Admission screening testing of patients and staff N95 respirators are cost-effective in reducing COVID-19 hospital-acquired infections.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks in acute care settings can have severe consequences for patients due to their underlying vulnerabilities, and can be costly due to additional patient bed-days and the need to replace isolating staff. This study assessed the cost-effectiveness of clinical staff N95 respirators and admission screening testing of patients to reduce COVID-19 hospital-acquired infections. METHODS: An agent-based model was calibrated to data on 178 outbreaks in acute care settings in Victoria, Australia between October 2021 and July 2023. Outbreaks were simulated under different combinations of staff masking (surgical, N95) and patient admission screening testing [none, rapid antigen test (RAT), polymerase chain reaction]. For each scenario, average diagnoses, COVID-19 deaths, quality-adjusted life years from discharged patients, and costs (masks, testing, patient COVID-19 bed-days, staff replacement costs while isolating) from acute COVID-19 were estimated over a 12-month period. FINDINGS: Compared with no admission screening testing and staff surgical masks, all scenarios were cost saving with health gains. Staff N95 respirators + RAT admission screening of patients was the cheapest scenario, saving A$78.4M [95% uncertainty interval (UI) 44.4M-135.3M] and preventing 1543 (95% UI 1070-2146) deaths state-wide per annum. Both interventions were individually beneficial: staff N95 respirators saved A$54.7M and 854 deaths state-wide per annum, while RAT admission screening of patients saved A$57.6M and 1176 deaths state-wide per annum. INTERPRETATION: In acute care settings, staff N95 respirators and admission screening testing of patients can reduce hospital-acquired COVID-19 and COVID-19 deaths, and are cost saving because of reduced patient bed-days and staff replacement needs.

Extended adjuvant temozolomide with cis-retinoic acid for adult glioblastoma.

OBJECTIVE: To determine the toxicity and effectiveness of 24 months of adjuvant temozolomide (tmz) with cis-retinoic acid (cra) for patients with glioblastoma. METHODS: This retrospective population-based review considered the charts of all patients diagnosed with glioblastoma in Manitoba and referred to a provincial cancer centre during 2002-2008. Consecutive patients came from a population-based referral centre and provincial cancer registry. All patients were treated according to the local standard of care with surgical resection followed by concurrent radiotherapy and tmz 75 mg/m(2) daily, followed by tmz 150-200 mg/m(2) for days 1-5, repeated every 28 days for up to 24 cycles, and cra 50 mg/m(2) twice daily for days 1-21, repeated every 28 days. The main outcome measures were safety, tolerability, and effectiveness of long-term tmz and cra. RESULTS: Of 247 patients diagnosed with glioblastoma in Manitoba during the study period, 116 started concurrent chemoradiotherapy, and 80 received adjuvant tmz. Of the patients who started concurrent chemoradiotherapy, 80 began adjuvant chemotherapy. Patients completed a median of 5.5 cycles of tmz and 3 cycles of cra. Grade 3 or 4 hematologic toxicity was noted in 16% of patients. Median overall survival was 15.1 months, and 26.7% of patients remained alive at 2 years. CONCLUSIONS: Extended adjuvant tmz and cra is well tolerated. However, the population-based effectiveness of this regimen is similar to the clinical trial efficacy of 6 months of adjuvant tmz. Future studies in glioblastoma should incorporate duration of adjuvant chemotherapy into the study design.

A National Cancer Institute of Canada Clinical Trials Group Study--IND.135: Phase I/II study of irinotecan (camptosar), oxaliplatin and raltitrexed (tomudex) (COT) in patients with advanced colorectal cancer.

Thirty-one patients with metastatic colorectal cancer were enrolled in this phase I/II trial of a triple combination of camptosar (C), oxaliplatin (O) and tomudex (T), all given on day one of a convenient three-week schedule. Patients received 257 cycles (1-18) in five cohorts. Toxicity was manageable and haematological toxicity was mild to moderate. Diarrhoea was the main dose-limiting toxicity; nausea and vomiting were common. Fatigue was frequent, moderate in severity and a reason for discontinuation in some patients. The recommended phase II doses were (C) 220 mg/m(2), (O) 100mg/m(2), (T) 2.75 mg/m(2). A 50% response rate in 30 evaluable patients was confirmed by an independent radiology review board; progression-free survival and overall median survival were 7.3 months and 16.6 months, respectively. Of the 16 patients treated at the recommended dose, 9 (56.3%) experienced partial response. Further evaluation in a randomized study compared to sequential doublets is warranted. Triple combinations could be relevant in curative settings for high-risk patients.

Biotransformation of alkaloids.

Biotransformations of alkaloids over the last decade have continued to encompass a wide variety of substrates and enzymes. The elucidation of novel alkaloid biosynthetic and catabolic pathways will continue to furnish new biocatalysts for the synthetic organic chemist. Furthermore, an improved understanding of the genetic and biochemical basis of metabolic pathways will also permit the engineering of pathways in plants and other heterologous hosts for the production of therapeutically important alkaloids. The combination of increasing commercial interest and advances in molecular biology will facilitate the availability of robust biocatalysts which are a prerequsite to achieve economically feasible processes for the production of alkaloid-based therapeutics.

An integrated assessment of long-term changes in the hydrology of three lowland rivers in eastern England.

The flow records of the Rivers Bure, Nar and Wensum in eastern England have been examined with the aim of identifying long-term changes in flow behaviour relating to variations in rainfall amount, land use, land drainage intensity and water resources use. In the study area, and since 1931, there is no evidence of long-term change in rainfall amount or distribution, on either an annual or seasonal basis. Despite changes in water resources use and catchment characteristics since the beginning of the century, such as the ending of water milling and increased land drainage and arable farming, rainfall-runoff modelling over the period 1964-1992 showed that the relationship between rainfall and runoff has remained essentially unchanged in the three study rivers. A catchment resource model used to 'naturalise' the historic flow records for the period 1971-1992 to account for the net effect of water supply abstractions and discharges revealed that mean river flows have been altered by surface water and groundwater abstractions, although the average losses to mean weekly flows due to net abstractions for all water uses was no greater than 3%. Greater losses occurred during drought periods as a result of increased consumptive use of water for spray irrigation and amounted to a maximum loss of 24% in the Nar catchment. In lowland areas such as eastern England that are prone to summer dry weather and periodic drought conditions, an integrated approach to river basin management, as advocated by the EU Framework Directive, is recommended for future management of surface and groundwater resources for public water supplies, river regulation purposes and industrial and agricultural demands.

An estimate of the cost of conducting phase II trials in lung cancer.

OBJECTIVE: Although it is commonly assumed that clinical trials are more costly than standard therapy, there have been no previous studies of the cost of conducting phase II trials in lung cancer. We retrospectively analyzed two National Cancer Institute of Canada phase II trials in previously untreated small cell lung cancer (SCLC) to determine the costs of conducting the trials in a cancer treatment centre. Both studies were clinical trials undertaken as part of the NCIC's Investigational New Drug program: IND 69 and IND 50 evaluated docetaxel (taxotere) and gemcitabine, respectively. METHODS: data management costs in a Canadian cancer treatment centre were determined from the time estimates provided by data managers to complete various protocol related tasks. Nursing and pharmacy personnel measured the time and supplies necessary to prepare and administer the chemotherapy. Physician fees were determined from the type and number of care visits required by the clinical protocols. Laboratory tests and imaging studies were costed according to the Ontario Health Insurance Plan (OHIP) Schedule of Fees and Benefits. To estimate whether phase II trials are more costly than standard treatment, we determined the cost of four cycles of VP-16-cisplatin, a standard treatment for SCLC. RESULTS: The total cost of performing the docetaxel study was $18443 for an average cost per case of $1317 and an average cost per treatment cycle of $683. The gemcitabine study cost more, due to the fact that the drug proved to be active against SCLC and more cycles of therapy were administered to a larger number of patients. Laboratory and administration costs were also higher, because of the drug administration schedule. The total cost of this study was estimated to be $64670 and the average cost per patient entered was $2230 with an average cost per treatment cycle of $898. In comparison, the estimated cost of four cycles of VP-16-cisplatin chemotherapy was $3948 or $987 per treatment cycle. The major cost drivers in the clinical trials were laboratory and imaging tests which made up 17 and 39%, respectively, of the costs of the taxotere study, and 29 and 27%, respectively, for the gemcitabine study. Data management costs contributed 21 and 13% of the total costs, respectively. CONCLUSION: As the main cost drivers in these phase II clinical trials are laboratory and imaging tests, the cost of clinical trials could potentially be reduced by ensuring that only essential tests are required by protocol. Not surprisingly, the cost of conducting a trial of an active agent is greater than for an inactive agent, because more patients are treated and each patient receives more treatment. The implications for the per-case funding of phase II clinical trials are discussed.

Nonintrusive optical measurements of aircraft engine exhaust emissions and comparison with standard intrusive techniques.

Nonintrusive systems for the measurement on test rigs of aeroengine exhaust emissions required for engine certification (CO, NO(x), total unburned hydrocarbon, and smoke), together with CO(2) and temperature have been developed. These results have been compared with current certified intrusive measurements on an engine test. A spectroscopic database and data-analysis software has been developed to enable Fourier-transform Infrared measurement of concentrations of molecular species. CO(2), CO, and NO data showed agreement with intrusive techniques of approximately ?30%. A narrow-band spectroscopic device was used to measure CO(2) (with deviations of less than ?10% from the intrusive measurement), whereas laser-induced incandescence was used to measure particles. Future improvements to allow for the commercial use of the nonintrusive systems have been identified and the methods are applicable to any measurement of combustion emissions.

Transformations of codeine to important semisynthetic opiate derivatives by Pseudomonas putida m10.

A biotransformation mixture which contained codeine and washed cells of Pseudomonas putida M10 gave rise to a number of transformation products that are of clinical importance which included hydrocodone, dihydrocodeine and 14beta-hydroxycodeine. Incubations with the same organism and codeinone gave rise to 14beta-hydroxycodeinone and 14beta-hydroxycodeine. Cell-free extracts and membrane fractions of P. putida M10 were shown to catalyse the 14beta-hydroxylation of codeinone. In addition, the potent analgesic oxycodone was shown to be produced from 14beta-hydroxycodeinone.

Mitoxantrone, prednimustine, and vincristine for elderly patients with aggressive non-Hodgkin's lymphoma.

Elderly patients with intermediate- or high-grade non-Hodgkin's lymphoma have a worse outcome than those who are younger than 60 years. It has been shown that aggressive combination chemotherapy is poorly tolerated in older patients resulting in a subsequent decrease in dose intensity. A phase II trial was conducted with mitoxantrone, prednimustine, and vincristine (NSO) in this group of patients. NSO consists of mitoxantrone 12 mg/M2 intravenously on day one, vincristine 1.4 mg/M2 intravenously on day 1 (maximum dose of two mg), and prednimustine 100 mg/M2 orally once a day for four days. NSO was repeated every 21 days. Thirty-six patients were able to be evaluated. There were 18 males and 18 females with the median age of 71 (range 60-85). NSO was well tolerated and nonhematological toxicities were uncommon. More than 80% of the patients received 90% or greater of the intended dose. The complete response rate was 60.6% and partial response was 21.8%. At 60 months the Kaplan-Meier estimate of progression-free survival was 47.9% (standard error 8.6%) and actual survival was 40.6% (standard error 8.8%). There were no differences in outcome between those with performance status (PS) of zero or one and those with PS > 1. NSO is well tolerated by elderly patients including those with PS > 1. These results compare favorably with other combinations in elderly patients with aggressive non-Hodgkin's lymphoma.

The accuracy of breast ultrasound in the evaluation of clinically benign discrete, symptomatic breast lumps.

INTRODUCTION: Recent reports have suggested that breast ultrasound (US) is of value in distinguishing malignant from benign processes. The aim of this study was to establish the accuracy of US in detecting invasive malignancy in clinically benign, discrete, symptomatic breast lumps. METHODS: The US appearances of 205 clinically benign breast masses were documented prospectively and prior to mammography by one radiologist (AJE). The US appearances were then correlated with the fine needle aspiration (FNA), core biopsy and surgical findings and compared with the mammographic findings. RESULTS: The US findings were normal 72 (35%), simple cyst 63 (31%), solid benign 51 (25%), solid indeterminate 15 (7%) and solid malignant four (2%). Ultrasound characterized 13 (93%) of the 14 patients found to have invasive carcinoma as indeterminate or malignant. No patients with normal or simple cyst US findings had invasive malignancy. Ultrasound had significantly better accuracy (97% vs 87%, P < 0.02) sensitivity (93% vs 57%, P < 0.05) and negative predictive value (99% vs 92%, P < 0.002) than mammography in the detection of invasive carcinoma when indeterminate and malignant imaging findings were taken as positive. CONCLUSION: US is a useful adjunct to FNA/core biopsy in confirming the nature of symptomatic, clinically benign breast masses and is superior to mammography in this clinical setting.

Pediatric all-terrain vehicle trauma: a 5-year statewide experience.

BACKGROUND/PURPOSE: This is a retrospective review of the pediatric all-terrain vehicle trauma victims who presented to the five major trauma centers serving the state of West Virginia during the 5-year period from January 1991 to December 1995. The purpose of this research is to characterize the nature of the injuries and the individuals injured to better appreciate the magnitude of the problem of ATV-related injuries in the pediatric population. METHODS: This study is a retrospective review of these 218 consecutive pediatric patients from trauma registry data and their medical records. RESULTS: Two hundred eighteen patients between the ages of 2 years and 16 years presented during the study period. Boys outnumbered girls three to one. The average Injury Severity Score (ISS) was 8.76, the average Glasgow Coma Score (GCS) was 14.4, and the average Trauma Score (TS) was 15.2. The most common injuries were orthopedic followed by head and facial injuries. The majority of the children did not wear helmets, and their injuries resulted in an average hospital length of stay of 4.3 days. Thirty-eight percent of the children required surgery. There were a total of four deaths for a mortality rate of 1.8%. The estimated total hospitalization cost for the 218 patients was $1,918,400.00. CONCLUSIONS: All-terrain vehicle-related trauma remains an ongoing safety concern facing society today. Every physician who cares for children should address this important issue when talking to children and parents about safety issues and injury prevention.

Reduction of the infectivity of scrapie agent as a model for BSE in the manufacturing process of Trasylol.

The Trasylol manufacturing process was investigated with respect to its capacity for the inactivation/removal of infectivity causing bovine spongiform encephalopathy (BSE). Four process steps were selected for this investigation and scaled down to laboratory scale. Authentic samples of bovine lungs used in the Trasylol manufacturing plant were taken and spiked in laboratory scale experiments with high infectious titres of the rodent adapted scrapie strain ME 7 which served as model for BSE. After performing the respective process steps the output samples collected were tested in C57BL mice carrying the Sinc gene. An overall reduction of the infectious agent in the order of 18 log10 was observed, indicating a very high capacity of the Trasylol process for the inactivation/removal of the BSE/scrapie agent. The discussed safety strategy for the product leads to the conclusion that Trasylol is BSE safe.

Degradation of cocaine by a mixed culture of Pseudomonas fluorescens MBER and Comamonas acidovorans MBLF.

A mixed culture that could utilize cocaine as the sole source of carbon and energy for growth was isolated by selective enrichment. The individual microorganisms within this mixed culture were identified as Pseudomonas fluorescens (termed MBER) and Comamonas acidovorans (termed MBLF). Each microorganism was shown to be unable to grow to any appreciable extent on 10 mM cocaine in the absence of the other. C. acidovorans MBLF was found to possess an inducible cocaine esterase which catalyzed the hydrolysis of cocaine to ecgonine methyl ester and benzoate. C. acidovorans was capable of growth on benzoate at concentrations below 5 mM but was unable to metabolize ecgonine methyl ester. P. fluorescens MBER was capable of growth on either benzoate as the sole source of carbon or ecgonine methyl ester as the sole source of carbon and nitrogen. P. fluorescens MBER was found to initiate the degradation of ecgonine methyl ester via ecgonine, pseudoecgonine, and pseudoecgonyl-coenzyme A. Subcellular studies resulted in the identification of an ecgonine methyl esterase, an ecgonine epimerase, and a pseudoecgonyl-coenzyme A synthetase which were induced by growth on ecgonine methyl ester or ecgonine. Further metabolism of the ecgonine moiety is postulated to involve nitrogen debridging, with the production of carbonyl-containing intermediates.

Carbon dioxide absorption is not linearly related to intraperitoneal carbon dioxide insufflation pressure in pigs.

BACKGROUND: Carbon dioxide absorption into the blood during laparoscopic surgery using intraperitoneal carbon dioxide insufflation may lead to respiratory acidosis, increased ventilation requirements, and possible serious cardiovascular compromise. The relationship between increased carbon dioxide excretion (VCO2) and intraperitoneal carbon dioxide insufflation pressure has not been well defined. METHODS: In 12 anesthesized pigs instrumented for laparoscopic surgery, intraperitoneal carbon dioxide (n = 6) or helium (n = 6) insufflation pressure was increased in steps, and VCO2 (metabolic cart), dead space, and hemodynamics were measured during constant minute ventilation. RESULTS: VCO2 increases rapidly as intraperitoneal insufflation pressure increases from 0 to 10 mmHg; but from 10 to 25 mmHg, VCO2 does not increase much further. PaCO2 increases continuously as intraperitoneal insufflation pressure increases from 0 to 25 mmHg. Hemodynamic parameters remained stable. CONCLUSIONS: By considering Fick's law of diffusion, the initial increase in VCO2 is likely accounted for by increasing peritoneal surface area exposed during insufflation. The continued increase in PaCO2 without a corresponding increase in VCO2 is accounted for by increasing respiratory dead space.

Isolation and characterization of a ntrC mutant of Bradyrhizobium (Parasponia) sp. ANU289.

A mutant of Bradyrhizobium (Parasponia) sp. ANU289 affected in the regulation of nitrogen metabolism was isolated. The mutant, designated ANU293, was unable to induce ammonium transport (Amt), nitrate reductase (NR) or glutamine synthetase II (GSII) activities under conditions that induce these activities in the wild-type. However, glutamine synthetase I (GSI), which is expressed constitutively in the wild-type, was present at normal levels in the mutant. The mutant also retained the ability to fix nitrogen in vitro and in planta, although nodule development on siratro (Macroptilium atropurpureum) was retarded. Southern blot analysis showed that ntrC, the product of which is involved in regulation of nitrogen metabolism, is the site of pSUP1021 insertion in ANU293. These results indicate that the transcriptional activator NtrC is required for the expression of Amt, NR and GSII, but not GSI or nitrogenase in Bradyrhizobium (Parasponia) sp. ANU289.