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.     

Histologic and functional aspects of the endometrium in the implantatory phase

The endometrium is receptive to an intrusive blastocyst during a limited time span, defined as the implantation window. No definite clinically applicable receptivity marker has been discovered yet. Current approaches of the endometrium are focusing on factors emerging in the implantation window or retrieved from animal or in-vitro studies. These data fail to correlate endometrial parameters with ongoing pregnancy. Morphological tools are limited by difficulties in interpretation and inter-observer variability. In recent studies, extremely deviant endometrial morphology on the day of oocyte retrieval in IVF cycles with embryo transfer has been associated with a deleterious effect on clinical pregnancy. Gene expression data have identified clusters of genes involved in the regulation of the implantation window. Ideally, future studies should link endometrial morphology and function in precisely timed biopsies, analyzing functional biological pathways in a selected endometrial target area.     

Anti-angiogenic effects of the tubulysin precursor pretubulysin and of simplified pretubulysin derivatives

BACKGROUND AND PURPOSE

The use of tubulin-binding compounds, which act in part by inhibiting tumour angiogenesis, has become an integral strategy of tumour therapy. Recently, tubulysins were identified as a novel class of natural compounds of myxobacterial origin, which inhibit tubulin polymerization. As these compounds are structurally highly complex, the search for simplified precursors [e.g. pretubulysin (Prt)] and their derivatives is mandatory to overcome supply problems hampering clinical development. We tested the anti-angiogenic efficacy of Prt and seven of its derivatives in comparison to tubulysin A (TubA).

EXPERIMENTAL APPROACH

The compounds were tested in cellular angiogenesis assays (proliferation, cytotoxicity, cell cycle, migration, chemotaxis, tube formation) and in vitro (tubulin polymerization). The efficacy of Prt was also tested in vivo in a murine subcutaneous tumour model induced with HUH7 cells; tumour size and vascularization were measured.

KEY RESULTS

The anti-angiogenic potency of all the compounds tested ran parallel to their inhibition of tubulin polymerization in vitro. Prt showed nearly the same efficacy as TubA (EC₅₀ in low nanomolar range in all cellular assays). Some modifications in the Prt molecule caused only a moderate drop in potency, while others resulted in a dramatic loss of action, providing initial insight into structure–activity relations. In vivo, Prt completely prevented tumour growth and reduced vascular density to 30%.

CONCLUSIONS AND IMPLICATIONS

Prt, a chemically accessible precursor of some tubulysins is a highly attractive anti-angiogenic compound both in vitro and in vivo. Even more simplified derivatives of this compound still retain high anti-angiogenic efficacy.