Systematic review of the prevalence of faecal incontinence.

BACKGROUND: Faecal incontinence (FI) is widely recognized as a significant problem in the community. Conjecture exists around the proportion of the population affected. This systematic review evaluated studies reporting the community prevalence of FI in terms of methodology, design and definitions. METHODS: MEDLINE, Embase, CINAHL, the Cochrane Collaboration and National Guideline databases were searched for studies investigating the prevalence of FI in community-based adults published from January 1966 to February 2015. Study data, including methodology, sample size, response rate, definition of FI and prevalence rates, were extracted on to a pro forma and appraised critically. Where possible, FI prevalence estimates were pooled. RESULTS: Thirty studies were analysed from 4840 screened articles. FI prevalence estimates varied from 1·4 to 19·5 per cent. This variation was explained by differences in data collection method and two factors within definitions of FI: type of stool and frequency of FI episodes. When these factors were accounted for, the FI prevalence at a threshold of at least once per month for liquid or solid stool was 8·3-8·4 per cent for face-to-face or telephone interviews, and 11·2-12·4 per cent for postal surveys. The pooled prevalence rate from studies for functional FI (defined by ROME II criteria) was 5·9 (95 per cent c.i. 5·6 to 6·3) per cent. CONCLUSION: When comparable methodologies and definitions are used, studies produce remarkably similar prevalence rates in different community populations. FI remains an unspoken symptom, with lower rates reported in personal interviews compared with anonymous postal questionnaires.

Clinical benefits and cost-effectiveness of allogeneic red-blood-cell transfusion in severe symptomatic anaemia.

BACKGROUND: It is well known that blood transfusion is life-saving, but also that it carries a serious risk of transmitting viral infections. Introduction of new methods of testing for transmissible diseases, blood banking and dispatch regulations has considerably increased the cost of blood products. However, the clinical benefits and cost-effectiveness of allogeneic red-blood-cell (ARBC) transfusion remain assumed yet undetermined. We assessed the clinical benefits and cost-effectiveness of ARBC transfusion in severe anaemia. METHODS: This was a multicenter observational study comparing Jehovah's Witness (JW) patients with matched ARBC-transfused patients. Inclusion criteria were age ≥15 years and severe anaemia (haemoglobin ≤ 80 g/l). Two JW patients with palliative care cancer and five JW patients with haemoglobin (Hb) concentration between 70·1 and 80 g/l, mild symptoms of anaemia and Auckland Anaemia Mortality Risk Score of 0-3 were excluded. RESULTS: The entry criteria were met by 103 JW patients and the same number of patients treated with ARBC transfusion. ARBC transfusion reduced mortality by 94%, shock by 88%, gastrointestinal bleeding by 81%, infective complications by 81%, cardiac arrhythmia by 96%, angina by 86%, ischaemic myocardial injury by 81%, acute/acute on chronic renal failure by 66%, neurologic complications by 92%, delirium by 76%, depression by 91% and syncopal episodes by 95%. The incremental cost-effectiveness ratio of ARBC transfusion was 2011 US$22 515 for death prevented. CONCLUSION: ARBC transfusion in anaemic patients is clinically beneficial and cost-effective.

Mortality risk stratification in severely anaemic Jehovah's Witness patients.

The aim of this retrospective cohort study was to identify early risk factors of mortality and develop a mortality risk stratification instrument for severely anaemic Jehovah's Witness patients. It has been shown that Jehovah's Witness patients with the Auckland Anaemia Mortality Risk Score (Auckland AMRS) of 0 to 3 had 4% mortality, Auckland AMRS 4 to 5 32%, Auckland AMRS 6 to 7 50% and Auckland AMRS 8 and above 83%. It is concluded that the Auckland AMRS predicts mortality of severely anaemic Jehovah's Witness patients.

Determining levels of fecal incontinence in the community: a New Zealand cross-sectional study.

BACKGROUND: Fecal incontinence is a socially stigmatized condition, and its prevalence in the community has been problematic to quantify because of difficulty with its definition. OBJECTIVE: This study estimates the community prevalence of fecal incontinence in New Zealand by 3 scales of measurement: patient perceptions of a "problem with bowel control," their symptoms, and their quality of life. DESIGN/MAIN OUTCOME MEASURES: A postal survey of 2000 people, aged >18, randomly selected from the national electoral roll, was performed. This used a validated, reliability-tested, anonymous questionnaire, the Comprehensive Fecal Incontinence Questionnaire, incorporating the identification of a "problem with bowel control," the Fecal Incontinence Severity Index, and the Fecal Incontinence Quality of Life Scale. RESULTS: The response rate was 68.7%. A total of 14.7% (95% CI: 12.6-16.7) of participants "felt they had a problem with bowel control" and 12.4% (95% CI: 10.5-14.5) had fecal incontinence when defined using the Fecal Incontinence Severity Index table as "leakage of liquid or solid stool ≥ 1/month." In terms of quality of life, 26.8% of the population (95% CI: 24.2-29.4) noted some impairment on the Fecal Incontinence Quality of Life Scale. In total, 155 (13.2%) participants reported at least 2 of the 3 possible diagnostic measures, and this may provide a way to incorporate the 3 measures into a new definition of fecal incontinence. LIMITATIONS: This study incorporated a new "generic" question enquiring about an individual's perception of a bowel control problem and also introduced a "cutoff" value for Fecal Incontinence Quality of Life Scale to attempt to identify those with any impairment "due to accidental bowel leakage." CONCLUSIONS: This study helps to highlight some of the challenges involved with suitably identifying those who have fecal incontinence within the community. The prevalence rate of 13.2% represents a realistic measure of the burden of fecal incontinence in the general population, and further research in this area is recommended.

Seasonal change in the concentration of progesterone receptor in breast cancer.

There are conflicting reports of seasonal changes in steroid hormone receptor levels in breast cancer tissue. Estrogen receptor and progesterone (PR) receptor levels from 1132 tumors were thus grouped according to month of initial tumor detection or month of tissue sampling/surgery. There was a significant circannual variation in the mean monthly PR receptor concentration in patients grouped according to month of tissue sampling/surgery with peak PR levels in April (late summer-early autumn) and nadir values in August and September (late winter-early spring). There was no significant cyclic variation in estrogen receptor values. A significant annual variation in tumor PR concentration was also seen when receptor levels from individual tumors were grouped according to month of initial tumor detection, with peak PR levels found in January and February. The time interval between tumor detection and biopsy/surgery was 3.3 +/- 5.3 months (mean +/- SD) which was close to the interval between the peak PR concentration expressed by month of tumor detection compared with month of tissue sampling for receptor assay. There was also a significant seasonal variation in the month of initial tumor detection, with peak detection occurring in December (summer). The close synchrony between month of maximum tumor detection and month of peak PR concentration suggests that seasonal changes in detection of breast cancer may in part relate to seasonal changes in hormone responsiveness within tumor tissue.

Vehicle interior interactions and kinematics of rear facing child restraints in frontal crashes.

The performance of rear facing child restraints in frontal crashes can be determined by controlling a) the child's kinematics and b) interactions with vehicle structures. Twelve sled tests were performed to analyze the effect of the location and structural properties of vehicle interior components. The role of restraint kinematics was studied by developing computational models which underwent idealized motions. Stiff structures originally offset from the restraint, but which contact the restraint late in the test, cause increased injury values. Attachment methods which reduce child restraint rotation and more rigidly couple the restraint to the vehicle result in the best safety performance.

The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599.

The anaesthetic profile of a novel water-soluble aminosteroid, Org 20599 [(2 beta, 3 alpha, 5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one methanesulphonate], and the ability of the compound to allosterically regulate the activity of the GABAA receptor, have been studied in comparison to the properties of established intravenous general-anaesthetic agents. Intravenously administered Org 20599 produced a rapid onset, short duration loss of the righting reflex in mice. The anaesthetic potency of Org 20599 was comparable to that of the steroids 5 alpha-pregnan-3 alpha-ol-20-one or alphaxalone, and exceeded that of propofol, thiopentone or pentobarbitone. Org 20599 and the reference anaesthetic agents allosterically displaced the binding of [35S]-t-butylbicyclophosphorothionate (TBPS) from GABAA receptors of rat-brain membranes with the order of potency: 5 alpha-pregnan-3 alpha-ol-20-one > Org 20599 > alphaxalone > propofol > thiopentone > pentobarbitone. At human recombinant alpha 1, beta 2, gamma 2L subunit-containing GABAA receptors expressed in Xenopus laevis oocytes, the anaesthetic agents produced a concentration-dependent and reversible potentiation of the peak amplitude of GABA-evoked currents. A similar positive allosteric action of Org 20599 was observed for the GABAA receptors expressed by bovine adrenal chromaffin cells maintained in culture. The rank order of potency in the aforementioned assays was identical to that determined from the displacement of TBPS binding. At concentrations greater than those required for potentiation of GABA, the anaesthetics exhibited GABA-mimetic effects with a rank order of potency that paralleled their modulatory activity. Such direct agonism varied greatly in maximal effect between compounds. The modulatory and direct agonist actions of Org 20599 were additionally confirmed utilizing rat hippocampal neurones in culture. The results indicate Org 20599 to be a potent and short-acting intravenous anaesthetic agent in mice and suggest positive allosteric regulation of GABAA receptor function to be a plausible molecular mechanism of action for the drug.

Antiarrhythmic activity of 17 beta-aminoestratrienes. Comparison of 3-ols and 3-acetates with the corresponding 3-(3-amino-2-hydroxypropyl) ethers.

The antiarrhythmic efficacy of 17 beta-amino- and 17 beta-amino-16 alpha-hydroxyestratrien-3-ols and 3-acetates (group 1) was compared with the efficacy of corresponding 3-[2-hydroxy-3-(isopropylamino)propyl] and 3-[2-hydroxy-3-(tert-butylamino)propyl] ethers (group II), substituents which are usually associated with beta-adrenoceptor blocking activity. Group I compounds exerted potent antiarrhythmic activity against both aconitine-induced arrhythmias in mice and ischemia-induced arrhythmias in rats and reduced the maximum following frequency of isolated guinea pig atria. Electrophysiological studies indicated that their mechanism of action is due to an ability to reduce the fast inward sodium current in cardiac cells (class I antiarrhythmic action). Group II compounds were inactive in the aconitine and atrial tests and electrophysiological studies confirmed that they were devoid of class I activity. However, these compounds, like both class I antiarrhythmic and beta-adrenoceptor blocking drugs, were active against ischemia-induced arrhythmias. Group II compounds, unlike group I compounds, exerted nonspecific beta-adrenoceptor blocking actions, which may account for their activity in the rat test. It was concluded that introduction of the 3-substituted ether group did not confer any advantage over the parent 3-ol or 3-acetate compounds.

Anesthetic activity of novel water-soluble 2 beta-morpholinyl steroids and their modulatory effects at GABAA receptors.

(3 alpha,5 alpha)-3-Hydroxypregnan-20-ones and (3 alpha,5 alpha)-3-hydroxypregnane-11,20-diones bearing a 2 beta-morpholinyl substituent were synthesized, and the utility of these steroids as anesthetic agents was evaluated through determination of their potency and duration of hypnotic activity in mice after intravenous administration. Alkylation of the morpholinyl substituent or chlorination at C-21 afforded the novel amino steroids (2 beta,3 alpha,5 alpha)-3-hydroxy-2-(2,2-dimethyl-4-morpholinyl)-pregnane-11,20-dione (19) and (2 beta,3 alpha,5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one (37) that were more potent and advantageously produced shorter sleep times than related compounds which were previously reported. Furthermore, salts of these and other amino steroids generally retained good aqueous solubility. In a radioligand binding assay the compounds inhibited the specific binding of [35S]-tert-butyl bicyclophosphorothionate to rat whole brain membranes, and in an electrophysiological assay they potentiated GABAA receptor-mediated currents recorded from voltage-clamped bovine chromaffin cells. These in vitro results are consistent with the anesthetic activity of the amino steroids being related to their modulatory effects at GABAA receptors.

Left ventricular function after cigarette smoking by chronic smokers: comparison of normal subjects and patients with coronary artery disease.

Twenty normal subjects and 25 patients with coronary artery disease underwent systolic time interval analysis before and after rapidly smoking two cigarettes. A slight increase in heart rate and arterial pressure was seen in both groups. In patients with coronary artery disease, preejection period/left ventricular ejection time ratio increased; in normal subjects it decreased. Left ventricular performance is diminished after cigarette smoking among subjects who have preexisting significant coronary artery disease.

The effects of disopyramide phosphate on early post-coronary artery ligation dysrhythmias and on epicardial ST-segment elevation in anaesthetized dogs.

1 The antidysrhythmic, haemodynamic and metabolic effects of intravenously administered disopyramide phosphate (1 to 5 mg/kg) have been studied in greyhounds, anaesthetized with trichloroethylene. 2 In doses of 2.5 and 5.0 mg/kg, disopyramide significantly reduced the ventricular dysrhythmias that occur in the initial 30-min period following acute coronary artery ligation. None of the disopyramide-treated animals developed ventricular fibrillations. 3 The metabolic consequences of coronary artery ligation, assessed by local coronary venous sampling from the ischaemic area, were not modified by disopyramide except that K+ egress was prevented. 4 There was evidence for substantial disopyramide-induced myocardial depression (decreased cardiac output and left ventricular dP/drmax with elevated ventricular filling pressure and pulmonary oedema and shunting) and it is suggested that great care be taken when the drug is administered intravenously in conditions where cardiac function is already compromised. Disopyramide also reduced myocardial blood flow. 5 In chloralose-anaesthetized mongrel dogs, disopyramide (2.5 mg/kg) significantly reduced the ST-segment elevation (assessed from epicardial recordings) that resulted from short (3 min) coronary artery occlusions. This could indicate a reduction in the extent and severity of myocardial injury or simply reflect decreased K+ efflux (since locally administered K+ itself increased ST-segment elevation).

Potentiation of the effects of adenosine on isolated cardiac and smooth muscle by diazepam.

1. Adenosine (10(-7) to 3 x 10(-4) M) or 2-chloroadenosine (10(-8) to 10(-5) M) produced concentration-dependent inhibition of the responses of the rat isolated vas deferens to electrical field stimulation. In electrically driven (2 Hz) guinea-pig isolated left atria, adenosine (10(-6) to 10(-3) M) or 2-chloroadenosine (10(-8) to 10(-7) M) produced concentration-dependent decreases in isometric tension. 2. Diazepam (10(-6) and 10(-5) M) had no direct effect per se, but significantly potentiated the inhibitory action of adenosine on both tissues without altering the inhibitory effect of 2-chloroadenosine. 3. The adenosine uptake inhibitors, hydroxynitrobenzylthioguanosine (HNBTG, 10(-5) M) and dipyridamole (10(-5) M) also potentiated the inhibitory actions of adenosine in rat vas deferens, but not hose of 2-chloroadenosine. 4. Following adenosine uptake inhibition in rat vas deferens by HNBTG (10(-5) M), diazepam (10(-5) M) failed to produce any significant further potentiation of the inhibitory action of adenosine. 5. It is concluded that the potentiation of adenosine by diazepam is possibly due to an inhibition of adenosine uptake.

Prophylactic lignocaine and early post-coronary artery occlusion dysrhythmias in anaesthetized greyhounds.

1. Lignocaine (1 mg kg-1 min-1 infused intravenously for 30 min) greatly reduced the incidence of ventricular ectopic beats that resulted from acute coronary artery ligation in anaesthetized greyhound dogs. However, the incidence of ventricular fibrillation was only slightly reduced by this treatment which caused significant myocardial depression. 2. There is no good evidence from this study that lignocaine is a particularly effective prophylactic in acute myocardial infarction.

Antiarrhythmic, haemodynamic and metabolic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one hydrochloride in greyhounds following acute coronary artery ligation.

1 The antiarrhythmic, haemodynamic and metabolic effects of a new amino steroid, ORG6001, have been investigated in experimental acute myocardial infarction in anaesthetized greyhounds. 2 ORG6001 administered either intravenously (2-10 mg/kg) or orally (50 mg/kg) significantly reduced the incidence of ventricular ectopic beats in the first 30 min after ligation of the left anterior descending coronary artery. 3 In dogs pretreated with ORG6001, metabolic changes indicative of myocardial ischaemia (lactate production and potassium efflux) were less marked than those occurring in control animals. 4 Antiarrhythmic doses of ORG6001 caused only minimal transient haemodynamic effects. 5 These results suggest that ORG6001 may possess distinct advantages over presently-used antiarrhythmic drugs in the prevention and treatment of the early arrhythmias which occur after myocardial infarction.

The beneficial actions of bepridil in acute myocardial infarction in anaesthetized dogs.

1 When administered intravenously shortly before acute coronary ligation in dogs anaesthetized with chloralose, bepridil (5 mg/kg) produced immediate and transient falls in coronary and systemic vascular resistance which were accompanied by marked decreases in myocardial oxygen extraction. These effects were followed by sustained decreases in heart rate and myocardial oxygen consumption. 2 This dose of bepridil reduced the number of premature ventricular beats and abolished fibrillation induced by coronary artery ligation without modifying the haemodynamic or metabolic consequences (lactate production) of myocardial ischaemia. 3 When administered 1.5-2 h after ligation, bepridil did not compromise the critical perfusion of the acutely ischaemic zone but reduced the lactate production and ST-segment elevation in the ischaemic zone. 4 These results suggest that bepridil may be a useful drug in the chronic treatment of angina pectoris and in this respect may possess advantages over beta-adrenoceptor antagonists.

The effects of dipyridamole on blood flow and oxygen handling in the acutely ischaemic and normal canine myocardium.

1. The effects of the intravenous administration of dipyridamole (0.25 mg/kg) were examined in a canine preparation that enabled simultaneous measurements to be made of blood flow in ischaemic and in essentially normal areas of the myocardium and also of oxygen handling (availability, consumption and extraction) in both these regions.2. When administered to dogs anaesthetized with trichlorethylene 2-3 h after acute ligation of the descending branch of the left coronary artery, dipyridamole markedly increased blood flow in essentially normal regions (left circumflex flow) but failed to increase flow in the area supplied by the ligated vessel (measured by (133)xenon clearance and by retrograde flow). In five of the six animals definite decreases in flow (; stealing ') were observed in the ischaemic region. These flow changes were related to the decreased trans-ventricular perfusion pressure (diastolic peripheral coronary pressure minus left ventricular end-diastolic pressure) and were accompanied by electrocardiographic evidence of increasingly severe myocardial ischaemia. The results support the suggestion that only increasing the perfusion gradient will usefully improve blood flow (and hence oxygen availability) to the acutely ischaemic myocardium.3. Despite these effects on ischaemic muscle blood flow, the oxygen tension of the blood draining the infarcting muscle was markedly elevated. The conclusion is drawn that dipyridamole decreases the efficiency of the myocardial circulation by opening up vessels that do not take part in tissue exchange.

The haemodynamic and metabolic effects of MG 8926, a prospective antidysrhythmic and antianginal agent.

1 The antidysrhythmic, haemodynamic and metabolic effects of a new prospective antianginal and antidysrhythmic agent, N-(3-3-dipenylpropyl)-alpha-methyl-beta-cyclohexylethylamine hydrochloride (MG 8926), have been compared with the chemically related substance, prenylamine, in anaesthetized greyhounds and guinea-pigs. 2 When given intravenously 20 min beforehand, both MG 8926 and prenylamine (5 mg/kg) significantly suppressed the early dysrhythmias induced by coronary artery ligation in anaesthetized greyhounds. At a dose of 1 mg/kg, MG 8926 also protected anaesthetized guinea-pigs from dysrhythmias induced by ouabain infusions. 3 In dogs pretreated with MG 8926, metabolic changes indicative of myocardial ischaemia (increased PCO2 and potassium efflux, decreased oxygen content and pH) were less marked than those occurring in control animals. 4 Evidence was obtained that MG 8926, when given either before or after coronary occlusion, was capable of decreasing the severity of myocardial ischaemia as assessed by ST-segment changes in epicardial electrocardiograms.

Comparative effects of propranolol and practolol in the early stages of experimental canine myocardial infarction.

1 The effects of propranolol and practolol, at equivalent myocardial beta-adrenoceptor blocking doses, (as assessed by the degree of shift of isoprenaline dose-response curves) were investigated in anaesthetized greyhounds before and after acute coronary artery ligation. 2 When administered intravenously to the intact close-chest dog, propranolol (0.1 mg/kg) and practolol (0.5 mg/kg) caused similar decreases in heart rate, left ventricular dP/dt max, myocardial blood flow and cardiac output. Only propranolol increased peripheral vascular resistance. 3 When administered 2-3h after acute coronary artery ligation, propranolol (0.1 mg/kg) significantly decreased blood flow in both normally perfused and ischaemic regions of the heart. There was also electrocardiographic evidence of further deterioration after propranolol; two out of seven animals died following this treatment. 4 Practolol (0.5 mg/kg) when administered after coronary artery ligation also decreased normal myocardial blood flow but flow in the ischaemic area remained unchanged. Evidence was obtained from electrocardiographic, myocardial temperature, myocardial O2 consumption and lactate measurements that the administration of practolol, in contrast to propranolol, benefited the ischaemic myocardium. 5 Analysis of the results suggests that this beneficial action of practolol may be related to at least two mechanisms. Firstly the ability of practolol to increase the period during diastole when perfusion of the subendocardium is possible, without decreasing the transventricular pressure during this period. Secondly that practolol does not unmask alpha-adrenoceptor vasoconstriction in the ischaemic region.

The antidysrhythmic aminosteroid, ORG 6001, reduces the ST-segment elevation produced by coronary occlusion in the dog.

ST-segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open-chest anaesthetized dogs. This was greatly reduced by the prior administration of the anti-dysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the extent and degree of myocardial ischaemia or to prevention of K+ egress from ischaemic cells.

Comparison of the electrophysiological effects of Org 7797, disopyramide, mexiletine and propafenone in anaesthetized dogs with myocardial infarcts.

1. The electrophysiological effects of intravenously administered Org 7797 were compared with those of disopyramide (class Ia), mexiletine (Ib) and propafenone (Ic) in anaesthetized dogs with 5-6 day-old left ventricular myocardial infarcts. 2. Org 7797 (0.5 mg kg-1) slowed conduction at all levels of the myocardium as shown by increases in St-A, AH, HV and QRS intervals, very modestly prolonged atrial and ventricular refractory periods and slightly shortened ventricular repolarization. Sinus node recovery time was increased whilst the RR interval was unchanged. A higher dose (2 mg kg-1) prolonged RR and rendered 5 out of 8 dogs unable to follow an atrial pacing stimulus of mean cycle length 322 ms. 3. Electrophysiological changes induced by propafenone (2 mg kg-1) were qualitatively similar to those of Org 7797 (0.5 mg kg-1). 4. Electrophysiological changes induced by mexiletine (2 mg kg-1) were small or insignificant. The most noticeable effect was a modest increase in the St-A interval and a slight shortening of ventricular repolarization. A higher dose (8 mg kg-1) additionally slowed conduction in the His-Purkinje system and in the ventricular myocardium. 5. Disopyramide (2 and 5 mg kg-1) prolonged all cardiac intervals including JTc, QTc and QT during pacing and prolonged cardiac refractory periods. 6. It was concluded that the electrophysiological profile of Org 7797 is more like that of the Ic agent propafenone than that of the class Ia and Ib drugs, disopyramide and mexiletine.