Asthma and multiple sclerosis: an inverse association in a case-control general practice population.

BACKGROUND: Th1/Th2 imbalance is hypothesized to up-regulate some diseases and down-regulate others. Compared to controls, multiple sclerosis (MS) (Th1-mediated) has been linked to a reduced risk of allergy and asthma (Th2-mediated), based on patient questionnaire studies and a review of asthma medication. AIM: To investigate whether MS is associated with a reduced risk of Th2-associated diseases and an increased risk of Th1-associated diseases. DESIGN: Retrospective matched case-control study. METHODS: Three hundred and twenty MS patients and controls matched for age, gender, location and smoking were selected from the Welsh General Practice Morbidity Database from 1995-99. Case and control records were assessed for Th1-mediated and Th2-mediated diseases. RESULTS: Overall, 346 MS patients were identified, giving a prevalence of 127 per 100 000. There was an inverse relationship between multiple sclerosis (MS) and asthma (OR 0.33; 95%CI 0.15-0.77). No statistically significant relationships emerged between other Th2-associated (eczema, dermatitis) or any Th1-associated (rheumatoid arthritis, thyroid disorders, inflammatory bowel disease [IBD], type 1 diabetes) diseases and MS, although no patient in either group had treated type 1 diabetes. A trend existed for IBD, with 5/320 of cases affected and no controls; OR infinity; 95%CI 1.30-infinity; p=0.063. DISCUSSION: This inverse association between MS and asthma is compatible with a Th1/Th2 imbalance. Although the Th1/Th2 theory is probably an over-simplification in MS, a shift from Th1 cytokine dominance towards Th2 may provide drug-targeting routes for MS.

Prescribing for multiple sclerosis patients in general practice: a case-control study.

OBJECTIVES: To examine the prescribing patterns for multiple sclerosis (MS) patients resident in Wales by general practitioners (GPs), compared to an age, gender and GP surgery matched control population. METHODS: Anonymised data for 1996 were obtained for all patients from 24 GP practices in the all-Wales General Practice Morbidity Database (GPMD). This covered 220 538 patient years at risk for 1996. Cases were selected as those with a Read code of MS at some point from 1993 to 1996 (therefore had consulted the GP at least once during this time). The controls were age, gender and surgery matched patients randomly selected from the GPMD. RESULTS: A total of 216 cases were identified, giving a prevalence of 97.9 per 105. Cases were prescribed a mean of 15 drugs each in 1996 compared to eight drugs for controls (P < 0.0005). Compared with controls, MS patients were prescribed significantly more laxatives, diuretics, hypnotics and anxiolytics, antidepressants, antiepileptics (mainly carbamazepine), corticosteroids, oxybutynin, vitamin B12 and skeletal muscle relaxants (predominantly baclofen; P < 0.05). Certain 'MS specific' drugs were not frequently prescribed, such as cytotoxic immunosuppressants (two cases), amantadine (one case) and isoniazid (no cases). No case was prescribed medication for erectile dysfunction. Over 80% (44/53) of corticosteroid prescriptions for MS were for oral prednisolone. Over one-third (39%, 9/23) of cases prescribed a corticosteroid received a 'chronic' course. Over one-third (5/14) of courses of selective-serotonin re-uptake inhibitors (SSRI) for cases were identified as subtherapeutic. CONCLUSIONS: MS patients were high users of prescribed medicines, having almost twice as many prescriptions from the GP compared to controls. GP prescribing often reflected available evidence from published controlled trials, hence cytotoxic immunosuppressants, drugs for fatigue and tremor were seldom prescribed, whereas drugs such as oxybutynin and skeletal muscle relaxants were frequently prescribed. However, the increased use of certain drugs compared to controls such as diuretics, vitamin B12, hypnotics and anxiolytics were unsubstantiated in the literature. Furthermore, no published well-controlled clinical trials were found utilizing oral prednisolone or assessing the possible therapeutic benefit of chronic courses of corticosteroids in MS, both of which were prescribed by the GP. The absence of medication for sexual dysfunction (prelicensing of sildenafil), a reportedly common MS problem, was discussed. The relatively high incidence of subtherapeutic courses of SSRIs needs further investigation, given the increased incidence of depression and suicide associated with MS.

Nonprescription medicine use in a multiple sclerosis clinic population.

AIMS: To determine the use of nonprescription medicines in a cohort of multiple sclerosis (MS) patients and to identify a subgroup of patients liable to spend more on nonprescription medicines METHODS: A questionnaire was given to MS patients attending a neurology out-patients clinic during the previous year. Medicines from a General Practitioner (GP), pharmacy and 'other' sources utilized in the last month were determined, along with demographic data. Additional information was obtained from hospital notes. RESULTS: One hundred and seventeen MS patients responded to the questionnaire, giving a response rate of 79% (117/148). Responders differed from nonresponders only in age, with responders being significantly older than nonresponders (P = 0.011). Over one-third of medicines taken in the last month were nonprescription medicines (35%; 219/627). A gamolenic acid containing preparation was the most popular, purchased by 28% of patients. Fifteen percent (17/117) of MS patients had exceeded the recommended daily allowance of a vitamin (frequently vitamins A, D and E), and one exceeded the upper safe level for daily self-supplementation of vitamin A and D. Females spent significantly more than males in the previous month ( pound10. 09 compared with pound5.53, respectively; P = 0.022). Patients who were older, reported worsening MS symptoms in the last year and those who exhibited greater disability were more likely to have been prescribed medicines by a GP (P < 0.0005), although they were not more likely to self-prescribe or take alternative remedies (P > 0. 05). However, those with poorer mobility were significantly less likely to have purchased a pharmacy medicine in the last month (P = 0.033). CONCLUSIONS: MS patients were high users of nonprescription medicines. A typical subgroup of MS patients that spent more on nonprescription medicines could not be identified, aside from females. Furthermore, the strong predictors for increased use of prescription medicines (increasing age, severity of symptoms in the last year and poorer mobility) were not found for nonprescription medicines. Excessive intake of the fat soluble vitamins could lead to hypervitaminosis, the effects of which could exacerbate or mimic MS symptoms. Health professionals should be aware of these issues and counsel the MS patient accordingly, particularly as the majority purchased products from 'other' sources where typically there is no health-professional available to give advice. The limited use of pharmacy medicines by the more disabled patient could indicate a problem with access to the pharmacy, or could reflect the greater use of prescription medicines.

Polypharmacy among older men in South Wales.

OBJECTIVE: To describe the pattern of polypharmacy (PP) among older men and to relate medication use to personal, social and medical information. METHODS: Information on medication use, both prescribed and 'over the counter' (OTC), was collected from 1906 men, aged 56-75 years, observed on up to four occasions since 1979 in a community survey the Caerphilly prospective study. On each visit, a variety of questionnaires regarding personal, social and medical factors were completed, and a brief medical examination was conducted. Medication use was related to some of the questionnaire information and biological measurements collected in order to identify factors associated with PP. RESULTS: A quarter of the men (475/1906) reported using three or more prescription-only medicines (PoMs), with 9% (163) using five or more (major PP). PP was related to increasing age, lower social class, not being in employment, smoking and obesity (high body mass index). Men with a medical history, especially of high blood pressure, angina, heart attack, or hospital admission in the last 5 years, comprised a large proportion of those on major PP. Higher levels of PoM use by this group had been apparent over the previous 14 years. Men on PP reported lower levels of self-rated health and higher rates of non-PoM use. Cardiovascular and, to a lesser extent, central nervous and respiratory system drugs were the main medicines used by men on major PP. CONCLUSIONS: PP is common among men aged 56-75 years in Caerphilly, South Wales. It is related to many personal, social and medical factors, and associated with lower self-rated health status and greater use of non-PoMs. Cardiovascular medicines are the main contributor to major PP. Those on PP require regular review and, where possible, PP should be reduced as it has many potential adverse effects.

Use of corticosteroids in multiple sclerosis by consultant neurologists in the United Kingdom.

OBJECTIVES: To survey the use of corticosteroids in multiple sclerosis as recommended by United Kingdom consultant neurologists. METHODS: A postal questionnaire covering the use of corticosteroids for acute multiple sclerosis relapse and chronic progressive multiple sclerosis with regard to frequency of use, type of corticosteroid, and dosage regime was sent to all members of the Association of British Neurologists with a United Kingdom address. RESULTS: Two hundred and twelve United Kingdom consultant neurologists replied to the survey (74% response rate). Eighty six per cent indicated that they prescribed corticosteroids in more than one quarter of acute multiple sclerosis relapses seen. Intravenous methylprednisolone was recommended at some time by 99% of consultant neurologists, the most popular regime being 1g daily for 3 days (74%; 154/ 208). Over one half (53%; 109/206) never recommended a subsequent tapering course of oral corticosteroids; of those that did, 25% (24/96) recommended a tapering course lasting more than 1 month. Eighty eight per cent (1811206) of prescribers of intravenous methylprednisolone were able to offer the course as a day case on the ward; 7% (151206) at an outpatient clinic; and 5% (111206) at home. Almost three quarters of neurologists recommended oral corticosteroids for some acute relapses, although the most popular response was for occasional use only (48%; 1011212). Forty five per cent (961211) at least occasionally recommended steroids for patients with chronic multiple sclerosis not experiencing an acute relapse. CONCLUSIONS: Although the vast majority of consultant neurologists would prescribe intravenous methylprednisolone for acute multiple sclerosis relapse at some time, the use of corticosteroids for multiple sclerosis was otherwise variable. There seemed to be little consensus about the use of oral steroids in acute relapse, the prescribing of a tapering course of oral steroids after intravenous methylprednisolone, or the utility of steroids in chronic multiple sclerosis. Variability of prescribing recommendations probably reflects a lack of clear evidence in the face of a wide range of clinical situations, variable access, and timing of access to neurologists in the acute phase of relapse and pressure on neurologists to treat in an otherwise "hopeless" situation. Large multicentred trials are needed to consider these issues.

Assessment of the impact of cancer on work, recreation, home management and sleep using a general health status measure.

A general health status measure (the UK Sickness Impact Profile) was used to assess health-related quality of life in 212 cancer patients [143 women, mean (SD-standard deviation) age 55.3 (11.7) years] compared to 105 age-sex matched control subjects [71 women, mean (SD) age 54.7 (12.2) years]. The four main areas of impairment in the cancer patient group were work, recreation and pastimes, home management and sleep and rest. The majority of patients were unable to work or working shorter hours due to their disease. A diagnosis of cancer was likewise found to have a major impact on active leisure pursuits and led to reduced participation in social and community activities. Patients had particular problems in carrying out household chores and maintenance or repair work in the house. Many patients had difficulty sleeping at night and tended to sleep during the day or rest for much of the day. The majority of studies of quality of life in oncology patients concentrate upon alterations in symptoms, such measures would fail to detect impairment in the aspects described above. Greater attention should be directed towards addressing issues such as changes in employment status and the need for help in the home to improve the overall care of cancer patients.

Preliminary investigation of the efficacy of sublingual verapamil in the management of acute atrial fibrillation and flutter.

The antiarrhythmic properties of sublingual verapamil were investigated in seven patients with acute fast atrial flutter (n = 2) or fibrillation (n = 5). A rapid and significant (P < 0.05) reduction in the ventricular rate was achieved in all seven patients. The ventricular rate at peak plasma verapamil concentration (+/- s.d.) was significantly slower than on admission (101.6 +/- 11.3 and 159 +/- 5.3 beats min-1 respectively, P < 0.01). The ventricular rate remained controlled for over 4 h. Sublingual verapamil was rapidly absorbed with the maximum peak plasma concentration (153.3 +/- 15.5 ng ml-1) being achieved after 1.21 +/- 0.18 h. Side-effects of sublingual verapamil were limited to one report of a bitter taste. The sublingual administration of verapamil may provide an alternative method for the control of acute fast atrial fibrillation and flutter in selected patients.

Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial.

A multicentre, randomized, double-blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyclosporin (5 mg/kg/day) on their health-related quality of life. Treatments were administered for 8-week periods. One group (n = 16) received placebo followed by cyclosporin, and the other (n = 17) received cyclosporin and then placebo. Health-related quality of life was assessed at 0, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema-specific measure, the Eczema Disability Index (EDI), and a global 5-point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators. UKSIP and EDI scores indicated significant improvement in quality of life (P < 0.05-P < 0.01) of patients with atopic dermatitis after treatment with cyclosporin. Although no patient required withdrawal from the study, 20 patients receiving cyclosporin reported adverse events, compared with eight taking placebo. There was a close correlation (P < 0.05-P < 0.01) between the UKSIP and EDI scores. In contrast, there was either no correlation, or only a very poor correlation, between the quality of life parameters and clinical measures of extent and activity of eczema. When cyclosporin was stopped, relapse was rapid, but the mean scores for disease activity and extent of disease were less than their baseline values (i.e. an improvement of greater than 25% was maintained in 11 patients at week 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Is there a need for improved pharmacy services to the operating theatre?

A study to assess the control and handling of drugs within an operating theatre complex (10 theatres) of an 850-bed hospital, has revealed the presence of unusable medication and thus highlighted the need for improved pharmacy services. The aims and objectives of the pharmacy department to enhance such services included improvement of drug control of stock medication and the introduction of clinical pharmacy services within the operating theatre. To undertake this, three systems were evaluated with reference to systems already in use in the U.S.A. Operating theatre visits by a clinical pharmacist, coupled with the expansion of the existing drug distribution service, were identified as the most cost-effective methods that would allow the objectives to be met. Consequently, this has now been implemented within the operating theatre complex.

Peritonitis rates in CAPD patients using the UVXD and O-set systems.

We report experience with O-set and UVXD systems. Sixty-nine O-set patients (34 male; mean age +/- SD = 45.7 +/- 13.2 years) were compared with 54 UVXD patients (27 male; 56.8 +/- 16.8 years). Total (mean +/- SD) experience were 974 (14.1 +/- 10.8) months on O-set and 1010.9 (18.7 +/- 15.7) months on UVXD. Thirty-two O-set patients avoided peritonitis; 37 had 91 episodes. Seventeen UVXD patients avoided peritonitis; 37 had 137 episodes. Peritonitis occurred each 10.7 months (O-set) versus 7.4 months (UVXD), which was significantly different (p = 0.032, Z test; 95% confidence interval = -0.142 to +0.226). There were 18 relapses in 9 O-set patients, 34 in 12 UVXD. Gram-positive organisms caused 58.2% and 66%; gram-negative, 13.2% and 8.8%; and culture negative, 24.2% and 23.4% of peritonitis in O-set and UVXD, respectively. The time to first peritonitis was not different, 7.4 +/- 6.6 months O-set and 7.2 +/- 7.9 months (UVXD). There was no difference in the peritonitis-free period, 13.0 +/- 10.0 months (O-set) and 16.5 +/- 14.3 months (UVXD). There were 1.12 (O-set) and 16.1 (UVXD) cases per patient year, and 10.7 (O-set) and 7.43 (UVXD) patient months per episode. The peritonitis rate odds ratio was 1:1.85 (O-set:UVXD).

A survey of prescription label preferences among community pharmacy patrons.

Fifty-five randomly selected community pharmacy patrons were surveyed regarding their preferences between four different prescription labels. The variables displayed on the four labels were: (i) laser printed, (ii) dot-matrix printed, (iii) glossy surface, and (iv) matt surface. The study population was stratified by age and gender. Statistical analysis of the results indicated a clear preference by all groups for the laser printed labels (P less than 0.001), and the only other statistically significant finding was the preference for the matt surface (P less than 0.05) of females between the ages of 16 and 39. The implications for these differences on label readability are discussed, and recommendations are offered for the use of improved laser technology for computer-generated prescription labels.

Pharmacokinetics and pharmacodynamics of verapamil following sublingual and oral administration to healthy volunteers.

1. The pharmacokinetics and pharmacodynamics of verapamil administered via the oral and sublingual routes were compared in a randomised, two-way cross-over study involving six healthy male volunteers. 2. Administered sublingually, a verapamil 40 mg (Securon) crushed tablet produced a significantly higher peak plasma concentration (P less than 0.05), a greater rate of absorption (P less than 0.05), and greater bioavailability (P less than 0.05) when compared with orally administered verapamil 40 mg (Securon). 3. In comparison with oral dosing, PR intervals were significantly (P less than 0.05) prolonged between 30 and 90 min after sublingual verapamil dosing. 4. Correlations between log plasma verapamil concentration and percentage increase in PR interval were greater after sublingual compared with oral dosing in all volunteers.

Validation of Sickness Impact Profile and Psoriasis Disability Index in Psoriasis.

A prospective cross-sectional questionnaire study of 32 patients with psoriasis was carried out in order to validate the use of the Sickness Impact Profile (SIP) in psoriasis and compare its sensitivity with the Psoriasis Disability Index (PDI). Overall PDI scores, but not overall SIP scores, correlated well with PASI scores (P less than 0.05). There was good correlation between the PDI and overall SIP scores (P less than 0.01). Psychosocial factors are more severely impaired than physical activities in patients with psoriasis. It is now possible to directly compare the disability experienced by psoriatic patients with that experienced by patients suffering from other systemic diseases, using the SIP. The PDI is an appropriate method to give a rapid overall measure of psoriasis disability.

Effect of long-term rolipram administration on the sensitivity of alpha 2-adrenoceptors in rat brain.

The effects of single and chronic doses of rolipram on the sensitivity of alpha 2-adrenoceptors have been compared with the phosphodiesterase inhibitors, isobutylmethylxanthine (IBMX) and ICI 63,197, and the antidepressant, desipramine. While pretreatment with a single dose of rolipram, ICI 63,197 or IBMX administered either 1 or 24 h prior to clonidine (0.1 mg/kg) enhanced clonidine-induced hypothermia and hypoactivity, chronic dosing (twice daily for 14 days) with desipramine (10 mg/kg) or rolipram (5 mg/kg) antagonized these behavioural effects. In contrast, chronic dosing with IBMX or ICI 63,197 failed to antagonize clonidine-induced hypothermia and hypoactivity. In binding studies neither ICI 63,197, IBMX, rolipram nor desipramine induced changes in the binding of 3H-labelled clonidine to rat cerebral cortical membranes following chronic administration. The failure of ICI 63,107 and IBMX to antagonize clonidine-induced hypothermia and hypoactivity suggests that the antidepressant effect of rolipram is independent of its phosphodiesterase inhibitor property.

Rapid and inexpensive enzyme inhibition assay of methotrexate.

A rapid and inexpensive enzyme inhibition procedure has been developed for the assay of methotrexate in biological fluids. The method achieves a high degree of sensitivity, reproducibility, and specificity. No prior separation procedures are required, and there is no cross-reaction with metabolites of methotrexate or other substances such as folinic acid, which is often given concurrently with methotrexate. Results are in good agreement with those given by the more expensive enzyme multiplied immunoassay technique. The new method is 30 times more sensitive than the enzyme multiplied immunoassay technique, being capable of determining concentrations as low as 1.0 X 10(-8) M (4.5 ng/ml), a distinct advantage over the enzyme multiplied immunoassay technique, since it may be successfully employed in conducting clinical pharmacokinetic studies.

Lormetazepam--plasma concentrations in volunteers following sublingual and oral dosing.

The plasma profile of lormetazepam has been determined in sixteen clinically healthy, adult male volunteers following 1 mg lormetazepam, administered either sublingually or by the oral route. Absorption of lormetazepam was found to be rapid following both sublingual and oral administration. While a trend was observed towards a more rapid rate of absorption after sublingual dosing, statistically, there was no significant difference (p greater than 0.05) between the speed with which lormetazepam was absorbed following sublingual and oral dosing. After absorption, plasma lormetazepam levels rapidly reached mean (+/- s.d.) peak concentrations of 4.9 +/- 0.9 ng/ml and 5.2 +/- 1.7 ng/ml for the sublingual and oral routes, respectively, there being no significant difference (p greater than 0.05) between these values. Likewise, there was no significant difference (p greater than 0.05) in the times at which peak plasma levels were attained in the two groups. Furthermore, measurement of the area under each plasma concentration-time curve showed that the bioavailability of lormetazepam was the same for the two routes of administration. Elimination of lormetazepam followed a similar pattern following sublingual and oral dosing, the mean terminal half-lives being 13.0 h and 13.8 h, respectively. The findings in the present study clearly indicate that the plasma profiles of lormetazepam attained on sublingual and oral dosing are similar, indeed the pharmacokinetic characteristics of this drug appear identical being independent of its route of administration.

Influence of the antidepressant binodaline on biogenic amine uptake and brain levels in the rat.

The influence of 1-(omega-dimethylaminoethylmethyl)-amino-3-phenylindole hydrochloride (binodaline, Sgd-Scha 1059) on the uptake of noradrenaline (norepinephrine, NA), 5-hydroxytryptamine (5-HT) and dopamine (DA) into pre-synaptic nerve endings has been studied using purified synaptosomal preparations from various regions of rat brain. Binodaline was found to be an effective inhibitor of biogenic amine uptake the IC50 values being 5.0 X 10(-6) mol/l (NA), 2.3 X 10(-7) mol/l (5-HT) and 1.5 X 10(-6) mol/l (DA). The desmethyl analogue of binodaline (Sgd 20578) also inhibited transmitter uptake into cerebral nerve endings, being more potent than the parent compound in inhibiting NA uptake (8.5 X 10 mol/l), of a similar potency with respect to 5-HT (3.2 X 10(-7) mol/l) and slightly less potent against DA (8.3 X 10(-6) mol/l). Neither binodaline nor the desmethyl derivative was found to influence cerebral levels of NA, 5-HT and DA following acute dosing in rats. Brain concentrations of the related metabolites 5-hydroxyindolacetic acid, dihydroxyphenylacetic acid and homovanillinic acid were also unchanged. It is concluded that binodaline owes its antidepressant activity at least in part to its ability to inhibit monoamine uptake into pre-synaptic cerebral nerve endings.