The impact of opioid-induced constipation among chronic pain patients with sufficient laxative use.

BACKGROUND: The impact of sufficient laxative use on opioid-induced constipation (OIC) is not known. AIM: To understand the experience and symptom burden over time among chronic non-cancer pain patients with OIC who are sufficient laxative users. METHODS: A prospective longitudinal study was conducted in United States, Canada, Germany and UK which included medical record abstraction, patient surveys and physician surveys. Patients on daily opioid therapy for ≥ 4 weeks for chronic non-cancer pain with OIC were recruited from physician offices and completed the survey at Baseline and Weeks 2, 4, 6, 8, 12, 16, 20 and 24. Sufficient laxative use was defined as at least one laxative remedy 4 or more times in the prior 2 weeks. RESULTS: Of the 489 patients who completed the Baseline survey and met OIC criteria, 234 (48%) were categorised as sufficient laxative users; 65% were female; 90% were white and 75 (32%) maintained sufficient laxative use for > 7 of the 8 follow-up periods. Patient Assessment of Constipation-Symptom (PAC-SYM) and Patient Assessment of Constipation-Quality of Life (PAC-QOL) scores indicated moderate symptom severity and impact. PAC-SYM and PAC-QOL scores remained relatively unchanged over time with a maximum score change of 0.5 points. Work productivity and activity impairment remained relatively constant. Mean per cent activity impairment because of constipation was 37% at Baseline and 34% at Week 24. CONCLUSIONS: These findings demonstrate constipation persists despite sufficient laxative use with little improvement in symptoms, HRQL or activity impairment. This ongoing burden emphasises the need to identify more efficacious constipation therapies for this chronic pain patient population.

Comorbidities and personal burden of urgency urinary incontinence: a systematic review.

AIMS: Studies on the burden and comorbidities associated with urgency urinary incontinence (UUI) are difficult to compare, partly because of the evolution of definitions for lower urinary tract symptoms and the various instruments used to assess health-related quality of life (HRQL). This article summarises published evidence on comorbidities and the personal burden associated specifically with UUI to provide clinicians with a clear perspective on the impact of UUI on patients. METHODS: A PubMed search was conducted using the terms: (urgency urinary incontinence OR urge incontinence OR mixed incontinence OR overactive bladder) AND (burden OR quality of life OR well-being OR depression OR mental health OR sexual health OR comorbid), with limits for English-language articles published between 1991 and 2011. RESULTS: Of 1364 identified articles, data from 70 retained articles indicate that UUI is a bothersome condition that has a marked negative impact on HRQL, with the severity of UUI a predictor of HRQL. UUI is significantly associated with falls in elderly individuals, depression, urinary tract infections, increased body mass index, diabetes and deaths. The burden of UUI appears to be greater than that of stress urinary incontinence or overactive bladder symptoms without UUI. UUI adversely impacts physical and mental health, sexual function and work productivity. CONCLUSIONS: UUI is associated with numerous comorbid conditions and inflicts a substantial personal burden on many aspects of patients' lives. Healthcare providers should discuss UUI with patients and be aware of the impact of UUI and its associated comorbidities on patients' lives.

Validation of a 3-item OAB awareness tool.

AIM: The purpose of this study was to validate a short awareness tool to assist patients in identifying if they have bothersome overactive bladder (OAB) symptoms. METHODS: This secondary analysis study utilised data from a cross-sectional study of adult patients presenting for primary care visits. Patients completed an 8-item OAB screener. The clinician probed for urinary frequency, urgency, nocturia and urgency urinary incontinence. If the patient screened positive or reported the presence of at least one OAB symptom, additional questions were asked regarding lifestyle and coping issues. The clinician then diagnosed the patient as having No OAB, Possible OAB, or Probable OAB. Multivariate logistic regressions were performed to assess the feasibility of deriving a shorter screener to raise awareness of OAB among primary care patients. RESULTS: The 1,260 patients in this study were 51.6±17.0 years old; 62% were women; and most (89%) were Caucasian. Clinicians diagnosed 12.1% of patients with Probable OAB, 19.7% with Possible OAB and 68.3% with No OAB. The logistic regression models were performed with OAB clinical diagnosis as the dependent variable comparing No OAB versus Probable OAB. Three items which included the symptoms of urinary frequency, urinary urgency and urine loss associated with a strong desire to urinate performed well as an awareness tool. A cut-point of four provided the most appropriate sensitivity (82%) and specificity (91%) when identifying Probable OAB and yielded adequate model fit. The final 3-item OAB Awareness Tool (OAB-V3) is gender neutral. CONCLUSION: The 3-item OAB Awareness Tool (OAB-V3) correctly identified patients with symptoms of OAB with high sensitivity and specificity and can be used as a conversation starter for patients with symptoms of OAB.

Persistence and adherence in the treatment of overactive bladder syndrome with anticholinergic therapy: a systematic review of the literature.

Overactive bladder syndrome (OAB) is a chronic condition that has an impact on patients' daily activities and health-related quality of life (HRQL). Anticholinergic therapy is often prescribed following insufficient results with behaviour modification alone; however, rates of treatment discontinuation are consistently high. This study systematically reviewed persistence and adherence data in patients with OAB treated with anticholinergic therapy. A search focused on the intersection of OAB, persistence/adherence, and anticholinergic therapy was conducted in MEDLINE and EMBASE. Articles published after 1998 were reviewed and selected for inclusion based on prespecified criteria. A total of 147 articles and two abstracts were included in the review. Results from 12-week clinical trials showed high rates of discontinuation, ranging from 4% to 31% and 5% to 20% in treatment and placebo groups, respectively. Unsurprisingly, rates of discontinuation found in medical claims studies were substantially higher, with 43% to 83% of patients discontinuing medication within the first 30 days and rates continuing to rise over time. Findings from medical claims studies also suggest that over half of patients never refill their initial prescription and that adherence levels tend to be low, with mean/median medication possession ratio (MPR) values ranging from 0.30 to 0.83. The low levels of persistence and adherence documented in this review reveal cause for concern about the balance between the efficacy and tolerability of anticholinergic agents. Strategies should be identified to increase persistence and adherence. New agents and non-pharmacologic alternatives with good efficacy and minimal side effects should be explored.

Assessing patients' descriptions of lower urinary tract symptoms (LUTS) and perspectives on treatment outcomes: results of qualitative research.

AIMS: Understanding the patient's experience and symptom descriptions is critical to assess outcomes. Thus, there is a need for qualitative research to better understand how patients describe their symptoms and treatment expectations. METHODS: Eight focus groups were conducted in two research phases: Phase 1 focused on eliciting patient's descriptions of urinary symptoms, and Phase 2 assessed patient perspectives on treatment outcomes. Participants with a range of lower urinary tract symptoms (LUTS) were recruited from urology clinics and community settings in the United States. All interviews were audio recorded and transcribed. Content and descriptive analyses were performed. RESULTS: A total of 33 men and 30 women participated. Mean ages for men and women were 55 and 61 in Phase 1, and 57 and 61 in Phase 2, respectively. About 73% of participants were white people, and most had a high school education or greater. A wide range of LUTS were emergently described, and the words, concepts and phrases were generally similar across groups. Most participants identified with the word 'bother', and thought it was important to assess both the frequency and bother of each symptom. Reasons for seeking care included symptom bother and fears about cancer and bladder infections. Most participants thought that a 50% improvement in a single symptom or group of symptoms would be a meaningful treatment outcome. CONCLUSION: This qualitative research provides a better understanding on how men and women describe their LUTS and their perspectives on treatment outcomes. This research can be used to inform the development of a new LUTS outcomes' tool.

Relationships between improvements in symptoms and patient assessments of bladder condition, symptom bother and health-related quality of life in patients with overactive bladder treated with tolterodine.

AIMS: Relationships were evaluated between treatment-related improvements in overactive bladder (OAB) symptoms as recorded in bladder diaries and patient-reported symptom bother, bladder-related problems and health-related quality of life (HRQL). METHODS: A post hoc analysis was performed on data from patients with OAB (n = 863) enrolled in a 12-week open-label trial of tolterodine extended release (ER) in a primary care setting. At baseline and week 12, patients recorded every micturition, urgency episode and urgency urinary incontinence episode in 3-day bladder diaries. Patients also completed the Overactive Bladder Questionnaire (OAB-q) and Patient Perception of Bladder Condition (PPBC). Relationships between week 12 changes in bladder diary variables and OAB-q and PPBC scores were evaluated using Spearman correlations. RESULTS: By week 12, tolterodine ER-related improvements in all bladder diary variables were significantly correlated with improvements on the PPBC (r = 0.26-0.36; p < 0.001), OAB-q Symptom Bother scale (r = 0.30-0.51; p < 0.001), and all OAB-q HRQL domains (r = -0.24 to -0.42; p < 0.001), although the correlations were generally small to moderate in size. Improvements on the PPBC were also significantly correlated with improvements on the OAB-q Symptom Bother scale (r = 0.63; p < 0.001) and all HRQL domains (r = -0.40 to -0.59; p < 0.001). CONCLUSIONS: Tolterodine ER-related improvements in OAB symptoms (assessed by diary variables) and patients' perceptions of the changes in symptom bother, bladder-related problems and HRQL (assessed by PPBC and OAB-q) were significantly correlated. The OAB-q and the PPBC provide a relevant and important patient perspective for OAB treatment evaluation.

Relationship of infarct artery patency and left ventricular ejection fraction to health-related quality of life after myocardial infarction: the GUSTO-I Angiographic Study experience.

BACKGROUND: Post-myocardial infarction global ejection fraction and infarct-related artery patency might be expected to be associated with health-related quality-of-life (HRQOL) outcomes, but this association has not been previously shown. The GUSTO-I Angiographic Study cohort 2-year follow-up afforded an examination of such potential relationships. METHODS AND RESULTS: A total of 1848 patients (87.7% response rate) who were enrolled in the GUSTO-I Angiographic Study were contacted for a telephone interview regarding their current HRQOL (physical function, psychological well-being, perceived health status, and social function) 2 years after MI. In multivariable models, left ventricular ejection fraction (EF) was significantly related to physical (P:=0.021) and social (P:=0.014) function, psychological well-being (P:=0.042), and perceived health status (P:=0.024). Infarct-related artery patency was not directly related to any HRQOL outcome. A decreasing EF was predictive of poorer outcomes in each HRQOL dimension. Men consistently had better outcomes in all HRQOL dimension with the exception of perceived health status. Increasing age was predictive of poorer outcomes in all dimensions of HRQOL except for psychological well-being where the inverse occurred; younger patients experienced greater depression, anxiety and worry than their older counterparts. The presence of comorbidities increased the likelihood of worse outcomes in all dimensions. CONCLUSIONS: This is the first study to demonstrate a significant relationship between EF and long-term HRQOL outcomes. This advantage in left ventricular function preservation should be added to the mortality advantage when considering the impact of treatment strategies for myocardial infarction.

Clinical predictors of early infarct-related artery patency following thrombolytic therapy: importance of body weight, smoking history, infarct-related artery and choice of thrombolytic regimen: the GUSTO-I experience. Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries.

OBJECTIVES: The purpose of this study was to determine patient characteristics that are a priori predictors of early infarct related artery patency following thrombolytic therapy, and to provide a paradigm which may identify patients who would be most likely to achieve restoration of normal (TIMI 3) coronary flow in response to thrombolytic therapy. BACKGROUND: Restoration of infarct-related artery perfusion in acute myocardial infarction is necessary for preservation of ventricular function and mortality reduction. Clinical variables that are a priori predictors of early patency with currently available thrombolytic regimens have not been fully characterized. METHODS: The probability of early infarct-related artery patency (TIMI 3 flow) was determined by multivariable logistic regression. We determined a reduced (parsimonious) model for predicting early (90 min) infarct-related artery patency (TIMI grade 3) based on data from 1,030 patients in the GUSTO-I Angiographic study. RESULTS: Predictors of 90 min TIMI 3 flow are use of an accelerated t-PA regimen (vs. streptokinase containing regimens) (chi2=39.1; p < or = 0.0001), infarct related artery (RCA/Lcx vs. LAD) (chi2=12.7; p=0.0004), body weight (chi2=10.3; p=0.001) and history of smoking (chi2=7.4; p=0.007). Time from symptom onset to treatment was not significant (p=0.71). CONCLUSIONS: The efficacy of currently available thrombolytic regimens is chiefly dependent on choice of thrombolytic regimen, body weight, infarct-related coronary artery and smoking history. Clinical variables alone correctly predict a priori TIMI 3 flow in the infarct-related artery 64% of the time. Patients with body weights greater than 85 kg are at a significant disadvantage with regard to achieving successful thrombolysis compared to those with lesser body weights.

A randomized trial comparing primary angioplasty with a strategy of short-acting thrombolysis and immediate planned rescue angioplasty in acute myocardial infarction: the PACT trial. PACT investigators. Plasminogen-activator Angioplasty Compatibility Trial.

OBJECTIVES: The study evaluated the efficacy and safety of a short-acting reduced-dose fibrinolytic regimen to promote early infarct-related artery (IRA) patency during the inherent delay experienced by infarct patients referred for angioplasty as the principal recanalization modality. BACKGROUND: Previous approaches using long-acting, full-dose thrombolytic infusions rarely showed benefit, but they did increase adverse event rates. METHODS: Following aspirin and heparin, 606 patients were randomized to a 50-mg bolus of recombinant tissue-type plasminogen activator (rt-PA) (alpha half-life 4.5 min) or to placebo followed by immediate angiography with angioplasty if needed. The end points included patency rates on catheterization laboratory (cath lab) arrival, technical results when PTCA (percutaneous transluminal coronary angioplasty) was performed, complication rates, and left ventricular (LV) function by treatment assignment and time to restored patency following angioplasty. RESULTS: Patency on cath lab arrival was 61% with rt-PA (28% Thrombolysis in Myocardial Infarction trial [TIMI]-2, 33% TIMI-3), and 34% with placebo (19% TIMI-2, 15% TIMI-3) (p = 0.001). Rescue and primary PTCA restored TIMI-3 in closed arteries equally (77%, 79%). No differences were observed in stroke or major bleeding. Left ventricular function was similar in both treatment groups, but convalescent ejection fraction (EF) was highest with a patent IRA (TIMI-3) on cath lab arrival (62.4%) or when produced by angioplasty within an hour of bolus (62.5%). However, in 88% of angioplasties, the delay exceeded 1 h: convalescent EF 57.3%. CONCLUSIONS: Tailored thrombolytic regimens compatible with subsequent interventions lead to more frequent early recanalization (before cath arrival), which facilitates greater LV function preservation with no augmentation of adverse events.

The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope.

Adenosine appears to be an important mediator of hypotension and bradycardia in certain subsets of patients with vasodepressor syncope. Adenosine receptor blockage with methylxanthines may hypothetically prevent the vasodepressor spell. We studied the chronotropic, hemodynamic, and cardiac autonomic responses to head-up tilt in patients (mean age 40.7 +/- 18.1 years) with vasodepressor syncope before and after treatment with oral theophylline. At baseline, hypotension and syncope or near syncope were induced at 11.7 +/- 2.3 minutes of 60 degrees head-up tilt in all patients. Cardiac vagal and sympathetic tone showed biphasic and directionally opposite changes during tilt. Repeat tilt during oral theophylline therapy (6-12 mg/kg/day for 14 +/- 6 days) did not provoke symptomatic hypotension in 82% of patients. During 10.7 +/- 6.1 months of follow-up, seven patients had no recurrence of vasodepressor syncope and seven patients discontinued theophylline because of adverse reactions. Low-dose theophylline prevents tilt-induced vasodepressor syncope and may prevent spontaneous vasodepressor syncope in selected patients who can tolerate theophylline.

Development and validation of a disease-specific treatment satisfaction questionnaire for gastro-oesophageal reflux disease.

BACKGROUND: Currently, no disease-specific, patient-based, treatment satisfaction instruments related to gastro-oesophageal reflux disease exist. AIM: To develop and validate a treatment satisfaction questionnaire for gastro-oesophageal reflux disease (TSQ-G). METHODS: A new questionnaire was developed from patient focus groups, clinician input and literature review. A validation study was conducted in treated gastro-oesophageal reflux disease patients. Ancillary measures included the Medical Outcomes Study Short Form-36, Quality of Life in Reflux and Dyspepsia, Gastrointestinal Symptom Rating Scale, Socially Desirable Response Scale, Patient Satisfaction Questionnaire-18 and physician and patient measures of symptoms and satisfaction. Statistical analyses included exploratory factor analysis, Cronbach's alpha, intra-class correlations, analyses of variance and t-tests. RESULTS: A total of 198 gastro-oesophageal reflux disease patients participated in the study, with a mean age of 50.7 years, 68% female and 84% Caucasian. The physician-rated severity of gastro-oesophageal reflux disease was mild (32%), moderate (50%) and severe (18%); 83% were on proton pump inhibitors. The final TSQ-G consisted of 28 items with seven sub-scales; Cronbach's alpha ranged from 0.58 to 0.94. Correlations with the expected sub-scales of the ancillary measures were moderate to strong. The TSQ-G sub-scales discriminated significantly between levels of physician-rated disease severity, symptom days and patient and physician ratings of satisfaction. CONCLUSIONS: The TSQ-G has excellent reliability and construct validity and appears to be a useful tool for the evaluation of treatment satisfaction in gastro-oesophageal reflux disease patients.

Assessment of functional status in patients with cardiac disease.

The evaluation of functional status as an outcome for patients with cardiac disease has become common practice in both clinical settings and research studies. However, the measurement of functional status lacks conceptual clarity, frequently focuses on only one dimension of functioning, and overlooks the individuality of the patient. Some measures of functional status have questionable sensitivity to capture change over time, or the ability to discriminate between groups, and lack reports of reliability and validity testing. The purpose of this article is to discuss critical issues related to the evaluation of functional status, with a focus on objective and subjective measures of functional status frequently used in cardiac populations.

Hypertension and current issues in compliance and patient outcomes.

Economic and human costs associated with untreated or inadequately controlled hypertension and its complications continue to be an issue in the United States despite the availability of numerous antihypertensive agents. Knowledge of hypertension, product profiles, tolerability concerns, convenience of dosing, health-related quality of life effects, and cost of therapy are some of the factors that may influence the compliance of patients to their medication regimens. Recent reports on patient noncompliance have focused on patient-provider relationships, psychosocial barriers, home blood pressure monitoring, and electronic monitoring systems to improve blood pressure control. The use of health-related quality of life assessment in antihypertensive studies and in routine clinical practice provides another opportunity to optimize a patient's regimen for short- and long-term hypertension control in a cost-effective manner.

The impact on health-related quality of life of stress, urge and mixed urinary incontinence.

OBJECTIVE: To examine the impact of each type of urinary incontinence (stress, urge, and mixed) on health-related quality of life (HRQL). SUBJECTS AND METHODS: The USA National Overactive Bladder Evaluation (NOBLE) programme of prevalence was used to identify respondents with incontinence based upon telephone survey responses. A nested case-control study was then conducted on respondents with symptoms of an overactive bladder (OAB), and on age and gender-matched controls; this consisted of the respondents completing a series of questionnaires, including the OAB-q (an HRQL scale for OAB), the Medical Outcomes Study (MOS) Short-Form-36 (SF-36), the MOS Sleep Scale, and the Center for Epidemiological Studies - Depression (CES-D) scale. Respondents were categorized into subgroups according to the primary cause of urine loss, i.e. sudden/uncomfortable urge to urinate (urge, UI), physical pressure (stress, SI), or both (mixed, MI). Descriptive analyses, t-tests and analysis of variance with post hoc comparisons were used. RESULTS: Of the 919 participants in the nested case-control study, 171 reported incontinence, i.e. UI (69), SI (62) and MI (40). Among this cohort, 82.5% were female, 85.4% were Caucasian and the population had a mean age of 55.9 years. All OAB-q subscale scores were significantly (P < 0.01) worse among those with MI than with SI. Respondents with UI reported significantly higher levels of symptom bother and lower sleep scores (both P < 0.001) than those with SI. There were no differences in HRQL between the MI and UI groups. Voiding frequency and nocturia episodes did not differ among the groups but compared with the SI group, both UI and MI groups reported significantly higher ratings of urinary urge intensity (P < 0.001) and rated their need for medical care significantly higher (P < 0.01). The MI group reported more incontinence episodes (P = 0.02) than the SI group. CONCLUSION: Compared with SI, respondents with UI and MI reported not only significantly greater ratings of urinary urge intensity and more incontinence episodes, but also significantly worse HRQL. These results are consistent with previous findings which indicated a greater impact on HRQL for the urge component of MI than for the stress component.

The discordant influences of infarct healing on the electrophysiologic effects of procainamide and N-acetylprocainamide.

Ischemic zone refractoriness and conduction delay respond differently to infarct healing and, hypothetically, may exert discordant influences on the electrophysiologic action of different classes of antiarrhythmic drugs. This study evaluated the influence of infarct healing on the electrophysiologic effects of procainamide (PA) and N-acetylprocainamide (NAPA) in a sedated, closed-chest canine model with a healing anterior wall myocardial infarction, indwelling myocardial electrodes and inducible sustained ventricular tachyarrhythmias (VT). Infarct zone refractory periods, conduction times and the inducibility of VT were tested at base line and during infusion of PA or NAPA in a crossover study design at 1, 4 and 8 weeks of infarct healing. Data were presented as the percent magnitude of change from base line induced by drug. The magnitude of change during PA infusion in infarct zone refractory periods, but not conduction times, decreased during infarct healing (P < .001). The magnitude of change in refractory period and conduction time during NAPA was not significantly altered by the stage of myocardial infarction healing. At week 1, PA prevented inducible VT in 9 of 14 animals vs. 3 of 15 during NAPA infusion (P < .05). At weeks 4 and 8 there was no significant difference in VT suppression between PA and NAPA. We conclude that the stage of infarct healing can selectively influence the response of the infarct zone to the effects of PA, but not NAPA. This discordant effect may be class-specific. These data may have important implications for the management of lethal ventricular arrhythmias soon after myocardial infarction.

Bedside monitoring of heparin therapy: comparison of activated clotting time to activated partial thromboplastin time.

Heparin anticoagulation is utilized during and after interventional cardiac catheterization procedures to reduce the risk of acute thrombotic coronary artery occlusion. The short half-life of heparin, the importance of maintaining therapeutic anticoagulation, and the time delay inherent in the processing and retrieval of the activated partial thromboplastin time (aPTT) by the hospital laboratory has generated interest in point-of-care heparin monitoring. The activated clotting time (ACT), the aPTT as assessed by both a new portable device, as well as the hospital laboratory, and heparin levels (H) were obtained from the same sample of blood in 100 patients receiving intravenous heparin. There was an excellent correlation between the aPTT determined at the bedside and by the hospital laboratory (r = .89). The ACT did not correlate well with either the laboratory or bedside aPTT (r = .63, .68 respectively). In the sub-therapeutic and therapeutic range, there was essentially no correlation between ACT and H. Only ACT values > 225 sec were predictive of therapeutic or supra-therapeutic aPTTs. ACT values < 225 sec, however, were not useful in predicting degree of anticoagulation. In situations in which the maintenance of therapeutic anticoagulation is critical as well as those in which the determination of lack of anticoagulation is required, the bedside determination of aPTT appears to be a useful tool.

The prevalence of nocturia and its effect on health-related quality of life and sleep in a community sample in the USA.

OBJECTIVE: To evaluate the prevalence of nocturia and its effects, with and without concomitant overactive bladder (OAB, i.e. urgency, frequency, urge incontinence and nocturia), on health-related quality of life (HRQoL) and sleep. SUBJECTS AND METHODS: A national survey was conducted in the USA to assess the prevalence of OAB and nocturia. A nested case-control study was conducted among respondents with OAB symptoms and age- and gender-matched controls, with participants completing a series of questionnaires on HRQoL (OAB-q, Short Form-36, and Medical Outcomes Study (MOS) sleep scale). Descriptive analyses, t-tests, analysis of variance with post hoc comparisons and multivariate regressions were used to analyse the data. RESULTS: In all, 5204 people participated in the survey, with 919 in the nested case-control study. The sample population had a mean age of 45.8 years, was 52.6% female and 80% Caucasian. In the community sample, 31% reported > 1 void/night and 14.2% reported > 2 voids/night. The prevalence of nocturia increased with age, with no gender differences. For OAB cases, 66.8% reported > 1 void/night and 42.2% reported > 2. In the case-control cohort there were significant HRQoL differences (P < 0.01), with increasing episodes of nocturia in all OAB-q subscales except social interaction. The amount of sleep per night was significantly correlated with the sleep, concern and social interaction OABq subscale scores. The number of nocturia episodes/night was also significantly (P = 0.02) associated with the number of hours of sleep/night. CONCLUSION: Nocturia is widely prevalent and increases with age, affecting men and women equally. Incremental increases in the number of voids/night have further negative effects on sleep, symptom bother, and HRQoL.

A randomized trial confirming the efficacy of reduced dose recombinant tissue plasminogen activator in a Chinese myocardial infarction population and demonstrating superiority to usual dose urokinase: the TUCC trial.

BACKGROUND: Reports from Japan suggest effective myocardial infarction (MI) treatment in Asian patients with much lower doses of tissue plasminogen activators (tPA) than used in European and American regimens. Because increasing doses of fibrinolytics lead to increased bleeding complications, identification of patients who respond to reduced doses is of importance. We conducted a trial in the People's Republic of China in which reduced-dose recombinant tPA was compared with the standard local therapy, urokinase. METHODS: Four hundred patients with acute MI within 12 hours of symptom onset were to be randomized to an 8-mg bolus of recombinant tPA followed by a 42-mg 90-minute infusion or 1.5 million units of urokinase as a 30-minute infusion. Patients received aspirin and heparin and underwent angiography to determine infarct artery patency 90 minutes after the start of therapy. RESULTS: The Data and Safety Monitoring Board recommended premature termination after 342 patients were recruited. Infarct artery patency (grade 2 or 3) occurred in 79% of patients receiving recombinant tPA and in 53% of patients receiving urokinase (P <.001); Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow was 48% and 28%, respectively (P <.001). The higher-patency-rate recombinant tPA growth had better posttreatment left ventricular ejection fractions, 58.6% versus 54.7%, P <.01. Adverse events were infrequent and not significantly different in the 2 groups. CONCLUSIONS: This study confirms that a substantially lower dose of recombinant tPA is effective in Asian patients compared with that required in Western patients even after consideration of body weight. Specific dose-response studies should be performed with fibrinolytic regimens to avoid overdosage with its attendant risks of excess bleeding.