Efficacy of non-steroidal anti-inflammatory drugs for low back pain: a systematic review of randomised clinical trials

PURPOSE—To assess the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) for low back pain.
DATA SOURCES—Computer aided search of published randomised clinical trials and assessment of the methods of the studies.
STUDY SELECTION—26 randomised clinical trials evaluating NSAIDs for low back pain were identified.
DATA EXTRACTION—Score for quality (maximum = 100 points) of the methods based on four categories: study population; interventions; effect measurement; data presentation and analysis. Determination of success rate per study group and evaluation of different contrasts. Statistical pooling of placebo controlled trials in similar patient groups and using similar outcome measures.
RESULTS—The methods scores of the trials ranged from 27 to 83 points. NSAIDs were compared with placebo treatment in 10 studies. The pooled odds ratio in four trials comparing NSAIDs with placebo after one week was 0.53 (95% confidence intervals 0.32 to 0.89) using the fixed effect model, indicating a significant effect in favour of NSAIDs compared with placebo. In nine studies NSAIDs were compared with other (drug) therapies. Of these, only two studies reported better results of NSAIDs compared with paracetamol with and without dextropropoxyphene. In the other trials NSAIDs were not better than the reference treatment. In 11 studies different NSAIDs were compared, of which seven studies reported no differences in effect.
CONCLUSIONS—There are flaws in the design of most studies. The pooled odds ratio must be interpreted with caution because the trials at issue, including the high quality trials, did not use identical outcome measures. The results of the 26 randomised trials that have been carried out to date, suggest that NSAIDs might be effective for short-term symptomatic relief in patients with uncomplicated low back pain, but are less effective or ineffective in patients with low back pain with sciatica and patients with sciatica with nerve root symptoms.

     

Imipramine decreases oesophageal pain perception in human male volunteers

Department of Medicine, Suite 501, Pepper Pavilion, Allegheny University Hospitals, Graduate, One Graduate Plaza, 1800 Lombard Street, Philadelphia, Pennsylvania 19146, USA

Correspondence to: Dr D O Castell.

Accepted for publication 19 January 1998

Background—Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed.
Aims—To investigate whether imipramine, which has a visceral analgesic effect, increases pain thresholds to experimental visceral pain.
Methods—Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The effect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1-3, 50 mg days 4-6, 75 mg days 7-12), with oesophageal perception studied on day 13. 
Results—Inflation volumes and intraballoon pressures at first sensation were not different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected by imipramine.
Conclusion—Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic effect.
(GUT 1998;:807-813)

Keywords: antidepressants;  imipramine;  visceral hyperalgesia;  oesophageal balloon;  distension;  functional bowel syndromes

     

The timing of glucocorticoid administration in rheumatoid arthritis

OBJECTIVE—To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process.
METHODS—26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group.
RESULTS—Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P << 0.001), joint pain (P < 0.001), Lansbury index (P << 0.001), Ritchie index (P << 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups.
CONCLUSIONS—Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.

     

Quality of life and perceived health status in surviving adults with univentricular heart

OBJECTIVE—To evaluate the quality of life in patients with univentricular heart and to determine the impact of sociodemographic and clinical characteristics.
DESIGN AND SETTING—Retrospective, cross sectional study conducted in a regional paediatric cardiology centre.
PATIENTS—The health records of 89 survivors with univentricular heart (median age 21 years; range 17-49 years) were reviewed. Sixty seven answered the Duke questionnaire. Sociodemographic and clinical variables were similar in the responders and non-responders. The impact of sociodemographic and clinical variables on individual Duke's measures was assessed.
RESULTS—The Duke scores of adults with univentricular heart were similar to the normal population. Cyanosis predicted a worse score for physical (p = 0.05) and perceived health measures (p = 0.02). A higher educational level predicted a better score for physical (p = 0.004), mental (p = 0.01), and general health measures (p = 0.02). Orthopaedic problems worsened the social score (p = 0.05). Psychosocial problems worsened the pain score (p = 0.04). In comparison with the other anatomical types, mitral atresia worsened the perceived health score (p = 0.02). Patients younger than 23 years scored better for almost all health and dysfunction measures.
CONCLUSIONS—Despite repeated interventions and other disease related everyday stresses, a selected group of adults with univentricular heart had a satisfying quality of life.


Keywords: congenital heart defect; quality of life; psychosocial problems; univentricular heart     

Associations of radiological osteoarthritis of the hip and knee with locomotor disability in the Rotterdam Study

OBJECTIVE—To assess the contribution of radiological osteoarthritis of the hips and knees to disabilities in the activities of daily living related to lower limb function.
METHODS—During a home interview 1156 men and 1739 women, randomly chosen from the source population of all independently living residents aged 55 years and over living in a district of Rotterdam (the Rotterdam Study) were asked about locomotor disability by six questions of the Health Assessment Questionnaire (HAQ) and about pain in the hips and knees in the past month. Radiographs of hips and knees were scored according to the Kellgren grading system for osteoarthritis.
RESULTS—The prevalence of locomotor disability, defined as at least some difficulty with three or more out of six lower limb functions, was 20.2% for men and 31.9% for women; hip pain was present in 8.3% of the men and 16.6% of the women; knee pain in 12.6% of the men and 22.3% of the women. The prevalence of radiological osteoarthritis grade 2+ of the hip was 14.1% for men and 15.9% for women, and of the knee 16.3% and 29.1% respectively. The odds ratio (OR) (95% confidence intervals) of hip radiological osteoarthritis for locomotor disability adjusted for age and all other variables was for men: 1.4 (0.9, 2.1) and for women: 2.2 (1.6, 2.9). The ORs of knee radiological osteoarthritis adjusted for age and all other variables were 1.1 (0.9, 2.1) and 1.4 (1.1, 1.8) respectively. Severe radiological osteoarthritis (grade 3+) was stronger associated. The ORs of pain in the hips or knees and morning stiffness were much higher (between 2.7 and 5.5 for men and between 2.1 and 5.1 for women).
CONCLUSIONS—Radiological osteoarthritis of the hip and knee are only weak independent predictors of locomotor disability in women, and not at all independently associated with locomotor disability in men. Age, pain of the hips and knees, and morning stiffness seem to be the most important independent determinants of locomotor disability.

Keywords: osteoarthritis; hip; knee; locomotor disability     

Improved functional outcome in patients with early rheumatoid arthritis treated with intramuscular gold: results of a five year prospective study

OBJECTIVE—To determine whether there is a relation between disease duration and functional outcome in patients with rheumatoid arthritis (RA) treated with intramuscular sodium aurothiomolate (gold) for five years.
METHODS—440 patients with RA were enrolled in a prospective trial of gold treatment. Initial demographic details were recorded. Disease activity was assessed at yearly intervals using a combination of clinical (pain score, Ritchie articular index, duration of morning stiffness) and laboratory (erythrocyte sedimentation rate, C reactive protein) parameters. Change in functional status was assessed using the health status questionnaire (HAQ). Patients were stratified according to disease duration at outset (group 1= 0-2 years n=106, group 2 = >2-5 years n=93, and group 3= >5 years n=235).
RESULTS—There were no significant differences between the groups at outset. A total of 160 patients completed five years of treatment (group 1 n=44 (42%), group 2 n=37 (40%), and group 3 n=79 (34%)). Patients in group 1 had a significantly lower HAQ from year 1 to year 5 with a mean improvement of 30% at the end of the study (p<0.001). Neither group 2 nor group 3 had a significant change in their HAQ at study end. There were significant improvements in all other variables (p<0.05) in each group apart from pain in group 2.
CONCLUSION—Patients with early RA have a larger reversible component to their HAQ. Only patients with disease duration of up to two years have a longlasting improvement in their functional ability after starting intramuscular gold treatment.

Keywords: gold; rheumatoid arthritis; function; HAQ     

Correlation between conventional disease activity measures in juvenile chronic arthritis

OBJECTIVE—To estimate in a cross sectional analysis the degree of colinearity among the disease activity measures more commonly used in juvenile chronic arthritis (JCA).
METHODS—This study assessed in a single clinical evaluation three subjective variables, three measures of functional capacity, eight articular indices, and two laboratory indicators of systemic inflammation in 55 consecutive children with JCA. The relation between the clinical measures of JCA activity was determined by Pearson correlation coefficients. An r value of 0.7 or greater was considered evidence of colinearity.
RESULTS—Among the subjective variables, parent global assessment of overall well being and parent assessment of pain were correlated with each other; the physician assessment of disease activity did not show evidence of colinearity with any other variable. The functional status measures were correlated with each other, but not with the indices of articular inflammation. There was a high degree of colinearity among the articular variables, with the number of active joints and the overall severity score being correlated with each other as well as with all the single articular indices. The laboratory variables were correlated with each other, but not with any of the articular, functional or subjective variables.
CONCLUSION—Our results show a high degree of colinearity among the disease activity measures belonging to the same category, whereas this is uncommon for variables that investigate different domains of disease activity. These data underline the need to include the evaluation of each domain in the assessment of JCA activity.

     

Poor prognosis of patients presenting with symptomatic myocardial infarction but without chest pain

OBJECTIVE—To describe the clinical features, prognosis, and treatment of patients presenting with atypical forms of acute myocardial infarction.
DESIGN—Consecutive cases of possible acute myocardial infarction were sought from coronary care registers, biochemistry records, and hospital management systems. Case notes were reviewed and predefined epidemiological and clinical variables were abstracted.
SETTING—20 adjacent hospitals in the former Yorkshire region.
PATIENTS—3684 consecutive cases of possible acute myocardial infarction admitted in a three month period were identified, of whom 2096 had a first episode of confirmed acute myocardial infarction.
RESULTS—20.2% of all patients admitted with an eventual diagnosis of acute myocardial infarction presented with symptoms other than chest pain. Compared with the group presenting with chest pain, these patients were older (76.6 v 69.1 years, p < 0.001), were more often women (54.6% v 35.3%, p < 0.001), and were more likely to have a history of heart failure (18.6% v 6.9%, p < 0.001). They had a higher 30 and 365 day mortality (49.2% and 61.0%, respectively) compared with patients presenting with chest pain (17.9% and 26.2%). In a Cox regression analysis the hazard ratio for presentation without chest pain was 1.60 (95% confidence interval 1.30 to 1.97) (p < 0.001) adjusted for age, heart rate, blood pressure, left ventricular impairment, and infarction with ST segment elevation as covariates. Importantly, they were also less likely to receive treatments with a proven ability to improve prognosis.
CONCLUSIONS—Atypical presentation of myocardial infarction without chest pain is common and associated with increased mortality. This may result in part from a failure to use beneficial treatment strategies.


Keywords: acute myocardial infarction; atypical presentation     

Non-cardiac, non-oesophageal chest pain: the relevance of psychological factors

Background—No cause has been determined for chest pain that is neither cardiac nor oesophageal in origin.
Aims—To compare the prevalence of lifetime psychiatric disorders and current psychological distress in three consecutive series of patients with chronic chest or abdominal pain.
Patients—Thirty nine patients with non-cardiac chest pain and no abnormality on oesophagogastroduodenoscopy, oesophageal manometry, and 24 hour pH monitoring; 22 patients with non-cardiac chest pain having endoscopic abnormality, oesophageal dysmotility, and/or pathological reflux; and 36 patients with biliary colic.
Methods—The Diagnostic Interview Schedule and the 28 item General Health Questionnaire were administered to all patients.
Results—Patients with non-cardiac chest pain and no upper gastrointestinal disease had a higher proportion of panic disorder (15%), obsessive-compulsive disorder (21%), and major depressive episodes (28%) than patients with gallstone disease (0%, p<0.02; 3%, p<0.02; and 8%, p<0.05, respectively). In contrast, there were no differences between patients with non-cardiac chest pain and upper gastrointestinal disease and patients with gallstone disease in any of the DSM-111 defined lifetime psychiatric diagnoses. Using the General Health Questionnaire, 49% of patients with non-cardiac chest pain without upper gastrointestinal disease scored above the cut off point (that is, more than 4), which was considered indicative of non-psychotic psychiatric disturbance, whereas only 14% of patients with gallstones did so (p<0.005). The proportions of such cases were however similar between patients with non-cardiac chest pain and upper gastrointestinal disease (27%) and patients with gallstones.
Conclusions—Psychological factors may play a role in the pathogenesis of chest pain that is neither cardiac nor oesophagogastric in origin.

Keywords: chest pain;  oesophageal manometry;  gastro-oesophageal reflux disease;  oesophageal pH monitoring;  psychiatric illness

     

Sexual activity as a trigger of myocardial infarction. A case-crossover analysis in the Stockholm Heart Epidemiology Programme (SHEEP)

OBJECTIVE—To investigate sexual activity as a trigger of myocardial infarction and the potential effect modification of physical fitness.
DESIGN—A case-crossover study nested in the Stockholm Heart Epidemiology Programme (SHEEP).
SETTING—Stockholm County from April 1993 to December 1994.
PATIENTS—All patients with a first episode of non-fatal acute myocardial infarction admitted to coronary care units were eligible, and 699 patients participated in an interview.
MAIN OUTCOME MEASURES—Relative risks with 95% confidence intervals.
RESULTS—Only 1.3% of the patients without premonitory symptoms had sexual activity during two hours before the onset of myocardial infarction. The relative risk of myocardial infarction was 2.1 (95% confidence interval (CI) 0.7 to 6.5) during one hour after sexual activity, and the risk among patients with a sedentary life was 4.4 (95% CI 1.5 to 12.9).
CONCLUSIONS—The increased risk of myocardial infarction after sexual activity and the further increase in risk among the less physically fit support the hypothesis of causal triggering by sexual activity. However, the absolute risk per hour is very low, and exposure is relatively infrequent. Thus having sex once a week only increases the annual risk of myocardial infarction slightly. Counselling should focus on encouraging patients to live a physically active life and not on abstaining from sexual activity.


Keywords: myocardial infarction; sexual activity     

Effects of α tocopherol and β carotene supplements on symptoms, progression, and prognosis of angina pectoris

Objective—To evaluate the effects of α tocopherol and β carotene supplements on recurrence and progression of angina symptoms, and incidence of major coronary events in men with angina pectoris.
Design—Placebo controlled clinical trial.
Setting—The Finnish α tocopherol β carotene cancer prevention study primarily undertaken to examine the effects of α tocopherol and β carotene on cancer.
Subjects—Male smokers aged 50-69 years who had angina pectoris in the Rose chest pain questionnaire at baseline (n = 1795).
Interventions—α tocopherol (vitamin E) 50 mg/day, β carotene 20 mg/day or both, or placebo in 2 × 2 factorial design.
Main outcome measures—Recurrence of angina pectoris at annual follow up visits when the questionnaire was readministered; progression from mild to severe angina; incidence of major coronary events (non-fatal myocardial infarction and fatal coronary heart disease).
Results—There were 2513 recurrences of angina pectoris during follow up (median 4 years). Compared to placebo, the odds ratios for recurrence in the active treatment groups were: α tocopherol only 1.06 (95% confidence interval (CI) 0.85 to 1.33), α tocopherol and β carotene 1.02 (0.82 to 1.27), β carotene only 1.06 (0.84 to 1.33). There were no significant differences in progression to severe angina among the groups given supplements or placebo. Altogether 314 major coronary events were observed during follow up (median 5.5 years) and the risk for them did not differ significantly among the groups given supplements or placebo.
Conclusions—There was no evidence of beneficial effects for α tocopherol or β carotene supplements in male smokers with angina pectoris, indicating no basis for therapeutic or preventive use of these agents in such patients.

Keywords: antioxidants;  angina pectoris;  prevention;  vitamin supplements     

A comparison of left ventricular abnormalities associated with glucose intolerance in African Caribbeans and Europeans in the UK

OBJECTIVE—To determine whether abnormalities of the left ventricle differ by glucose tolerance status, to explore reasons for differences, and to assess ethnic differences in these relations.
DESIGN—Population based prevalence study.
SETTING—London, UK.
PATIENTS—1152 African Caribbeans and Europeans.
METHODS—Echocardiograms, blood pressure, obesity, fasting and two hour blood glucose, insulin and lipids, and urinary albumin excretion rate were measured.
MAIN OUTCOME MEASURES—Left ventricular mass index, wall thickness, and early (E) to atrial (A) wave ratio.
RESULTS—Left ventricular mass index was greater in diabetic Europeans than in normoglycaemic Europeans (mean (SE), 95.6 (5.0) v 79.7 (0.8) g/m², p = 0.001) and in diabetic African Caribbeans than in normoglycaemic African Caribbeans (88.6 (2.5) v 82.4 (0.9) g/m², p = 0.02). Similar, but weaker associations were observed for the E:A ratio. β Coefficients between left ventricular mass index and fasting glucose in the normoglycaemic range, adjusted for age and sex, were 2.43 in Europeans (p = 0.05) and 3.74 in African Caribbeans (p = 0.02). These were attenuated to 1.19 (p = 0.4) and 3.03 (p = 0.08) in Europeans and African Caribbeans, respectively, when adjusted further for blood pressure and obesity. Adjustments for other risk factors made little difference to the coefficients. There were no ethnic differences in risk factor relations.
CONCLUSIONS—Abnormalities of the left ventricle occur in response to glucose intolerance and are observable into the normoglycaemic range. These disturbances are largely accounted for by associated obesity and hypertension. African Caribbeans have a greater degree of left ventricular structural impairment, emphasising the importance of tight blood pressure control.


Keywords: echocardiography; glucose tolerance; left ventricular mass index; ethnic differences     

Estimating the burden of musculoskeletal disorders in the community: the comparative prevalence of symptoms at different anatomical sites, and the relation to social deprivation

BACKGROUND—Epidemiologically-based rheumatology healthcare needs assessment requires an understanding of the incidence and prevalence of musculoskeletal disorders in the community, of the reasons why people consult in primary care, and of the proportion of people who would benefit from referral to secondary care and paramedical services. This paper reports the first phase of such a needs assessment exercise.
SPECIFIC OBJECTIVE—To estimate the relative frequency of musculoskeletal pain in different, and multiple, anatomical sites in the adult population.
SETTING—Three general practices in the former Tameside and Glossop Health Authority, Greater Manchester, UK, a predominantly urban area.
DESIGN—Population survey.
METHODS—An age and sex stratified sample of 6000 adults from the three practices was mailed a questionnaire that sought data on demographic factors, musculoskeletal symptoms (pain in the past month lasting for more than a week), and physical disability (using the modified Health Assessment Questionnaire- mHAQ). The areas of pain covered were neck, back, shoulder, elbow, hand, hip, knee, and multiple joints. The Carstairs index was used as a measure of social deprivation of the postcode sector in which the person lived.
RESULTS—The response rate after two reminders was 78.5%. Non-responders were more likely to live in areas of high social deprivation. People who lived in more deprived areas were also more likely to report musculoskeletal pain, especially backpain. After adjusting for social deprivation the rates of musculoskeletal pain did not differ between the practices and so their results were combined. After adjustment for social deprivation, the most common site of pain was back (23%; 95% CI 21, 25) followed by knee (19%; 95% CI 18, 21), and shoulder (16%; 95% CI 14, 17). The majority of subjects who reported pain had pain in more than one site. The prevalence of physical disability in the community rose with age. It was highest in those with multiple joint problems but was also high in those with isolated back or knee pain.
CONCLUSION—Musculoskeletal pain is common in the community. People who live in socially deprived areas have more musculoskeletal symptoms. Estimates of the overall burden of musculoskeletal pain that combine the results of site specific surveys will be too high, those that do not adjust for socioeconomic factors will be too low.

Keywords: prevalence; pain; social deprivation     

Methotrexate treatment in patients with adult onset Still's disease—retrospective study of 13 Japanese cases

OBJECTIVE—To evaluate methotrexate treatment in patients with active adult onset Still's disease (AOSD).
METHODS—Methotrexate was initially given as a single weekly oral dose of 5 mg and adjusted individually afterwards in 13 patients with active AOSD. Symptoms and laboratory findings were investigated.
RESULTS—Signs of AOSD activity disappeared (remission) in eight patients between 3 and 16 weeks after starting methotrexate. In these patients, significant improvements in C reactive protein, erythrocyte sedimentation rate, white blood count, and serum ferritin were observed at 8, 12, 14, and 16 weeks after starting methotrexate, respectively. In six of these eight patients, steroids or non-steroidal anti-inflammatory drugs could be reduced or discontinued. In four patients methotrexate was not effective despite 12 or 16 weeks of treatment, and one patient discontinued treatment after 2 weeks because of severe nausea. Five patients suffered from adverse reactions, including acute interstitial pneumonia (one patient) and liver toxicity (two patients). Five out of eight patients successfully treated with methotrexate were HLA-DR4 positive (four homozygotes), and all the unsuccessfully treated patients were DR2 positive.
CONCLUSIONS—Methotrexate is useful for controlling disease activity in AOSD, not only for refractory patients but also for patients who have never taken steroids or for those with steroid associated toxicity. However, serious adverse reactions can occur, as with rheumatoid arthritis. It is important to determine the critical factors, such as the immunogenetic background, that are associated with response to methotrexate treatment.

     

Manometry based randomised trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction

BACKGROUND—Endoscopic sphincterotomy for biliary-type pain after cholecystectomy remains controversial despite evidence of efficacy in some patients with a high sphincter of Oddi (SO) basal pressure (SO stenosis).
AIM—To evaluate the effects of sphincterotomy in patients randomised on the basis of results from endoscopic biliary manometry.
METHODS—Endoscopic biliary manometry was performed in 81 patients with biliary-type pain after cholecystectomy who had a dilated bile duct on retrograde cholangiography, transient increases in liver enzymes after episodes of pain, or positive responses to challenge with morphine/neostigmine. The manometric record was categorised as SO stenosis, SO dyskinesia, or normal, after which the patient was randomised in each category to sphincterotomy or to a sham procedure in a prospective double blind study. Symptoms were assessed at intervals of three months for 24 months by an independent observer, and the effects of sphincterotomy on sphincter function were monitored by repeat manometry after three and 24 months.
RESULTS—In the SO stenosis group, symptoms improved in 11 of 13 patients treated by sphincterotomy and in five of 13 subjected to a sham procedure (p = 0.041). When manometric records were categorised as dyskinesia or normal, results from sphincterotomy and sham procedures did not differ. Complications were rare, but included mild pancreatitis in seven patients (14 episodes) and a collection in the right upper quadrant, presumably related to a minor perforation. At three months, the endoscopic incision was extended in 19 patients because of manometric evidence of incomplete division of the sphincter.
CONCLUSION—In patients with presumed SO dysfunction, endoscopic sphincterotomy is helpful in those with manometric features of SO stenosis.


Keywords: sphincter of Oddi; manometry; endoscopic sphincterotomy; motility; bile duct; pancreas     

N-terminal proatrial natriuretic peptide correlates with systolic dysfunction and left ventricular filling pattern in patients with idiopathic dilated cardiomyopathy

OBJECTIVE—To investigate the diastolic Doppler filling pattern in patients with idiopathic dilated cardiomyopathy and its relation to N-terminal pro-atrial natriuretic peptide (NT-pro-ANP).
METHODS—32 patients (26 male, six female) with idiopathic dilated cardiomyopathy were investigated. All were in sinus rhythm. Conventional M mode echocardiography and Doppler echocardiography was done in each patient. Pulsed wave Doppler inflow signals were obtained and the following variables were measured: maximum E wave, maximum A wave, E/A ratio, E wave deceleration time, A wave deceleration time. NT-pro-ANP was measured using radioimmunoassay.
RESULTS—Mean (SD) left ventricular ejection fraction was 34 (7)% and mean left ventricular end diastolic diameter on M mode echocardiography was 69 (7) mm. Left ventricular filling indices were as follows: maximum E wave velocity, 0.86 (0.22) m/s; maximum A wave velocity, 0.71 (0.24) m/s; E/A ratio, 1.41 (0.65). Mean E wave deceleration time was 140 (50) ms; mean A wave deceleration time was 100 (20) ms. In a stepwise forward regression model, NT-pro-ANP correlated significantly with left atrial diameter (r = 0.603; p < 0.001), left ventricular ejection fraction (r = −0.758; p < 0.001), and Doppler derived E/A ratio (r = 0.740; p < 0.001).
CONCLUSIONS—In patients with idiopathic dilated cardiomyopathy there is a relation between NT-pro-ANP and both systolic and diastolic variables. In a multivariate model NT-pro-ANP correlated with left atrial diameter, left ventricular ejection fraction, and Doppler derived E/A ratio on transmitral inflow.


Keywords: idiopathic dilated cardiomyopathy; transmitral Doppler filling; N-terminal pro-ANP; atrial natriuretic factor     

Impaired cardiac adrenergic innervation assessed by MIBG imaging as a predictor of treatment response in childhood dilated cardiomyopathy

OBJECTIVE—To evaluate the prognostic value of metaiodobenzylguanidine (MIBG) imaging in childhood cardiomyopathy.
DESIGN—Prospective cohort study.
SETTING—Tertiary referral centre.
PATIENTS—40 children (21 boys, 19 girls; mean (SD) age, 7.0 (5.6) years) with heart failure resulting from idiopathic dilated cardiomyopathy (n = 23) or various other disorders (n = 17).
METHODS—At the initial examination, cardiac ¹²³I-MIBG uptake and release, circulating noradrenaline (norepinephrine) concentration, x ray cardiothoracic ratio, and echocardiographic variables were recorded. Cardiac MIBG uptake was obtained by measuring the heart to mediastinum activity ratio on the planar image obtained four hours after MIBG injection. MIBG washout rate was evaluated using relative decrease in cardiac activity measured at 20 minutes and four hours. Patients were treated with angiotensin converting enzyme inhibitors, diuretics, and digitalis, and were followed up for 12 (10) months. Fifteen patients did not respond to medical treatment (12 heart transplants; three deaths), and 25 did respond (improved or stable).
RESULTS—Cardiac MIBG uptake was positively correlated with x ray cardiothoracic index (r = 0.55, p = 0.0008) and echocardiographic left ventricular fractional shortening (r = 0.68, p < 0.0001). Among all the clinical and laboratory variables tested, multivariate discriminant analysis showed that the only independent predictor of an unfavourable outcome was a low MIBG uptake (p < 0.001). Survival curves had a mean threshold value of 1.54 for MIBG uptake.
CONCLUSIONS—Impaired cardiac adrenergic innervation is strongly related to adverse outcome in children with dilated cardiomyopathy, independently of the aetiology. MIBG imaging may help to stratify risk in such patients.


Keywords: noradrenaline; MIBG; single photon imaging; children; cardiomyopathy     

Effect of a three month course of ciprofloxacin on the outcome of reactive arthritis

BACKGROUND—Treatment of reactive arthritis (ReA) with antibiotics has so far remained controversial. Eradication of the causative microbe appears logical, but short term antibiotic treatment has no beneficial effect on the outcome of ReA.
OBJECTIVE—To evaluate the effect of a three month course of ciprofloxacin on ReA.
METHODS—In a randomised, double blind, placebo controlled trial, between December 1992 and February 1996, 71 patients with acute ReA triggered by a gastrointestinal or a urogenital infection were randomly assigned to receive ciprofloxacin 500 mg or placebo twice daily for three months. Patients were assessed at study entry, at 6 weeks, 3 months, 6 months, and 12 months. Sixty two patients were valid for the efficacy analysis. The primary outcome measures were erythrocyte sedimentation rate, number of swollen joints, patients self assessment, and complete recovery.
RESULTS—Adverse events were mostly mild and occurred in both treatment groups. There were no statistically significant differences in any of the primary or secondary efficacy variables between the study groups at baseline or during the 12 month follow up. All primary outcome measures indicated that the condition of the patients improved during the study.
CONCLUSION—Both groups tended to recover. Ciprofloxacin, given as a three month course, had no advantage over placebo treatment.

     

Fibrinolytic potential is significantly increased by oestrogen treatment in postmenopausal women with mild dyslipidaemia

Objective—To study the effects of oestrogen replacement treatment on fibrinolytic potential in postmenopausal women.
Design—Randomised, double blind, placebo controlled trial of oral 17β-oestradiol.
Setting—Subjects were evaluated in the outpatient setting.
Patients—Nineteen postmenopausal women with mild dyslipidaemia, aged 44 to 69 years (mean (SD) 55.7 (6.7)).
Main outcome measures—Fibrinolytic activity (fibrin plate assay) and tissue plasminogen activator (t-PA) antigen were measured at baseline and after three, six, and nine weeks of each treatment.
Results—After nine weeks of 2 mg oestradiol treatment, there was a significant increase in fibrinolytic potential compared with placebo, as indicated by an increase in fibrinolytic activity (mean (SEM), 80 (9) v 54 (5) mm² of lysis in the fibrin plate, 2 mg v placebo, p = 0.002) and a decrease in t-PA antigen (5.8 (0.9) v 8.4 (1.2) ng/ml, 2 mg v placebo, p < 0.001). There was a similar trend with the 1 mg dose but the changes were less noticeable.
Conclusions—Hormone replacement treatment with 17β-oestradiol for nine weeks significantly increased fibrinolytic potential in postmenopausal women with mild dyslipidaemia. This suggests that the cardioprotective effect of oestrogen may be mediated, in part, by an increase in fibrinolytic potential.

Keywords: oestrogen;  fibrinolysis;  randomised controlled trial;  dyslipidaemia     

Prognostic implications of ventricular fibrillation in acute myocardial infarction: new strategies required for further mortality reduction

OBJECTIVE—To determine the changing risk of ventricular fibrillation, the prognostic implications, and the potential long term prognostic benefit of earlier hospital admission, after acute myocardial infarction.
DESIGN—Prospective observational study.
SETTING—A district general hospital in east London.
PATIENTS—1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction.
MAIN OUTCOME MEASURES—Time of onset of pain and ventricular fibrillation, and long term survival of patients admitted with acute myocardial infarction.
RESULTS—The rate of ventricular fibrillation in these hospital inpatients was high in the first hour from onset of pain (118 events/1000 persons/h; 95% confidence interval (CI) 50.7 to 231) and fell rapidly to an almost constant low level by six hours; 27.4% of patients with early ventricular fibrillation died in hospital, compared with 11.6% of those without (p < 0.0001), but mortality in patients who survived to hospital discharge was not altered by early ventricular fibrillation (five year survival: 75.0% (95% CI 60.0% to 84.8%) with ventricular fibrillation v 73.3% (95% CI 69.6% to 76.6%) without ventricular fibrillation).
CONCLUSIONS—Patients successfully resuscitated from early ventricular fibrillation have the same prognosis as those without ventricular fibrillation after acute myocardial infarction. Faster access to facilities for resuscitation must be achieved if major improvements in the persistently high case fatality of patients after acute myocardial infarction are to be made.


Keywords: ventricular fibrillation; acute myocardial infarction; prognosis