The effect of each of twelve mammalian lignan derivatives on the growth of human mammary tumor ZR-75-1 cells was examined. At a concentration less than 10 micrograms/ml, tumor cell growth was inhibited from 18-68%. The effect of 2,3-dibenzylbutane-1,4-diol(hattalin) was found to be strongest, inhibiting growth by 50% at a concentration (EC50) of 2.1 micrograms/ml. Hattalin inhibited membrane Na+, K(+)-ATPase of canine kidney cortex. It also inhibited the ATPase of the plasma membrane fraction from both cultured cells and a section of human breast cancer tissue at a concentration ranging from 0.5 to 2.0 mM. However, only a few percent of membrane ATPase from either ZR-75-1 cells or breast carcinoma tissue was inhibited by 2.0 mM of ouabain, suggesting that the target ATPase of hattalin was other than ouabain-sensitive ATPase. The relative incorporation of [3H]thymidine per 1 x 10(5) cells into the acid-precipitable fraction of ZR-75-1 cells was not affected by 1-50 micrograms/ml of hattalin, while a marked decrease resulted from 1-10 micrograms/ml of 5-fluorouracil (5-FU). These results suggest that the suppressive effect of hattalin on tumor cell growth may not occur through inhibition of DNA synthesis but rather partly by inhibition of the plasma membrane ATPase other than Na+ and K(+)-dependent ones.

OBJECTIVES:The Affordable Care Act established the Hospital Readmission Reduction Program (HRRP) and the Bundled Payments for Care Initiative (BPCI), which may reduce Medicare payments to hospitals. We assessed these programs' impact on hospital budget, focusing on the potential to reduce penalties via improved short-term percutaneous coronary intervention (PCI) outcomes. METHODS: A budget impact model was developed to quantify the financial penalties associated with HRRP and the difference between fee-forservice and bundled payments under BPCI for a hospital. HRRP penalties were associated with excess readmissions for patients admitted with acute myocardial infarction (AMI), pneumonia, and heart failure. The model also computed payment reductions under BPCI for all PCI patients regardless of diagnosis. An example hospital with high volume catheterization lab (1000 PCIs/year; 50% Medicare) and total Medicare DRG-based payments of $110 million/year was considered. The hospital was assumed to have excess readmission ratios at the seventy-fifth percentile for each condition. Based on recent clinical trials of stent platforms, we assumed an absolute 1% reduction in PCI-related readmission due to AMI and revascularization over 30 days following PCI. RESULTS: Total HRRP penalties for the example hospital were calculated to be $669,025, with $199,130 additional reduction in payments under BPCI. Our model projected that reducing readmission post-PCIs by 1% would reduce excess readmission ratio for patients with AMI from 1.052 to 1.037 and thus HRRP penalties by $80,975. Total cost of care for the 500 Medicare patients receiving PCI was reduced by $43,791 due to reduction of subsequent clinical events, a savings accrued by hospitals under BPCI, resulting in net hospital savings of $124,766. Achieving these savings with newer stent platforms would result in effective hospital savings of $156/stent. CONCLUSIONS: A 1% reduction in PCI-related readmissions may substantially reduce penalties under HRRP and BPCI. Such reductions may be achievable using new stent platforms.

BackgroundThe prescription of fixed-dose combinations (FDC) of antihypertensive drugs has increased rapidly since the relaxation of the prescription-term restriction.In this study, we used the opportunity of this policy change in Japan as an instrument to assess the causal impact of switching to FDC on hypertensive treatment costs.MethodsClaims data from 64 community pharmacies located in Tokyo were used to identify hypertensive patients under continuous treatment with angiotensin-receptor blockers (ARBs). Patients switching to FDC between December 2010 and April 2011 were compared to patients who did not receive FDC (control group). Changes in annual antihypertensive drug costs were compared using a difference-in-differences approach to adjust for patient characteristics and use of concomitant medication. Subpopulation analyses were also performed, taking into account pre-index treatment patterns and prescribers’ characteristics.ResultsThere were 542 patients who switched to FDC and 9664 patients in the control group. No significant differences were observed between the 2 groups, except for antihypertensive drug use patterns before the policy change and prescribers’ characteristics. The switch to FDC was associated with an annual saving of 10,420 yen (US$112.0) in antihypertensive drug costs. Approximately 20% of the FDC patients, however, switched from ARB alone, and their drug costs increased by 2376 yen (US$25.5).ConclusionsFor hypertensive patients who required ARB-based combination therapy, switching to FDC drugs had a significant cost-saving effect. However, the policy change of relaxing the prescription-term restriction could encourage aggressive treatment, i.e., switching to a combination therapy from monotherapy, regardless of medical conditions. Further research is required to evaluate the possible negative aspects of FDC drugs.

Background: Chronic pain is often difficult to treat, and many patients are not satisfied with analgesic treatment. The authors assessed patient satisfaction with oral analgesics in patients with chronic pain in Japan. Research design and methods: This was an observational cross-sectional study conducted in dispensing pharmacies. A patient satisfaction questionnaire survey was conducted in 781 patients prescribed one nonsteroidal anti-inflammatory drug (NSAID) or neuropathic pain (NeP) drug for at least 90 consecutive days. The primary endpoint was patient satisfaction with analgesics. The secondary endpoints were pain relief, activity of daily living (ADL) improvement and doctor-patient communication. Results: The proportions of patients who answered 'satisfied if anything' or better for patient satisfaction in the NSAID and NeP drug groups were 70.0% and 65.2%, respectively, whereas those of patients who answered 'satisfied' were 43.3% and 29.4%, respectively. The proportions of patients with improved pain relief, ADL improvement, and good doctor-patient communication were numerically higher than those of patients who answered 'satisfied if anything' or better. Conclusions: Approximately two-thirds of the patients were satisfied with current analgesics. Patient satisfaction with oral analgesics could be influenced by multiple factors. Clinical trial registration number: UMIN000036456.

We examined the tendencies of topical adverse effects caused by different dermatological formulations of diclofenac based on the results of our previous study. In patients with adverse effects expressed by gel (n = 64) and tape formulation (n = 174), the most common adverse effect was contact dermatitis, accounting for 59.1％ and 80.0％ , respectively. The peak month of adverse effects of the gel group was in May, and the peak month of adverse effects of the tape group was in August. We divided the subjects into two groups: elderly and young people and investigated the number of adverse effects and the relative incidence of adverse effects for each group. As a result, the incidence of the young people in the gel group was extremely high in March. In the elderly group, the adverse effects peaked in May, which suggests that they contribute to the peak of the total adverse effects in the gel group through the year. On the other hand, the incidence in the elderly group is higher than that in the young group in each month, and the peaks of incidence were in August and December in the tape group. In both the elderly and young groups, the peak of incidence by tape formulation was in August and the difference between the two groups was remarkable in December. In view of these results, the topical adverse effects of non-steroidal anti-inflammatory drug dermatological formulations could be reduced by the pharmacist providing suitable advice on medications considering the season and patient background, such as age.