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Integrated advanced information management systems: a twenty-year history at the University of Cincinnati.

The University of Cincinnati (UC) has been active in the National Library of Medicine's Integrated Advanced Information Management Systems (IAIMS) program since IAIMS' inception in 1984. UC received IAIMS planning and modeling grants in the 1980s, spent the 1990s practicing its own form of "iaims" and refining its vision, and, in May 2003, received an IAIMS operations grant in the first round of awards under "the next generation" program. This paper discusses the history of IAIMS at UC and describes the goals, methods, and strategies of the current IAIMS program. The goals of UC's IAIMS program are to: improve teaching effectiveness by improving the assessment of health professional students and residents in laboratory and clinical teaching and learning environments; improve the ability of researchers, educators, and students to acquire and apply the knowledge required to be more productive in genomic research and education; and increase the productivity of researchers and administrators in the pre-award, post-award, and compliance phases of the research lifecycle.

Academic Medical Centers↗

Single dose piroxicam for acute postoperative pain.

BACKGROUND: Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. OBJECTIVES: To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. SEARCH STRATEGY: Published reports were identified from systematic searching of Medline, Biological Abstracts, Embase, The Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult patients, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. DATA COLLECTION AND ANALYSIS: Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-harm were calculated. MAIN RESULTS: Three trials (141 patients) compared oral piroxicam 20 mg with placebo and one (15 patients) compared oral piroxicam 40 mg with placebo. For single doses of piroxicam 20 mg and 40 mg the respective numbers-needed-to-treat for at least 50% pain relief were 2.7 (2.1 to 3.8) [95% confidence interval] and 1.9 (1.2 to 4.3) [95% confidence interval] compared with placebo over 4-6 hours in moderate to severe postoperative pain. The reported incidence of adverse effects was no higher with piroxicam (20 mg or 40 mg) than with placebo. REVIEWER'S CONCLUSIONS: Piroxicam appears to be of similar efficacy to other non-steroidal anti-inflammatory drugs (NSAIDs) and intramuscular morphine 10 mg when used as a single oral dose in the treatment of moderate to severe postoperative pain.

Acute Disease↗

Screening and case finding instruments for depression.

BACKGROUND: Screening or case finding instruments have been advocated as a simple, quick and inexpensive method to improve detection and management of depression in non-specialist settings, such as primary care and the general hospital. However, screening/case finding is just one of a number of strategies that have been advocated to improve the quality of care for depression. The adoption of this seemingly simple and effective strategy should be underpinned by evidence of clinical and cost effectiveness. OBJECTIVES: To determine the clinical and cost effectiveness of screening and case finding instruments in: (1) improving the recognition of depression; (2) improving the management of depression, and (3) improving the outcome of depression. SEARCH STRATEGY: The researchers undertook electronic searches of The Cochrane Library (Issue 4, 2004); The Cochrane Depression, Anxiety and Neurosis Group's Register [2004); EMBASE (1980-2004); MEDLINE (1966-2004); CINAHL (to 2004) and PsycLIT (1974-2004). References of all identified studies were searched for further trials, and the researchers contacted authors of trials. SELECTION CRITERIA: Randomised controlled trials of the administration of case finding/screening instruments for depression and the feedback of the results of these instruments to clinicians, compared with no clinician feedback. Trials had to be conducted in non-mental health settings, such as primary care or the general hospital. Studies that used screening strategies in addition to enhanced care, such as case management and structured follow up, were specifically excluded. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by researchers, papers ordered, re-inspected and quality assessed. Data were also independently extracted. Data relating to: (1) the recognition of depression; (2) the management of depression and (3) the outcome of depression over time were sought. For dichotomous data the Relative Risk (RR), 95% confidence interval (CI) were calculated on an intention-to-treat basis. For continuous data, weighted and standardised mean difference were calculated. A series of a priori sensitivity analyses relating to the method of administration of questionnaires and population under study were used to examine plausible causes of heterogeneity. MAIN RESULTS: Twelve studies (including 5693 patients) met our inclusion criteria. Synthesis of these data gave the following results:(1) the recognition of depression: according to case note entries of depression, screening/case finding instruments had borderline impact on the overall recognition of depression by clinicians (relative risk 1.38; 95% confidence interval 1.04 to 1.83). However, substantial heterogeneity was found for this outcome. Screening and feedback, irrespective of baseline score of depression has no impact on the detection of depression (relative risk 1.00; 95% confidence interval 0.89 to 1.13). In contrast, three small positive studies using a two stage selective procedure, whereby patients were screened and only patients scoring above a certain threshold were entered into the trial, did suggest that this approach might be effective (relative risk 2.66; 95% confidence interval 1.78 to 3.96). Separate pooling according to this variable reduced the overall level of heterogeneity. Publication bias was also found for this outcome.(2) the management of depression: according to case note entries for active interventions and prescription data, a selected subsample of all studies reported this outcome and found that there was there was an overall trend to showing a borderline higher intervention rate amongst those who received feedback of screening/case finding instruments (relative risk 1.35; 95% confidence interval 0.98 to 1.85), although substantial heterogeneity between studies existed for this outcome. This result was dependant upon the presence of one highly positive study.(3) the outcome of depression: few studies reported the impact of case finding/screening instruments on the actual outcome of depression, and no statistical pooling was possible. However, three out of four studies reported no clinical effect (p<0.05) at either six months or twelve months. No studies examined the cost effectiveness of screening/case finding as a strategy. AUTHORS' CONCLUSIONS: There is substantial evidence that routinely administered case finding/screening questionnaires for depression have minimal impact on the detection, management or outcome of depression by clinicians. Practice guidelines and recommendations to adopt this strategy, in isolation, in order to improve the quality of healthcare should be resisted. The longer term benefits and costs of routine screening/case finding for depression have not been evaluated. A two stage procedure for screening/case finding may be effective, but this needs to be evaluated in a large scale cluster randomised trial, with a prospective economic evaluation.

Depression↗

Intraventricular antibiotics for bacterial meningitis in neonates.

BACKGROUND: Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm. OBJECTIVES: To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone. SEARCH STRATEGY: MEDLINE, EMBASE, The Cochrane Library, Issue 2, 2004, Science Citation Index, and the Oxford Database of Perinatal Trials were searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 - April 2004) as were reference lists of identified trials and personal files. No language restrictions were applied. SELECTION CRITERIA: Selection criteria for study inclusion were: Randomized or quasi-randomized controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalization, neonatal and/or infant mortality, neurodevelopmental outcome, duration of hospitalization, duration of culture positivity of CSF and side effects. DATA COLLECTION AND ANALYSIS: All reviewers abstracted information for outcomes reported and one reviewer checked for discrepancies and entered data into RevMan 4.2. Relative risk (RR), risk difference (RD), number needed to treat (NNT) or number needed to harm (NNH), and mean difference (MD), using the fixed effects model are reported with 95% confidence intervals (CI). The fixed effect model was used for meta-analysis. MAIN RESULTS: One study was included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone [RR 3.43 (95% CI, 1.09, 10.74; RD 0.30 (95% CI, 0.08, 0.53); NNH was 3 (95% CI; 2 ,13)]. Duration of CSF culture positivity did not differ significantly (MD -1.20 days (95% CI, -2.67, 0.27). REVIEWERS' CONCLUSIONS: In one trial, enrolling infants with gram negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a 3 fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.

Anti-Bacterial Agents↗

Molecular aspects of the calbindins.

Studies from our laboratory concerning regulation of calbindin include regulation by 1,25-dihydroxycholecalciferol [1,25(OH)2D3], receptor regulation as a possible mechanism for modulating calbindin's response to hormone, tissue specific regulation and regulation by factors other than 1,25(OH)2D3. With regard to receptor regulation, we found that the induction of calbindin mRNA in intestine and kidney by 1,25(OH)2D3 is not accompanied by a corresponding alteration in vitamin D receptor (VDR) mRNA in the vitamin D-deficient, low calcium rat. However, in the vitamin D-replete rat, administration of 1,25(OH)2D3 results in an induction of both calbindin and VDR mRNA in these tissues. These results suggest the presence of an inhibitor of 1,25(OH)2D3-mediated receptor up-regulation in the vitamin D-deficient, low calcium animal. Glucocorticoids can also regulate calbindin gene expression. Dexamethasone treatment (50 micrograms.100 g body weight-1.d-1 for 4 d) results in a 75% decrease in rat intestinal calbindin-D9k mRNA. This decrease may be related to the inhibition of intestinal calcium absorption previously observed after glucocorticoid administration. Kidney calbindin-D28k mRNA is unaffected by glucocorticoid treatment, indicating tissue specificity of the glucocorticoid response. To evaluate more precisely the means whereby 1,25(OH)2D3 and other modulators can influence calbindin gene expression, we isolated the chromosomal gene for calbindin-D28k by screening a mouse genomic library in cosmid. Ros 17/2.8 cells were transfected with recombinant plasmids in which the mouse calbindin promoter is fused to the reporter gene encoding chloramphenicol acetyltransferase. Deletion studies have enabled us to identify sequence elements in the mouse calbindin-D28k gene that confer basal activation and a hormone inducible response.

Animals↗

Six Sigma: not for the faint of heart.

Six Sigma is an excellent quality and performance improvement tool. Like any tool, the results of using it are highly dependent on whether you use it with competence and on the right problem. This article will help you decide if your problem is well-suited for a Six Sigma approach and will suggest the optimum approach for planning and implementing Six Sigma methodology. Performance improvement methods can be grouped into two broad categories, based on the problem to be addressed. When the problem is relatively minor and localized, "evolutionary" methods may be suitable (e.g., quality circles, problem-solving staff meetings, continuous quality improvement [CQI], total quality management [TQM]). These tools work best when modest incremental improvements are sought, when major process redesign is not thought to be necessary, and when the avoidance of workplace disruption is desired. Reengineering and Six Sigma are the best-known examples of the "revolutionary" performance improvement methods. These methods should be used when major (drastic, do or die, etc.) improvements are needed. Problems that cross departmental boundaries need these methods. When a process is so dysfunctional that you feel like you need to tear up the standard operating procedure (SOP) and start all over again, you need a revolutionary method. A Six Sigma project requires a major expenditure of money and employee time, and a willingness to make some hard decisions about jobs, employee retention and relationships among stakeholders. An institution's culture should be considered as part of the decision about using Six Sigma. If the institution has a history of making data-driven decisions, or at least has displayed openness to operating in that manner, Six Sigma has a good chance of success. A radiology-driven Six Sigma project should not be undertaken until a comprehensive written description of the scope of the project is approved by the radiology department leadership team and by the appropriate higher-level institutional leaders. This document should address the specific outcomes desired, the resources available, a rough tentative timeline, and any political constraints imposed on the project (e.g., inviolate HR policies, compatibility with enterprise strategic goals). The document should be comprehensive enough and explicit enough to be useful as a major component of the bid package for hiring a consultant or for writing the job description for the hiring of an in-house expert. A full-time project manager should be designated if an in-house expert is not hired. This person should be a senior leader in the department, but not the department director. Leading a Six Sigma project is a full-time job in itself and cannot be performed as an additional duty. Although it may be tempting to appoint a senior staff technologist or nurse, keep in mind that the project manager must have sufficient authority to expect cooperation from departmental supervisors without resorting to frequent appeals to the department director. Contact the institution's CIO and ask that a knowledgeable person on the IT staff be appointed to serve as the IT liaison for the project. This person should have in-depth familiarity with the HIS and the ways that it interfaces with the RIS (if the RIS is not a module within the HIS). Most importantly, this liaison must understand the exact data definitions and the origins of the data that are passed between the HIS and the RIS. The steering committee should consist of at least one physician and one department-level administrator from outside of the radiology department. From within the radiology department, there should be at least one radiologist and one senior modality manager (whose modality is not the primary focus), the project manager, and the manager of a radiology component that is a focus of the project (e.g., the film library manager). The consultant should be an ex officio member without vote. The steering committee should be small enough to be manageable, yet large enough to provide insight from both the radiology department and the rest of the institution. Because of the size of the steering committee and the difficulty of bringing so many people together for meetings, the day-to-day governance of the project will be provided by an informal "operations committee." When we consider "change" in the context of a Six Sigma project, we talk about a wide variety of topics, but they can be summarized usefully as dealing with processes, policies, physical plant and equipment, personnel, and politics (or culture). The first three of these lend themselves to quantitative analysis, or at least rigorously qualitative analysis. The final two, however, are subjective, ill-defined or not readily acknowledged, and fraught with potentially major challenges when it becomes necessary to implement changes in the first three. The Six Sigma process, as taught by GE, consists of five phases summarized by the acronym DMAIC: Define, Measure, Analyze, Improve and Control. This article deals mostly with the time period from first consideration of a possible Six Sigma project through the early part of the Define phase. It also discusses pitfalls that must be considered anytime throughout a project, from first thoughts of conducting a project until recommended changes become ingrained in the department's operations. Six Sigma compares baseline or historical data to data obtained after implementation of Six Sigma-driven changes in order to determine if desired changes in performance have been achieved. When historical data are not available, the Six Sigma team must collect baseline data as one of their earliest tasks. A Six Sigma project can easily last 18 to 24 months or longer. We must be sure that the data we collect during Month 18 are collected identically to the data we collected at baseline. A major performance improvement project is likely to require 12 to 24 months or longer. Upper management initially may be reluctant to appoint the "cream of the crop" to the project teams. Success is predicated on having the most knowledgeable personnel involved in the project. Without them, the chances of success are reduced. A Six Sigma project's length always exceeds the attention span of the vast majority of its participants. The department director and project manager must anticipate this and devote special efforts to maintaining motivation and momentum after the initial flurry of activity. The complexity of a Six Sigma project will be greatly increased, and all of the pitfalls discussed here will be exacerbated, if your facility has multiple sites. At the simplest, the multiple sites will introduce complications in getting personnel to come to project meetings. The complications will escalate if the sites are under different management, such as a confederated health system. The project manager and the consultant will expend additional time and effort dealing with these issues, which likely will lengthen the project unavoidably. The project manager must spend time with the department's external customers who have significant stakes in the project. At a minimum, this should include relatively formal meetings with other department directors or subordinate managers and key physician and nurse leaders, and attendance at their managerial or staff meetings (you may need to ask to be invited). Although paper or e-mail surveys can be helpful, only sustained personal contact with a stakeholder will truly allow you to understand how they interact with radiology and what their concerns are. As with daily operational management, a performance improvement project requires attention to policies, procedures, processes, physical plant and infrastructure, personnel, and perhaps most importantly, to politics.

Efficiency, Organizational↗

A novel gene activated in regenerating islets.

Administration of poly(ADP-ribose) synthetase inhibitors such as nicotinamide to 90% depancreatized rats induces regeneration of pancreatic islets, thereby ameliorating the surgical diabetes (Yonemura, Y., Takashima, T., Miwa, K., Miyazaki, I., Yamamoto, H., and Okamoto, H. (1984) Diabetes 33, 401-404). In screening the regenerating islet-derived cDNA library, we came across a novel gene encoding a 165-amino acid protein. The gene was expressed in regenerating islets but not in normal pancreatic islets, insulinomas, or regenerating liver. In 90% depancreatized and nicotinamide-injected rats, the expression of the gene was increased 1 month after the partial pancreatectomy and reached a peak 3 months after the operation. The increase in expression of the gene was temporally correlated with the increase in size of regenerating islets and the decrease in urinary glucose level. The gene was also found to be activated in hyperplastic islets of aurothioglucose-treated mice. Thus, the expression of the gene in both regenerating and hyperplastic islets suggests possible roles for this gene in replication, growth, and maturation of islet beta-cells. We also found that a human pancreas-derived cDNA library contained a homologue to the gene.

Amino Acid Sequence↗

Does neostigmine administration produce a clinically important increase in postoperative nausea and vomiting?

Neostigmine is used to antagonize neuromuscular blocker-induced residual neuromuscular paralysis. Despite the findings of a previous meta-analysis, the effect of neostigmine on postoperative nausea and vomiting remains unresolved. We reevaluated the effect of neostigmine on postoperative nausea and vomiting while considering the different anticholinergics as potentially confounding factors. We performed a systematic literature search using MEDLINE, Embase, Cochrane library, reference listings, and hand searching with no language restriction through December 2004 and identified 10 clinical, randomized, controlled trials evaluating neostigmine's effect on postoperative nausea and vomiting. Data on nausea or vomiting from 933 patients were extracted for the early (0-6 h), delayed (6-24 h), and overall (0-24 h) postoperative periods and analyzed with RevMan 4.2 (Cochrane Collaboration, Oxford, UK) and multiple logistic regression analysis. The combination of neostigmine with either atropine or glycopyrrolate did not significantly increase the incidence of overall (0-24 h) vomiting (relative risk, 0.91; 95% confidence interval, 0.70-1.18; P = 0.48) or nausea (relative risk, 1.24; 95% confidence interval, 0.98-1.59; P = 0.08). Multiple logistic regression analysis indicated that there was not a significant increase in the risk of vomiting with large compared with small doses of neostigmine. Contrasting a previous analysis, we conclude that there is insufficient evidence to conclude that neostigmine increases the risk of postoperative nausea and vomiting.

Humans↗

Intravenous or enteral loop diuretics for preterm infants with (or developing) chronic lung disease.

BACKGROUND: Lung disease in preterm infants is often complicated with lung edema. OBJECTIVES: The aim of this review was to assess the risks and benefits of administration of a diuretic acting on the loop of Henle (loop diuretic) in preterm infants with or developing chronic lung disease (CLD). Primary objectives were to assess changes in need for oxygen or ventilatory support and effects on long-term outcome, and secondary objectives were to assess changes in pulmonary mechanics and potential complications of therapy. SEARCH STRATEGY: We used the standard search method of the Cochrane Neonatal Review Group. We used the following keywords: ¿ or ¿ and , limited to and limited to or . We searched Medline (1966-1998), Embase (1974-1998) and the Cochrane Controlled Trials Register (CCTR) from the Cochrane Library (1998, issue 4). In addition, we hand searched several abstract books of national and international American and European Societies. SELECTION CRITERIA: We included in this analysis trials in which preterm infants with or developing chronic lung disease and at least 5 days of age were all randomly allocated to receive a loop diuretic either enterally or intravenously. Eligible studies needed to assess at least one of the outcome variables defined a priori for this systematic review. Primary outcome variables included important clinical outcomes, and secondary outcome variables included toxicity and pulmonary mechanics (e.g., lung compliance and airway resistance). DATA COLLECTION AND ANALYSIS: We used the standard method for the Cochrane Collaboration which is described in the Cochrane Collaboration Handbook. Two investigators extracted, assessed and coded separately all data for each study, using a form that was designed specifically for this review. Any disagreement was resolved by discussion. We combined parallel and cross-over trials and, whenever possible, transformed baseline and final outcome data measured on a continuous scale into change scores using Follmann's formula. MAIN RESULTS: The only loop diuretic used in the studies which met the selection criteria was furosemide. Most studies focused on pathophysiological parameters and did not assess effects on important clinical outcomes defined in this review, or the potential complications of diuretic therapy. In preterm infants < 3 weeks of age developing CLD, furosemide administration has either inconsistent effects or no detectable effect. In infants > 3 weeks of age with CLD, a single intravenous dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for 1 hour. Chronic administration of furosemide improves both oxygenation and lung compliance. REVIEWER'S CONCLUSIONS: In preterm infants > 3 weeks of age with CLD, acute and chronic administration of furosemide improve lung compliance. Chronic administration of intravenous or enteral furosemide improves oxygenation. In view of the lack of data from randomized trials concerning effects on important clinical outcomes, routine or sustained use of systemic loop diuretics in infants with (or developing) CLD cannot be recommended based on current evidence. Randomized trials are needed to assess the effects of furosemide administration on survival, duration of ventilatory support and oxygen administration, length of hospital stay, potential complications and long-term outcome.

Chronic Disease↗

Oral immunoglobulin for the prevention of rotavirus infection in low birth weight infants.

BACKGROUND: Rotavirus infection is the most common neonatal nosocomial viral infection. Epidemics with the newer P(6)G9 strains have been reported in neonatal units worldwide. These strains can cause severe symptoms in infected infants. Infection control measures become necessary and the utilisation of hospital resources increase. Local mucosal immunity in the intestine to rotavirus is important in the resolution of infection and protection against subsequent infections. Boosting local immunity by oral administration of anti-rotaviral immunoglobulin preparations might be a useful strategy in preventing rotaviral infections, especially in low birth weight babies. OBJECTIVES: To determine the effectiveness and safety of oral immunoglobulin preparations for the prevention of rotavirus infection in hospitalised low birthweight infants (birth weight less than 2500 gms) SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2002), MEDLINE, EMBASE and CINAHL were searched. Science Citation Index was searched for all articles which referenced Barnes 1982. The proceedings of the Pediatric Academic Societies which were published in the journal, Pediatric Research from 1991 onwards were searched as well as abstracts of doctoral dissertations and theses from 1960 onwards. The above mentioned search strategy was completed in June 2002. Authors prominent in the field were contacted for any unpublished articles and more information on published articles was sought. Reference lists of identified clinical trials and personal files were reviewed. SELECTION CRITERIA: The criteria used to select studies for inclusion were: 1) DESIGN: randomised or quasi-randomised controlled trials. 2) PARTICIPANTS: Hospitalised low birthweight infants. 3) INTERVENTION: Oral immunoglobulin preparations for prevention of rotavirus infection compared to placebo OR no intervention. 4) At least one of the following outcomes were reported: All cause mortality during hospital stay, mortality due to rotavirus infection during hospital stay, rotavirus infection, duration of diarrhoea, need for rehydration, duration of viral excretion, duration of infection control measures, length of hospital stay in days, recurrent diarrhoea or chronic diarrhoea. DATA COLLECTION AND ANALYSIS: The two reviewers independently abstracted data from the included trials MAIN RESULTS: One published study (Barnes 1982) was eligible for inclusion in this review. Two additional studies are awaiting assessment re eligibility for inclusion. Barnes 1982 found no significant difference in the rates of rotavirus infection after oral gammaglobulin versus placebo in hospitalised low birthweight babies [RR 1.27 (95% CI 0.65-2.37)]. In the subset of infants who became infected with rotavirus after receiving gammaglobulin or placebo for prevention of rotavirus infection, there was no significant difference in the duration of rotavirus excretion between the group who had gammaglobulin (mean 2 days, range 1-4 days) and the group who had placebo (mean 3 days, range 1-6 days). No adverse effects were reported by Barnes 1982 after administration of oral immunoglobulin preparations. REVIEWER'S CONCLUSIONS: Current evidence from one randomised controlled trial does not support the routine use of oral immunoglobulin preparations for the prevention of rotavirus infection in low birth-weight infants. However, newer immunoglobulin preparations which have been found to be effective in older children have not been tested in neonatal trials. Therefore, researchers should be encouraged to conduct well designed trials in neonates at risk for rotavirus infections using the newer preparations of anti-rotaviral immunoglobulins (colostrum, egg yolk immunoglobulins). Such trials should also include cost effectiveness evaluations.

Administration, Oral↗

Single dose dihydrocodeine for acute postoperative pain.

BACKGROUND: Dihydrocodeine is a synthetic opioid analgesic developed in the early 1900s. Its structure and pharmacokinetics are similar to that of codeine and it is used for the treatment of postoperative pain or as an antitussive. It is becoming increasingly important to assess the relative efficacy and harm caused by different treatments. Relative efficacy can be determined when an analgesic is compared with control under similar clinical circumstances. OBJECTIVES: To quantitatively assess the analgesic efficacy and adverse effects of single-dose dihydrocodeine compared with placebo in randomised trials in moderate to severe postoperative pain. SEARCH STRATEGY: Published reports were identified from a variety of electronic databases including Medline, Biological Abstracts, Embase, the Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports. SELECTION CRITERIA: The following inclusion criteria were used: full journal publication, clinical trial, random allocation of patients to treatment groups, double blind design, adult patients, pain of moderate to severe intensity at baseline, postoperative administration of study drugs, treatment arms which included dihydrocodeine and placebo and either oral or injected (intramuscular or intravenous) administration of study drugs. DATA COLLECTION AND ANALYSIS: Data collection and analysis: Summed pain intensity and pain relief data over 4-6 hours were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Single-dose adverse effect data were collected and used to calculate relative risk and number-needed-to-harm. MAIN RESULTS: Fifty-two reports were identified as possible randomised trials which assessed dihydrocodeine in postoperative pain. Four reports met the inclusion criteria; all assessed oral dihydrocodeine. Three reports (194 patients) compared dihydrocodeine with placebo and one (120 patients) compared dihydrocodeine (30 mg or 60 mg) with ibuprofen 400 mg. For a single dose of dihydrocodeine 30 mg in moderate to severe postoperative pain the NNT for at least 50% pain relief was 8.1 (95% confidence interval 4.1 to 540) when compared with placebo over a period of 4-6 hours. Pooled data showed significantly more patients to have reported adverse effects with dihydrocodeine 30 mg than with placebo. When compared to ibuprofen 400 mg both dihydrocodeine 30 mg and 60 mg were significantly inferior. REVIEWER'S CONCLUSIONS: A single 30 mg dose of dihydrocodeine is not sufficient to provide adequate pain relief in postoperative pain. Statistical superiority of ibuprofen 400 mg over dihydrocodeine (30 mg or 60 mg) was shown.

Acute Disease↗

Antifungal agents for preventing fungal infections in non-neutropenic critically ill patients.

BACKGROUND: Invasive fungal infections, important causes of morbidity and mortality in critically ill patients, may be preventable with the prophylactic administration of antifungal agents. OBJECTIVES: This study aims to systematically identify and summarize the effects of antifungal prophylaxis in non-neutropenic critically ill adult patients on all-cause mortality and the incidence of invasive fungal infections. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, Issue 3, 2005), MEDLINE (1966 to 2 September 2005), and EMBASE (1980 to week 36, 2005). We also handsearched reference lists, abstracts of conference proceedings and scientific meetings (1998 to 2004), and contacted authors of included studies and pharmaceutical manufacturers. SELECTION CRITERIA: We included randomized controlled trials in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal, or another antifungal agent or regimen in non-neutropenic critically ill adult patients. DATA COLLECTION AND ANALYSIS: Two authors independently applied selection criteria, performed quality assessment, and extracted data using an intention-to-treat approach. We resolved differences by discussion. We synthesized data using the random effects model and expressed results as relative risk with 95% confidence intervals. MAIN RESULTS: We included 12 unique trials (eight comparing fluconazole and four ketoconazole with no antifungal or a nonabsorbable agent) involving 1606 randomized patients. For both outcomes of total mortality and invasive fungal infections, almost all trials of fluconazole and ketoconazole separately showed a non-significant risk reduction with prophylaxis. When combined, fluconazole/ketoconazole reduced total mortality by about 25% (relative risk 0.76, 95% confidence interval 0.59 to 0.97) and invasive fungal infections by about 50% (relative risk 0.46, 95% confidence interval 0.31 to 0.68). We identified no significant increase in the incidence of infection or colonization with the azole-resistant fungal pathogens Candida glabrata or C. krusei, although the confidence intervals of the summary effect measures were wide. Adverse effects were not more common amongst patients receiving prophylaxis. Results across all trials were homogeneous despite considerable heterogeneity in clinical and methodological characteristics. AUTHORS' CONCLUSIONS: Prophylaxis with fluconazole or ketoconazole in critically ill patients reduces invasive fungal infections by one half and total mortality by one quarter. Although no significant increase in azole-resistant Candida species associated with prophylaxis was demonstrated, trials were not powered to exclude such an effect. In patients at increased risk of invasive fungal infections, antifungal prophylaxis with fluconazole should be considered.

Adult↗

Biologic markers in ethylene oxide-exposed workers and controls.

Ethylene oxide (EtO) is an alkylating agent and a model direct-acting mutagen and carcinogen. This study has evaluated a panel of biologic markers including EtO-hemoglobin adducts (EtO-Hb), sister-chromatid exchanges (SCEs), micronuclei, chromosomal aberrations (CAs), DNA single-strand breaks (SSB) and an index of DNA repair (ratio of UDS to NA-AAF-DNA binding) in the peripheral blood cells of 34 workers at a sterilization unit of a large university hospital and 23 controls working in the university library. Comprehensive environmental histories were obtained on each subject including detailed occupational and smoking histories. Industrial hygiene data obtained prior to the study and personal monitoring during the 8 years preceding the study showed that workers were subject to low-level exposure near or below the current Occupational Safety and Health Administration (OSHA) standard of 1 ppm (TWA). Personal monitoring data obtained during 2 weeks prior to blood sampling were uniformly less than 0.3 ppm (TWA). After adjusting for smoking, EtO workplace exposure was significantly (p less than 0.001) associated with EtO-Hb (a carcinogen-protein adduct) and 2 measures of SCEs [the average number of SCEs/cell (SCE50) and the number of high frequency cells (SCEHFC)]. There was an apparent suppression of DNA repair capacity in EtO-exposed individuals as measured by the DNA repair index; i.e., the ratio of unscheduled DNA synthesis (UDS) and NA-AAF-DNA binding (p less than 0.01). No association of DNA repair index with smoking was found. Another important finding of this study is the highly significant correlation between EtO-Hb adduct levels and SCEHFC (p less than 0.01) and SCEs (p less than 0.02) which provides evidence of a direct link between a marker of biologically effective dose and markers of genotoxic response. In contrast, micronuclei, CAs and SSBs were not significantly elevated in the workers. The activity of the u-isoenzyme of glutathione-S-transferase (GT) was measured as a possible genetic marker of susceptibility and a modulator of biomarker formation. However, possibly because of confounding by age, no significant relationships were found between GT and any of the exposure-related markers by ANOVA or among other independent variables by regression. This study demonstrates significant effects of low-level EtO exposure, independent of smoking history, near or below 1 ppm on multiple biomarkers and suggests that the current OSHA standard may not be adequately protective. Previously described effects of smoking on EtO-Hb adducts, SCEs and SCEHFC were also seen in this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Vitamin A for treating measles in children.

BACKGROUND: Measles is a leading cause of childhood morbidity and mortality. Vitamin A deficiency is a recognised risk factor for severe measles. The World Health Organization (WHO) recommends administration of an oral dose of 200,000 IU (or 100,000 IU in infants) of vitamin A per day for two days to children with measles in areas where vitamin A deficiency may be present. OBJECTIVES: The purpose of this review is to determine whether vitamin A when commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other complications in children. SEARCH STRATEGY: MEDLINE and the Cochrane Library, Issue 4, 1999 were searched. SELECTION CRITERIA: Only randomized controlled trials in which children with measles were given vitamin A or placebo along with standard treatment were considered. DATA COLLECTION AND ANALYSIS: Studies were assessed independently by two reviewers. The analysis of dichotomous outcomes was done using the StatExact software package. Sub-group analyses were done for dose, formulation, age, hospitalisation and pneumonia specific mortality. Weighted mean difference with 95% CI were calculated for continuous outcomes. MAIN RESULTS: The relative risks (RR) and 95% Confidence Intervals (CI) are based on the estimates from the StatExact software package. There was no significant reduction in mortality in the vitamin A group when all the studies were pooled together (RR 0.60; 95% CI 0.32 to 1.12)(Statexact estimate). There was a 64% reduction in the risk of mortality in children who were given two doses of 200,000 IU of vitamin A (RR=0.36; 95% CI 0.14 to 0.82) as compared to placebo. Two doses of water based vitamin A were associated with a 81% reduction in risk of mortality (RR=0.19; 95% CI 0.02 to 0.85) as compared to 48% seen in two doses of oil based preparation (RR=0.52; 95% CI 0.16 to 1.40). Two doses of oil and water based vitamin A were associated with a 82% reduction in the risk of mortality in children under the age of 2 years (RR=0.18; 95% CI 0.03 to 0.61) and a 67% reduction in the risk of pneumonia specific mortality (RR=0.33; 95% CI 0.08 to 0.92). There was no evidence that vitamin A in a single dose of 200,000 IU was associated with a reduced risk of mortality among children with measles (RR=0.77; 95% CI 0.34 to 1.78). Sub-groups like age, dose, formulation, hospitalisation and case fatality in the study area were highly correlated and there were not enough studies to separate out the individual effects of these factors. There was a 47% reduction in the incidence of croup (RR=0.53; 95% CI 0.29 to 0.89), while there was no significant reduction in the incidence of pneumonia (RR=0.92; 95% CI 0.69 to 1.22) or of diarrhoea (RR=0.80; 95% CI 0.27 to 2.34). Duration of diarrhoea was measured in days and there was a reduction in its duration of almost two days WMD -1.92, 95% CI -3.40 to -0.44. Only one study evaluated otitis media and found a 74% reduction in its incidence (RR=0.26, 95% CI, 0.05 to 0.92). We did not find evidence that a single dose of 200,000 IU of vitamin A per day, given in oil-based formulation in areas with low case fatality, was associated with reduced mortality among children with measles. However, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. REVIEWER'S CONCLUSIONS: Although we did not find evidence that a single dose of 200,000 IU of vitamin A per day was associated with reduced mortality among children with measles, there was evidence that the same dose given for two days was associated with a reduced risk of overall mortality and pneumonia specific mortality. The effect was greater in children under the age of two years. There were no trials that compared a single dose with two doses, although the precision of the estimates of trials that used a single dose were similar to the trials that used two doses.

Adolescent↗

Antibiotics for community acquired pneumonia in children.

BACKGROUND: Pneumonia is the leading cause of mortality in children. In developing countries, pneumonia is usually caused by bacterial pathogens. The early administration of empirical antibiotics improves the patients' clinical outcomes. There are currently no systematic reviews of clinical trials on this subject. OBJECTIVES: To identify effective antibiotic drug therapy for community acquired pneumonia (CAP) in children by comparing various antibiotics. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2005), MEDLINE (OVID) (1966 to January 2006) and EMBASE (WebSPIRS) (1990 to September 2005). There were no language restrictions. SELECTION CRITERIA: Randomized controlled trials (RCTs) in children of either sex, which compared at least two antibiotics for CAP in hospital or ambulatory settings. DATA COLLECTION AND ANALYSIS: Data from full articles of selected studies were independently extracted by two authors. MAIN RESULTS: The review of these studies suggests that for treatment of pneumonia, co-trimoxazole is inferior in efficacy to both amoxycillin (failure rates odds ratio (OR) 1.33; 95% CI 1.05 to 1.67) and procaine penicillin (cure rates OR 2.64; 95% CI 1.57 to 4.45). Penicillin in conjunction with gentamycin was better than chloramphenicol alone (re-hospitalization rates OR 1.61; 95% CI 1.02 to 2.55). Co-amoxyclavulanic acid was better than amoxycillin alone (cure rates OR 10.44; 95% CI 2.85 to 38.21). There was no differences between injectable penicillin and oral amoxycillin (failure rates OR 1.03; 95% CI 0.81 to 1.31); azithromycin and erythromycin (cure rates OR 1.17; 95% CI 0.70 to 1.95); cefpodoxime and amoxycillin (cure rates OR 0.69; 95% CI 0.18 to 2.60); or azithromycin and co-amoxyclavulanic acid (cure rates OR 1.02; 95% CI 0.54 to 1.95, failure rates OR 1.42; 95% CI 0.43 to 4.66). AUTHORS' CONCLUSIONS: There were many studies each investigating multiple antibiotics with different methodologies. For treatment of ambulatory patients with CAP, amoxycillin was better than co-trimoxazole; there was no difference between azithromycin and erythromycin, or between cefpodoxime and co-amoxyclavulanic acid. For hospitalized patients, procaine penicillin was better than co-trimoxazole; and the combination of penicillin and gentamycin was better than chloramphenicol alone. Injectable penicillin and oral amoxycillin had similar failure rates. For the rest of the antibiotics there were only single studies available. There is a need for more studies with large patient populations and similar methodologies in order to compare newer antibiotics.

Anti-Bacterial Agents↗

Pyrazoloheteroaryls: novel p38alpha MAP kinase inhibiting scaffolds with oral activity.

A test library with three novel p38alpha inhibitory scaffolds and a narrow set of substituents was prepared. Appropriate combination of substituent and scaffold generated potent p38alpha inhibitors, for example, pyrazolo[3,4-b]pyridine 9, pyrazolo[3,4-d]pyrimidine 18a and pyrazolo[3,4-b]pyrazine 23b with potent in vivo activity upon oral administration in animal models of rheumatoid arthritis.

Administration, Oral↗

Bromocriptine in rheumatic and autoimmune diseases.

BACKGROUND AND OBJECTIVES: Multiple lines of evidence support the concept that the anterior pituitary hormone prolactin has a pathogenic role in rheumatic and autoimmune diseases including, but not limited to, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Reiter's syndrome, psoriatic arthritis, and uveitis. Conversely, the dopaminergic agonist bromocriptine appears to have therapeutic effects through suppression of pituitary prolactin secretion and, perhaps, through actions on peripheral dopamine receptors. This article reviews the experimental and clinical data supporting the therapeutic use of bromocriptine as a nonstandard or adjunctive therapy in rheumatic and autoimmune diseases. METHODS: Data addressing the potential therapeutic role of bromocriptine in rheumatic and autoimmune diseases, as well as frequently associated comorbidities, was accumulated from the author's work, online literature search of the National Library of Medicine, and references from these identified publications. RESULTS: There have been a number of clinical therapeutic trials using 2.5 to 30 mg of bromocriptine per day in a single or divided dose, which have shown efficacy with minimal side effects in the treatment of rheumatic and autoimmune diseases. In RA, bromocriptine administration has induced immunosuppression of several immune parameters and has been associated with improvements in morning stiffness, grip strength, numbers of swollen/painful joints, and the Health Assessment Questionnaire disability index. In two blinded studies, bromocriptine reduced the number of SLE flares and was as effective as hydroxychloroquine in reducing lupus disease activity indices, respectively. In case reports, bromocriptine has been used successfully in the treatment of Reiter's syndrome enthesopathy and psoriatic arthritis. The potential efficacy of bromocriptine in the treatment of uveitis and multiple sclerosis is suggested but remains to be verified. CONCLUSIONS: Double-blind, placebo-controlled studies are limited, but clinical observations and trials support the use of bromocriptine as a nonstandard primary or adjunctive therapy in the treatment of recalcitrant RA, SLE, Reiter's syndrome, and psoriatic arthritis and associated conditions unresponsive to traditional approaches. Additional investigation is needed to verify this conclusion and extend preliminary results. RELEVANCE: In patients with rheumatic and autoimmune diseases, bromocriptine may be a relatively safe and efficacious alternative therapy. Semin Arthritis Rheum 31:21-32.

Adjuvants, Immunologic↗

Antibiotics versus placebo for prevention of postoperative infection after appendicectomy.

BACKGROUND: Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. The cause of appendicitis is unclear and the mechanism of pathogenesis continues to be debated. Despite improved asepsis and surgical techniques, postoperative complications, such as wound infection and intraabdominal abscess, still account for a significant morbidity. Several studies implicate that postoperative infections are reduced by administration of antimicrobial regimes. OBJECTIVES: This review evaluated the use of antibiotics compared to placebo or no treatment in patients undergoing appendectomy. Will these patients benefit from antimicrobial prophylaxis? The outcomes were described according to the nature of the appendix, as either simple appendicitis (including the non-infectious stage) and complicated appendicitis. The efficacy of different antibiotic regimens were not evaluated. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (Cochrane Library 2005 issue 1); Pubmed ; EMBASE; and the Cochrane Colorectal Cancer Group Specialised Register (April 2005). In addition, we manually searched the reference lists of the primary identified trials. SELECTION CRITERIA: We evaluated Randomised Controlled Trials (RCTs) and Controlled Clinical Trials (CCTs) in which any antibiotic regime were compared to placebo in patients suspected of having appendicitis, and undergoing appendectomy. Both studies on children and adults were reviewed. The outcome measures of the studies were: Wound infection, intra abdominal abscess, length of stay in hospital, and mortality. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed, recorded and cross-checked by two reviewers. MAIN RESULTS: Forty-five studies including 9576 patients were included in this review. The overall result is that the use of antibiotics is superior to placebo for preventing wound infection and intraabdominal abscess, with no apparent difference in the nature of the removed appendix. Studies exclusively on children and studies examining topical application reported results in favour to the above, although the results were not significant. AUTHORS' CONCLUSIONS: Antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomised patients, whether the administration is given pre-, peri- or post-operatively, and could be considered for routine in emergency appendectomies.

Abdominal Abscess↗