Validation of a new patient-reported outcome instrument of health-related quality of life specific to patients with alcohol use disorder: the Alcohol Quality of Life Scale (AQoLS).

PURPOSE: The Alcohol Quality of Life Scale (AQoLS) is a new patient-reported outcome 34-item questionnaire measuring health-related quality of life (HRQOL), specific to patients with an alcohol use disorder, developed from the patients' perspective. This is the first report establishing evidence in support of measurement reliability and validity of the AQoLS. METHODS: A total of 285 randomly selected patients receiving interventions for alcohol use disorder in addiction specialised care settings in France were included in the study (response rate 80.1 %). Exploratory factor analysis was conducted to evaluate the hypothesised-during-development-stage dimensional structure of the AQoLS. Internal consistency of the total score and the dimensions subscores were assessed through Cronbach's alpha coefficients. Construct validity was tested through correlations with the Short-Form 36 Health Survey (SF-36) and EuroQol 5 dimensions (EQ-5D). RESULTS: Exploratory analysis indicated seven observed dimensions which differed slightly from the 7 dimensions defined a priori in the framework hypothesised during the scale development: activities, relationships, living conditions, negative emotions, self-esteem, control and sleep. A major common factor allows the summing of the 34 items to obtain a total score. All the 34 items were acceptable. Cronbach's alpha for the AQoLS total score was 0.96 and ranged from 0.8 to 0.9 for the dimensions subscores. Negative correlations between AQoLS and all dimensions of the SF-36, but general health and positive correlations between AQoLS and all items of the EQ-5D were shown. As expected, the correlations were mostly moderate in magnitude, low with scores referring to physical areas and the highest with the SF-36 MSC. CONCLUSION: This study provides evidence of the measure's psychometric properties in terms of construct validity and internal consistency. The "control" and "self-esteem" dimensions are of particular interest as these concepts are not captured in existing HRQOL. Further longitudinal validation of the scale is necessary to assess sensitivity to change.

Development of the Alcohol Quality of Life Scale (AQoLS): a new patient-reported outcome measure to assess health-related quality of life in alcohol use disorder.

PURPOSE: The development of patient-centred approaches and of reduction in consumption strategies in alcohol use disorder requires giving a larger place to qualitative assessments that are closer to patients' concerns and more clinically relevant than drinking outcomes and generic health-related quality of life instrument. Our purpose was to develop from patients input the Alcohol Quality of Life Scale (AQoLS), a disease-specific measure for alcohol use disorder (AUD). METHODS: Concept elicitation focus groups were conducted with AUD patients in the UK and France. Thematic analysis was used to identify key areas of impact of AUD, and draft items were developed to capture these issues. The draft items underwent expert review to ensure clinical and cross-cultural applicability. Two iterative rounds of cognitive debriefing interviews were conducted with AUD patients in both countries, to assess face and content validity. RESULTS: From focus groups conducted with 38 AUD patients, seven areas of impact emerged, forming the basis for the AQoLS: relationships, activities, looking after self, emotional impact, control, living conditions, and sleep. An initial pool of 90 items was reduced to 50 following the review process. In cognitive interviews, the measure took less than 10 min to complete, and patients reported that items were relevant to their experience. Following Round 1 interviews (n = 16), 14 items were removed because patients felt they were unclear or uneasy to respond to, 2 were combined, 7 were revised, and 4 new items were added. The recall period of 2 weeks was changed to 4 weeks, based on patient comments. Following Round 2 interviews (n = 15), 5 items were removed and 3 were modified to produce the 34-item AQoLS. CONCLUSION: As the only de novo measure of health-related quality of life developed specifically for AUD, the AQoLS offers the potential of increased sensitivity to show the effectiveness of therapeutic interventions from the patient's perspective.

Upstream use of tirofiban in patients admitted for an acute coronary syndrome in hospitals with or without facilities for invasive management. PRISM-PLUS Investigators.

Management and prognosis of acute coronary syndromes may be influenced by the availability of catheterization facilities at admitting hospitals. Treatment effects of tirofiban were examined in a Canadian cohort of 834 patients enrolled in the Canadian Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial according to admission into hospitals without (n = 322) or with catheterization facilities (n = 512). Hospital transfers for cardiac catheterization were facilitated using preexisting networks accelerated for the purposes of the protocol. In hospitals without facilities, the relative risks for occurrence of death, infarction, or refractory ischemia among patients receiving tirofiban plus heparin compared with heparin alone were 0.52 at 7 days (p = 0.02), 0.59 at 30 days (p = 0.03), and 0.70 at 180 days (p = 0.09); and for death or infarction, 0.32 (p = 0.02), 0.46 (p = 0.04,) and 0.51 (p = 0.03), respectively. Benefit was seen regardless of transfer status, with no statistically significant interaction between treatment, hospital type, and catheterization for any end point at any time point. The incidence of Thrombolysis In Infarction defined major bleeding with respect to therapy was not significantly different between hospital types. Thus, upstream treatment with tirofiban plus heparin confers clinical benefits in unstable angina and/or non-ST-segment elevation infarction patients regardless of whether initial presentation is to a hospital without catheterization facilities or to a hospital with such facilities.

Age-related serum levels of insulin-like growth factor-I, -II and IGF-binding protein-3 following myocardial infarction.

Aging retards the repair process by decreasing hormone secretion from the somatotrophic axis, which plays a major role in tissue reconstruction after injury. The aim of this study was to determine the effect of aging on serum insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding protein-3 (IGFBP-3) levels following myocardial infarction (MI). For four consecutive days, we monitored the variation of serum IGF-I, IGF-II and IGFBP-3 concentrations in 26 patients aged 19-71 years who were diagnosed with MI. Serum IGF-I, IGF-II and IGFBP-3 were measured daily by double antibody radioimmunoassay. Daily serum IGF-I concentrations showed a significant negative correlation with age (r = -0.528, P< 0.001). Total serum IGF-I was significantly (P = 0.002) higher in the younger age group (patients under 50 years) compared to the older group (50 years and over); 206 +/- 16 ng/ml vs 136 +/- 12 ng/ml. During this investigation, younger patients (under 50 years) showed no significant daily variations in IGF-I levels compared to older patients (50 years and over) who presented a significant decline (P = 0.012). Total serum IGF-II in both groups decreased significantly with time. Total serum IGFBP-3 in the younger age group was significantly higher (P = 0.046) than in the older age group (3.42 +/- 0.18 microgram/ml vs 2.95 +/- 0.13 microgram/ml). MI patients in both groups showed significantly lower IGF-I and IGF-II (IGFs) with higher IGFBP-3 compared to age- and sex-adjusted levels of normal adults (controls). The present results confirm that age and cardiac condition affect IGFs and IGFBP-3 levels. We are inclined to believe that older patients with a cardiac condition are less able to maintain their blood IGF-I levels during the recovery period compared to younger patients. Given the biological impact of IGF-I on regeneration, this could explain why older patients take longer to recover and heal poorly in comparison to younger patients.

Combination therapy with tirofiban and enoxaparin in acute coronary syndromes.

BACKGROUND: Tirofiban, an intravenous glycoprotein IIb/IIIa antagonist, and enoxaparin, a low molecular weight heparin, have each been shown to be effective at reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q-wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. MATERIALS AND METHODS: Fifty-five patients with non-Q-wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microgram/kg/min i.v.) for 48-108 h coadministered with either enoxaparin (1 mg/kg sc q 12 h) (n=26) or unfractionated heparin (i.v. adjusted to activated partial-thromboplastin time) (n=27) to evaluate pharmacokinetics, pharmacodynamics, and safety. The primary objective of the study was to investigate the effect of unfractionated heparin versus enoxaparin on the plasma clearance of tirofiban. RESULTS: Coadministration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was 176.7+/-59.8 and 187.5+/-81.8 ml/min, respectively, for enoxaparin and unfractionated heparin-treated patients (P=NS). The mean difference was well within the prespecified criterion for comparability. Administration of tirofiban with enoxaparin vs. unfractionated heparin resulted in lesser variability and a trend towards greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation >70% in the tirofiban and enoxaparin group (84% vs. 65%, P=0.19). Median bleeding time was 21 min for tirofiban and enoxaparin vs. > or =30 min for tirofiban and unfractionated heparin (P=NS). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 vs. 24.9 min, P=0.02). Tirofiban plasma concentration and clearance were comparable whether coadministered with enoxaparin or unfractionated heparin. There were no major or minor bleeding events in either group by the TIMI criteria. INTERPRETATION: The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin vs. tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These data from the first clinical report of coadministration of a glycoprotein IIb/IIIa receptor antagonist and a low molecular weight heparin are consistent with prior data which show differential pharmacodynamic effects of enoxaparin and unfractionated heparin on platelet aggregation.

Angiotensin-converting enzyme inhibition in myocardial infarction--Part 1: Clinical data.

There is an increasing body of clinical trial evidence to support the use of angiotensin-converting enzyme (ACE) inhibitors in the management of patients following myocardial infarction (MI). Enthusiasm for the use of ACE inhibitors in the acute phase of MI had previously been tempered by the adverse results of an early trial. However, exciting new information is available from several large, randomized studies that has not only quelled those initial concerns but also attests to the efficacy of using this class of medication in the first 24 h after an acute MI. A Canadian National Opinion Leader Symposium was held in November 1995 to review the results of the major ACE inhibitor clinical trials and to discuss key issues and controversies surrounding their use in acute MI. The focus of this paper, the first of two parts, is on the results of the major ACE inhibitor clinical trials.

Angiotensin-converting enzyme inhibition in myocardial infarction--Part 2: Clinical issues and controversies.

Over the past 10 years, several clinical studies have concluded that, in patients already receiving conventional therapies, angiotensin-converting enzyme (ACE) inhibitors further reduce the risk of death following myocardial infarction (MI). Post-MI ACE inhibitors have proven to be effective as long term therapy in high risk patients as well as when used for much shorter periods in a broad patient population. However, while considerable mortality data have been collected, the effects of ACE inhibitors post-MI on other cardiovascular outcomes have not been as well documented. In addition, a number of issues regarding the most effective use of these agents remain unresolved. This paper, the second of two parts, focuses on the clinical issues and controversies surrounding the use of ACE inhibitors following acute MI. The effects of ACE inhibitors on the outcomes of sudden death, nonsudden death, recurrent angina, mitral regurgitation and left ventricular dysfunction are reviewed and potential mechanisms of action are proposed. In addition, ACE inhibitor therapy is discussed in terms of patient selection criteria, choice of agent, optimal dosing regimen, concomitant use of other therapies and relative costs of treatment. Finally, potential mechanisms of action of ACE inhibitors are proposed for each of the outcomes examined.

Late coronary aneurysm formation following coronary angioplasty.

In a 38-year-old man with recurrent chest pain 14 months following percutaneous transluminal coronary angioplasty (PTCA) of the left anterior descending coronary artery, two aneurysms were noted at previous PTCA sites without evidence of restenosis. Although the precise mechanism of formation of these aneurysms is not known, it is possible that medial dissection and weakening of the artery provoked aneurysm formation.

Efficacy of delayed percutaneous transluminal coronary angioplasty after intravenous use of streptokinase in myocardial infarction.

Between June 1984 and December 1986, 35 patients with acute myocardial infarction received streptokinase intravenously within 3 hours after the beginning of chest pain and underwent percutaneous transluminal coronary angioplasty (PTCA) either immediately (in 2 cases) or 1 to 19 (mean 4.4) days later (in 33). The rate of successful PTCA was 89%. Reocclusion occurred in one patient. The mean percentage of stenosis decreased from 86% to 11%. The mean trans-stenotic gradient was reduced from 41 to 11 mm Hg. The results suggest that in patients whose condition is stable, PTCA performed a few days after thrombolysis is a valuable alternative to more aggressive treatment with immediate PTCA.

Usefulness of a rapid initial increase in plasma creatine kinase activity as a marker of reperfusion during thrombolytic therapy for acute myocardial infarction.

This study evaluates a new nonangiographic marker of reperfusion--a rapid initial increase in plasma creatine kinase (CK) and CK-MB activity--in 50 patients receiving intracoronary streptokinase. Blood for CK and CK-MB activity was sampled at 30-minute intervals and angiography performed at 15-minute intervals or earlier if there were clinical signs suggestive of reperfusion. An absolute first-hour increase in CK activity of 480 +/- 345 IU/liter (range 54 to 1,440 IU/liter), or a relative first-hour increase of 34 +/- 18% (range 13 to 67% of the peak rise), or an absolute first-hour increase in CK-MB activity of 48 +/- 36 IU/liter (range 10 to 144 IU/liter) or a relative first-hour increase of 27 +/- 13% (range 13 to 57%) was found in patients immediately after reperfusion with Thrombolysis In Myocardial Infarction (TIMI) grade 3 perfusion of the artery of infarction. The onset of rapid increase in CK and CK-MB activity closely reflected the time of angiographic documentation of reperfusion. In contrast, in the absence of reperfusion, the absolute rate of increase in CK activity measured in the last hour of the 2 1/2-hour period beginning with the start of treatment was only 15 +/- 9 IU/liter on the average (range 2 to 30 IU/liter) and the relative rate of rise was 3 +/- 2% on the average (range 1 to 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Time course and characteristics of ventricular arrhythmias after reperfusion in acute myocardial infarction.

The time course and characteristics of ventricular arrhythmias were studied in 45 consecutive patients with acute myocardial infarction who received intravenous streptokinase and underwent 24-hour Holter monitoring both after admission and before discharge 8 +/- 3 days later. In 41 of the 45 patients, thrombolytic treatment resulted in reperfusion as determined by characteristic clinical signs, i.e., rapid relief of pain associated with rapid resolution of ST-segment elevation and simultaneous abrupt increase in serum creatine kinase-MB activity. During the first 24 hours after reperfusion, the prevalence of ventricular premature complexes (VPCs) and couplets was nearly 100%, with an average frequency of 67 VPCs (range 1 to 1,336, median 44) and 6 couplets per hour per patient (range 1 to 97, median 4). Ninety percent of patients had an average of 8 runs of accelerated idioventricular rhythm per hour per patient (range 1 to 226, median 5) and 23% of the patients had an average of 2 runs of ventricular tachycardia per hour per patient (range 1 to 22, median 2) during the first 24 hours after reperfusion. The frequency of arrhythmias began to decrease 8 to 12 hours after reperfusion. Except for VPCs, ventricular arrhythmias were rare during the predischarge Holter study. Arrhythmias after reperfusion did not produce clinical symptoms and did not degenerate into ventricular fibrillation even though the patients were not receiving antiarrhythmic therapy. In the 4 patients without signs of reperfusion, the prevalence and frequency of all ventricular arrhythmias during the 24 hours after treatment was lower than in patients with reperfusion, and none had an accelerated idioventricular rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Ratio of ST-segment depression in lead V2 to ST-segment elevation in lead aVF in evolving inferior acute myocardial infarction: an aid to the early recognition of right ventricular ischemia.

The potential value of the ratio of precordial ST-segment depression to inferior ST-segment elevation as a sign of concomitant right ventricular (RV) ischemia was examined. The study group consisted of 68 patients, admitted within 3 hours of the onset of inferior acute myocardial infarction (AMI), in whom there was no evidence of prior AMI. In 27 of the 34 patients in whom inferior AMI was the result of right coronary artery occlusion proximal to the RV branch, the magnitude of ST-segment depression in lead V2 was 50% or less of the magnitude of ST-segment elevation in lead aVF, whereas in only 3 of the 34 patients in whom the site of occlusion was either distal to the RV branch (n = 23) or in the left circumflex artery (n = 11) was this ratio 50%; in no patient was it less than 50% (p less than 0.001). All 34 patients with occlusion of the right coronary artery proximal to the RV branch also had regional or global ischemic RV dysfunction by radionuclide ventriculography, with a mean RV ejection fraction of 30 +/- 10% compared with 42 +/- 6% in patients with occlusion distal to the RV branch or in the left circumflex artery (p less than 0.001). In conclusion, in patients with evolving inferior AMI, ST-segment depression in lead V2 of 50% or less of the magnitude of ST-segment elevation in lead aVF may be a useful sign (sensitivity 79%, specificity 91%, positive predictive value 90% and negative predictive value 82%) for identifying patients with concomitant RV ischemia.

Transient heart failure in an adult with Kawasaki disease.

Kawasaki disease is a mucocutaneous lymph node syndrome with important cardiovascular complications that usually afflicts young children. We describe a 31-year-old woman who developed transient heart failure during the acute phase of Kawasaki disease. The diagnosis was supported by the presence of all six criteria of the disease: fever, conjunctivitis, strawberry tongue, cervical lymphadenopathies, truncal exanthem, and periungual membranous desquamation. Related clinical and laboratory findings included heart failure, arthralgias, transverse nail grooves, thrombocytosis, and elevated serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and bilirubin. Alternative diagnoses were excluded. During her acute febrile illness, the patient developed tachycardia, hypotension, pulmonary rales, S3 gallop, and hepatojugular reflux. The chest roentgenogram showed new Kerley A and B lines. A first-pass isotopic ventriculography showed diffuse hypokinesia and decreased ventricular ejection fractions; spontaneous recovery occurred after a few days. A coronarography performed two months later showed no aneurysmal dilatation. Kawasaki disease is a cause, albeit rare, of myocardial dysfunction in the adult human, and should be sought for actively in a patient with heart failure during the course of an acute febrile illness, associated with mucocutaneous changes.

The hypotensive effect of intravenous streptokinase in patients with acute myocardial infarction.

We studied the hypotensive effect of a rapid intravenous infusion of high-dose streptokinase in 98 patients with an acute myocardial infarction. The systolic blood pressure fell from 132 +/- 20 (range 90 to 174) to 97 +/- 21 mm Hg (range 58 to 152) at 15 +/- 8 min (range 4 to 40) after the commencement of the streptokinase infusion (p less than .001). A fall in diastolic blood pressure from 80 +/- 16 (range 51 to 105) to 61 +/- 15 mm Hg (range 32 to 92) accompanied the fall in systolic pressure (p less than .001). The fall in blood pressure was associated with an increase in heart rate (73 +/- 14 to 78 +/- 17 beats/min, p less than .001), preceded the appearance of clinical signs of reperfusion by 37 +/- 38 min and was similar in magnitude and timing in patients with anterior and inferior infarction. There were direct relationships between the rate of infusion of streptokinase and both the magnitude (r = .49, p less than .001) and the rate of fall of systolic blood pressure (r = .67, p less than .001) as well as both the magnitude and rate of fall of diastolic blood pressure. In most patients, the fall in blood pressure was transient (9 +/- 6 min, range = 2 to 30) and easily managed by slowing or stopping the infusion, placing the patient in the Trendelenburg position, or by administering an infusion of low-dose norepinephrine or dopamine. However, in four patients with severe left ventricular dysfunction, severe hypotension persisted for more than 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of the rate of intravenous infusion of streptokinase and the duration of symptoms on the time interval to reperfusion in patients with acute myocardial infarction.

We studied the influence of the following variables on the time interval from initiation of an intravenous infusion of 750,000 U of streptokinase until reperfusion (reperfusion time) in 140 consecutive patients with an evolving acute myocardial infarction: (1) the rate of infusion of streptokinase, (2) the duration of chest pain before initiation of treatment, (3) patient age, (4) patient sex, (5) location of infarction, (6) history of previous myocardial infarction, and (7) pretreatment pathologic Q waves. The time of reperfusion was recognized by clinical criteria that were completely concordant with the anatomic findings in all 119 patients in whom patency or occlusion of the artery of infarction was established at delayed angiography (n = 116) or at postmortem examination (n = 3). The mean reperfusion time for the 129 patients for whom data were available was 49 +/- 36 min. The reperfusion time was inversely related to the rate of infusion of streptokinase (r = .41, p less than .001), but this effect of infusion rate appeared to plateau at rates of greater than 500 U/kg/min. In the 64 patients receiving infusions at rates of 500 U/kg/min or less, the mean reperfusion time was 60 +/- 40 min, whereas in the 58 patients receiving the drug at rates greater than 500 U/kg/min it was 35 +/- 22 min (p less than .001). The duration of chest pain before treatment was the only other studied variable found to influence the reperfusion time, but only at infusion rates of less than 250 U/kg/min (r = .6, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolytic therapy with intracoronary or intravenous streptokinase during acute myocardial infarction.

This report compares the results of intracoronary (IC) and intravenous (IV) streptokinase in a sequential series of 200 patients (IC = 81 and IV = 119) admitted within 3 hours of the onset of an acute myocardial infarction. Reperfusion was achieved in 71 of 81 (88%) patients in the IC group and in 113 of 119 (95%) patients in the IV group (p = NS) 35 +/- 27 and 42 +/- 33 minutes after commencement of treatment respectively (p = NS). The interval from onset of symptoms to reperfusion was significantly longer in the IC than in the IV group, 235 +/- 62 versus 175 +/- 61 minutes (p less than 0.001). Mean values of peak creatine kinase-MB were 152 +/- 117 IU/L in the IC group and 117 +/- 79 IU/L in the IV group (p less than 0.05). Three patients in the IC group and 16 patients in the IV group suffered major hemorrhagic complications. In-hospital mortality was 7 of 81 (8.7%) in the IC group and 10 of 119 (8.4%) in the IV group (p = NS). We conclude that IV administration of streptokinase in patients with an acute myocardial infarction is at least as efficacious as IC administration.