Meta-analysis of the prognostic value of CpG island methylator phenotype in rectal cancer.

PURPOSE: The pathological and prognostic importance of CpG island methylator phenotype (CIMP) in rectal cancer, as a sub-population of colorectal cancer, is unknown. A meta-analysis was preformed to estimate the prognostic significance of CIMP in rectal cancer. METHODS: A systematic search was performed of PubMed, Embase, MEDLINE, PubMed Central, and Cochrane electronic databases for articles pertaining to CIMP and rectal cancer. Articles were analysed and data extracted according to PRISMA standards. RESULTS: Six studies including 1529 patients were included in the analysis. Following dichotomisation, the prevalence of CIMP-positive tumours was 10 to 57%, with a median of 12.5%. Meta-analysis demonstrated the pooled odds ratio for all-cause death for CIMP-positive tumours vs CIMP-negative tumours was 1.24 (95% CI 0.88-1.74). Z test for overall effect was 1.21 (p = 0.23). Heterogeneity between the studies was low (X2 5.96, df 5, p = 0.31, I2 = 16%). A total of 15 different loci were used for assessing CIMP across the studies, with a median of 6.5 loci (range 5-8). CONCLUSIONS: No significant association between CIMP and poor outcomes in rectal cancer was demonstrated. There was a high degree of heterogeneity in CIMP assessment methodologies and in study populations. Rectal cancer datasets were frequently not extractable from larger colorectal cohorts, limiting analysis.

Evaluation of engraftment and immunological tolerance after reduced intensity conditioning in a rhesus hematopoietic stem cell gene therapy model.

Reduced intensity conditioning (RIC) is desirable for hematopoietic stem cell (HSC) targeted gene therapy; however, RIC may be insufficient for efficient engraftment and inducing immunological tolerance to transgenes. We previously established long-term gene marking in our rhesus macaque autologous HSC transplantation model following 10 Gy total body irradiation (TBI). In this study, we evaluated RIC transplantation with 4 Gy TBI in two rhesus macaques that received equal parts of CD34(+) cells transduced with green fluorescent protein (GFP)-expressing lentiviral vector and empty vector not expressing transgenes. In both animals, equivalently low gene marking between GFP and empty vectors was observed 6 months post-transplantation, even with efficient transduction of CD34(+) cells in vitro. Autologous lymphocyte infusion with GFP marking resulted in an increase of gene marking in lymphocytes in a control animal with GFP tolerance, but not in the two RIC-transplanted animals. In vitro assays revealed strong cellular and humoral immune responses to GFP protein in the two RIC-transplanted animals, but this was not observed in controls. In summary, 4 Gy TBI is insufficient to permit engraftment of genetically modified HSCs and induce immunological tolerance to transgenes. Our findings should help in the design of conditioning regimens in gene therapy trials.

Preparation of poly(epsilon-caprolactone)/continuous bioglass fibre composite using monomer transfer moulding for bone implant.

Poly(epsilon-caprolactone) (PCL)/continuous bioglass fibre composite was prepared using the monomer transfer moulding technique coupled with a surface initiated polymerisation. The bioglass fibres were surface treated with an amine ended silane in order to initiate polymerisation of epsilon-caprolactone from the fibre surface. Surface initiated polymerisation significantly improved the Young's modulus and flexural strength and water resistance of the composite. Initial in vitro biocompatibility assessment suggests that amine ended silane treatment of bioglass fibres before their inclusion in the composite does not have a negative effect on the biological responses in terms of macrophage activation as measured by IL-1beta release and craniofacial osteoblast attachment.

Tularemia: a 30-year experience with 88 cases.

Drawing upon our experience with 88 cases and a survey of the English literature, we reviewed the clinical, pathophysiological, and epidemiological aspects of tularemia. Tularemia can be thought of as two syndromes--ulceroglandular and typhoidal. This dichotomy simplifies earlier nomenclature and emphasizes the obscure typhoidal presentation. Clinical manifestations suggest that the two syndromes reflect differences in host response. In ulceroglandular tularemia the pathogen appears to be well contained by a vigorous inflammatory reaction. Pneumonia is less common and the patient's prognosis is good. In typhoidal disease there are few localizing signs; pneumonia is more common; and the mortality without therapy is much higher, suggesting that the host response is somehow deficient. Francisella tularensis is an extremely virulent pathogen capable of initiating infection with as few as 10 organisms inoculated subcutaneously. During an incubation period of 3 to 6 days the host responds first with polymorphonuclear leukocytes and then macrophages. Granulocytes are unable to kill the pathogen without opsonizing antibody leaving cellular immunity to play the major role in host defense. One to 2 weeks after infection, a vigorous T-lymphocyte response can be detected in vitro with lymphocyte blast transformation assays and in vivo with an intradermal skin test, which, unfortunately, is not commercially available. Humoral immunity, often used as a diagnostic modality, appears 2 to 3 weeks into the illness. Cellular immunity is long-lasting, accounting for the common reoccurrence of localized disease upon repeated exposures to the pathogen. There are no symptoms that distinguish the ulceroglandular from the typhoidal syndrome. A pulse-temperature dissociation is seen in less than half of the patients. The location of ulcers and enlarged lymph nodes give a clue to the likely vector since lesions located on the upper extremities are more commonly associated with mammalian, and those of the head and neck and lower extremities with arthropod, vectors. Pharyngitis, pericarditis, and pneumonia can complicate both syndromes, although the latter is much more common in typhoidal disease. Hepatitis, usually of a mild degree, is common and occasionally erythema nodosum is seen. No specific laboratory tests characterize tularemia, and cultures of the pathogen are often difficult to obtain because of the special growth requirements of Francisella tularesis and the inability of many clinical laboratories to handle the dangerous pathogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Infection control in gene therapy.

Gene therapy is now being studied for the treatment of a wide variety of acquired and inherited diseases. Viruses used as vectors for gene transfer include retroviruses, adenoviruses, vaccinia viruses, adeno-associated viruses, and herpesviruses. These vectors, developed in the laboratory and in animal studies, are now being introduced into the clinical arena Infection control practitioners will be involved invariably in reviewing the use of these agents in their clinics and hospitals. This review summarizes key aspects of the more common vectors and makes recommendations for infection control.

Vancomycin use in a university medical center: comparison with hospital infection control practices advisory committee guidelines.

OBJECTIVE: To compare actual vancomycin use in a hospital with the guidelines proposed by the Hospital Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention. DESIGN: One-month prospective survey of all patients given vancomycin. Data were collected from patient and laboratory records and discussions with prescribing physicians. SETTING: Four hundred sixty-one-bed tertiary-care university hospital. RESULTS: Only 35% of the 101 vancomycin orders written during the audit were consistent with HICPAC guidelines. Twenty-eight patients were begun on vancomycin for the treatment of documented infections due to beta-lactam-resistant gram-positive bacteria or because preliminary culture results suggested such bacteria were present. Seven methicillin-resistant Staphylococcus aureus, two ampicillin-resistant enterococci, and 10 coagulase-negative staphylococci were recovered. Vancomycin use was judged inappropriate in 66 patients. The drug was used empirically without obtaining appropriate cultures (44 patients), as surgical prophylaxis (6 patients), for primary treatment of antibiotic-associated colitis (3 patients), for convenience in a hemodialysis patient (1 patient), or for other reasons not recommended by HICPAC (12 patients). CONCLUSIONS: Vancomycin use in our teaching center often was inconsistent with HICPAC guidelines. Information from the audit will be useful for designing strategies to improve vancomycin use.

Vancomycin use in a university medical center: effect of a vancomycin continuation form.

OBJECTIVE: To examine the impact of a new policy to ensure appropriate use of vancomycin in a 461-bed tertiary-care hospital. DESIGN: We instituted a policy that allowed physicians to prescribe vancomycin but that required them to complete a vancomycin continuation form and document that use conformed to Hospital Infection Control Practices Advisory Committee (HICPAC) guidelines if they wished to continue the drug beyond 72 hours. Vancomycin was stopped automatically at 72 hours if use was not consistent with guidelines, if an infectious diseases consultant did not approve the drug, or if the form was not completed. A pharmacist and infectious diseases specialist monitored use of vancomycin prospectively and interacted with prescribers when indicated. Educational efforts were limited to printing the HICPAC guidelines on the form and providing information about the policy in a newsletter. Patterns of prescribing and the economic impact of the form were evaluated over a 6-month period. RESULTS: Only 29% to 48% of vancomycin orders initially met HICPAC guidelines, but 77% to 96% of use was appropriate after 72 hours when the form was used. Inappropriate surgical prophylaxis, empirical therapy of intensive-care unit and transplant patients, and therapy for inadequately documented coagulase-negative staphylococcal infections remained problems. Vancomycin use fell from a mean of 136 (+/-52) g/1,000 patient days in the 12 months before the form to 78 (+/-22) g/1,000 patient days in the 9 months after institution of the form (P<.05). Net vancomycin acquisition costs and costs of ordering vancomycin serum levels fell by $357 and $19 per 1,000 patient days, respectively (P<.05). This represented annualized saving of approximately $47,000 in drug and monitoring costs. No adverse patient outcomes were seen as a result of the program. CONCLUSIONS: A vancomycin continuation form can decrease inappropriate vancomycin use and may save money. Additional educational efforts may be required to increase compliance with HICPAC guidelines during initial prescribing.

Clinical infection control in gene therapy: a multidisciplinary conference.

Gene therapy is being studied for the treatment of a variety of acquired and inherited disorders. Retroviruses, adenoviruses, poxviruses, adeno-associated viruses, herpesviruses, and others are being engineered to transfer genes into humans. Treatment protocols using recombinant viruses are being introduced into clinical settings. Infection control professionals will be involved in reviewing the safety of these agents in their clinics and hospitals. To date, only a limited number of articles have been written on infection control in gene therapy, and no widely available recommendations exist from federal or private organizations to guide infection control professionals. The goals of the conference were to provide a forum where gene therapy experts could share their perspectives and experience with infection control in gene therapy and to provide an opportunity for newcomers to the field to learn about issues specific to infection control in gene therapy. Recommendations for infection control in gene therapy were proposed.

Influenza control in acute care hospitals.

BACKGROUND: Influenza causes increased morbidity and mortality among patients in longterm care facilities, but little information is available on the impact of influenza in acute care settings. We wished to have such information when revising our hospital influenza control policy. METHODS: We reviewed recent reports of influenza among patients in acute care hospitals and surveyed large (approximately 500-bed) acute care teaching hospitals by telephone to determine the nature of their influenza control policies. RESULTS: Seventeen reports of influenza outbreaks in acute care hospitals were published from 1959 to 1994. Influenza A caused 13 of these outbreaks. Five involved children and 12 involved adults. The mean number of patients in each outbreak was 14 (range 1 to 49), with a mortality rate of 0% to 50% (median 0%, mean 6.5%). Health care workers were implicated in transmission in five reports. Vaccine was used infrequently during the outbreaks, and use of chemoprophylaxis was not reported. Our survey of current practices in 15 university-affiliated hospitals from 12 states revealed that all offered vaccine in the fall but none required either immunoprophylaxis or chemoprophylaxis at any time. Only three had formal policies detailing management of influenza in the hospital. CONCLUSIONS: Nosocomial influenza in acute care hospitals is infrequently reported and associated with a low mortality rate. Health care workers rarely comply with preventive measures, and few institutions have formal influenza control policies.

The involvement of the frontal lobes in cognitive estimation.

Ninety-six patients with localised cerebral lesions were tested on a task of providing reasonable answers to Cognitive Estimate questions. These questions are ones that can be answered using general knowledge available to almost all subjects, but for which no immediately obvious strategy is available. It was found that patients with frontal lesions gave significantly more bizarre answers than patients with more posterior lesions. This effect is interpreted in terms of Luria's (1966) theory of the planning functions of the frontal lobes.

An evaluation of statewide strategies to reduce antibiotic overuse.

BACKGROUND: The rapid increase of antibiotic resistance poses a significant threat to human health. Overuse of antibiotics has been linked to rates of antibiotic resistance. This study assessed the utility of two common interventions--1) practice profiling and feedback and 2) patient education materials--implemented to decrease antibiotic prescribing for pediatric upper respiratory infections (URIs). METHODS: Based on Medicaid regions in Kentucky, primary care physicians managing pediatric respiratory infections in Medicaid were randomized into four groups. Groups received either 1) performance feedback only, 2) patient education materials only, 3) both feedback and education materials, or 4) no intervention. Participating physicians had their antibiotic prescribing assessed for the period of July 1, 1996, to November 30, 1997, with an intervention in June 1997. The study included 216 physicians and 124,092 episodes of care. RESULTS: All groups increased in proportion of episodes with antibiotics between the pre-intervention and post-intervention periods. Prescribing in the patient education group and the patient education and feedback group increased at a significantly lower rate than in the control group. Physicians did not change their coding of illness to justify antibiotics after the intervention, and there was no significant generalization of effect of the pediatric intervention on prescribing for adult URIs. CONCLUSIONS: These interventions demonstrate little if any impact on promoting appropriate antibiotic prescribing. Antibiotic prescribing for viral respiratory infections continues to increase, suggesting concomitant increases in antibiotic resistance.

Conducting research in culturally diverse inner-city neighborhoods: some lessons learned.

Social, behavioral, and health research among disenfranchised groups in inner cities poses problems in collecting data. It is a challenge to achieve data of sufficient quantity and quality necessary to be scientifically usable. This article describes the experiences of a research team during two phases of data collection in a mental health intervention study in New York's South Bronx. Challenges in addressing human subject concerns, the formation of a fieldwork team, enrollment and retention of respondents, and administration of instruments are described and solutions are discussed. Emphasis is placed on researchers' approaches to the selection, orientation, and safety of interviewers, interviewer-respondent race and ethnic matching, contacts and rapport with respondents, and the handling of such interpersonal issues as distrust, poor cooperation, and family dynamics. The procedures developed took into consideration the culture and life conditions of the population to ensure a satisfactory response rate and high-quality data.

Ehrlichiosis in Kentucky.

Ehrlichiosis is a recently described tick-borne disease characterized by headache, fever and chills, leukopenia, thrombocytopenia, and transaminase elevation. The presentation is similar to Rocky Mountain spotted fever but the rash is less frequently present in ehrlichiosis. The diagnosis is confirmed by elevated antibody titers to Ehrlichia chaffeensis or visualization of inclusions in white blood cells and the disease is easily cured with tetracyclines or chloramphenicol. Cases of ehrlichiosis are reported from southeastern, southcentral and midatlantic states. We report three cases of Ehrlichia infection acquired in Pulaski County and Fort Knox, KY during 1992-93.

Patterns of antibiotic-resistant Streptococcus pneumoniae in children in a day-care setting.

BACKGROUND: Streptococcus pneumoniae is one of the primary causes of illness and death among young children, and evidence suggests that the prevalence of antibiotic-resistant S pneumoniae is increasing. The purpose of this study was to investigate the prevalence of antibiotic-resistant S pneumoniae in a sample of children in day-care facilities in a region that includes both rural and urban communities. METHODS: Nasopharyngeal cultures were obtained from 104 children in eight day-care centers located in rural and urban central Kentucky in April and May, 1997. Thirty-five of the children produced isolates positive for S pneumoniae. Each isolate was tested for susceptibility to penicillin, trimethoprim-sulfamethoxazole, erythromycin, tetracycline, vancomycin, and cefotaxime. RESULTS: Of the children with S pneumoniae isolates, 54% had isolates that were resistant to penicillin and 40% that were resistant to trimethoprim-sulfamethoxazole. Twenty-one (60%) of the isolates had resistance to at least one of the six tested antimicrobials, with 15 (43%) having resistance to more than one of the antimicrobials. The mean age of children with isolates resistant to penicillin was significantly less (2.7 + 1.6) than those with penicillin-susceptible isolates (3.7 + 1.1, P = .02). There was no relation between resistance and rural or urban day-care location. CONCLUSIONS: A substantial proportion of S pneumoniae isolates in young children are resistant to antibiotics. Limiting the effect of S pneumoniae drug resistance may require a reexamination of outpatient treatment strategies for childhood respiratory tract infections.

Using a model to structure psychosocial nursing [corrected].

1. Specifying a model to guide research projects helps clarify the study, permits several investigators to work in a coordinated fashion on large projects, and facilitates comparisons across studies. 2. This model is composed of seven domains and indicates some of the hypothesized relationships between domains. Adapting the model to individual studies may result in a different number of domains and in the specification of other hypothesized relationships. 3. When possible, researchers should make use of minimum data sets to enhance the comprehensiveness and generalizability of their research.

Conflict in healthcare organizations.

Healthcare organizations struggle with internal and external causes of conflict. Successful organizations evaluate and retool existing conflict management systems to constructively, cost-effectively and practically control the negative impact.

Working smarter: the use of priorities and a model in designing nursing research.

It is imperative to maximize our limited resources conducting nursing research through targeting studies in priority areas and structuring projects to foster comprehensiveness and generalizability. This paper reviews priorities for nursing research and presents a model for research, detailing its component domains and the relationships among these domains. It further applies the model to a specific research project concerned with comparing the outcomes of two intensive community-based service programs for children with serious emotional disturbances and discusses the implications of applying this model.

Intensive case management for children and youth with serious emotional disturbance: an emergent role for nursing?

Since 1988 New York state's Children and Youth Intensive Case Management (CYICM) program has enrolled more than 1700 children. The program goal is to maintain children in the least restrictive environment appropriate to their needs. This linkage and advocacy focused program uses a small caseload (10) and flexible service money to meet its goal. This paper reviews the program model, describes the enrollees, and presents the outcomes related to hospitalization. It also presents a case study of an encounter between a nurse case manager and parents of one of her clients. Finally, it considers the role of case management as an emergent for nurses.

1988 Delphi survey of nursing research priorities for New York State.

In order to inform decisions about nursing research and health care policy, the Council on Nursing Research of the New York State Nurses Association (NYSNA) conducted a Delphi survey to identify the priorities for nursing research in New York state. The Delphi technique is a method of eliciting judgements from experts for the purpose of short-term forecasting and planning. The survey was conducted by mail in three rounds during 1988. Round I required participants to identify three primary research priorities for the nursing profession. In Round II participants ranked the 37 most frequently identified categories from Round I. The highest 16 categories from Round II were ranked by participants in Round III to provide the final 10 nursing research priority categories for New York state. All members of the New York State Nurses Association holding a minimum of a master's degree in nursing were invited to participate. The response rates were: Round I, 34% (N = 872); Round II, 38% (N = 985); Round III 37% (N = 974). Of the 10 nursing research priority categories identified in the final round, 5 relate to nurses, 2 relate to nursing, and 3 relate to clients. None of the high-risk conditions or populations with whom nurses work appear in the top 10, and only 2 of these are ranked in the top 15 priority categories. These priority categories will be used by the NYSNA Council on Nursing Research to influence its future agenda and activities. They can be used by the nursing profession and others for planning, policy making, and establishing nursing research funding priorities.(ABSTRACT TRUNCATED AT 250 WORDS)