Self-medication of a single headache episode with ketoprofen, ibuprofen or placebo, home-monitored with an electronic patient diary

1The objective of this study was to investigate the efficacy of home-medicated non-steroidal anti-inflammatory (NSAID) analgesics, using an electronic patient diary. Single doses of ketoprofen 25 mg and ketoprofen 50 mg were compared with ibuprofen 200 mg and placebo in the treatment of a single occasion of episodic tension-type headache, using a double-blind, randomized, parallel group design. 2A total of 166 patients with headache compatible with episodic tension-type headache and no refractory headaches or contraindications to NSAIDs were contacted by advertisements and selected by questionnaires. Patients performed the study at home, using an electronic diary for headache assessment, with a form to allow comments and corrections. Visual analogue scales (VAS 10 cm) of headache severity, five-item headache relief rating (HRR) scales, and time of intake of ‘escape’ analgesics were scored regularly, for 4 h following intake of trial medication. 3VAS-scores (n=1407) and HRRs (n=452) were returned by 159 patients. Of these scores, 1.5% were inadvertedly omitted from the electronic diary or modified on the comment forms. 4Headache (VAS and HRR) improved more with all three NSAIDs than with placebo, although the effect of ibuprofen was significant for HRR only. After 2 and 4 h respectively, the reduction in VAS-ratios was 17 and 19% with placebo, 18 and 53% with ibuprofen 200 mg, 41 and 61% with ketoprofen 25 mg, and 47 and 59% with ketoprofen 50 mg. After 4 h, headache improved strongly (highest HRR) in 18% of patients on placebo, 39% on ibuprofen 200 mg, 62% on ketoprofen 25 mg, and 55% on ketoprofen 50 mg. Headache disappeared completely (VAS-score=0) in one patient (3%) with placebo (after 180 min), 10% with ibuprofen 200 mg (average 211 min), 18% with ketoprofen 25 mg (159 min), and 28% with ketoprofen 50 mg (146 min). 5The effects of ketoprofen 50 mg were more pronounced than those of ibuprofen 200 mg, which seemed to start later. Ketoprofen 25 mg and 50 mg were very similar, suggesting a maximal effect of the lower dose. Mild to moderate adverse events were reported by 9% of the patients, half of which occurred with ketoprofen 50 mg. Treatment of headache with ketoprofen can start with 25 mg, and possibly less. 6Although a direct comparative study would be necessary to determine the relative benefits of the novel electronic patient diaries over traditional paper-and-pencil methods, this study has shown the usefulness of this newer technique to detect differences in efficacy between low doses of analgesics under ambulant conditions, with very limited loss of data. Electronic patient diaries appear to be an important new attribute for the efficacy assessment of self-medicated drugs.     

Effect of time of admission on compliance with deep vein thrombosis prophylaxis in a tertiary medical intensive care unit

Summary.  Objective : We sought to evaluate deep vein thrombosis (DVT) prophylaxis compliance according to time of admission in a medical intensive care unit (MICU). Methods : This was a retrospective cohort study at a closed tertiary MICU. We classified patients into three groups (week days, weekends, and week nights), according to time of admission. An unweighted risk factor score (RFS) was calculated from 20 known risk factors. We defined DVT prophylaxis compliance as any type of prophylaxis (mechanical or pharmacologic) for RFS ≤ 3 or both types of prophylaxis for RFS > 3. Non-compliance was defined as no prophylaxis or single-type prophylaxis for RFS > 3. Results : We analyzed 105 admissions. Eighty (76.19%) patients received compliant DVT prophylaxis, and 25 (23.81%) patients received non-compliant regimens of whom 11 (10.48%) were not on any prophylaxis. DVT prophylaxis compliance was not different across the three admission groups. The non-compliant DVT prophylaxis group had a higher RFS (3.48 ± 2.1 vs. 2.25 ± 1.5; P  = 0.011), a trend towards fewer female patients (40% vs. 60%; P =  0.079), and a higher percentage of admissions by interns at the first postgraduate year (PGY) level (28% vs. 5.4%; P =  0.01). Logistic regression revealed that only RFS and PGY level were independent predictors for compliance ( P =  0.015 and 0.005 respectively). Time of admission was not a significant factor. Conclusions : Time of admission did not influence DVT prophylaxis compliance. Compliance improved with higher PGY level and lower RFS. A higher level of knowledge probably explains the association with PGY level; however, we cannot explain the inverse relationship between RFS and compliance.     

THE PROLACTIN RESPONSE TO METOCLOPRAMIDE IN GROWTH HORMONE DEFICIENT ADOLESCENT MALES

The growth hormone (GH) and prolactin (PRL) responses following administration of 10 mg i.v. metoclopramide (MCP) (‘Maxolon’—Beecham Pharmaceuticals) have been examined in thirty adolescent males with short stature and delayed puberty, eight of whom have isolated growth hormone deficiency. The results demonstrate that peak GH and PRL levels following stimulation were highly significantly correlated when all subjects were analysed together (r=0·61, P < 0·001) but when the responses of the GH deficient and non-deficient groups of subjects were analysed separately no significant correlation was obtained (P > 0·1), this reflected the fact that the PRL response to MCP was significantly lower in the GH deficient group (P < 0·0002). In addition two boys who demonstrated biochemical GH deficiency prior to puberty only, showed PRL responses similar to boys with normal GH reserves. The results suggest that the PRL response to MCP may be of value in the assessment of stimulation tests of GH reserve, as well as in the selection of patients for treatment with G.H.     

Pericardial Repair of Endocardial Defect Following Regional Endocardial Resection for Ventricular Tachycardia

Regional endocardial resection is the accepted surgical treatment for sustained monomorphic ventricular tachycardia. In patients requiring extensive endocardial resection, or with large aneurysms involving the interventricular septum, the resulting defect may result in weakened myocardium and, ultimately, ventricular septal defect or ventricular rupture. A new approach for repair of the resulting defect is proposed using an autogenous pericardial patch sutured to normal endocardium and included in the aneurysm repair. This technique was performed in six patients undergoing surgery for drug refractory ventricular tachycardia. All patients had large anterior left ventricular aneurysms with endocardial scar extending onto the septum. The large endocardial defect left after endocardial resection and aneurysmectomy was repaired with a pericardial patch. No intraoperative complications (e.g., suture line bleeding) were observed as a result of this technique. All patients are alive, and five of the six patients no longer have inducible ventricular tachycardia. An improvement in congestive heart failure symptoms at 1-9 months of follow-up was noted following surgery. We conclude that the pericardium can be safely used to cover endocardial defects resulting from regional endocardial resection for sustained ventricular tachycardia.     

Prolactin Dynamics and Tumour Size in the Prediction of Surgical Outcome for Prolactinoma

Each of 62 females were studied for a period of between twoand 72 months ( mean 36 months) following the removal of a prolactinomaby transsphenoidal pituitary surgery. Our aims were to definethe relationships between pre- and post-operative features,the operative findings and the functional outcome. Pre-operativeserum prolactin (PRL) concentrations correlated with tumourdiameter (r = 0.55, p < 0.001). Following surgery two groupsof patients were identified: Group 1, 46 spontaneously and regularlymenstruating patients and Group 2, 16 patients with persistentamenorrhoea. The patients in Group 1 had significantly lowerpre-operative and postoperative serum (PRL) concentrations (p< 0.02 and p < 0.001 respectively) and significantly greaterPRL responses to thyrotrophin releasing hormone (TRH) and metoclopramidestimulation after surgery (p < 0.001). There was not a significantdifference in tumour size between the groups. Forty-four (96per cent) of the patients in Group 1 had normal post-operativeserum PRL concentrations within one week of surgery. By comparison(p < 0.001) only 42 and 20 per cent respectively of Group1 patients who were tested had normal TRH and metoclopramideevoked PRL secretion following surgery. Return of regular menstruationwas associated with cessation of galactorrhoea in 44 patients(96 per cent) and ovulation occurred in 37 of 38 menstruatingpatients for whom data are available. All patients with normalTRH and metoclopramide stimulation tests menstruated spontaneously.Nevertheless most patients who menstruated did so in spite ofretaining suppressed PRL responses. Of 46 patients followedto date whose serum PRL was normal one week after surgery, sevenlater were found to have an elevation of serum PRL outside thenormal range but in only two has this been persistent. We suggestthat a single measurement of serum PRL one week following transsphenoidalpituitary surgery for prolactinoma provides a good basis fordeciding about the future management of patients who desiremenstruation and pregnancy.     

The use of benzodiazepines among regular amphetamine users

The relationship between benzodiazepine and regular amphetamine use was examined in a sample of 301 regular amphetamine users. Benzodiazepine use was widespread, with 37% of subjects having used them in the month preceding interview, and 55% in the preceding 6 months. Injectors of amphetamines were more likely to have ever used, and to be currently using, benzodiazepines. Comparisons of benzodiazepine users with other subjects indicated that benzodiazepine users had higher levels of polydrug use and psychopathology, as well as poorer health and social functioning than non-users. The odds of benzodiazepine using injectors having injected with a borrowed used needle in the preceding month were 3.8 times those of non-benzodiazepme-using injectors. These results are consistent with studies of other groups of illicit drug users, such as heroin users, in indicating that benzodiazepine use is associated with greater levels of risk and psycho-social dysfunction.     

Drug self-administration methods in abuse liability evaluation

The human drug self-administration paradigm is an extension of the animal model developed in the 1960s. The paradigm can be used to investigate the determinants and correlates of drug-seeking and drug-taking behavior and has proven useful in the development of medications for treating drug dependence. This paper describes the basic components of the human self-administration model and discusses studies that illustrate some of its applications, including assessment of the reinforcing effects of drugs, analysis of behavioral and pharmacological mechanisms of drug self-administration and measurement of the abuse liability, behavioral toxicity, and aversive effects of drugs. Some of the strengths and limitations of using the paradigm with human research subjects are also presented. It is concluded that the drug self-administration model should not replace other measures of abuse liability testing in humans, but should be incorporated into comprehensive programs of drug abuse assessment wherever possible.