Quantile regression for the statistical analysis of immunological data with many non-detects

Background

Hemolytic uremic syndrome (HUS) leading to acute kidney failure, is a condition linked to the production of primarily Shiga toxin 2 (Stx2) by some E. coli serotypes. We have previously shown that Stx2 A subunit-specific human monoclonal antibody (HuMAb) 5C12, and B subunit-specific HuMAb 5H8 inhibit cultured cell death, and protect mice and piglets from fatal Stx2-intoxication. We have also shown that 5H8 blocks binding of Stx2 to its cell-surface receptor globotriaosyl ceramide (Gb₃), whereas Stx2 when complexed with 5C12 binds Gb₃ with higher affinity than Stx2. The mechanism by which 5C12 neutralizes Stx2 in vitro involves trapping of Stx2 in the recycling endosomes and releasing it into the extracellular environment. Because of the clinical implications associated with the formation of Stx2/antibody complexes and the potential for trapping and clearance through a severely damaged kidney associated with HUS, we investigated the likely site(s) of Stx2/antibody localization and clearance in intoxicated mice treated with antibody or placebo.

Results

Mice were injected with radiolabeled Stx2 (¹²⁵I-Stx2) 4 hours after administration of 5C12, 5H8, or phosphate buffered saline (PBS) and the sites of localization of labeled Stx2, were investigated 3, 24 and 48 hours later. The liver recorded statistically much higher concentrations of labeled Stx2 for groups receiving 5C12 and 5H8 antibodies after 3, 24 and 48?hours, as compared with the PBS group. In contrast, highest levels of labeled Stx2 were detected in the kidneys of the PBS group at all 3 sampling times. Mice receiving either of the two HuMAbs were fully protected against the lethal effect of Stx2, as compared with the fatal outcome of the control group.

Conclusions

The results suggest that HuMAbs 5C12 and 5H8 promoted hepatic accumulation and presumably clearance of toxin/antibody complexes, significantly diverting Stx2 localization in the kidneys, the target of Stx2 and the cause of HUS. This is in contrast to the fatal outcome of the control group receiving PBS. The results also confirm earlier observations that both HuMAbs are highly and equally protective against Stx2 intoxication in mice.     

Effect of surgical training course on performance of minor surgical procedures in family medicine physicians' offices: an observational study

Aim

To examine the influence of a practical surgical course on the number of minor surgical procedures performed by family physicians.

Methods

We compared the number of minor surgical procedures performed by family physicians in 59 offices in the city of Osijek and surrounding rural area, Croatia, during 12 months before and after the 40-hour practical surgical course held in September 2006 by surgeons and family medicine specialists. Minor surgical procedures taught in the course included management of ingrown toenails, abscesses/comedones, and minor wounds, anesthesia application, disinfection, use and sterilization of surgical instruments, and antibiotic treatment.

Results

The number of minor surgical procedures performed in family medicine offices almost doubled (503 vs 906 after the course, P<0.001, Wilcoxon test). The median number of abscesses/comedones treatments per physician increased from 1 to 6 (P<0.001, Wilcoxon test), the number of managed wounds increased from 111 to 217 (P<0.001, Wilcoxon test), while the number of ingrown toenail resections increased from 120 to 186 (P = 0.004, Wilcoxon test). Fifty percent of physicians did not treat patients surgically, irrespective of the training. We found no association between the number of performed procedures and age, length of employment, or location of the physician’s office (urban vs rural). However, we found that male physicians performed more surgical treatments both before and after the course (abscesses/comedones: P<0.001 and P = 0.108 respectively; ingrown toenail resections: P = 0.008 and P = 0.008 respectively; minor wounds: P = 0.030 and P<0.001; respectively).

Conclusion

Practical courses can encourage practitioners to treat the patients surgically in their offices and, thus, increase the number of services offered in primary care. Female physicians should be more encouraged to perform minor surgical procedures in their offices.Surgical problems are a part of everyday routine of a family physician. Although some of the procedures are usually performed in the office, others, such as surgical treatment of comedones, abscesses, ingrown toenails or minor wounds management, are believed to be more complicated (1-3) and are usually referred to a surgeon. In fact, there is no reason for such a practice, because the complexity of these procedures, need for specialist’s knowledge and skills, or legal aspects do not exceed family physician’s competence and technical and logistical support (4-7).Primary health care practitioners, such as family physicians, should be encouraged to offer broader range of medical services in their every day work, including surgical ones (3,7-10). However, to do so, they should be not only properly equipped, but adequately trained as well.As a lack of time or practical experience (11) and inadequate training (12) are frequently cited as reasons for not performing minor surgical procedures in family medicine offices, an obvious solution would be to include more practical surgical workshops in the program of continuous medical education of family physicians. To confirm this hypothesis, we explored the influence of a course in practical surgery on the number of minor surgical procedures performed in family medicine offices, expecting to detect a significant increase.     

The strategic management: the methodology applied by the "Centre Hospitalier Regional Universitaire"

This work is a general presentation of the "Démarche Stratégique", a strategic process applied by the "Centre Hospitalier Régional Universitaire" (CHRU) at Lille, France. The hospital management methodology relies on the strategic analysis of the best alternatives for rationalizing the hospital mission. It takes into account a competitive environment, in which it is necessary to structure health care networks based on the negotiation of inpatient care goals. The author presents the phases and main methodological tools of the approach, as well as a preliminary evaluation of its potentials.     

三维超声心动图测定机械瓣瓣口面积初步经验

观察三维超声心动图测定机械瓣瓣口面积的可行性。方法１１例机械瓣置换病例,用任意 切面（ａｎｙｐｌａｎｅ）３ＤＥ测定机械瓣瓣口有效面积,将测定值与多普勒超声心动图（ＤＥ）测定的有效瓣口面积（包括实测值和文献报道测值）及生产厂商提供的离体瓣口面积比较。