Modifiable factors affecting inpatient violence in an acute child and adolescent psychiatric unit: A 16‐year retrospective study

Violent incidents in acute inpatient units for children and adolescents are a major and persistent problem. The demographic, clinical, and modifiable (environmental–organizational) risk factors that affect inpatient violence in an Acute Child and Adolescent Psychiatric Unit were investigated via a retrospective study. Data were collected from nursing and medical reports and the unit's census and included 100 days per year for 16 years. Incidents of violence and assault types were recorded, and variables such as the diagnostic category of assailants, total number of patients, and staffing factors during the incident were examined. Of the 2390 violent incidents recorded, 50% were attributed to cases of physical violence towards another patient, 17% to physical violence towards nursing staff, 19% to physical violence towards self and 14% to destruction of property. According to the final multivariable model, for each additional patient in the unit, the risk of a violent event increased by 9.51%; for each additional offender patient, the risk increased by 14.06%; the number of assistant nurses was associated with a 25.03% increased risk; and, after 2006, the risk increased by 68.99%. The most significant factor associated with a 59.98% decreased risk was the total number of nursing staff. All variables significantly and independently contributed to the model. Acute inpatient psychiatric units with a small number of hospitalized patients, adequate, well‐trained and specialized nursing staff, and the hospitalization of different types of patients in separate wards or units are expected to facilitate a reduction in the frequency of violent incidents.     

Elevated Intraesophageal Pressure in Patients with Achalasia: A Common and Important Manometric Finding

There is a subgroup of patients with achalasia in which manometry shows elevated intraesophageal pressure, expressed by elevation of esophageal baseline relative to gastric pressure. The aim of this study was to determine the prevalence of elevated intraesophageal pressure in patients with achalasia and its relationship to clinical, radiographic, endoscopic, and other manometric findings. Manometric studies of 62 patients with achalasia were analyzed and elevated intraesophageal pressure was considered any positive elevation of esophageal baseline relative to gastric pressure. Multiple regression analysis was used to determine independent risk factors associated with elevated intraesophageal pressure. Elevated intraesophageal pressure was found in 32 patients (51.6%). Lower esophageal sphincter pressure was the only independent variable associated with elevated intraesophageal pressure (P = 0.0167). Mean lower esophageal sphincter pressure was significantly higher in patients with elevated compared to those with normal intraesophageal pressure (34 +/- 1.96 vs 26.5 +/- 1.73 mm Hg; P = 0.006). In addition, lower esophageal sphincter pressure had a positive correlation with intraesophageal pressure (r = 0.49, P < 0.001). Conversely, no correlation was found between elevated intraesophageal pressure and various symptoms, disease duration, radiologic dilation, a finding of retained fluid during endoscopy, and esophageal length. We conclude that elevated intraesophageal pressure is a common manometric finding in patients with achalasia, with a prevalence of 51.6%, and is associated with significantly higher lower esophageal sphincter pressure.     

SDPR functions as a metastasis suppressor in breast cancer by promoting apoptosis

Metastatic dissemination of breast cancer cells represents a significant clinical obstacle to curative therapy. The loss of function of metastasis suppressor genes is a major rate-limiting step in breast cancer progression that prevents the formation of new colonies at distal sites. However, the discovery of new metastasis suppressor genes in breast cancer using genomic efforts has been slow, potentially due to their primary regulation by epigenetic mechanisms. Here, we report the use of model cell lines with the same genetic lineage for the identification of a novel metastasis suppressor gene, serum deprivation response (SDPR), localized to 2q32-33, a region reported to be associated with significant loss of heterozygosity in breast cancer. In silico metaanalysis of publicly available gene expression datasets suggests that the loss of expression of SDPR correlates with significantly reduced distant-metastasis–free and relapse-free survival of breast cancer patients who underwent therapy. Furthermore, we found that stable SDPR overexpression in highly metastatic breast cancer model cell lines inhibited prosurvival pathways, shifted the balance of Bcl-2 family proteins in favor of apoptosis, and decreased migration and intravasation/extravasation potential, with a corresponding drastic suppression of metastatic nodule formation in the lungs of NOD/SCID mice. Moreover, SDPR expression is silenced by promoter DNA methylation, and as such it exemplifies epigenetic regulation of metastatic breast cancer progression. These observations highlight SDPR as a potential prognostic biomarker and a target for future therapeutic applications.The metastatic progression of breast cancer accounts for the majority of disease-related mortality. A major rate-limiting step in metastasis is the loss of function of the metastasis suppressor genes, which block a cascade of crucial steps including the loss of adhesion of primary tumor cells, intravasation into the blood and lymphatics with subsequent extravasation at distant sites, and the formation of new colonies. Despite the identification of the first metastasis suppressor gene, nonmetastatic 23 (NM23), nearly two decades ago (1), only a handful of new metastasis suppressors have been identified in recent years using candidate gene approaches (2, 3). It is likely that the current catalog of metastasis suppressor genes remains incomplete despite the vast sequencing efforts due to the possibility that a subset of genes regulated by epigenetic mechanisms may have eluded traditional discovery procedures (4–6). To identify these elusive metastasis suppressor genes, which are functionally compromised in late-stage disease (7–9), we took advantage of a well-established breast cancer progression cell line model system sharing the same genetic linage (Fig. 1A) (10). This model system consists of five cell lines that represent the various stages of breast cancer progression based on the MCF10A cell line: MCF10AneoT (NeoT), MCF10AT1Kcl2 (MII), MCF10CA1h (MIII), and MCF10CA1a (MIV). NeoT cells were generated by overexpression of HRAS in MCF10A cells and rarely exhibit growth following injection into nude mice. MII cells were generated by single xenograft passaging of NeoT cells. When injected subcutaneously (s.c.) into nude mice, MII cells generally form benign tumors that progress to carcinoma one out of four times; hence they mimic the early stage, carcinoma in situ. MIII and MIV cells were isolated from tumors formed by MII cells. MIII cells represent carcinoma, as in general they metastasize at a very low frequency, which requires a prolonged incubation period. On the other hand, MIV cells have the potential to readily seed lung metastases and represent the final stages of a breast cancer, metastatic carcinoma. We compared the gene expression profiles of these latter three model cell lines and leveraged large amounts of publically available breast tumor gene expression profiling data (11–13) by applying multiple bioinformatics filters to identify candidate metastasis suppressor genes.Open in a separate windowFig. 1.Identification of SDPR as a candidate metastasis suppressor gene. (A) Schematic depiction of the generation of breast cancer progression cell line model system. The model consists of five cell lines representing different stages of breast cancer progression. MI, normal breast epithelial cells; NeoT and MII, carcinoma in situ; MIII, carcinoma; and MIV, metastatic carcinoma. (B) Hierarchical clustering of gene expression profiles from MII, MIII, and MIV cells for the genes whose expression differ at least twofold between each cell line. Two clusters, cluster 6 and 7, are magnified because expressions of the genes in these two clusters are significantly suppressed in metastatic MIV cells compared with nonmetastatic MII and MIII. (C) The schematic summary of our strategy for the selection of SDPR as the top candidate metastasis suppressor.Here, we report the discovery of the phosphatidylserine-interacting protein, serum deprivation response (SDPR) (also known as cavin-2), as a bona fide metastasis suppressor. Thus far, studies on SDPR function have been limited to its role as a regulator of caveolae formation (14), and its potential direct involvement in cancer has not been previously described. However, it has been reported that SDPR expression is down-regulated significantly in not only breast cancer but also in cancers of kidney and prostate (15). Moreover, SDPR protein down-regulation was observed in serum from patients with malignant kidney tumors, and hence it was suggested as a possible diagnostic marker to discriminate malignant tumors from benign formations (16). Interestingly, SDPR is localized to 2q32-33, a region with a significant level of loss of heterozygosity that is associated with a high degree of recurrence in breast cancer (17, 18). Our results indicate that SDPR is capable of specifically inhibiting the metastatic growth of breast cancer cells.     

Education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council CPR/AED course

Objectives

To examine whether education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council (ERC) CPR/AED course.

Background

Because of the importance of bystander CPR/AED skills in the setting of cardiac arrest, acquisition and retention of resuscitation skills has gained a great amount of interest.

Methods

The ERC CPR/AED course format for written and practical evaluation was used. Eighty lay people were trained and evaluated at the end of the course, as well as at one, three, and six months.

Results

Retention of CPR/AED skills improved over time, recording the lowest practical scores at one month after initial training and the lowest written scores at initial training. In practical evaluation scores, when examined longitudinally, age presented a significant adverse effect and higher background education presented a non-significant positive effect. Moreover, regarding written evaluation scores, when examined longitudinally, education presented a significant positive effect while age did not significantly correlate with written scores.

Conclusions

Education and age affected retention of CPR/AED skills in lay rescuers. Also, our results suggest that the ERC CPR/AED course format may be poorly designed to discriminate between participants with different levels of practical and written resuscitation skills and merit a thorough investigation in future studies.