Resource implications of running a sacral neuromodulation service: a 10-year experience.

AIM: In this study we reviewed our 10-year experience of the medium- to long-term success of sacral nerve stimulation (SNS) for faecal incontinence, with particular reference to the resource implications of running such a service. METHOD: All patients treated with permanent SNS implants for faecal incontinence from 2001 to 2012 were identified from a prospective database. The patients underwent follow up at 3 and 6 months, with annual review thereafter. They were divided into four groups: group 1, patients optimized after two reviews; group 2, patients optimized after further review; group 3, patients who failed to reach a satisfactory state; and group 4, patients who had a good initial result with subsequent failure. RESULTS: Eighty-five patients underwent permanent SNS with a median follow up of 24 (range: 3-108) months. Group 1 included 30 (35%) patients; group 2 included 27 (32%) patients [median of two (range: 2-6) additional visits]; group 3 included 18 (21%) patients [median of six (range: 3-10) additional visits]; and group 4 included 10 (12%) patients [median interval to failure was 54 (range: 24-84) months]. Twenty-seven per cent of our patients had an unsatisfactory outcome and the cost of follow up for these patients was £36,854 (48.7% of the total follow-up costs). CONCLUSION: The study highlights the significant resource implications of running an SNS service with a large proportion of patients requiring prolonged review, with more than one-quarter having an unsatisfactory outcome at a substantial cost.

The association between prucalopride efficacy and constipation type.

BACKGROUND: Prucalopride is a selective serotonin receptor agonist with prokinetic activity, indicated for women with chronic constipation in whom laxatives have failed to provide adequate relief. Data suggests an improvement in about 50 % of such patients but whether the therapeutic effect is on patients with slow transit constipation (STC) and/or obstructed defaecation syndrome (ODS), or even those with constipation-predominant irritable bowel syndrome (IBS-C) is unknown. We therefore assessed whether there is any association between prucalopride efficacy and constipation type. METHODS: All patients receiving prucalopride between June 2010 and April 2012 at our institution were identified, and data analysed following a 4-week "test" period. Patients were sub-grouped as those suffering with ODS, STC, mixed (ODS and STC) or IBS-C based on symptomatology and investigations. Subjective assessment of patient satisfaction and continuation of medication were taken as positive outcomes and analysed for each sub-type along with any side effects. RESULTS: Sixty-nine patients met our criteria. Data were available for 59 women (median age 46 years, range 17-79 years). Sixty-five per cent of prescriptions came from colorectal surgeons. Overall, 25 out of 59 (42 %) patients improved, according to our criteria, after the 4-week trial period. Seventeen patients (29 %) had ODS, 26 (44 %) had STC, 7 (12 %) had mixed symptoms and 9 (15 %) had IBS-C. At 4 weeks, 10 out of 17 patients (59 %) with ODS had improved compared with 4 out of 9 patients (44 %) with IBS-C, 3 out of 7 patients (43 %) with mixed symptoms and 8 out of 26 (31 %) patients with STC. The underlying disorder did not predict whether or not a patient responded to the 4-week trial period (p = 0.32). Nine patients (15 %) experienced side effects that precluded further use. CONCLUSIONS: Patients with all categories of constipation may respond to prucalopride. A trial regime may be indicated regardless of the aetiology of the constipation.

The pharmacokinetics of intravenous ciprofloxacin 400 mg 12 hourly in patients with severe sepsis: the effect of renal function and intra-abdominal disease.

Serum concentrations of ciprofloxacin were reviewed in 22 patients given ciprofloxacin 400 mg intravenously 12 hourly for severe infection. No dosage modifications were made in patients with renal impairment. Patients who had either bowel or liver pathology in addition to renal failure had significantly higher serum concentrations than all other patients. Dosage reduction of ciprofloxacin in patients with severe sepsis and impaired renal function is not required unless they have co-existent intra-abdominal disease.

The pharmacokinetics and protein-binding of fusidic acid in patients with severe renal failure requiring either haemodialysis or continuous ambulatory peritoneal dialysis.

Fusidic acid is metabolized and excreted by the liver. It is generally assumed that renal impairment has no effect on serum concentrations. However, there are few data on the pharmacokinetics of fusidic acid in patients with chronic renal failure, particularly in those requiring dialysis. Seven patients with chronic renal failure on haemodialysis were given 500 mg sodium fusidate orally every 8 h for the 48 h between dialysis. Seven patients on continuous ambulatory peritoneal dialysis (CAPD) were given the same dosage regimen for seven doses. Fusidic acid concentrations were measured by HPLC. Accumulation was seen, and in 12 of the 14 patients steady-state pharmacokinetics had not been achieved by the third day. In haemodialysis patients, mean (range) Cmax values for the first dose were 13.0 (2.0-25.5) mg/L and for the sixth dose were 40.5 (10.1-69.9) mg/L. Serum concentrations were not reduced by haemodialysis. In CAPD patients mean Cmax values for the first dose were 16.0 (4.8-33.8) mg/L and for the seventh dose were 33.9 (23.4-61.9) mg/L. Fusidic acid concentrations of 1.0-2.3 mg/L were detected in peritoneal dialysis fluid in six of the seven CAPD patients. In both patient groups there was a tendency towards increased T(1/2) with repeated dosing. Protein-binding of fusidic acid in patient serum samples was 87.6-94.6%.

The pharmacokinetics of once-daily oral 400 mg ofloxacin in patients with peritonitis complicating continuous ambulatory peritoneal dialysis.

Seven patients with end-stage renal disease requiring support by continuous ambulatory peritoneal dialysis received once-daily 400 mg oral ofloxacin for 7 days for the treatment of bacterial peritonitis. Serum and peritoneal dialysis fluid (PDF) were collected for assay throughout the course of the study and for 5 days thereafter. Ofloxacin, desmethyl ofloxacin and ofloxacin-N-oxide accumulated over the course of therapy and could still be detected in serum and PDF 5 days after the end of therapy. The mean elimination half-life of ofloxacin in serum was 32 +/- 7 h, desmethyl ofloxacin 45 +/- 26 h and for ofloxacin-N-oxide 44 +/- 15 h. The total mean recovery of ofloxacin and its metabolites from the PDF was 15.4%. This regimen results in serum and PDF concentrations likely to be effective for the treatment of infection for at least 10 days.

The pharmacokinetics of meropenem in surgical patients with moderate or severe infections.

The pharmacokinetics of meropenem were studied in a group of 11 surgical patients (four male, seven female; mean age 63 years; mean weight 72 kg) all of whom had moderate or severe infection and who received a mean dose of 14.5 mg/kg +/- 2.7 meropenem 8-hourly iv for a minimum of 4 days. Venous blood samples were collected at timed intervals after the first dose on day 1 and the second dose on the fourth or fifth day of therapy. Serum meropenem concentrations were assayed by HPLC and fitted to a two compartment pharmacokinetic model. The mean pharmacokinetic parameters (+/- standard deviation) on day 1 were T1/2 84.6 +/- 24.1 min, Vdss 0.22 +/- 0.06 L/kg, AUC 6028 +/- 1983.2 mg.min/L, Cltot 188 +/- 67 mL/min and MRT 89.1 +/- 67.8 min. On the fourth or fifth days of therapy the values were T1/2 79.9 +/- 18.2 min, Vdss 0.17 +/- 0.8 L/kg, AUC 6000.7 +/- 2417 mg.min/L, Cltot 190 +/- 60 mL/min and MRT 67.8 +/- 30.4 min. Although the T1/2, Vdss and MRT decreased from day 1 to day 4 or 5 these changes were not statistically significant (Student's t-test, P > 0.05). Total clearance of meropenem was linearly related to creatinine clearance or patient age on the first day of therapy. Although the T1/2 and MRT were longer and the Cltot lower than those reported for young healthy volunteers, they were similar to those found in elderly volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

The pharmacokinetics of lomefloxacin in elderly patients with urinary tract infection following daily dosing with 400 mg.

Eleven elderly patients (mean age 83 years; range 75-90) with microbiologically proven urinary tract infections were given 400 mg lomefloxacin as a single daily dose for up to seven days. On the first and final day of treatment blood was taken at timed intervals and drug concentration-time curves plotted. Blood was also taken immediately before each of the other doses for assay of pre-dose concentrations. The mean (+/- S.D.) peak serum concentration of lomefloxacin on the first day was 4.8 mg/l (+/- 1.5) observed at a mean of 156 min (+/- 88) and on the final day was 6.3 mg/l (+/- 2.5) at a mean of 119 min (+/- 68). The mean serum half-life on the first day was 10.0 h (+/- 2.8) and on the final day 10.3 h (+/- 2.5). The daily pre-dose serum concentrations of lomefloxacin showed no accumulation of the drug. No serious adverse events were reported and all patients were cured although two had persistent pyuria. It is suggested that a once daily dose of 400 mg lomefloxacin is suitable for the elderly and that no dosage modification is needed in this patient group.