Use of a door handle disinfection system to reduce the risks associated with microbial loads on fomites in a healthcare setting.

BACKGROUND: Pathogenic organisms, including those that are multidrug resistant, can survive for extended periods of time on surfaces. Numerous studies show that contaminated hand-touch sites, such as door handles, pose a serious risk for onward transfer to patients. AIM: To compare microbial levels on the handles of ten frequently used door locations, with and without a door handle disinfection system in place, in a busy rehabilitation unit consisting of two wards at the National Orthopaedic Hospital, Dublin. METHODS: A door handle disinfection system (Handle Hygiene®), utilizing an atomizing pump (non-aerosol), automatically delivered a pulse of disinfectant to a door handle each time the door was used. Microbial levels on the handles of frequently used door locations were monitored over a 16-week period, to compare microbial loads with and without a door handle disinfection system in place. Samples of two disinfectant types, Steri-7 (broad-spectrum disinfectant) and Dew (hypochlorous acid), were used in the study. FINDINGS: Levels of ≤2.5 cfu/cm2 were recorded on 93% of samples collected where a door handle disinfection system was in use, with 66% of samples showing no microbes recovered. Where a level of >2.5 cfu/cm2 was recorded, the door handle disinfection system reduced this to a negligible level by the time the next sample was taken, compared with several days where no system was in place. CONCLUSION: Door handle disinfection systems offer an effective solution to reducing microbial levels on frequently touched door handles, as an automated solution with minimal additional costs.

A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result.

BACKGROUND: New screening methods that can add predictive diagnostic value for aggressive (high-grade, Gleason score ⩾ 7) prostate cancer (PCa) are needed to reduce unnecessary biopsies for patients with non-aggressive PCa. This is particularly important for men presenting for an initial biopsy with an equivocal PSA in the 2-10 ng ml(-1) range. PCA3 and ERG are biomarkers that can add predictive value for PCa in urine; however, with a limited utility as a digital rectal exam (DRE) is required. METHODS: First-catch urine samples were collected at six sites from men scheduled to undergo a prostate biopsy. Exosomal RNA was extracted, RNA copy numbers of ERG and PCA3 were measured by reverse transcription-quantitative PCR (RT-qPCR), and the EXO106 score (the sum of normalized PCA3 and ERG RNA levels) was computed. Performance was compared with standard of care (SOC; PSA, age, race or family history) parameters. Contingency table, logistic regression, receiver operating characteristics curve and box-plot analyses were performed. RESULTS: In this cohort (N=195), a dichotomous EXO106 score demonstrated good clinical performance in predicting biopsy result for both any cancer and high-grade disease. For high-grade disease, the negative and positive predictive values were 97.5% and 34.5%, respectively. The discrimination between high-grade and Gleason score ⩽ 6 (including benign) biopsy results by a combination of EXO106 and SOC (area under the curve (AUC)=0.803) was significantly improved compared with SOC without EXO106 (AUC=0.6723, P=0.0009). The median EXO106 score correlated (P<0.001; Spearman's rank order) with histologic grade. CONCLUSIONS: A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with 'gray zone' serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.

Capecitabine in the treatment of colorectal cancer.

The fluorinated pyrimidines have been an important part of cancer treatment since the introduction of 5-fluorouracil several decades ago. Capecitabine is an oral fluoropyrimidine which is converted to 5-fluorouracil primarily in tumor tissue, and has the advantages of ease-of-administration, acceptable toxicity and significant antineoplastic activity. It is currently the only oral fluoropyrimidine approved for use in USA, and has an established role as monotherapy in the treatment of metastatic breast and colorectal cancers. Moreover, the addition of capecitabine to docetaxel in anthracycline-pretreated metastatic breast cancer significantly improved overall survival. The toxicity profile of capecitabine includes hand-foot syndrome, stomatitis and diarrhea, with minimal hematologic side effects. The combination of capecitabine with other anticancer agents is currently being investigated. The focus of the present article will be the role of capecitabine in the treatment of colorectal cancer.

Oral cancer treatment: developments in chemotherapy and beyond.

Oncology is one of the few areas of medicine where most patients are treated intravenously rather than receiving oral drugs. Recently, several oral anti-cancer drugs have been approved and there are many more in development. Oral chemotherapy is attractive because of its convenience and ease of administration, particularly in the palliative setting. With an increasing number of oral agents emerging, we can expect to see a rapid rise in the use of oral chemotherapy in years to come. This article reviews recent developments in oral chemotherapy, both of traditional cytotoxics and novel, targeted agents, from the viewpoint of patients, physicians, drug developers and health-care providers.

A dose-finding study of carboplatin-epirubicin-docetaxel in advanced epithelial ovarian cancer.

The docetaxel-carboplatin combination is active and well tolerated in patients with epithelial ovarian cancer. We added epirubicin to this combination to investigate additional benefits of anthracyclines in epithelial ovarian cancer. Twenty-one patients, FIGO Ic-IV, performance status 0-1, were treated in four dose cohorts. Docetaxel was fixed at 75 mg m(-2), carboplatin doses were AUC 4-5 and epirubicin doses were 50-60 mg m(-2). Drugs were given on day 1, every 3 weeks, except in cohort 3, where epirubicin was given on day 8. Dexamethasone was given prophylactically. One dose-limiting toxicity occurred in cohorts 1, 2 and 4, two occurred in cohort 3. Complicated neutropenia occurred in two patients in cohorts 1 and 2 and one patient in cohorts 3 and 4. Two patients experienced grade III diarrhoea or stomatitis in cohort 1 and two in cohort 3. There were no treatment-related deaths. Grade II sensory neuropathy occurred in one patient. No cardiac toxicity or significant oedema was observed. The overall response rate was 36%, and 62% were CA125 responders. The predefined maximum tolerated dose was exceeded in cohort 3. The cohort 4 dose level (epirubicin 50 mg m(-2), carboplatin AUC 4, docetaxel 75 mg m(-2)), warrants further study.

Phase I trial of intraperitoneal injection of the E1B-55-kd-gene-deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer.

PURPOSE: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the E1B 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. PATIENTS AND METHODS: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 x 10(9) plaque forming units (pfu), 1 x 10(10) pfu, 3 x 10(10) pfu, and 1 x 10(11) pfu. RESULTS: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 x 10(10) pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reached at 10(11) pfu, and at this dose level patients did not experience significant toxicity. There was no clear-cut evidence of clinical or radiologic response in any patient. Blood samples were taken for adenovirus DNA and neutralizing antibodies. Polymerase chain reaction data indicating presence of virus up to 10 days after the final (day 5) infusion of dl1520 are suggestive of continuing viral replication. CONCLUSION: This article therefore describes the first clinical experience with the intraperitoneal delivery of any replication-competent/-selective virus in cancer patients.

Spontaneous acute tumour lysis syndrome in patients with metastatic germ cell tumours. Report of two cases.

Acute tumour lysis syndrome (TLS), a condition resulting from rapid destruction of tumour cells with massive release of cellular breakdown products, has been described following the treatment of various malignancies. However, spontaneous TLS has been described only rarely. Germ cell tumours (GCT) have a rapid cell turnover and often present with bulky metastatic disease. We report two cases of patients with metastatic GCT presenting with acute renal failure attributable to spontaneous TLS. All clinical and biochemical features of the syndrome were present. Both patients were treated with haemodialysis and intravenous administration of single-agent etoposide between dialysis sessions, resulting in recovery of renal function and marked decrease in tumour bulk within the first week after presentation. These cases are the first reported instances of spontaneous TLS in poor-risk metastatic GCT. Successful treatment with dialysis and chemotherapy is possible, and prophylactic vigorous hydration and allopurinol may be warranted in this setting.

A retrospective analysis of Hickman line-associated complications in patients with solid tumours undergoing infusional chemotherapy.

We present a retrospective analysis of Hickman line use and associated complications in patients with solid tumours undergoing treatment with infusional chemotherapy. One hundred and ten lines were inserted in 94 patients (55 females and 39 males, median age 51), of whom 107 were placed under radiological screening, the remainder by a surgical approach. Catheters were in situ for a total of 9670 days (median 101 days, range 1-278). Fifty-five complications occurred during the lifespan of 39 catheters (35.5%), giving an overall complication rate of 4.03/1000 catheter days. Early complications included pneumothorax (4%), arterial puncture (1%) and failure of placement (1%). Late complications included sepsis (superficial and systemic) (24.5%), venous thrombosis (9%), line displacement (10%) and catheter blockage (1%). Fifteen episodes of systemic sepsis occurred in 12 patients, giving an overall sepsis rate of 1.55/1000 catheter days, while complications requiring catheter removal occurred in 20 cases (18% of insertions, 2.07/1000 catheter days). We conclude that the use of Hickman catheters as a means of long-term venous access in infusional chemotherapy patients is generally safe, but is associated with significant morbidity.

Outpatient management of deep vein thrombosis.

OBJECTIVE: To assess whether patients with deep vein thrombosis (DVT) could be satisfactorily treated on an outpatient basis with low molecular weight (LMW) heparin and warfarin. DESIGN: A 22 month prospective study of adults attending St Peter's Hospital accident and emergency department with DVT. RESULTS: 1093 patients were referred and assessed; 160 were venogram positive, of which 159 patients between the ages of 22 and 89 years of age have now been treated with LMW heparin as outpatients. Direct liaison with community nurses has minimised the impact on general practitioner workload. CONCLUSIONS: 1272 bed days were saved during this period (an estimated 320,000 pounds). The outpatient treatment of thromboembolism has been shown to be effective and safe.

Agreement between company-recorded and self-reported estimates of duration and frequency of occupational fumigant exposure.

Investigators must often rely on self-reported work history information collected with questionnaires. However, little is known about the agreement between self-reported estimates of exposure and records kept by companies. As part of a cross-sectional medical study of structural fumigation workers, self-reported work history information was collected on both duration and frequency of exposure using an interviewer-administered questionnaire. All company records available on these workers were also collected. Only 15 of 81 structural fumigation companies identified by study participants as current or past structural fumigation employers had records suitable for comparison. These 15 companies employed 32 of the workers who participated in the cross-sectional medical study. The exposure information provided by the 32 workers was compared to information obtained from company records. By examining the agreement between these two data sources, potential limitations were identified in both the self-reported and company-recorded exposure data. By recognizing these limitations in the exposure data, we identified the most appropriate exposure measures to be used in subsequent data analyses. This exercise also demonstrated the difficulties in undertaking these exposure comparisons in an industry consisting of many small, independent companies. Similar difficulties with assessing exposures may be experienced by investigators studying other service industries consisting of many small, independent companies (e.g., dry cleaning, auto repair).

Audit of oxygen therapy.

We audited the use of oxygen in our hospital. Over three days we found 119 patients using oxygen, 21 wearing their mask incorrectly or not at all. The commonest indication was chronic obstructive pulmonary disease. Forty patients had no record of arterial gas analysis. Of those who had, 29 did not require oxygen and the average time from last arterial gas analysis was 5.7 days and only eight patients were being monitored with an oximeter. Taking into account the risk of exacerbating carbon dioxide retention and the problems that arise when discharging a patient who has been receiving oxygen therapy for the duration of their admission, we fee oxygen therapy should only be administered with the knowledge of the arterial gases and with frequent reassessment during therapy.

Conserved sequences in both coding and 5' flanking regions of mammalian opal suppressor tRNA genes.

The rabbit genome encodes an opal suppressor tRNA gene. The coding region is strictly conserved between the rabbit gene and the corresponding gene in the human genome. The rabbit opal suppressor gene contains the consensus sequence in the 3' internal control region but like the human and chicken genes, the rabbit 5' internal control region contains two additional nucleotides. The 5' flanking sequences of the rabbit and the human opal suppressor genes contain extensive regions of homology. A subset of these homologies is also present 5' to the chicken opal suppressor gene. Both the rabbit and the human genomes also encode a pseudogene. That of the rabbit lacks the 3' half of the coding region. Neither pseudogene has homologous regions to the 5' flanking regions of the genes. The presence of 5' homologies flanking only the transcribed genes and not the pseudogenes suggests that these regions may be regulatory control elements specifically involved in the expression of the eukaryotic opal suppressor gene. Moreover the strict conservation of coding sequences indicates functional importance for the opal suppressor tRNA genes.

A human opal suppressor tRNA gene and pseudogene.

A human DNA library, cloned in bacteriophage lambda, was screened with an opal suppressor tRNA probe. Two genes were isolated, subcloned into pBR322, and sequenced. One is a normal opal suppressor tRNA gene 87 nucleotides in length without intervening sequences. It has a TCA anticodon demonstrating that the mature tRNA reads the termination codon UGA. The 5' internal control region for transcription has two extra nucleotides compared to the consensus sequence for eucaryotic tRNA genes, while the 3' internal control region is normal. This gene differs from a previously sequenced chicken opal suppressor serine tRNA gene (Hatfield, D., Dudock, B., and Eden, F. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 4940-4944) only at position 11. The second human gene appears to be a pseudogene truncated near the 3' end, since in the cloverleaf form of the mature tRNA there are three noncomplementary bases in the acceptor stem. The two human genes have a high degree of homology and, excluding the truncated 3' terminus of the pseudogene, differ in only two positions. The flanking sequences of the pseudogene are about 90% homologous to the consensus sequence of the human Alu family of repeated sequences. This gene appears to have been inserted between two adjacent Alu family members.

Epoxide hydrolase activity in human skin.

1 Epoxide hydrolase (EH) activity was measured in biopsied skin (n = 42) using 7-[H3]-styrene oxide as substrate, and separation of the products by high performance liquid chromatography. 2 EH activity (mean +/- s.d.) was present in separated epidermis (139 +/- 105 pmol glycol formed mg-1 min-1) and dermis (165 +/- 120 pmol glycol formed mg-1 microsomal protein min-1). 3 Whole skin EH activity (mean +/- s.d.) varied widely (433 +/- 254 pmol glycol formed mg-1 microsomal protein min-1) 4 No significant difference in EH activity was observed in skin from breast, penis and leg. 5 Skin EH activity does not appear to contribute significantly to the systemic metabolism of epoxide, but may be important in determining the effects of epoxides formed within the epidermis.