Cost-effectiveness of outpatient parenteral antibiotic therapy: a simulation modelling approach.

Objectives: In the UK, patients who require intravenous antimicrobial (IVA) treatment may receive this in the community through outpatient parenteral antimicrobial therapy (OPAT) services. Services include: IVA administration at a hospital outpatient clinic (HO); IVA administration at home by a general nurse (GN) or a specialist nurse (SN); or patient self-administered (SA) IVA administration following training. There is uncertainty regarding which OPAT services represent value for money; this study aimed to estimate their cost-effectiveness. Methods: A cost-effectiveness decision-analytic model was developed using a simulation technique utilizing data from hospital records and a systematic review of the literature. The model estimates cost per QALY gained from the National Health Service (NHS) perspective for short- and long-term treatment of infections and service combinations across these. Results: In short-term treatments, HO was estimated as the most effective (0.7239 QALYs), but at the highest cost (£973). SN was the least costly (£710), producing 0.7228 QALYs. The combination between SN and HO was estimated to produce 0.7235 QALYs at a cost of £841. For long-term treatments, SN was the most effective (0.677 QALYs), costing £2379, while SA was the least costly at £1883, producing 0.666 QALYs. A combination of SA and SN was estimated to produce 0.672 QALYs at a cost of £2128. Conclusions: SN and SA are cost-effective for short- and long-term treatment of infections, while combining services may represent the second-best alternative for OPAT in the UK.

Clinical and cost-effectiveness, safety and acceptability of community intravenous antibiotic service models: CIVAS systematic review.

OBJECTIVE: Evaluate evidence of the efficacy, safety, acceptability and cost-effectiveness of outpatient parenteral antimicrobial therapy (OPAT) models. DESIGN: A systematic review. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Cochrane Library, National Health Service (NHS) Economic Evaluation Database (EED), Research Papers in Economics (RePEc), Tufts Cost-Effectiveness Analysis (CEA) Registry, Health Business Elite, Health Information Management Consortium (HMIC), Web of Science Proceedings, International Pharmaceutical Abstracts, British Society for Antimicrobial Chemotherapy website. Searches were undertaken from 1993 to 2015. STUDY SELECTION: All studies, except case reports, considering adult patients or practitioners involved in the delivery of OPAT were included. Studies combining outcomes for adults and children or non-intravenous (IV) and IV antibiotic groups were excluded, as were those focused on process of delivery or clinical effectiveness of 1 antibiotic over another. Titles/abstracts were screened by 1 reviewer (20% verified). 2 authors independently screened studies for inclusion. RESULTS: 128 studies involving >60 000 OPAT episodes were included. 22 studies (17%) did not indicate the OPAT model used; only 29 involved a comparator (23%). There was little difference in duration of OPAT treatment compared with inpatient therapy, and overall OPAT appeared to produce superior cure/improvement rates. However, when models were considered individually, outpatient delivery appeared to be less effective, and self-administration and specialist nurse delivery more effective. Drug side effects, deaths and hospital readmissions were similar to those for inpatient treatment, but there were more line-related complications. Patient satisfaction was high, with advantages seen in being able to resume daily activities and having greater freedom and control. However, most professionals perceived challenges in providing OPAT. CONCLUSIONS: There were no systematic differences related to the impact of OPAT on treatment duration or adverse events. However, evidence of its clinical benefit compared with traditional inpatient treatment is lacking, primarily due to the dearth of good quality comparative studies. There was high patient satisfaction with OPAT use but the few studies considering practitioner acceptability highlighted organisational and logistic barriers to its delivery.

Community IntraVenous Antibiotic Study (CIVAS): protocol for an evaluation of patient preferences for and cost-effectiveness of community intravenous antibiotic services.

INTRODUCTION: Outpatient parenteral antimicrobial therapy (OPAT) is used to treat a wide range of infections, and is common practice in countries such as the USA and Australia. In the UK, national guidelines (standards of care) for OPAT services have been developed to act as a benchmark for clinical monitoring and quality. However, the availability of OPAT services in the UK is still patchy and until quite recently was available only in specialist centres. Over time, National Health Service (NHS) Trusts have developed OPAT services in response to local needs, which has resulted in different service configurations and models of care. However, there has been no robust examination comparing the cost-effectiveness of each service type, or any systematic examination of patient preferences for services on which to base any business case decision. METHODS AND ANALYSIS: The study will use a mixed methods approach, to evaluate patient preferences for and the cost-effectiveness of OPAT service models. The study includes seven NHS Trusts located in four counties. There are five inter-related work packages: a systematic review of the published research on the safety, efficacy and cost-effectiveness of intravenous antibiotic delivery services; a qualitative study to explore existing OPAT services and perceived barriers to future development; an economic model to estimate the comparative value of four different community intravenous antibiotic services; a discrete choice experiment to assess patient preferences for services, and an expert panel to agree which service models may constitute the optimal service model(s) of community intravenous antibiotics delivery. ETHICS AND DISSEMINATION: The study has been approved by the NRES Committee, South West-Frenchay using the Proportionate Review Service (ref 13/SW/0060). The results of the study will be disseminated at national and international conferences, and in international journals.

Is increased time to diagnosis and treatment in symptomatic cancer associated with poorer outcomes? Systematic review.

BACKGROUND: It is unclear whether more timely cancer diagnosis brings favourable outcomes, with much of the previous evidence, in some cancers, being equivocal. We set out to determine whether there is an association between time to diagnosis, treatment and clinical outcomes, across all cancers for symptomatic presentations. METHODS: Systematic review of the literature and narrative synthesis. RESULTS: We included 177 articles reporting 209 studies. These studies varied in study design, the time intervals assessed and the outcomes reported. Study quality was variable, with a small number of higher-quality studies. Heterogeneity precluded definitive findings. The cancers with more reports of an association between shorter times to diagnosis and more favourable outcomes were breast, colorectal, head and neck, testicular and melanoma. CONCLUSIONS: This is the first review encompassing many cancer types, and we have demonstrated those cancers in which more evidence of an association between shorter times to diagnosis and more favourable outcomes exists, and where it is lacking. We believe that it is reasonable to assume that efforts to expedite the diagnosis of symptomatic cancer are likely to have benefits for patients in terms of improved survival, earlier-stage diagnosis and improved quality of life, although these benefits vary between cancers.

The role of primary care in cancer diagnosis via emergency presentation: qualitative synthesis of significant event reports.

BACKGROUND: Patients diagnosed with cancer in the context of an emergency presentation (EP) have poorer outcomes. It is often assumed that such patients present to the emergency department without consulting their general practitioner (GP). Little work has been done to identify primary care involvement before hospital attendance. METHODS: Participating primary care practices completed a significant event audit (SEA) report for the last patient diagnosed with cancer as a result of an EP. Accounts were synthesised and a qualitative approach to analysis undertaken. RESULTS: SEAs for 222 patients were analysed. A range of cancers were included, the most common being lung (32.4%) and upper gastrointestinal (19.8%). In most cases, patients had contact with their practice before diagnosis, primarily in the period immediately before admission. In only eight cases had there been no input from primary care. Accounts of protracted primary care contact generally demonstrated complexity, often related to comorbidity, patient-mediated factors or reassurance provided by negative investigations. Learning points identified by practices centred on the themes of presentation and diagnosis, consultation and safety-netting, communication and system issues, patient factors and referral guidelines. CONCLUSIONS: There is extensive primary care input into patients whose diagnosis results from EP, and for the most part potential 'delay' in referral can be reasonably explained by the complexity of the presentation or by coexisting patient factors.

Risk factors for delayed presentation and referral of symptomatic cancer: evidence for common cancers.

BACKGROUND: It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation. METHODS: We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these. RESULTS: Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, 'misdiagnosis' occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results. CONCLUSION: Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately.

Computer use by general practitioners in Scotland.

BACKGROUND: Despite the widespread adoption by general practitioners (GPs) of desktop computers, there has been very little evaluation of the way in which the computer is actually used during consultations and the way in which it affects patient satisfaction. AIM: To ascertain the extent to which the computer is used in the consultation and to investigate the possible relationship between computer use and patient satisfaction. METHOD: Six GPs completed a short questionnaire about the extent to which they use the computer during surgeries. Eighty-four consultations from the surgeries of these GPs were video recorded. Patient satisfaction data on these 84 patients were collected at the time of the surgery using the previously validated Consultation Satisfaction Questionnaire. RESULTS: All six GPs stated that they usually used the computer during consultations. However, video observation revealed that the computer was used in just 51% of surgeries. The proportion of time that the computer was used for varied from 0.03 to 0.4, with a mean value of 0.12. The commonest function for which the computer was used was prescribing. The consultations in which the computer was used (CU) were on average 148 seconds longer than the non-computerized consultations (NCU). There was no difference in patient satisfaction between the two groups. CONCLUSION: Despite this group of GPs having a self-declared interest in the use of computers, the extent to which the computer was used was much lower than expected from the GPs' self-reported use. This may be partly explained by the fact that using the computer takes up valuable time within the consultation and does not appear to contribute to patient satisfaction. If desktop computers are to be used to their full potential in general practice, more work is required to evaluate their impact on the consultation process itself.

A method for the isolation of nuclear DNA from cotton (Gossypium) leaves.

Cotton leaves contain high levels of polyphenolic compounds that irreversibly interact with proteins and nucleic acids during DNA isolation. A procedure to isolate nuclear DNA from cotton (Gossypium hirsutum L.) has been developed. The method is based on the rapid initial isolation of nuclei in a glucose medium designed to stabilize nuclear structure and composition while preventing covalent interactions with polyphenolics. The resulting DNA is high in yield and purity and is suitable for Southern-blot hybridization analysis and restriction fragment length polymorphism analysis.

Phase I/II trial of etoposide and carboplatin in extensive small-cell lung cancer. A report from the Cancer and Leukemia Group B.

Previously untreated extensive small-cell lung cancer (SCLC) patients with performance status 0-2 were treated with etoposide 200 mg/m2/day on days 1-3 and carboplatin doses of 50, 100, or 125 mg/m2/day on days 1-3 in a Phase I format. Among the ten eligible patients treated with 125 mg/m2/day of carboplatin, grade 3 or 4 infection occurred in six patients, grade 4 thrombocytopenia in four patients, and there was one death with myelosuppression. Thus, this dose was considered the maximum tolerated dose (MTD), and a Phase II trial was then conducted utilizing this treatment program. In the Phase II trials, 81% of the 48 eligible patients had grade 3 or 4 leukopenia, 76% had grade 3 or 4 thrombocytopenia, and 55% had grade 3 or 4 anemia. There were three (6%) toxic deaths from myelosuppression. The objective response rate was 63% (17% complete responders) with a median response duration of 6.2 months for complete responders and 6.4 months for partial responders. Median survival was 12 months. The MTD defined by this Phase I trial represents a 67-100% increase in etoposide and a 25% increase in carboplatin compared to prior studies. Cancer and Leukemia Group B (CALGB) plans to study further dose intensification of this regimen with colony-stimulating factors.

Vanadium and ascorbate effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase, cholesterol and tissue minerals in guinea pigs fed low-chromium diets.

Vanadium has been reported to affect numerous physiological processes; however, a demonstration that vanadium deficiency consistently impairs biological function is lacking. The purpose of this study was to determine if the activity of hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme in cholesterol synthesis, is affected by dietary supplementation of vanadate and/or chronic ascorbic acid deficiency. To determine if vanadium and/or ascorbic acid affected mineral metabolism, tissue minerals also were analyzed. Weanling male guinea pigs were assigned randomly to groups of 10 in a 2 x 2 factorial design. The dietary variables were ascorbate, 0.5 or 10 mg/day, and vanadium < 0.01 microgram or 0.5 microgram/g diet as NH4VO3 in a low Cr diet containing < 0.07 microgram Cr/g diet. After 21 weeks on this diet, guinea pigs receiving more ascorbate had lower liver weight/body weight ratios and increased bone copper. Testes weight/body weight ratios, hepatic glycogen and bone copper decreased while hepatic lipids, fecal bile acids, plasma cortisol and bone calcium and magnesium were increased by vanadium supplementation. An interaction between vanadium and ascorbate affected cholesterol excretion in feces, hepatic iron, plasma cholesterol concentration and the activity of HMG CoA reductase. This study provides evidence of increased bone mineral concentrations with vanadium supplementation and of an interaction between vanadium and ascorbate which affected cholesterol metabolism.

Replication of cauliflower mosaic virus DNA in leaves and suspension culture protoplasts of cotton.

Cauliflower mosaic virus (CaMV) replicated in protoplasts and in inoculated leaves of the non-host, cotton (Gossypium hirsutum, L.). Protoplasts prepared from suspension-cultured cotton cells were infected by incubation with liposome-encapsulated CaMV virions. During a 1-week culture period the amount of CaMV nucleic acid as detected by nucleic acid hybridization in the protoplasts increased significantly regardless of whether or not the protoplasts contained vacuoles. In leaves inoculated with CaMV virions or CaMV DNA, viral DNA sequences were found by leaf skeleton hybridization to be located in small circular areas. DNA extracted from ultracentrifugal pellets of homogenates of inoculated leaves contained circular, gapped CaMV DNA only when inocula contained CaMV virions, CaMV DNA, or partial nested dimer CaMV plasmid DNA. When plants had been heavily watered, the CaMV DNA recovered contained degraded CaMV DNA. The results suggest that the host range limitation for CaMV is not due to an inability to replicate or spread locally in inoculated leaves.

The L-aspartate oxidase reported to be present in higher plants is actually glutamic oxaloacetic transaminase.

We previously reported (Biochem. Biophys. Res. Commun. (1983) 111, 188-193) that cotton callus cells contain an L-aspartate oxidase which requires an unidentified cofactor with an apparent molecular weight of 1,050. Further study has revealed that this report was in error. The enzyme is actually glutamic oxaloacetic transaminase and the "cofactor" has been identified as alpha-ketoglutarate.

Control of phosphorylation and decarboxylation of mevalonic acid and its metabolites in cultured human fibroblasts and in rat liver in vivo.

The activity of mevalonate kinase and of mevalonate pyrophosphate decarboxylase in human skin fibroblasts grown in culture was increased when whole fetal calf serum in the incubation medium was replaced with lipid-deficient serum. The drug demecolcine interfered with low density lipoprotein binding by cells and increased sterol synthesis and activities of hydroxymethylglutaryl-CoA reductase and mevalonate kinase. In contrast to normal cells, fibroblasts from a patient with homozygous familial hypercholesterolemia did not show any lower mevalonate kinase activity following incubation with whole serum compared with that in cells incubated with lipid-deficient serum. Insulin increased the activity of mevalonate kinase in fibroblasts. Livers of rats fed for 7 days with a diet containing 1% cholesterol showed reduced activity of mevalonate kinase and mevalonate phosphate kinase. These results are consistent with the possibility that enzymatic reactions other than those catalyzed by hydroxymethylglutaryl-CoA reductase may play a role in the physiological regulation of sterol synthesis in mammalian tissues.

Radio Tracking of a Fin Whale (Balaenoptera physalus).

A tagged whale of the genus Balaenoptera was intermittently tracked by radio for 27.8 hours over a distance of about 145 kilometers. Data on breathing and movement show that during that time the whale took 58 breaths in 130 minutes and traveled 20 kilometers at more than 9 kilometers per hour. Precise measurements of such parameters and of other features of the life history of great whales, which travel long distances over the high seas, often in groups, are now possible through radio tagging.