Feasibility of Dose-escalated Hypofractionated Chemoradiation in Human Papilloma Virus-negative or Smoking-associated Oropharyngeal Cancer.

AIMS: Oropharyngeal squamous cell carcinoma (OPSCC) can be divided into favourable and poor prognostic groups by association with human papilloma virus (HPV) and smoking. This study prospectively investigated a dose-intensified schedule in poor/intermediate prognosis OPSCC. MATERIALS AND METHODS: Patients with p16/HPV-negative or p16-positive N2b OPSCC with a greater than 10 pack-year smoking history were eligible. Patients were planned to receive 64 Gy in 25 fractions with cisplatin. The primary end point was absence of grade 3 mucositis at 3 months. RESULTS: Fifteen patients were recruited over 14 months. All patients completed a minimum of 2 years of follow-up. All patients completed full-dose radiotherapy within a median treatment time of 32 days (31-35). Grade 3 mucositis was absent in all patients at 3 months. There was one grade 4 toxicity event due to cisplatin (hypokalaemia). Complete response rates at 3 months were 100% and 93% for local disease and lymph nodes, respectively. One patient developed metastatic disease and subsequently died. Overall survival at 2 years was 93% (95% confidence interval 61-99%). CONCLUSIONS: The schedule of 64 Gy in 25 fractions with concomitant chemotherapy is tolerable in patients with poor and intermediate prognosis OPSCC.

Comparison of Edwardsiella ictaluri isolates from different hosts and geographic origins.

The intraspecific variability of E. ictaluri isolates from different origins was investigated. Isolates were recovered from farm-raised catfish (Ictalurus punctatus) in Mississippi, USA, tilapia (Oreochromis niloticus) cultured in the Western Hemisphere and zebrafish (Danio rerio) propagated in Florida, USA. These isolates were phenotypically homologous and antimicrobial profiles were largely similar. Genetically, isolates possessed differences that could be exploited by repetitive-sequence-mediated PCR and gyrB sequence, which identified three distinct E. ictaluri genotypes: one associated with catfish, one from tilapia and a third from zebrafish. Plasmid profiles were also group specific and correlated with rep-PCR and gyrB sequences. The catfish isolates possessed profiles typical of those described for E. ictaluri isolates; however, plasmids from the zebrafish and tilapia isolates differed in both composition and arrangement. Furthermore, some zebrafish and tilapia isolates were PCR negative for several E. ictaluri virulence factors. Isolates were serologically heterogenous, as serum from a channel catfish exposed to a catfish isolate had reduced antibody activity to tilapia and zebrafish isolates. This work identifies three genetically distinct strains of E. ictaluri from different origins using rep-PCR, 16S, gyrB and plasmid sequencing, in addition to antimicrobial and serological profiling.

Multidose pharmacokinetics of orally administered florfenicol in the channel catfish (Ictalurus punctatus).

Plasma disposition of florfenicol in channel catfish was investigated after an oral multidose (10 mg/kg for 10 days) administration in freshwater at water temperatures ranging from 24.7 to 25.9 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After the administration of florfenicol, the mean terminal half-life (t(1/2)), maximum concentration at steady-state (Css (max)), time of Css (max) (T(max)), minimal concentration at steady-state (Css (min)), and Vc /F were 9.0 h, 9.72 µg/mL, 8 h, 2.53 µg/mL, and 0.653 L/kg, respectively. These results suggest that florfenicol administered orally at 10 mg/kg body weight for 10 days could be expected to control catfish bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of <2.5 µg/mL.

Efficacy of florfenicol for control of mortality associated with Francisella noatunensis subsp. orientalis in Nile tilapia, Oreochromis niloticus (L.).

Francisella noatunensis subsp. orientalis (Fno) (syn. F. asiatica) is an emergent Gram-negative facultative intracellular bacterium. Although it is considered one of the most pathogenic bacteria in fish, there are no commercially available treatments or vaccines. The objective of this project was to determine the most efficacious concentration of florfenicol (FFC) [10, 15 or 20 mg FFC kg(-1) body weight (bw) per days for 10 days] administered in feed to control experimentally induced infections of Fno in Nile tilapia, Oreochromis niloticus (L.), reared in a recirculating aquaculture system. The cumulative mortality of fish that received 0, 10, 15 or 20 mg FFC kg(-1)  bw per day was 60, 37, 14 and 16%, respectively. Francisella noatunensis subsp. orientalis genome equivalents were detected in water from all challenged groups with slight reduction in the concentration in the florfenicol-treated groups 4 days after treatment. The mean LOG of CFU Fno mg(-1) spleen was 3-5 and was present in all challenged groups at necropsy 11 days after treatment (21 days after challenge). Results show that florfenicol administered at doses of 15 and 20 mg FFC kg(-1)  bw per days for 10 days significantly reduced mortality associated with francisellosis in Nile tilapia.

Single intravenous and oral dose pharmacokinetics of florfenicol in the channel catfish (Ictalurus punctatus).

Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10 mg/kg) of intravenous (i.v.) or oral administration in freshwater at a mean water temperature of 25.4 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After i.v. florfenicol injection, the terminal half-life (t(1/2)), volume of distribution at steady state (V(ss)), and central volume of distribution (V(c)) were 8.25 h, 0.9 and 0.381 L/kg, respectively. After oral administration of florfenicol, the terminal t(1/2), C(max), T(max), and oral bioavailability (F) were 9.11 h, 7.6 µg/mL, 9.2 h, and 1.09, respectively. There was a lag absorption time of 1.67 h in oral dosing. Results from these studies support that 10 mg florfenicol/kg body weight in channel catfish is an efficacious dosage following oral administration.

In vitro evaluation of the susceptibility of Edwardsiella ictaluri, etiological agent of enteric septicemia in channel catfish, Ictalurus punctatus (Rafinesque), to florfenicol.

In vitro studies were conducted to assess the sensitivity of Edwardsiella ictaluri, the etiological agent of enteric septicemia of catfish (ESC), to the antibacterial drug florfenicol (FFC). Twelve different E. ictaluri isolates from cases submitted between 1994 and 1997 to the Thad Cochran National Warmwater Aquaculture Center fish diagnostic laboratory (Stoneville, MS) were used for testing. These isolates originated from channel catfish (Ictalurus punctatus) infected with E. ictaluri through natural outbreaks of ESC in the commercial catfish ponds in Mississippi. Seven hundred sixty-seven additional cultures of E. ictaluri were obtained from channel catfish infected experimentally with E. ictaluri. In some of these experimental infections, FFC was used for treatment. These cultures of E. ictaluri were identified by morphological and biochemical tests. Kirby-Bauer zones of inhibition (in mm) for FFC against E. ictaluri were determined using standard methods. The minimum inhibitory concentration (MIC) of FFC was determined for the natural outbreak E. ictaluri isolates and arbitrarily selected experimental cultures. The zones of inhibition for FFC tested with E. ictaluri ranged from 31 to 51 mm. The MIC for FFC tested with E. ictaluri was consistently 0.25 microg/ml. Edwardsiella ictaluri tested in these studies were highly sensitive to FFC in vitro.

Assessing staff attitudes towards information security in a European healthcare establishment.

Information security is now recognized as an important consideration in modern healthcare establishments (HCEs), with a variety of guidelines and standards currently available to enable the environments to be properly protected. However, financial and operational constraints often exist which influence the practicality of these recommendations. This paper establishes that the staff culture of the organization is of particular importance in determining the level and types of security that will be accepted. This culture will be based upon staff awareness of and attitudes towards security and it is, therefore, important to have a clear idea of what these attitudes are. To this end, two surveys have been conducted within a reference environment to establish the attitudes of general users and technical staff, allowing the results to be fed back to HCE management to enable security policy to be appropriately defined. These results indicated that, although the establishment had participated in a European healthcare security initiative, staff attitudes and awareness were still weak in some areas.

Ciprofloxacin resistant Campylobacter spp. in humans: an epidemiological and laboratory study.

From the end of April 1991 until the end of 1991, 2209 isolates of Campylobacter spp. have been collected in Plymouth PHL of which 91 (4.1%) were resistant to ciprofloxacin. None of the 91 patients involved had taken a quinolone, but 30/91 (33%) had travelled abroad (16 to the Iberian peninsula) in the three months preceding isolation of the ciprofloxacin-resistant Campylobacter spp. In the case-control study 12/15 (80%) of the cases had recently consumed poultry as had 20/24 (83%) of controls with enteritis due to ciprofloxacin-susceptible Campylobacter spp. A small study of poultry purchased from the supermarket revealed that only 1/37 campylobacters isolated from 64 UK bred chickens was resistant to ciprofloxacin, whereas 7/26 campylobacters isolated from 50 imported chickens were ciprofloxacin-resistant. Of the 75 clinical isolates of ciprofloxacin-resistant Campylobacter spp. subjected to detailed analysis, 68 were Campylobacter jejuni, six were Campylobacter lari, and one was Campylobacter coli. All isolates from man and poultry were resistant to ciprofloxacin, norfloxacin, sparfloxacin and tosufloxacin, and there was an association between fluoroquinolone-resistance and increased MICs of tetracycline. The range of susceptibility to erythromycin and kanamycin were typical of the species. gyrA from C. jejuni P6 (a case with history of travel to Spain) and C. jejuni P16 (isolate from imported chicken) contained point mutations corresponding to an amino acid substitution of isoleucine for threonine at codon 86. It has been suggested that veterinary use of quinolones, notably enrofloxacin, is providing a selective pressure for emergence of resistance to ciprofloxacin amongst human isolates. Now that enrofloxacin has been licensed for use in broiler flocks in the UK, it will be interesting to monitor the prevalence of resistance of campylobacters to quinolones in UK-produced poultry and in UK-acquired human infection.

A generic methodology for health care data security.

The aim is to outline the framework of a generic methodology for specifying countermeasures in health care environments. The method is specifically aimed at the enhancement of security in existing health care systems, and a key element is the use of predetermined 'profiles' by which these may be classified. Example scenarios are presented to illustrate how the concept could be applied in practice. The paper is based upon work that was initially carried out as part of the Commission of European Communities SEISMED (Secure Environment for Information Systems in MEDicine) project, the aim of which is to provide security recommendations for European health care establishments (HCEs).

The need for security--a clinical view.

Systems which process patient health data of any kind are considered to be medical information systems. Some data can be categorized as non-personal, non-identifiable, or non-patient-based such as knowledge bases. Others are considered as highly sensitive because of the 'need to know' to deliver health care to patient. Access is not only justifiable for doctors and nurses, but, for specific purposes to administrative personnel and public health organisations. Of special concern are registers on sexually transmitted diseases, mental health and genetic diseases. In future, patients might gain more autonomy and also have access to some parts of their own record. Telematics allows them to update a data base and to consult a knowledge base. Clearly, physicians in charge of the cases have a responsibility that has been recognised by law in all Western countries. Access to patient's data should take into account this responsibility. Although most health professionals would still believe that confidentiality is the main issue, it appears that data integrity and availability are as important in the context of the 'paperless' electronic record. Information should be complete and correct, to be only accessed by authorized persons. The health care environment is characterised by an open nature of clinics that leaves them vulnerable to theft, damage and unauthorized access. Disclosure of information may affect the patient's social standing as well as their general health. The health professions lack sufficiently well-defined organisational structure, culture and perceptions to support security.

Audit in infection control--data analysis and infections in the intensive care unit.

The importance of high standards of infection control practices in intensive care units is widely accepted. Despite this, few objective measures of the efficacy of such practices have been developed. This hampers clinical audit, which is essential if nosocomial infections are to be kept to a minimum. Small sample size, multiple dependent variables, difficulty in matching populations, and the covert effects of confounding factors and bias, all add to the problems of designing meaningful audit programmes in intensive care settings. Nevertheless, useful analysis can be attempted now that appropriate standards and scoring systems are available. Computer systems can simplify data collection, analysis and reporting but they are no substitute for careful preparation and good statistical technique.

Information in infection control.

Effective infection control depends upon a clear understanding of the activities of surveillance, control, communication and management and of the nature and source of information required. Surveillance uses diverse information and computerization of hospital information provides the potential for automated detection of patients at risk of, or affected by, nosocomial infection. Routine visits to all hospital wards by the infection control team is widely advocated but is an inefficient use of a limited resource. 'Targeting' clinical areas with particular problems is more efficient but requires the means to find cases and perform risk assessment through surveillance. While microbiology laboratory reports are effective for case finding, sensitivity and specificity are low. The increasing use of computer held clinical data presents new opportunities for automated surveillance to guide the daily activities of the infection control team. It is essential to stress the importance of infection surveillance to those designing hospital information systems.

A case of septicaemia due to Aeromonas hydrophila.

A case of Aeromonas hydrophila septicaemia is reported, arising from the use of leeches in an attempt to salvage a replanted arm. It is believed that this is the first report of this complication.