老年大鼠松质骨骨重建的组织形态计量学研究

目的：研究老年大鼠及在促骨合成药前列腺素E2（PGE2）作用下松质骨骨重建和骨建造的形态计量学改变，探讨动物骨重建形态学新参数测量方法及其意义。方法：50只20月龄雄性Wistar大鼠随机分成5组，年龄对照组（基础组、10d和30d年龄对照组），PGE2给药组（分别10d和30d给予3mg/kg/d处理组）。用体内双荧光标记，不脱钙组织切片，粘合线（cement line）染色，骨组织形态计量学方法，测定骨重建和骨建造参数。结果：20月龄雄性大鼠胫骨近端松质骨的形成表面大多数为骨重建单位（占63．3％），少部分为骨建造单位（占26．7％）；PGE2用药后骨重建单位增加1．5倍，骨建造单位增加4倍，比值倒置，成骨细胞10d时明显增多。说明PGE2通过刺激成骨细胞骨合成而介民导骨建造性骨增加和骨重建性骨量增加，并以前为主。结论：老年雄性大鼠 松质骨以骨重建活动为主，仍有骨建造活动。PGE2主要通过刺激成骨细胞骨建造而增加骨量。     

The Basis of Racial Differences in the Incidence of Thyroid Cancer

Background The incidence of thyroid cancer in black Americans is half that in white Americans. It is unknown whether this gap represents a population difference in disease or is attributable to inferior cancer screening in the black population. Methods A population-based cohort study of 53,990 patients (1973–2003) was performed using the National Cancer Institute’s Surveillance Epidemiology End Results database. Socioeconomic variables were explored using the Healthcare Cost and Utilization Project database and macroeconomic data. Results Since 1973, thyroid cancer incidence among whites has increased 150.2% (4.0 to 9.9 of 100,000), while incidence among blacks has increased 73.2% (3.0 to 5.1 of 100,000). Across 17 regions, the incidence correlated with the percentage of the population with health insurance (r = 0.56, P = .02). Regression analysis suggested that half of the black-white incidence gap might be attributable to differences in health insurance status. Patients with thyroid cancer were more likely to be insured or reside in wealthier ZIP codes. Black patients were more likely to present at advanced age (RR 1.08, P < .0001) and with tumors >4 cm in size (RR 1.13, P <.0001). Black patients were slightly less likely to present with advanced disease (RR 0.96, P = .0008). Cancer-specific mortality was identical in the two populations. Discussion Sociodemographic data and differences at presentation support a small detection disparity in thyroid cancer, which may contribute to part of the incidence gap. However, this effect is not sufficiently strong to fully explain the incidence gap. A population difference in the incidence of disease may be coexistent.     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Haemorrhagic complications of pancreaticoduodenectomy

BACKGROUND: Haemorrhagic complication occurs in 5-16% of patients following pancreaticoduodenectomy (PD). We report an analysis of patients with post-PD bleed, to identify predictors of bleed, predictors of survival following bleed and the management of post-PD bleed. METHODS: Two hundred and eighteen patients with periampullary cancers underwent PD from 1989 to 2002. Forty-four (20.2%) patients had a bleeding complication. Of these, 25 patients had an intra-abdominal (IA) bleed and 21 had gastrointestinal (GI) bleed (two had both IA and GI bleed). Clinical, biochemical and tumour characteristics were analysed to identify factors influencing bleeding complications. RESULTS: The median time to presentation was 4.5 days (0-21 days). Serum bilirubin (P = 0.000, OR: 1.090) and pancreaticojejunostomy (PJ) leak (P = 0.009, OR: 3.174) were significant independent factors predicting bleeding complications. Forty-three per cent of patients each had early bleed (<48 h after PD) or delayed bleed (7 days after PD). Comparison of early and late bleeds showed that IA bleed (P = 0.02) presented as early bleeds. Male sex (P = 0.00) longer duration of jaundice (P = 0.02), PJ leak (P = 0.001), HJ leak (P = 0.001), duct to mucosa type of PJ anastomosis (P = 0.03) and IA abscess (P = 0.00) were associated with a significantly higher incidence of late bleeds. Overall mortality after PD was 9.6% with 34% and 3% in bleeders and non-bleeders, respectively. Septicaemia (P = 0.01, OR: 5.49), and acute renal failure (P = 0.01) were associated with increased mortality. CONCLUSIONS: Bleeding complications following PD were seen in one-fifth of patients and were associated with high mortality. Serum bilirubin levels and PJ leak were significant factors associated with bleeding complications. Septicaemia and acute renal failure were significant factors associated with mortality in the bleeders.     

Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

Cost-effectiveness Analysis for Technology Acquisition

Background

In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology.

Methods

The present study analysed cost-effectiveness of an “In-house” magnetic resonance imaging (MRI) scan facility of a large service hospital against outsourcing possibilities. Cost per unit scan was calculated by operating costing method and break-even volume was calculated. Then life-cycle cost analysis was performed to enable total cost visibility of the MRI scan in both “In-house” and “outsourcing of facility” configuration. Finally, cost-effectiveness analysis was performed to identify the more acceptable decision option.

Result

Total cost for performing unit MRI scan was found to be Rs 3,875 for scans without contrast and Rs 4,129 with contrast. On life-cycle cost analysis, net present value (NPV) of the “In-house” configuration was found to be Rs-(4,09,06,265) while that of “outsourcing of facility” configuration was Rs-(5,70,23,315). Subsequently, cost-effectiveness analysis across eight Figures of Merit showed the “In-house” facility to be the more acceptable option for the system.

Conclusion

Every decision for acquiring high-end technology must be subjected to life-cycle cost analysis.Key Words: Technology assessment, Cost benefit analysis, Cost-effectiveness analysis     

Cost-effectiveness analysis for technology acquisition

Background: In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology.