Making health care safer: a critical analysis of patient safety practices.

OBJECTIVES: Patient safety has received increased attention in recent years, but mostly with a focus on the epidemiology of errors and adverse events, rather than on practices that reduce such events. This project aimed to collect and critically review the existing evidence on practices relevant to improving patient safety. SEARCH STRATEGY AND SELECTION CRITERIA: Patient safety practices were defined as those that reduce the risk of adverse events related to exposure to medical care across a range of diagnoses or conditions. Potential patient safety practices were identified based on preliminary surveys of the literature and expert consultation. This process resulted in the identification of 79 practices for review. The practices focused primarily on hospitalized patients, but some involved nursing home or ambulatory patients. Protocols specified the inclusion criteria for studies and the structure for evaluation of the evidence regarding each practice. Pertinent studies were identified using various bibliographic databases (e.g., MEDLINE, PsycINFO, ABI/INFORM, INSPEC), targeted searches of the Internet, and communication with relevant experts. DATA COLLECTION AND ANALYSIS: Included literature consisted of controlled observational studies, clinical trials and systematic reviews found in the peer-reviewed medical literature, relevant non-health care literature and "gray literature." For most practices, the project team required that the primary outcome consist of a clinical endpoint (i.e., some measure of morbidity or mortality) or a surrogate outcome with a clear connection to patient morbidity or mortality. This criterion was relaxed for some practices drawn from the non-health care literature. The evidence supporting each practice was summarized using a prospectively determined format. The project team then used a predefined consensus technique to rank the practices according to the strength of evidence presented in practice summaries. A separate ranking was developed for research priorities. MAIN RESULTS: Practices with the strongest supporting evidence are generally clinical interventions that decrease the risks associated with hospitalization, critical care, or surgery. Many patient safety practices drawn primarily from nonmedical fields (e.g., use of simulators, bar coding, computerized physician order entry, crew resource management) deserve additional research to elucidate their value in the health care environment. The following 11 practices were rated most highly in terms of strength of the evidence supporting more widespread implementation. Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk; Use of perioperative beta-blockers in appropriate patients to prevent perioperative morbidity and mortality; Use of maximum sterile barriers while placing central intravenous catheters to prevent infections; Appropriate use of antibiotic prophylaxis in surgical patients to prevent postoperative infections; Asking that patients recall and restate what they have been told during the informed consent process; Continuous aspiration of subglottic secretions (CASS) to prevent ventilator-associated pneumonia; Use of pressure relieving bedding materials to prevent pressure ulcers; Use of real-time ultrasound guidance during central line insertion to prevent complications; Patient self-management for warfarin (Coumadin) to achieve appropriate outpatient anticoagulation and prevent complications; Appropriate provision of nutrition, with a particular emphasis on early enteral nutrition in critically ill and surgical patients; and Use of antibiotic-impregnated central venous catheters to prevent catheter-related infections. CONCLUSIONS: An evidence-based approach can help identify practices that are likely to improve patient safety. Such practices target a diverse array of safety problems. Further research is needed to fill the substantial gaps in the evidentiary base, particularly with regard to the generalizability of patient safety practices heretofore tested only in limited settings and to promising practices drawn from industries outside of health care.

Screening and surveillance for colorectal cancer.

Colorectal cancer is the second most common cause of cancer death among American men and woman. Currently available screening and surveillance techniques are effective in detecting early-stage colorectal cancer and its premalignant precursor lesion, the adenomatous polyp (adenoma). Removal of adenomas by colonoscopic polypectomy significantly reduces the incidence of colorectal cancer. Appropriate screening and surveillance recommendations should be based on the individual's colorectal cancer risk stratification. High-risk groups, such as patients with hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), should be offered genetic counseling and specialized screening recommendations for colorectal and associated extracolonic malignancies.

Screening and surveillance for colorectal carcinoma.

Screening and surveillance examinations are effective in lowering colorectal cancer risk. Screening tests have been demonstrated to reduce colorectal cancer mortality. Colonoscopic removal of adenomatous polyps has been determined to reduce colorectal cancer incidence. High-risk individuals and their family members should be identified and offered more aggressive recommendations for appropriate screening and surveillance guidelines. Colorectal cancer screening strategies are in an acceptable range of cost effectiveness.

Developmental expression of SI is regulated in transgenic mice by an evolutionarily conserved promoter.

Developmental expression of the sucrase-isomaltase (SI) gene in the mouse intestine involves two major transitions that correspond to critical developmental events. Low levels of SI mRNA were first identified in day 16.5 fetal mouse intestine, immediately after the transition from stratified endoderm to a columnar epithelium organized in nascent villi. Low levels were maintained until the third week of life, when induction of SI mRNA to adult levels was observed coincident with the time of weaning. The mechanism of this pattern of SI gene expression was studied in transgenic mice using a reporter gene construct containing an SI gene promoter that is evolutionarily conserved between mouse and human (nucleotides -201 to +54 of the mouse SI gene). This promoter included the necessary regulatory information to direct transcription to enterocytes in developmental and differentiation-dependent patterns that recapitulated the expression of the endogenous SI gene. However, transgenes lacked the ability to direct induction of precocious expression in suckling animals after administration of corticosteroids. These findings define a short SI gene promoter that contains cis-acting elements that are responsible for developmental and differentiation-dependent transcriptional regulation.

Regulation of lineage-specific transcription of the sucrase-isomaltase gene in transgenic mice and cell lines.

Sucrase-isomaltase (SI), a gene expressed exclusively in absorptive enterocytes, was used to examine the molecular mechanisms that regulate cell-specific gene expression in the intestinal epithelium. Transgenic mice were made with a construct containing nucleotides -8,500 to +54 of the mouse SI gene linked to a human growth hormone reporter gene. In adult transgenic animals, high-level transgene expression was limited to the small intestine, with low levels of ectopic expression in the colon. In contrast to the endogenous gene that is expressed only in enterocytes, the transgene was expressed in all four cell lineages, including enterocytes, enteroendocrine, goblet, and Paneth cells. To examine this process of lineage-specific expression further we studied Caco-2 and COLO DM cell lines, which model enterocytes and enteroendocrine cells, respectively. Reminiscent of results in transgenic animals, only Caco-2 cells transcribed the endogenous SI gene, whereas both Caco-2 and COLO DM cells supported transcription from chimeric SI reporter gene constructs. Taken together, these data suggest that each intestinal cell lineage has the cellular machinery to transcribe the SI gene. Moreover, these findings imply that transcription is normally repressed in nonenterocytic cells, possibly via a transcriptional silencer residing outside of the region of the SI gene examined in these studies.

A man with type III glycogenosis associated with cirrhosis and portal hypertension.

Type III glycogenosis, an inherited disorder of glycogen metabolism that results from reduced or absent activity of the enzyme amylo-1,6-glycosidase (debranching enzyme), has not been frequently associated with cirrhosis and portal hypertension in adults. An adult Caucasian man with well-document type IIIa glycogenosis, who presented with a variceal hemorrhage secondary to hepatic cirrhosis, is described here. No other cause of cirrhosis was found.

Murine intestinal disaccharidases: identification of structural variants of sucrase-isomaltase complex.

This study was directed to determine the extent of variability in structure or expression of intestinal disaccharidase [gamma-glucoamylase (gamma-GA), sucrase-isomaltase (SI), and lactase] between different strains of mice. Reduced levels of sucrase activity (approximately 20 U/g of protein) were observed in three strains of mice belonging to the CBA/Ca lineage. Four other strains of mice analyzed exhibited higher levels of sucrase activity (approximately 50 U/g of protein). Decreased levels of sucrase in CBA/Ca mice were not associated with decreased levels of activity associated with the isomaltase subunit or with decreased levels of SI mRNA expression. High-performance liquid chromatographic gel filtration, heat inactivation, and kinetic analysis indicated that the differences between strains in sucrase activity might be attributed to structural differences in the sucrase subunit of the SI complex, thus rendering it more susceptible to cleavage and inactivation. However, no differences in kinetic properties of the sucrase subunit were observed between strains. Murine gamma-GA was found to account for a greater proportion of maltase activity (approximately 70%) than that observed in other species (i.e., approximately 20%). In addition, CBA/Ca mice were found to be deficient in intestinal maltase activity (approximately 60 U/g) compared with the other strains studied (approximately 300 U/g).

The human sucrase-isomaltase gene directs complex patterns of gene expression in transgenic mice.

Sucrase-isomaltase (SI) is an enterocyte-specific gene that is expressed in complex developmental and spatial patterns. In this study, we examine the ability of regulatory elements within the human SI (hSI) gene to direct appropriate cell lineage and spatial patterns of expression in transgenic mice. Transgenic mouse lines were established using a construct containing bases -3424 to +54 of the hSI gene linked to the human growth hormone (hGH) structural gene. In each transgenic line, hGH mRNA and protein were expressed only in the small intestine and colon. In contrast to the endogenous mouse SI (mSI) gene, which was expressed along the entire length of the small intestine, hGH mRNA expression was predominantly found in the distal jejunum and ileum, with very low levels in more proximal portions of the small intestine. However, the pattern of transgene expression along the small intestinal crypt-villus axis was identical to the pattern of the endogenous mSI gene. These results suggest that regulatory elements necessary for intestine-specific transcription and differential expression along the intestinal crypt-villus axis are included in the 5'-flanking region of the hSI gene. Furthermore, these data suggest that different DNA regulatory regions regulate transcription along the horizontal intestinal axis. In the colon, there was aberrant expression of hGH in a subpopulation of enteroendocrine cells that contained peptide tyrosine tyrosine (PYY). This suggests that there are DNA regulatory elements, missing in the transgene construct, which normally suppress expression of the endogenous mSI gene in these cells. Taken together, these findings define the SI gene as a useful model for studies of differentiation, cell lineage determination, and mechanisms of complex spatial gene expression in the intestine.