Tacrolimus dosage requirements after initiation of azole antifungal therapy in pediatric thoracic organ transplantation

Azole antifungals inhibit the metabolism of tacrolimus mediated by CYP3A4. Upon initiation of azole therapy, the required dose reduction of tacrolimus is unknown. We reviewed our experience with azole antifungals in our pediatric thoracic transplant population receiving tacrolimus. Tacrolimus levels and dosage requirements were compared before and during azole therapy. Thirty-one patients received both tacrolimus and an azole antifungal (fluconazole = 9, itraconazole = 22). The tacrolimus dose was empirically reduced by approximately one-third when azole therapy was initiated. Mean tacrolimus dose requirements decreased by 68% within the first month of therapy (pre-azole: 0.27 +/- 0.14 mg/kg/day; 30 day post-azole: 0.087 +/- 0.069 mg/kg/day; p < 0.001). Despite a mean decrease in tacrolimus dose from baseline of 33, 42, and 55% on day 1, 2, and 4 of azole therapy, respectively, there was still an unintended 38% increase in tacrolimus levels during the first month of azole therapy. A calculated dose-reduction protocol of 50% on day of azole initiation, 70% on day 3, and 75% on day 14 should result in minimal mean changes in the tacrolimus levels. There was no difference in tacrolimus dose reduction between fluconazole and itraconazole groups. Azole antifungals markedly decrease tacrolimus requirements within the first few days of therapy. An initial reduction in tacrolimus dose by one-third is insufficient, and dose reduction of at least 50% upon azole initiation seems warranted. Once azole antifungal therapy is initiated, frequent therapeutic drug monitoring is required.     

A generic model for the assessment of disease epidemiology: the computational basis of DisMod II

Reliable and comparable analysis of risks to health is key for preventing disease and injury. Causal attribution of morbidity and mortality to risk factors has traditionally been conducted in the context of methodological traditions of individual risk factors, often in a limited number of settings, restricting comparability.     

52Fe for additional marrow ablation before bone marrow transplantation

The effectiveness of bone marrow transplantation (BMT) for malignant blood diseases remains limited by the inability of the preparative regimen to eliminate the disease without causing toxicity to normal organs. We have used 52Fe to deliver radiotherapy selectively to the BM. Fourteen patients with hematologic malignancies received 52Fe before a conventional BMT conditioning regimen. The median 52Fe dose was 58 mCi (range, 32 to 85 mCi). As evaluated by quantitative scanning, the median percentage of 52Fe taken up by the BM was 82% (range, 36% to 90%). This resulted in a median radiation-absorbed dose to the BM of 632 rad (range, 151 to 1,144 rad). The median uptake of 52Fe by the liver was 18% (range, 10% to 64%) and the median radiation- absorbed dose to the liver was 239 rad (range, 82 to 526 rad). The median whole body radiation-absorbed dose was 46 rad (range, 22 to 68 rad). No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The median follow-up was 8 months and three patients have relapsed. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before marrow transplantation without increasing toxicity.     

黄河流域11个地区51个干休所离退休干部认知障碍及老年痴呆危险因素分析

目的:调查兰州部队辖区黄河流域老年痴呆及认知障碍的患病率并分析其危险因素。方法:应用《长谷川智力量表》(22～30.5分为轻度异常,10.5～21.5分为痴呆前期,≤10分为痴呆期)和《临床记忆量表》(≤80分为异常),对黄河流域11个地区51个干休所16538人群中2944名60岁以上人员进行调查。采用挨家挨户一对一的的方法开展调查检测,只有2个量表评分均为异常才列为病例组,同时对一般情况、驻地海拔高度、家族遗传史、既往病史、生活习惯等5个方面30个危险因素进行调查,并应用SPSS10.0软件包将调查结果进行多元回归分析。结果:2944名受试者全部完成测试进入结果分析。①老年痴呆的患病率分别为痴呆0.71%,痴呆前期2.11%,轻度异常28.46%,总患病率为31.28%。②多元回归分析结果:脑萎缩(t=-6.304)、重大生活事件(t=-5.328)、高龄(t=-5.415)、无喝茶嗜好(t=-3.802)、脑梗死(t=-3.343)、女性(t=-2.604)、冠心病(t=2.496)、低文化程度(t=1.973)、职业(t=1.965)、高海拔地区(t=1.957)与老年痴呆相关(P均<0.05)。结论:①黄河流域老年痴呆及认知障碍发生与脑萎缩、重大生活事件、高龄、无喝茶嗜好、脑梗死、女性、冠心病、低文化程度、职业、高海拔地区等10种危险因素有关。②结果显示痴呆发病率较低,而痴呆前期及轻度异常发病率较高,所以应重视痴呆前期及轻度异常患者的干预治疗。     

The role of pancreatic venous sampling in the localization of occult insulinomas

The palpation and enucleation of occult insulinomas (less than 15 mm) can be a difficult surgical problem even with good arteriographic localization. In the authors' limited experience, confirmation of arteriographic findings by pancreatic venous sampling provided little additional localizing information. However, if arteriography is negative or equivocal, venous sampling can indicate the segment of pancreas to be "blindly" resected if the adenoma is not palpable. Venous sampling may be misleading in polyendocrine syndromes because of the frequency of multiple adenomas and variable hormone production.     

Estimating health care delivery system value for each US state and testing key associations

ObjectiveTo estimate health care systems'' value in treating major illnesses for each US state and identify system characteristics associated with value.Data sourcesAnnual condition‐specific death and incidence estimates for each US state from the Global Burden Disease 2019 Study and annual health care spending per person for each state from the National Health Expenditure Accounts.Study designUsing non‐linear meta‐stochastic frontier analysis, mortality incidence ratios for 136 major treatable illnesses were regressed separately on per capita health care spending and key covariates such as age, obesity, smoking, and educational attainment. State‐ and year‐specific inefficiency estimates were extracted for each health condition and combined to create a single estimate of health care delivery system value for each US state for each year, 1991–2014. The association between changes in health care value and changes in 23 key health care system characteristics and state policies was measured.Data collection/extraction methodsNot applicable.Principal findingsUS state with relatively high spending per person or relatively poor health‐outcomes were shown to have low health care delivery system value. New Jersey, Maryland, Florida, Arizona, and New York attained the highest value scores in 2014 (81 [95% uncertainty interval 72‐88], 80 [72‐87], 80 [71‐86], 77 [69‐84], and 77 [66‐85], respectively), after controlling for health care spending, age, obesity, smoking, physical activity, race, and educational attainment. Greater market concentration of hospitals and of insurers were associated with worse health care value (p‐value ranging from <0.01 to 0.02). Higher hospital geographic density and use were also associated with worse health care value (p‐value ranging from 0.03 to 0.05). Enrollment in Medicare Advantage HMOs was associated with better value, as was more generous Medicaid income eligibility (p‐value 0.04 and 0.01).ConclusionsSubstantial variation in the value of health care exists across states. Key health system characteristics such as market concentration and provider density were associated with value.     

World health system performance revisited: the impact of varying the relative importance of health system goals

Background

In 2002, the World Health Organization published a health system performance ranking for 191 member countries. The ranking was based on five indicators, with fixed weights common to all countries.

Methods

We investigate the feasibility and desirability of using mathematical programming techniques that allow weights to vary across countries to reflect their varying circumstances and objectives.

Results

By global distributional measures, scores and ranks are found to be not very sensitive to changes in weights, although differences can be large for individual countries.

Conclusions

Building the flexibility of variable weights into calculation of the performance index is a useful way to respond to the debates and criticisms appearing since publication of the ranking.     

玻璃体切除术治疗外伤性眼内炎62例

0　引言　外伤性眼内炎是眼外伤的常见并发症 ,对视力及眼球威协极大 .由于病原体随致伤物直接进入眼内 ,在眼内和玻璃体繁殖 ,产生剧烈炎症反应 ,对眼内组织造成严重破坏 .如不及时而有效的控制 ,终使视力丧失 ,眼球萎缩 .近年随着现代玻璃体手术的发展 ,外伤性眼内炎的治愈率明显提高 .现将我科收治的 6 2例报告如下 .1　对象和方法1 .1　对象 1 996 - 0 6 / 1 998- 0 6我院连续收治 6 2例外伤性眼内炎 ,其中男 5 0例 ,女 1 2例 ,年龄 2～ 45岁 ,平均 1 6 .5岁 .1 4岁以下儿童 38例 ,占 6 1 .3% .以致伤原因分类 :角膜穿通伤30例 ,巩膜穿…