a Japanese cost-effectiveness study found XELOX had superior cost-effectiveness. This study compared the costs of XELOX and FOLFOX4 in patients with MCRC recently treated in two oncology departments in Hong Kong.</p> <p>Methods</p> <p>Cost data were collected from the medical records of 60 consecutive patients (30 received XELOX and 30 FOLFOX4) from two hospitals. Drug costs, outpatient visits, hospital days and investigations were recorded and expressed as cost per patient from the healthcare provider perspective. Estimated travel and time costs were included in a societal perspective analysis. All costs were classed as either scheduled (associated with planned chemotherapy and follow-up) or unscheduled (unplanned visits or admissions and associated tests and medicines). Costs were based on government and hospital sources and expressed in US dollars (US$).</p> <p>Results</p> <p>XELOX patients received an average of 7.3 chemotherapy cycles (of the 8 planned cycles) and FOLFOX4 patients received 9.2 cycles (of the 12 planned cycles). The scheduled cost per patient per cycle was$2,046 for XELOX and $2,152 for FOLFOX4, while the unscheduled cost was$240 and $421, respectively. Total treatment cost per patient was$16,609 for XELOX and $23,672 for FOLFOX4; the total cost for FOLFOX4 was 37$17,836 for XELOX and $27,455 for FOLFOX4. Sensitivity analyses showed XELOX was still less costly than FOLFOX4 when using full drug regimen costs, incorporating data from a US model with costs and adverse event data from their clinical trial and with the removal of oxaliplatin from both treatment arms. Capecitabine would have to cost around four times its present price in Hong Kong for the total resource cost of treatment with XELOX to equal that of FOLFOX4.</p> <p>Conclusion</p> <p>XELOX costs less than FOLFOX4 for this patient group with MCRC from both the healthcare provider and societal perspectives.</p

Feeding \u3ci\u3eDrosophila\u3c/i\u3e a biotin-deficient diet for multiple generations increases stress resistance and lifespan and alters gene expression and histone biotinylation patterns

Caloric restriction increases stress resistance and lifespan in Drosophila melanogaster and other species. The roles of individual nutrients in stress resistance and longevity are largely unknown. The vitamin biotin is a potential candidate for mediating these effects, given its known roles in stress signaling and gene regulation by epigenetic mechanisms, i.e., biotinylation of histones. Here, we tested the hypothesis that prolonged culture of Drosophila on biotin-deficient medium increases stress resistance and lifespan. Flies were fed a biotin-deficient diet for multiple generations; controls were fed a biotin-normal diet. In some experiments, a third group of flies was fed a biotin-deficient diet for 12 generations and then switched to control diets for two generations to eliminate potential effects of short-term biotin deficiency. Flies fed a biotin-deficient diet exhibited a 30% increase in lifespan. This increase was associated with enhanced resistance to the DNA-damaging agent hydroxyurea and heat stress. Also, fertility increased significantly compared with biotin-normal controls. Biotinylation of histones was barely detectable in biotin-deprived flies, suggesting that epigenetic events might have contributed to effects of biotin deprivation

Cost-Effectiveness of Apixaban versus Warfarin in Chinese Patients with Non-Valvular Atrial Fibrillation: A Real-Life and Modelling Analyses.

Many of the cost-effectiveness analyses of apixaban against warfarin focused on Western populations but Asian evidence remains less clear. The present study aims to evaluate the cost-effectiveness of apixaban against warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) from a public institutional perspective in Hong Kong.We used a Markov model incorporating 12 health state transitions, and simulated the disease progression of NVAF in 1,000 hypothetical patients treated with apixaban/warfarin. Risks of clinical events were based on the ARISTOTLE trial and were adjusted with local International Normalized Ratio control, defined as the time in therapeutic range. Real-life input for the model, including patients' demographics and clinical profiles, post-event treatment patterns, and healthcare costs, were determined by a retrospective cohort of 40,569 incident patients retrieved from a Hong Kong-wide electronic medical database. Main outcome measurements included numbers of thromboembolic and bleeding events, life years, quality-adjusted life years (QALYs) and direct healthcare cost. When comparing apixaban and warfarin, treatment with incremental cost-effectiveness ratio (ICER) less than one local GDP per capita (USD 33,534 in 2014) was defined to be cost-effective.In the lifetime simulation, fewer numbers of events were estimated for the apixaban group, resulting in reduced event-related direct medical costs. The estimated ICER of apixaban was USD 7,057 per QALY at base-case analysis and ranged from USD 1,061 to 14,867 per QALY under the 116 tested scenarios in deterministic sensitivity analysis. While in probabilistic sensitivity analysis, the probability of apixaban being the cost-effective alternative to warfarin was 96% and 98% at a willingness to pay threshold of USD 33,534 and 100,602 per QALY, respectively.Apixaban is likely to be a cost-effective alternative to warfarin for stroke prophylaxis in Chinese patients with NVAF in Hong Kong

Long-term statin adherence in patients after hospital discharge for new onset of atherosclerotic cardiovascular disease: a population-based study of real world prescriptions in Taiwan

Abstract Background Despite the recommendations of statins treatment for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), treatment adherence and persistence are still a concern. This study examined the real world practice of long-term adherence and persistence to statins treatment initiated after hospital discharge for ASCVD, and their associated factors in a nationwide cohort. Methods Post discharge statin prescriptions between 2006 and 2012 were extracted from the Taiwan National Health Insurance claims database. Good adherence, defined as proportion of days covered (PDC) ≥0.8 and mean medication possession ratio (MPR), was measured every 180-day period. Non-persistence was defined on the date patients failed to refill statin for 90 days after the end of the last prescription. Their associations with influential factors were analyzed using a generalized estimating equation and Cox’s proportional hazard model. Results There was a total of 185,252 post-discharge statin initiations (from 169,624 patients) and followed for 467,398 patient-years in the study cohort. Percentage of good adherence (mean MPR) was 71% (0.87) at 6-months; declined to 54% (0.68), 47% (0.59), and 42% (0.50) at end of year 1, 2, and 7, respectively. Persistence in statin treatment was 86, 67, 50, and 25% at 6-month, 1-, 2-, and 7-year, respectively. Comparing the statin-cohort initiated from year 2006 to 2012, 1-year persistence increased from 58 to 73%, and 1-year good adherence improved from 45 to 61%. Factors associated with sub-optimal adherence and non-persistence included: prescription by primary care clinics or non-cardiology specialties; patients’ age > 75 years; no history of previous statin use; ASCVD events with ischemic stroke diagnosis; comorbidities of renal disease, liver disease, depression, and chronic obstructive pulmonary disease. Conclusions Despite the improving trends, long-term adherence and persistence of statin treatment were suboptimal in Taiwan. Strategies to maintain statin treatment adherence and persistence need to be implemented to further enhance the positive trend

Probabilistic sensitivity analysis of apxiaban versus warfarin.

<p>Probabilistic sensitivity analysis of apxiaban versus warfarin.</p

Data sources for Markov cohort simulation.

<p>ARISTOTLE: Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; CDARS: Clinical Data Analysis and Reporting System of Hong Kong; NVAF: non-valvular atrial fibrillation.</p

Health and cost outcome estimations in base-case analysis.

<p>Health and cost outcome estimations in base-case analysis.</p