Evaluating a systematic voiding programme for patients with urinary incontinence after stroke in secondary care using soft systems analysis and Normalisation Process Theory: findings from the ICONS case study phase.

BACKGROUND: Urinary incontinence (UI) affects between 40 and 60% of people in hospital after stroke, but is often poorly managed in stroke units. OBJECTIVES: To inform an exploratory trial by three methods: identifying the organisational context for embedding the SVP; exploring health professionals' views around embedding the SVP and measuring presence/absence of UI and frequency of UI episodes at baseline and six weeks post-stroke. DESIGN: A mixed methods single case study included analysis of organisational context using interviews with clinical leaders analysed with soft systems methodology, a process evaluation using interviews with staff delivering the intervention and analysed with Normalisation Process Theory, and outcome evaluation using data from patients receiving the SVP and analysed using descriptive statistics. SETTING: An 18 bed acute stroke unit in a large Foundation Trust (a 'not for profit' privately controlled entity not accountable to the UK Department of Health) serving a population of 370,000. PARTICIPANTS: Health professionals and clinical leaders with a role in either delivering the SVP or linking with it in any capacity were recruited following informed consent. Patients were recruited meeting the following inclusion criteria: aged 18 or over with a diagnosis of stroke; urinary incontinence (UI) as defined by the International Continence Society; conscious; medically stable as judged by the clinical team and with incontinence classified as stress, urge, mixed or 'functional'. All patients admitted to the unit during the intervention period were screened for eligibility; informed consent to collect baseline and outcome data was sought from all eligible patients. RESULTS: Organisational context: 18 health professionals took part in four group interviews. Findings suggest an environment not conducive to therapeutic continence management and a focus on containment of UI. Embedding the SVP into practice: 21 nursing staff took part in six group interviews. Initial confusion gave way to embedding of processes facilitated by new routines and procedures. Patient outcome: 43 patients were recruited; 28 of these commenced the SVP. Of these, 6/28 (21%) were continent at six weeks post-stroke or discharge. CONCLUSION: It was possible to embed the SVP into practice despite an organisational context not conducive to therapeutic continence care. Recommendations are made for introducing the SVP in a trial context.

Repetitive task training for improving functional ability after stroke.

BACKGROUND: The active practice of task-specific motor activities is a component of current approaches to stroke rehabilitation. OBJECTIVES: To determine if repetitive task training after stroke improves global, upper or lower limb function, and if treatment effects are dependent on the amount, type or timing of practice. SEARCH STRATEGY: We searched the Cochrane Stroke Trials Register (October 2006), The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, SportDiscus, Science Citation Index, Index to Theses, ZETOC, PEDro, and OT Seeker (to September 2006), and OT search (to March 2006). We also searched for unpublished/non-English language trials, conference proceedings, combed reference lists, requested information on bulletin boards, and contacted trial authors. SELECTION CRITERIA: Randomised/quasi-randomised trials in adults after stroke, where the intervention was an active motor sequence performed repetitively within a single training session, aimed towards a clear functional goal, and where the amount of practice could be quantified. DATA COLLECTION AND ANALYSIS: Two authors independently screened abstracts, extracted data and appraised trials. Assessment of methodological quality was undertaken for allocation concealment, blinding, loss to follow up and equivalence of treatment. We contacted trial authors for additional information. MAIN RESULTS: Fourteen trials with 17 intervention-control pairs and 659 participants were included. PRIMARY OUTCOMES: results were statistically significant for walking distance (mean difference (MD) 54.6, 95% CI 17.5 to 91.7); walking speed (standardised mean difference (SMD) 0.29, 95% CI 0.04 to 0.53); sit-to-stand (standard effect estimate 0.35, 95% CI 0.13 to 0.56); and of borderline statistical significance for functional ambulation (SMD 0.25, 95% CI 0.00 to 0.51), and global motor function (SMD 0.32, 95% CI -0.01 to 0.66). There were no statistically significant differences for hand/arm function, or sitting balance/reach. SECONDARY OUTCOMES: results were statistically significant for activities of daily living (SMD 0.29, 95% CI 0.07 to 0.51), but not for quality of life or impairment measures. There was no evidence of adverse effects. Follow-up measures were not significant for any outcome at six or twelve months. Treatment effects were not modified by intervention amount or timing, but were modified by intervention type for lower limbs. AUTHORS' CONCLUSIONS: Repetitive task training resulted in modest improvement in lower limb function, but not upper limb function. Training may be sufficient to impact on daily living function. However, there is no evidence that improvements are sustained once training has ended. The review potentially investigates task specificity rather more than repetition. Further research should focus on the type and amount of training, and how to maintain functional gain.

Predicting spasticity after stroke in those surviving to 12 months.

OBJECTIVE: To measure muscle tone in a cohort of patients 12 months after stroke and develop a preliminary model, using data recorded routinely after stroke, to predict who will develop spasticity. DESIGN: A cohort study. SETTING: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, United Kingdom. SUBJECTS: One hundred and six consecutively presenting stroke patients surviving to 12 months. MAIN OUTCOME MEASURES: Spasticity measured at a range of joints using the Tone Assessment Scale. RESULTS: The Tone Assessment Scale revealed spasticity in 38 (36%) patients and more severe spasticity in 21 (20%) of the 106 patients. Logistic regression analysis revealed that lower day 7 Barthel Index score and early arm or leg weakness were significant predictors of abnormal muscle tone; and lower day 7 Barthel Index score, left-sided weakness and ever smoked to be significant predictors of more severe muscle tone. CONCLUSIONS: Using the models, it may be possible to predict whether or not spasticity will develop in patients 12 months after stroke. The utility of the models is aided by their use of predictor variables that are routinely collected as part of stroke care in hospital and which are easy to measure. The models need testing prospectively in a new cohort of patients in order to test their validity, reliability and utility and to determine if other data could improve their efficiency.

Prevalence of spasticity post stroke.

OBJECTIVES: To establish the prevalence of spasticity 12 months after stroke and examine its relationship with functional ability. DESIGN: A cohort study of prevalence of spasticity at 12 months post stroke. SETTING: Initially hospitalized but subsequently community-dwelling stroke survivors in Liverpool, UK. SUBJECTS: One hundred and six consecutively presenting stroke patients surviving to 12 months. MAIN OUTCOME MEASURES: Muscle tone measured at the elbow using the Modified Ashworth Scale and at several joints, in the arms and legs, using the Tone Assessment Scale; functional ability using the modified Barthel Index. RESULTS: Increased muscle tone (spasticity) was present in 29 (27%) and 38 (36%) of the 106 patients when measured using the Modified Ashworth Scale and Tone Assessment Scale respectively. Combining the results from both scales produced a prevalence of 40 (38%). Those with spasticity had significantly lower Barthel scores at 12 months (p < 0.0001). CONCLUSION: When estimating the prevalence of spasticity it is essential to assess both arms and legs, using both scales. Despite measuring tone at several joints, spasticity was demonstrated in only 40 (38%) patients, lower than previous estimates.

Reliability of measurements of muscle tone and muscle power in stroke patients.

OBJECTIVES: to establish the reliability of the modified Ashworth scale for measuring muscle tone in a range of muscle groups (elbow, wrist, knee and ankle; flexors and extensors) and of the Medical Research Council scale for measuring muscle power in the same muscle groups and their direct antagonists. DESIGN: a cross-sectional study involving repeated measures by two raters. We estimated reliability using the kappa statistic with quadratic weights (Kw). SETTING: an acute stroke ward, a stroke rehabilitation unit and a continuing care facility. SUBJECTS: people admitted to hospital with an acute stroke-35 patients, median age 73 (interquartile range 65-80), 20 men and 15 women. RESULTS: inter- and intra-rater agreement for the measurement of power was good to very good for all tested muscle groups (Kw = 0.84-0.96, Kw = 0.70-0.96). Inter- and intra-rater agreement for the measurement of tone in the elbow, wrist and knee flexors was good to very good (Kw = 0.73-0.96, Kw = 0.77-0.94). Inter- and intra-rater agreement for the measurement of tone in the ankle plantarflexors was moderate to good (Kw = 0.45-0.51, Kw = 0.59-0.64). CONCLUSIONS: the Medical Research Council scale was reliable in the tested muscle groups. The modified Ashworth scale demonstrated reliability in all tested muscle groups except the ankle plantarflexors. If reliable measurement of tone at the ankle is required for a specific purpose (e.g. to measure the effect of therapeutic intervention), further work will be necessary.

Effects of the CCKB antagonist L-365, 260 on benzodiazepine withdrawal-induced hypophagia in rats.

The effect of the selective CCKB antagonist L-365, 260 on chlordiazepoxide (CDP) withdrawal-induced hypophagia was assessed in two related studies in rats pretreated for 21 days with CDP at doses escalated from 10 to 30 mg/kg per day (b.i.d). L-365, 260 was studied at doses from 0.001 to 10 mg/kg (b.i.d). There was no evidence that L-365, 260 at any dose alleviated CDP withdrawal-induced hypophagia. These data contrast with reports that CCKB antagonists alleviate behavioural benzodiazepine (BZ) withdrawal symptoms considered to be indicative of "anxiogenesis". Presumably, such positive effects of CCKB antagonists are due to "functional antagonism", with enhanced anxiety during BZ withdrawal being attenuated by anxiolytic actions of CCKB antagonists. Collectively, studies with CCKB antagonists and other agents involving a number of different BZ withdrawal signs suggest that BZ withdrawal is a heterogeneous syndrome, with various different underlying mechanisms. CCKB antagonists appear to alleviate only a subset of possible BZ withdrawal signs.

Assessment of the benzodiazepine-like dependence potential in rats of the putative 5-HT(1A) agonist anxiolytic S-20499.

The dependence potential of the putative 5-HT(1A) agonist anxiolytic S-20499 was assessed in rats in a study in which the benzodiazepine chlordiazepoxide (CDP) was used as a "positive control". S-20499 was administered b.i.d. (at 10.00 and 16.00h) for 21 days, at constant doses of either 0.5, 3 or 18mg/kg i.p. Subsequently, spontaneous withdrawal from S-20499 was studied over 7 days. Acutely, S-20499 decreased body weight and food intake and complete tolerance developed to these effects. When S-20499 was withdrawn there was no evidence of any effect on body weight or food intake. CDP was also administered b.i.d. (at 10.00 and 16.00h) for 21 days at doses escalated from 10 to 30mg/kg i.p. CDP differed from S-20499 in some of its acute effects, stimulating body weight and food intake. In contrast to S-20499 withdrawal, CDP withdrawal induced weight loss and aphagia. Acutely, S-20499 resembled CDP in inducing hypothermia. Full tolerance developed to this effect of both drugs. However, only CDP withdrawal induced hyperthermia. Thus S-20499 appeared to be devoid of benzodiazepine-like dependence potential after administration for a relatively long period of time, at doses that are substantially greater than "anxiolytic doses" in rats.

Assessment of the dependence potential of the potent high-efficacy 5-HT1A agonist S-14506 in rats.

This study assessed the dependence potential of S-14506 [ 1- [ 2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxy napthyl) piperazine], a novel, potent 5-HT(1A) full agonist with anxiolytic and antidepressant actions in animal models. The dependence potential of S-14506 was compared with that of the benzodiazepine (BZ) chlordiazepoxide (CDP). BZ withdrawal caused weight loss, aphagia and hyperthermia after chronic b.i.d. treatment for 21 days. None of these withdrawal effects were seen after similar b.i.d. S-14506 treatment at high doses. However, the acute pharmacological actions of CDP and S-14506 differed on a number of indices. Specifically, CDP increased food intake and body weight, whilst S-14506 decreased these measures, possibly due to the induction of the serotonin syndrome. Of particular interest was the observation that S-14506 induced marked hypothermia, to which complete tolerance developed very rapidly (after only 1 day). The observation of marked, rapid tolerance to S-14506-induced hypothermia, in conjunction with the absence of withdrawal hyperthermia after prolonged chronic treatment at high doses, suggests that tolerance to this effect of S-14506 can be dissociated from dependence. Collectively, the data reported suggest that the full 5-HT(1A) agonist S-14506 is devoid of dependence potential, other human and animal studies having previously suggested that partial 5-HT(1A) agonists typically induce no, or minimal, dependence.

Actions of ritanserin, a 5-HT(2/1C) antagonist, in benzodiazepine-dependent rats.

The effects of ritanserin on spontaneous benzodiazepine (BZ) withdrawal-induced weight loss, anorexia and hypodipsia were studied. Groups of female rats initially received i.p. injections b.i.d. (11.00 and 17.00h) of either saline or chlordiazepoxide (CDP). CDP doses increased by 2mg/kg/day from 10mg/kg to a final does of 30mg/kg. Treatment was maintained for 26 days. Over the next 6 days animals were either treated b.i.d. with vehicle, CDP, or ritanserin at one of three doses (0.16,0.63 and 2.5mg/kg). In CDP-pretreated animals subsequently treated with vehicle, significant weight loss, anorexia and hypodipsia were seen, relative to controls. In saline-pretreated animals ritanserin had no effect on body weight. However, CDP withdrawal-induced weight loss was actually exacerbated by ritanserin, in a dose-related fashion. Thus, ritanserin potentiated withdrawal-induced weight loss, by a process which did not involve functional (additive) effects of withdrawal and ritanserin treatment. Ritanserin stimulated food intake in saline-pretreated animals. Despite this effect it failed to alleviate CDP withdrawal-induced anorexia. However, in contrast to the weight loss index, no evidence was obtained for potentiation of withdrawal-induced anorexia. In saline-pretreated animals ritanserin had no effect on water intake, nor did it alleviate or potentiate CDP withdrawal-hypodipsia. Thus the effects of ritanserin on somatic BZ withdrawal signs depended upon the specific sign studied, different signs showing potentiation or no effect. However, for none of the signs studied was there any evidence that ritanserin alleviated the effect of CDP withdrawal. 5-HT(2/1C) antagonists may therefore be of limited value in the treatment of somatic aspects of the BZ withdrawal syndrome. They may even exacerbate some BZ withdrawal signs, although a full characterization of the effects of such drugs on BZ withdrawal requires that a number of other different withdrawal signs and symptoms should be studied, since it seems likely that different BZ withdrawal signs involve different underlying mechanisms.

Evidence for a dissociation between benzodiazepine withdrawal signs.

The relationship between benzodiazepine-withdrawal induced weight loss and conditioned taste aversion was studied. Rats were treated with chlordiazepoxide (CDP) for 10 days (n = 37) or with vehicle (n = 39). Significant withdrawal-induced weight loss was observed. On day 11 all animals received an intra-oral infusion of saccharin. In a subsequent saccharin vs water choice test significant withdrawal-induced conditioned taste aversion was observed, as CDP pretreated animals drank less saccharin than controls. The two withdrawal indices were not correlated in the CDP pretreated animals [r = + 0.05], despite the fact that we studied a large group of rats. These data are in agreement with suggestions that drug withdrawal syndromes may be heterogeneous phenomena with a number of different underlying neural mechanisms.

Effects of the 5-HT3 antagonist ICS 205-930 on benzodiazepine withdrawal signs in rats.

Effects of the 5-HT3 antagonist ICS 205-930 on chlordiazepoxide (CDP) withdrawal were assessed in rats treated for 21 days with doses of CDP up to 40mg/kg/day (b.i.d.). Withdrawal signs recorded were body weight and 24h food intake, which both fell during withdrawal and then recovered. ICS 205-930 (0.001-1.0mg/kg) was administered b.i.d. during withdrawal. At no dose over the wide range tested did ICS 205-930 reduce withdrawal signs. These data contrast with published findings with the 5-HT3 antagonist ondanestron, some of which indicated that ondansetron completely alleviated the "anxiogenic" suppression of exploratory behaviour observed during benzodiazepine (BZ) withdrawal. Possible reasons for these differing findings are discussed. Collectively, these findings suggest that 5-HT3 antagonists may have limited utility in the clinical treatment of BZ withdrawal.

Effects of the 5-HT3 antagonist ondansetron on benzodiazepine-induced operant behavioural dependence in rats.

This study was designed to assess whether rats made tolerant to the suppressant action on Fixed Ratio operant responding of the benzodiazepine (BZ) chlordiazepoxide (CDP) would show behavioural disruption on drug withdrawal--so-called operant behavioural dependence. In addition, the study examined the effects of the 5-HT3 antagonist ondansetron on such operant behavioural dependence. During 42 consecutive days of CDP treatment, at doses escalated from 10 to 30 mg/kg/day, marked tolerance developed to the rate-suppressant action of CDP. On subsequent days, during spontaneous withdrawal, response rates declined significantly by around 30% in animals treated with saline, although some recovery of responding was seen over successive days of withdrawal. Similar reductions in responding followed by recovery were seen in rats treated with the 5-HT3 antagonist ondansetron (0.01-0.1 mg/kg, b.i.d.). These findings demonstrate for the first time that it is possible to use operant procedures to detect spontaneous BZ withdrawal. They also suggest, in agreement with recent studies from this laboratory (Leathley and Goudie 1992), that 5-HT3 antagonists may have relatively limited utility in treating some signs of BZ dependence.

Effects of the 5HT(1A) agonist anxiolytic gepirone on benzodiazepine withdrawal signs in rats.

The effects of gepirone at 3, 9 and 27mg/kg (b.i.d.) on benzodiazepine (BZ) withdrawal signs were studied in rats pretreated with chlordiazepoxide for 21 days at doses up to 40mg/kg b.i.d. The BZ withdrawal indices studied were weight loss and anorexia. At 9 and 27, but not 3mg/kg (b.i.d.) gepirone potentiated the weight loss and anorexia seen during BZ withdrawal. These effects could not be attributed simply to high dose drug-induced "malaise" inhibiting food intake, since in drug-naive animals gepirone stimulated food intake and increased bodyweight. These data show clearly that gepirone potentiates BZ withdrawal signs. Similar findings have been reported recently in studies with ipsapirone (Goudie and Leathley, 1991). Such effects could be mediated by the a(2)-adrenoceptor antagonist actions of 1-(2-pyrimidinyl)piperazine (1-PP), an active metabolite of both gepirone and ipsapirone. Such findings may explain why prior BZ experience impairs the clinical response to buspirone-type anxiolytics acting at the 5-HT(1A) receptor.

Increased incidence of nosocomial pneumonia in mechanically ventilated patients with subclinical aspiration.

Nosocomial pneumonia is frequent and is associated with high mortality in intubated mechanically ventilated patients. To determine whether there is a significant relationship between subclinical aspiration from nasogastric feeding and development of nosocomial pneumonia, we studied 24 ventilated patients who received nasogastric feeding. Endotracheal aspirates were tested twice daily for the presence of glucose using a glucose oxidase reagent strip. Subclinical aspiration was defined by the presence of glucose in nonbloody endotracheal aspirates. Nosocomial pneumonia was defined by the presence of all of the following conditions: (1) new or worsening infiltrate on chest roentgenogram consistent with pneumonia, (2) temperature greater than 38 degrees C and/or white blood cell count greater than 10,000/mm3 with 10% or more band forms, (3) culture of a new organism in the sputum, and (4) purulent tracheobronchial secretions. Twelve patients had no positive glucose tests of their endotracheal aspirates during their intensive care unit stay, one of whom developed nosocomial pneumonia. Twelve patients had endotracheal aspirates that were positive for glucose on 1 to 5 occasions. Of these patients, seven had bloody glucose-positive aspirates, four of whom developed clinical pneumonia. The remaining five patients had nonbloody glucose-positive endotracheal aspirates and all developed nosocomial pneumonia. There was a significantly greater incidence of pneumonia among patients who had nonbloody glucose-positive aspirates than among patients without glucose-positive aspirates (p less than 0.001, Fisher's exact test). We conclude that subclinical aspiration of nasogastric feeding, as detected by nonbloody glucose-positive endotracheal aspiration, is associated with the development of nosocomial pneumonia.

Evaluation of the dependence potential of the selective 5-H1A agonist ipsapirone in rats and of its effects on benzodiazepine withdrawal.

Two initial studies investigated: i) the effects of withdrawal from ipsapirone [a putative non-benzodiazepine (BZ) anxiolytic] and chlordiazepoxide (CDP); and ii) effects of ipsapirone in animals withdrawn from CDP. Rats were injected b.i.d. for 21 days with saline, ipsapirone or CDP at doses up to 40 mg/kg/injection. Subsequently, controls received the treatment administered previously, other subjects received saline during withdrawal from ipsapirone or CDP. Further subjects received ipsapirone (3, 10 or 30 mg/kg b.i.d.) during CDP withdrawal. Withdrawal indices recorded were body weight and food intake. Withdrawal signs were absent after ipsapirone treatment but present after CDP treatment, when food intake and bodyweight measures fell and then recovered. At the high dose of 30 mg/kg (b.i.d.) ipsapirone potentiated CDP withdrawal signs. Potentiation of withdrawal was not seen in animals treated with ipsapirone at lower doses (3 and 10 mg/kg, b.i.d.). In a subsequent study we found that ipsapirone conditioned a taste aversion, a possible index of drug-induced "malaise", at doses as low as 7.5 mg/kg. Therefore a possible explanation for the potentiation of BZ withdrawal in subjects treated with high doses of ipsapirone was that drug-induced "malaise" reduced food intake and body weight, rather than ipsapirone causing true potentiation of BZ withdrawal. However, in a further study we showed that the ipsapirone treatment regime which potentiated BZ withdrawal did not significantly reduce food intake or body weight, suggesting that high doses of ipsapirone potentiate BZ withdrawal by a mechanism that does not simply involve "malaise".(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of the 5-HT3 antagonist GR38032F (ondansetron) on benzodiazepine withdrawal in rats.

Effects of the 5-HT3 receptor antagonist GR38032F (ondansetron) on chlordiazepoxide withdrawal were assessed in rats which received chlordiazepoxide b.i.d. for 21 days at doses up to 40 mg/kg per injection. Withdrawal signs recorded were: body weight and food intake, which fell and then recovered over 9 days. Saline or GR38032F (1.0, 0.1 or 0.01 mg/kg) were administered b.i.d. during withdrawal. Clear withdrawal signs were seen in rats treated with saline after chronic chlordiazepoxide. However, GR38032F at 0.1 mg/kg reduced the severity of withdrawal. At 0.01 mg/kg GR38032F shortened withdrawal duration, but did not diminish peak withdrawal signs. At 1.0 mg/kg GR38032F, did not attenuate withdrawal signs at all. GR38032F (0.01-1.0 mg/kg) had no effect on ad lib food intake, therefore the attenuation of withdrawal was probably not simply due to stimulation of appetite. These data support recent claims that GR38032F attenuates benzodiazepine withdrawal, and they indicate that this effect shows an inverted U-shaped dose-response curve.