The effectiveness of clinical pathway software in inpatient settings: A systematic review.

BACKGROUND: Various studies have assessed the effectiveness of clinical pathways (CPs) in inpatient settings and provided systematic evidence that they positively affect patient outcomes and efficiency of care, thus lowering costs. In recent years, CP implementation is often combined or extended with clinical pathway software (CPS). Until now, no systematic literature review appears to exist which synthesizes the evidence on the effectiveness of CPS in inpatient settings, in relation to the CPs they support. OBJECTIVES: The purpose of this study was to systematically review evidence on (perceived) effectiveness of clinical pathway software (CPS) and investigate mechanisms explaining the effects of CPS implementation on outcomes. METHODS: We searched MEDLINE via PubMed and Scopus, for English-language original articles. Articles were included if they examined the effectiveness and/or the perceived effectiveness of CPS in the inpatient setting. They were analyzed for evidence on structure, process and outcome effects, as well as for mechanisms explaining such effects in relation to contextual factors. RESULTS: From 2904 articles, 12 studies met our inclusion criteria. The seven studies reporting on adherence provide conclusive evidence that CPSs can improve adherence. We also found conclusive evidence of improvement of process related measures regarding appropriate diagnostics, timeliness of care, and length of stay (LOS). Evidence on costs and outcomes is weak and/or less conclusive. This holds true both for patient outcomes (e.g. mortality/patient satisfaction) and caregiver outcomes (e.g. user satisfaction). The studies presented no direct evidence on mechanisms explaining how CPS relate to process and outcome improvements. CONCLUSIONS: The primary effects of CPS to increase adherence may in turn positively impact other process indicators such as LOS, timeliness of care, and diagnostic effectiveness. Subsequent effects on costs, outcomes for patients, physicians and nurses remain inconclusive and call for further research. Further research should explicitly take context into account. The scarce and weak evidence-base relating CPS implementation to process and outcome effects needs development along the same lines.

Perceived effectiveness of clinical pathway software: A before-after study in the Netherlands.

BACKGROUND: Clinical pathways (CPs) increase in popularity and are known to lead to several benefits in the hospital environment. Clinical pathways can be either paper-based or software-based. It is known that paper-based CPs can result in more paperwork instead of simplifying daily routines of healthcare workers. Insufficient research has been done on the acceptance of software-based CPs by different user groups. Our aim in this study was to assess the effectiveness of the software-based CPs (CPS) from the perspective of healthcare professionals in the hospital environment as well as to investigate the differences in perceived effectiveness between user groups. METHODS: Using surveys and interviews, data were collected in four departments of an academic medical center. A distinction was made between decision makers (DM) and executive staff (ES). The surveys contained questions based on the Technology Acceptance Model and four objectives of the software defined by the hospital. Statistical tests were used to investigate the effectiveness of CPS and study the differences between DM and ES. Interviews were recorded and transcribed based on grounded theory principals. RESULTS: After implementation, monitoring protocol-based working was significantly improved (p = .026) and significantly higher efficiency on the work floor was reported (p = .046). ES perceived the software as less useful than expected (Md = 3.25 vs. Md = 2.75, p = .028) compared to DM and were less convinced of its ability to improve monitoring protocol-based working. The most important benefits of CPS as perceived by its users are the better overview of tasks it provides and facilitating documentation. Negative aspects mentioned were the lack of usability and the inflexibility of the software, and particularly ES claimed that the software did not increase their effectiveness. CONCLUSION: Our study showed that CPS is effective from healthcare professionals' perspective due to its ability to increase monitoring of protocol-based working and by enhancing the efficiency on the work floor. However, the users also acknowledge that the software lacks usability and is not flexible enough, which results in an additional workload. Policy makers should be more focused on informing and training executive staff more thoroughly when implementing a CPS. Our results strongly suggest that executive staff members need to be convinced of its usefulness and the added value a CPS provides. Preferably, they should be involved in the design phase of the software.

Pros and Cons of Clinical Pathway Software Management: A Qualitative Study.

In this study we aimed to assess the perceived effectiveness of clinical pathway management software for healthcare professionals. A case study on the clinical pathway management software program Check-It was performed in three departments at an academic medical center. Four months after the implementation of the software, interviews were held with healthcare professionals who work with the system. The interview questions were posed in a semi-structured interview format and the participant were asked about the perceived positive or negative effects of Check-It, and whether they thought the software is effective for them. The interviews were recorded and transcribed based on grounded theory, using different coding techniques. Our results showed fewer overlooked tasks, pre-filled orders and letters, better overview, and increased protocol insight as positive aspects of using the software. Being not flexible enough was experienced as a negative aspect.

Aberrant promoter hypermethylation of selected apoptotic genes in childhood acute lymphoblastic leukemia among North Indian population.

Promoter hypermethylation mediates gene silencing in many neoplasms. Acute leukemia has been reported to harbor multiple genes aberrantly silenced by hypermethylation. AIM: In present study, we investigated the prevalence of hypermethylation of caspase-8 (CASP8), TMS1 and DAPK genes in correlation with clinicopathological factors in childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A case-control study has been conducted based on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls. Methylation specific polymerase chain reaction (PCR) and bisulfite sequencing PCR was performed to analyze the methylation status of these genes. Reverse transcription PCR and real time PCR was carried out to determine changes in the mRNA expression level of the genes due to hypermethylation. RESULTS: Hypermethylation of the 5´CpG islands of the CASP8, TMS1 and DAPK gene promoters was found in 3.2, 6.4, and 13.6% of 125 childhood ALL samples from north Indian population, respectively. There were significant differences in pattern of hypermethylation of TMS1 (p = 0.045) and DAPK (p < 0.001) between patients and healthy controls. Down-regulation of mRNA expression was found in cases in which CASP8, TMS1 and DAPK were hypermethylated. CONCLUSIONS: The present study indicated the impact of hypermethylation-mediated inactivation of CASP8, TMS1 and DAPK genes, which is associated with risk of childhood ALL. This abnormality occurs in leukemogenesis and it may be used as a biomarker and for predicting the prognosis of ALL.

Assessment of the quality of fall detection and management in primary care in the Netherlands based on the ACOVE quality indicators.

UNLABELLED: We determined adherence to nine fall-related ACOVE quality indicators to investigate the quality of management of falls in the elderly population by general practitioners in the Netherlands. Our findings demonstrate overall low adherence to these indicators, possibly indicating insufficiency in the quality of fall management. Most indicators showed a positive association between increased risk for functional decline and adherence, four of which with statistical significance. INTRODUCTION: This study aims to investigate the quality of detection and management of falls in the elderly population by general practitioners in the Netherlands, using the Assessing Care of Vulnerable Elders (ACOVE) quality indicators. METHODS: Community-dwelling persons aged 70 years or above, registered in participating general practices, were asked to fill in a questionnaire designed to determine general practitioner (GP) adherence to fall-related indicators. We used logistic regression to estimate the association between increased risk for functional decline-quantified by the Identification of Seniors At Risk for Primary Care score-and adherence. We then cross-validated the self-reported falls with medical records. RESULTS: Of the 950 elders responding to our questionnaire, only 10.6 % reported that their GP proactively asked them about falls. Of the 160 patients who reported two or more falls, or one fall for which they visited the GP, only 23.1 % had fall documentation in their records. Adherence ranged between 13.6 and 48.6 %. There was a significant positive association between the ISAR-PC scores and adherence in four QIs. Documentation of falls was highest (36.7 %) in patients whom the GP had proactively asked about falls. CONCLUSION: Based on patient self-reports, adherence to the ACOVE fall-related indicators was poor, suggesting that the quality of evaluation and management of falls in community-dwelling older persons in the Netherlands is poor. The documentation of falls and fall-related risk factors was also poor. However, for most QIs, adherence to them increased with the increase in the risk of functional decline.

Tissue fatty acid composition and secretory phospholipase-A2 activity in oral squamous cell carcinoma

Purpose: Oral squamous cell carcinoma (OSCC) is a remarkable health problem worldwide, but its pathogenesis remains unknown. The aim of this study was to compare fat composition and secretory phospholipase-A2 (sPLA2) activity between the malignant and adjacent normal squamous tissues in patients with OSCC. Methods: Paired samples of malignant squamous and adjacent normal-appearing tissues were collected from 27 patients with OSCC. The fatty acid composition in the obtained tissues was determined by gas liquid chromatography. Tissue enzyme activities of sPLA2 were measured using the standard assay with Diheptanoyl Thio-Phosphatidylcholine as substrate. Results: In the OSCC tissue, the level of stearic acid (18:0) and activity of sPLA2 were higher (P < 0.001), and the levels of oleic acid (18:1n-9) and linoleic acid (18:2n-6) were lower than that in the adjacent normal-appearing squamous tissue (P < 0.001). The activity of sPLA2 in OSCC was strongly negatively correlated with the amount of 18:2n-6 (r = −0.41, P < 0.001). Negative significant associations were observed between the OSCC invasion and tissue levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHE). Conclusion: The changes in the fatty acid composition and sPLA2 activity may be regarded as indicators of altered lipid metabolism occurring in vivo during squamous cell carcinogenesis (AU)

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Catalytic aerobic oxidation of phenols to ortho-quinones with air-stable copper precatalysts.

A range of air-stable copper species was examined for catalytic activity in the catalytic aerobic transformation of phenols into ortho-quinones. Efficient catalysis was obtained with commercially available copper(II) acetate. The stability of all constituents before mixing makes for a practical process that advances previously reported copper(I)-based oxygenations.

Tissue fatty acid composition and secretory phospholipase-A2 activity in oral squamous cell carcinoma.

PURPOSE: Oral squamous cell carcinoma (OSCC) is a remarkable health problem worldwide, but its pathogenesis remains unknown. The aim of this study was to compare fat composition and secretory phospholipase-A2 (sPLA2) activity between the malignant and adjacent normal squamous tissues in patients with OSCC. METHODS: Paired samples of malignant squamous and adjacent normal-appearing tissues were collected from 27 patients with OSCC. The fatty acid composition in the obtained tissues was determined by gas liquid chromatography. Tissue enzyme activities of sPLA2 were measured using the standard assay with Diheptanoyl Thio-Phosphatidylcholine as substrate. RESULTS: In the OSCC tissue, the level of stearic acid (18:0) and activity of sPLA2 were higher (P < 0.001), and the levels of oleic acid (18:1n-9) and linoleic acid (18:2n-6) were lower than that in the adjacent normal-appearing squamous tissue (P < 0.001). The activity of sPLA2 in OSCC was strongly negatively correlated with the amount of 18:2n-6 (r = -0.41, P < 0.001). Negative significant associations were observed between the OSCC invasion and tissue levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHE). CONCLUSION: The changes in the fatty acid composition and sPLA2 activity may be regarded as indicators of altered lipid metabolism occurring in vivo during squamous cell carcinogenesis.

Polymorphisms of MTHFR and MTR genes are not related to susceptibility to childhood ALL in North India.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most worldwide common type of childhood cancer. Methylenetetrahydrofolate reductase (MTHFR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) participate in folate pathways and are known as critical factors for DNA integrity as well as DNA hypomethylation. The aim of this work is to investigate frequency of MTHFR (677C→T and 1298A→C) and MTR (2756A→G) polymorphisms and their interaction with respect to possible effect on risk of childhood ALL among North Indian population. PROCEDURE: A case control study from has been conducted on bone marrow and peripheral blood samples from 125 ALL patients and 100 sex-age matched healthy controls using PCR-RFLP method. RESULTS: No statistically significant differences were observed for different genotypes between patients and controls (p>0.05). Significant difference for the risk of ALL in individuals having genotype of MTHFR 677TT (OR=0.61, 95% CI=0.21-1.77) and MTHFR 1298CC (OR=0.56, 95% CI=0.18-1.68) was not observed. The correlation of SNP of MTR gene and risk of ALL was not observed, too. CONCLUSIONS: The differences in distribution of possible combined genotypes of MTHFR (677C→T, 1298A→C) and MTR (2756A→G) between ALL patients and controls were statistically insignificant.

The -137G/C polymorphism of interleukin 18 promoter and risk of HIV-1 infection and its progression to AIDS.

A growing body of evidence suggests that host genetic factors play an important role both in susceptibility to human immunodeficiency virus 1 (HIV-1) infection and in progression to AIDS. Interleukin 18 (IL-18) is a pleiotropic proinflammatory cytokine that serves as an important regulator of immune responses. It plays a key role in induction of both Th1 and Th2 cytokines and, thereby, modulates their immune responses. Single nucleotide polymorphisms in the IL-18 gene promoter region may lead to an altered transcriptional activity and IL-18 production, and so this may account for individuals' variation to the risk of HIV-1 infection. With this perspective, the -137G/C polymorphism in the promoter region of the IL-18 gene was studied in 500 patients with HIV-1/AIDS and an equal number of sex and age matched healthy controls using sequence specific polymerase chain reaction analysis. We did not observe any significant association of the heterozygous G/C genotype with the risk of HIV-1-infection/AIDS. However, statistically significant associations of the G allele and homozygous G/G genotype of -137 G/C polymorphism of IL-18 promoter with increased risk of HIV-1/AIDS were identified. The data of the present study suggest that IL-18 -137 G allele and G/G genotype seem to be involved in the pathogenesis of HIV-1 infection among North Indians.

Reducing the absorbed dose in analogue radiography of infant chest images by improving the image quality, using image processing techniques.

Radiographic inspection is one of the most widely employed techniques for medical testing methods. Because of poor contrast and high un-sharpness of radiographic image quality in films, converting radiographs to a digital format and using further digital image processing is the best method of enhancing the image quality and assisting the interpreter in their evaluation. In this research work, radiographic films of 70 infant chest images with different sizes of defects were selected. To digitise the chest images and employ image processing the two algorithms (i) spatial domain and (ii) frequency domain techniques were used. The MATLAB environment was selected for processing in the digital format. Our results showed that by using these two techniques, the defects with small dimensions are detectable. Therefore, these suggested techniques may help medical specialists to diagnose the defects in the primary stages and help to prevent more repeat X-ray examination of paediatric patients.

A closed form for the electrostatic interaction between two rod-like charged objects.

We have calculated the electrostatic interaction between two rod-like charged objects with arbitrary orientations in three dimensions. We obtained a closed-form formula expressing the interaction energy in terms of the separation distance between the centers of the two rod-like objects, r, their lengths (denoted by 2l1 and 2l2) and their relative orientations (indicated by θ and φ). When the objects have the same length (2l1 = 2l2 = l), for particular values of separations, i.e. for r ≤ 0.8l, two types of minimum appear in the interaction energy with respect to θ. By employing the closed-form formula and introducing a scaled temperature t, we have also studied the thermodynamic properties of a 1D system of rod-like charged objects. For different separation distances, the dependence of the specific heat of the system to the scaled temperature has been studied. It is found that, for r < 0.8l, the specific heat has a maximum.

IL-18 Gene Promoter Region 607C/A Polymorphism in HIV-1 Infected North Indian Population.

Several host genetic factors play an important role in susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and in its progression to acquired immune deficiency syndrome (AIDS). The interleukin-18 (IL-18) is a multifunctional proinflammatory cytokine that regulates immune responses and plays a pathogenic role in HIV-1 infection by enhancing viral replication. Single nucleotide polymorphisms (SNPs) in the IL-18 gene promoter region may lead to altered transcriptional activity and IL-18 production, and may account for variation in the risk of HIV-1 infection. We have investigated the association between IL-18 promoter polymorphism -607C>A and HIV-1 infection through a case-control study of 500 patients with HIV-1/AIDS and an equal number of age and sex matched controls in a north Indian population. Genotyping using sequence specific primer-polymerase chain reaction (SSP-PCR) showed a statistically significant reduced risk of HIV-1 infection for the A>A genotype [odds ratio (OR) = 0.57, 95% confidence interval (95% CI) = 0.33-0.98, p = 0.040], but not for the C>A genotype (OR = 0.87, 95% CI = 0.66-1.14, p = 0.321). We concluded that the -607A allele of the IL-18 gene promoter polymorphism may play a protective role against the progression of HIV-1 infection in this population.

Microarray sampling-platform fabrication using bubble-jet technology for a biochip system.

The fabrication of microarrays containing PCR-amplified genomic DNA extracts from mice tumors on a Zetaprobe membrane using a modified thermal ink-jet printer is described. A simple and cost-effective procedure for the fabrication of microarrays containing biological samples using a modified bubble-jet printing system is presented. Because of their mass-produced design, ink-jet printers are a much cheaper alternative to conventional spotting techniques. The usefulness of the biochip microarray platform is illustrated by the detection of human fragile histidine triad (FHIT), a tumor suppressor gene. Subcutaneous carcinomas were induced with MKN/FHIT and MKN/E4 cell lines in immunodeficient mice. Several weeks into their development, the tumors from both groups of mice were removed and subjected to DNA extraction by lysis of tissue samples. The extracted DNA samples were amplified by PCR (30 cycles) using the primers corresponding to nucleotides 2 to 18 of the FHIT sequence. The resulting solution was transferred to the individual reservoirs of a three-color cartridge from a conventional thermal ink-jet printer (HP 694C), and arrays were printed on to a Zetaprobe membrane. After spotting, these membranes were used in a hybridization assay, using fluorescent probes, and detected with a biochip.

Application of an antibody biochip for p53 detection and cancer diagnosis.

Detection of the p53 tumor suppressor gene is important in early cancer diagnostics because alterations in the gene have been associated with carcinogenic manifestations in several tissue types in humans. We have developed an antibody-based detection instrument, the biochip, to detect the presence of the anti-p53 antibody in human serum. The design of this highly integrated detector system is based on miniaturized phototransistors having multiple optical sensing elements, amplifiers, discriminators, and logic circuitry on an IC board. The system utilizes laser excitation and fluorescence signals to detect complex formation between the p53 monoclonal antibody and the p53 antigen. Recognition antibodies are immobilized on a nylon membrane platform and incubated in solutions containing antigens labeled with Cy5, a fluorescent cyanine dye. Subsequently, this membrane is placed on the detection platform of the biochip and fluorescence signal is induced using a 632.8-nm He-Ne laser. Using this immuno-biochip, we have been able to detect binding of the p53 monoclonal antibody to the human p53 cancer protein in biological matrices. The performance of the integrated phototransistors and amplifier circuits of the biochip, previously evaluated through measurement of the signal output response for various concentrations of fluorescein-labeled molecules, have illustrated the linearity of the microchip necessary for quantitative analysis. The design of this biochip permits sensitive, selective and direct measurements of a variety of antigen-antibody formations at very low concentrations. Furthermore, the acquisitions of the qualitative and quantitative results are accomplished rapidly, in about 15 min. These features demonstrate the potential of this antibody-based biochip for simple, rapid and early biomedical diagnostics of cancer.

Estrogenic and DNA-damaging activity of Red No. 3 in human breast cancer cells.

Exposure to pesticides, dyes, and pollutants that mimic the growth promoting effects of estrogen may cause breast cancer. The pesticide DDT and the food colorant Red No. 3 were found to increase the growth of HTB 133 but not estrogen receptor (ER) negative human breast cells (HTB 125) or rat liver epithelial cells (RLE). Red No. 3, beta-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. Site-specific DNA binding by p53 in RLE, HTB 125, HTB 133, and MCF-7 cells was increased when they were treated with Red No. 3, which suggests that cellular DNA was damaged by this colorant. Red No. 3 increased binding of the ER from MCF-7 cells to the estrogen-responsive element. Consumption of Red No. 3, which has estrogenlike growth stimulatory properties and may be genotoxic, could be a significant risk factor in human breast carcinogenesis.

DDT mimicks estradiol stimulation of breast cancer cells to enter the cell cycle.

Estrogens play a critical role in the etiology of found breast cancer. Estradiol promotes the growth of breast cancer cells in vivo and in vitro. Exogenous estrogens in both the environment and in the human diet increase the growth of breast cancer cells in vitro. A role for xenoestrogens in breast cancer etiology has been proposed but remains controversial. We examined the effects of the xenoestrogenic pesticide 1,1,1-trichloro-2,2-bis(chlorophenyl)ethane (DDT) on estrogen-receptor (ER)-positive MCF-7 and T-47D human breast cancer cells as well as on ER-negative HS 578Bst breast cancer cells and rat liver cells. Estradiol and DDT were found to increase the growth of MCF-7 cells in the presence of insulin. The activity of cyclin-dependent kinase (Cdk)2 increased in growth-arrested T-47D and MCF-7 cells treated with beta-estradiol or DDT. The steroidal antiestrogen ICI 182,780 prevented both growth and Cdk2 activation induced by estradiol or DDT. Increased phosphorylation of Cdk2 and the retinoblastoma protein (pRb1O5) was observed in ER-positive cells treated with DDT or estradiol. Cdk2 activity was not affected by DDT or estradiol in ER-negative HS 578Bst breast cancer cells or in rat liver epithelial cells. Cyclin D1 protein synthesis was increased by DDT and estradiol in MCF-7 cells. DDT and estradiol-induced ER-dependent transcriptional activation of estrogen response elements (EREs) in stably transfected MVLN cells, and ERE activation by low doses of DDT was increased by insulin. These findings suggest that DDT can stimulate breast cancer cells to enter into the cell cycle by directly affecting key regulatory elements. The relative potency of DDT in inducing cell-cycle progression appears to be only 100-300 times less than that of estradiol when measured in the presence of insulin. Therefore, the cancer risks associated with DDT exposure may be greater than first thought, especially when additional mitogenic stimuli are present.

Carcinogenic potential of benzene and toluene when evaluated using cyclin-dependent kinase activation and p53-DNA binding.

Benzene is carcinogenic, whereas toluene is thought to have little carcinogenic potential. Benzene and toluene were found to activate cyclin-dependent kinase 2 in rat liver epithelial (RLE) and HL60 cells. pRb105 was hyperphosphorylated in RLE cells treated with either solvent. Kinase activation and subsequent hyperphosphorylation of pRb105 and p53 by benzene or toluene may be responsible for their growth promotional effects, but it does not account for increased potential of benzene to induce cancer. Therefore, we examined the ability of these solvents to increase p53-DNA site-specific binding in RLE cells. Benzene increased p53-DNA site-specific DNA binding in RLE cells compared to control levels or the effects of toluene. Increased p53-DNA site-specific binding by benzene may be caused by damage to cellular DNA. If so, although both solvents appear to have promotional activity, the increased potential of benzene to damage DNA may be responsible to the difference in the ability of benzene to cause cancer.

Effectiveness of Purge-and-Trap for Measurement of Volatile Organic Compounds in Aged Soils.

The U.S. EPA-recommended method for measurement of trace levels of volatile organic compounds (VOCs) in soil, purge-and-trap, measures the readily desorbable organic contaminants from soil pore spaces and external soil surfaces. It does not, however, measure contamination that has diffused into internal micropores of soil matrix. Thus, the purge-and-trap method measures only a small fraction of total soil contaminants, especially in long-contaminated soils, where ∼90-99% of contamination may be in the interior of the soil matrix. We compared three methods for determination of VOCs in aged field samples: purge-and-trap, methanol immersion, and hot solvent extraction. Hot solvent extraction proved to be much more effective than the U.S. EPA-approved purge-and-trap technique. For three long-contaminated soils containing such VOCs as trichloroethene, benzene, toluene, chloroform, methylene chloride, and cis-1,1-dichloroethylene, recovery from purge-and-trap ranged between 1.5 and 41.3% that of hot solvent extraction. Our data show that purge-and-trap may not be the best methodology for measuring soil VOCs concentrations, particularly in aged soils. It is clear from this and previous studies that the best overall choice for soil VOCs measurements is hot solvent extraction. These results also indicate the inefficiency of purge-and-trap as a method for evaluating vapor extraction remediation technology. Our results suggest that the EPA should review the use of the purge-and-trap method for measuring VOCs concentrations in soils.