Repeated intratumoral administration of ONCOS-102 leads to systemic antitumor CD8+ T-cell response and robust cellular and transcriptional immune activation at tumor site in a patient with ovarian cancer.

Adenoviruses are excellent immunotherapeutic agents with a unique ability to prime and boost immune responses. Recombinant adenoviruses cause immunogenic cancer cell death and subsequent release of tumor antigens for antigen presenting cells, resulting in the priming of potent tumor-specific immunity. This effect may be further enhanced by immune-stimulating transgenes expressed by the virus. We report a case of a 38-year-old female with Stage 3 metastatic micropapillary serous carcinoma of the ovary. She was treated in a Phase I study with a granulocyte-macrophage colony stimulating factor (GMCSF)-expressing oncolytic adenovirus, Ad5/3-D24-GMCSF (ONCOS-102). The treatment resulted in progressive infiltration of CD8+ lymphocytes into the tumor and concomitant systemic induction of several tumor-specific CD8+ T-cell populations. The patient was alive at the latest follow up more than 20 months after initiation of the study.

The cost effectiveness of amoxicillin/clavulanic acid as antibacterial prophylaxis in abdominal and gynaecological surgery.

The objective of this study was to compare the cost effectiveness of amoxicillin/clavulanic acid with other antibacterial regimens for prophylaxis of infection after elective abdominal or gynaecological surgery. Data from 21 previously published comparative clinical trials were used to calculate statistical confidence intervals for differences in postoperative wound infection rate. A simple model was used to produce a tabular sensitivity analysis of cost effectiveness over a wide range of costs of wound infection and potential differences in efficacy. For more expensive comparator regimens, including combination regimens utilising gentamicin and metronidazole, amoxicillin/clavulanic acid was either likely to be more cost effective or equally cost effective. For example, in trials of colonic surgery the comparators were on average 11.39 pounds more expensive than amoxicillin/clavulanic acid, which was > 95% likely to be more cost effective unless the cost of wound infection was estimated to be > 1519 pounds. Amoxicillin/clavulanic acid was more expensive than only 2 of the 21 comparators. Furthermore, in one of these 2 trials it was also significantly more effective than the comparator. In this trial, amoxicillin/clavulanic acid was > 95% likely to be more cost effective as prophylaxis in hysterectomy than rectal metronidazole, provided that the cost of wound infection was estimated to be > 179 pounds. In conclusion, this analysis shows that amoxicillin/clavulanic acid, given as monotherapy, is likely to be equally or more cost effective than a wide range of comparator regimens for prophylaxis of elective abdominal or gynaecological surgery.

A meta-analysis of the use of amoxycillin-clavulanic acid in surgical prophylaxis.

The efficacy of amoxycillin-clavulanic acid as antibiotic prophylaxis in surgery has been assessed in numerous clinical studies, chiefly in abdominal and gynaecological surgery. A meta-analysis of 21 trials covering 2685 patients given amoxycillin-clavulanic acid and 2220 patients given comparator regimens is presented. Monotherapy with amoxycillin-clavulanic acid was as effective as the comparators, including combination regimens utilizing gentamicin or metronidazole, in preventing wound infections (median wound infection rates were 6% and 10% respectively). The antibacterial activity of amoxycillin-clavulanic acid covers the broad range of aerobic Gram-negative and anaerobic organisms that have a major role in postoperative infections. In addition, amoxycillin-clavulanic acid may have benefits in terms of convenience, tolerance and cost.

A comparison of the costs of ceftazidime therapy and gentamicin combinations in three UK hospitals.

This study compares the utilization costs of ceftazidime therapy with those of gentamicin in combination with other antibacterial drugs. The results show that the relatively high purchase cost of ceftazidime compared to combinations is more than counterbalanced by the additional materials used for drug administration and serum antibiotic assays, even when other drugs were combined with ceftazidime. The average drug and equipment costs were 230.13 pounds for ceftazidime regimens and 253.94 pounds for gentamicin regimens. It is also shown that ceftazidime therapy is associated with a reduction in personnel time compared to gentamicin regimens. The average times per patient for administration and assay were 1 h 43 min for ceftazidime and 4 h 57 min for gentamicin regimens. We conclude that ceftazidime regimens are cheaper than gentamicin regimens when all drug and equipment costs are quantified. Moreover, the use of ceftazidime will release staff time for other purposes.

Comparison of minimal and conventional surgery in patients with bleeding peptic ulcer: a multicentre trial.

A multicentre randomized prospective trial compared minimal surgery (under-running the vessel or ulcer excision and adjuvant ranitidine) with conventional ulcer surgery (vagotomy and pyloroplasty or partial gastrectomy) for the treatment of bleeding peptic ulcer. This report is based on 137 patients (eight withdrawn through misdiagnosis or lost data), of whom 62 received conservative surgery and 67 conventional operation. Twenty-nine patients died, 16 (26 per cent) after conservative surgery and 13 (19 per cent) after conventional operations. The only significant difference between the groups was the incidence of fatal rebleeding, which occurred in six patients after conservative surgery compared with none after conventional surgery (P less than 0.02, Fisher's exact test).

Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers.

In a multicentre study the effect of ranitidine on healing non-steroidal anti-inflammatory drug (NSAID) associated peptic ulcers was compared in a group of patients who had stopped NSAID treatment with another group who continued with NSAID treatment. A total of 190 patients with confirmed ulcers were randomised to continue or stop NSAID treatment. All patients in addition received ranitidine 150 mg twice daily. Patients were endoscopically monitored at four, eight, and 12 weeks. Gastric ulcers at eight weeks had healed in 63% of those taking NSAIDs compared with 95% of those who had stopped NSAID treatment. For duodenal ulcer the healing rates at eight weeks were 84% in the group continuing NSAIDs compared with 100% in those who stopped NSAIDs. The differences in healing rates were statistically significant for both gastric ulcer (p = 0.001) and for duodenal ulcer (p = 0.006). At 12 weeks, 79% of gastric ulcers and 92% of duodenal ulcers were healed in the group continuing with NSAIDs. All patients with gastric and duodenal ulcers who stopped taking NSAIDs were healed at 12 weeks. The study shows that ranitidine 150 mg twice daily effectively heals NSAID associated peptic ulcers. Healing is more successful when NSAID treatment stops but even if these drugs are continued, substantial healing rates are achievable.

Maintenance treatment of duodenal ulceration: ranitidine 300 mg at night is better than 150 mg in cigarette smokers.

Two hundred patients received either ranitidine 150 mg or 300 mg at night for 18 months to prevent duodenal ulcer relapse. Recurrence rates were lower in patients receiving the higher dose of ranitidine (3.1% v 9.7%, p = 0.78; 6.5% v 16.7%, p = 0.037; and 8.9% v 17.0%, p = 0.121 at six, 12, and 18 months respectively). In patients receiving ranitidine 150 mg, recurrences were significantly more common in smokers than non-smokers after 12 and 18 months, while in patients receiving ranitidine 300 mg recurrence rates were similar in smokers and non-smokers. Ranitidine 300 mg at night abolishes the adverse effect of smoking observed during maintenance treatment with ranitidine 150 mg at night and may therefore be an appropriate maintenance dose for smokers who relapse during standard dose maintenance treatment.

A large scale, general practice based investigation into the clinical efficacy and tolerability of cefuroxime axetil in women with uncomplicated urinary tract infection.

Female patients presenting to their general practitioner with symptoms of uncomplicated urinary tract infection (cystitis) were entered into one of three therapeutic trials in a study programme of cefuroxime axetil (125 mg twice daily or 250 mg twice daily) conducted throughout the United Kingdom. On entry to the study, demographic information, infection recurrence rate and clinical signs and symptoms were recorded and the patient given medication for 7-days' treatment. Post-treatment, clinical signs and symptoms were re-assessed and adverse event data collected. Of the 672 patients who entered the programme, 605 patients completed the course of treatment of whom 510 were taking the 125 mg and 95 taking the 250 mg dosage. No significant difference in clinical efficacy or adverse events was found between the two dosage regimens. Analysis of the changes in symptom severity from the pre-treatment to the post-treatment evaluation for all patients showed a highly significant improvement (p less than 0.001). One hundred and five (15.6%) of the patients who entered the study reported a total of 132 adverse events, 16 of whom were withdrawn from treatment. The most frequent event was diarrhoea/loose motions. This study shows that cefuroxime axetil appears to be effective and well-tolerated for the treatment of cystitis in general practice.