Incidence and prevalence of multiple sclerosis in the UK 1990-2010: a descriptive study in the General Practice Research Database.

OBJECTIVES: To estimate the incidence and prevalence of multiple sclerosis (MS) by age and describe secular trends and geographic variations within the UK over the 20-year period between 1990 and 2010 and hence to provide updated information on the impact of MS throughout the UK. DESIGN: A descriptive study. SETTING: The study was carried out in the General Practice Research Database (GPRD), a primary care database representative of the UK population. MAIN OUTCOME MEASURES: Incidence and prevalence of MS per 100 000 population. Secular and geographical trends in incidence and prevalence of MS. RESULTS: The prevalence of MS recorded in GPRD increased by about 2.4% per year (95% CI 2.3% to 2.6%) reaching 285.8 per 100 000 in women (95% CI 278.7 to 293.1) and 113.1 per 100 000 in men (95% CI 108.6 to 117.7) by 2010. There was a consistent downward trend in incidence of MS reaching 11.52 per 100 000/year (95% CI 10.96 to 12.11) in women and 4.84 per 100 000/year (95% CI 4.54 to 5.16) in men by 2010. Peak incidence occurred between ages 40 and 50 years and maximum prevalence between ages 55 and 60 years. Women accounted for 72% of prevalent and 71% of incident cases. Scotland had the highest incidence and prevalence rates in the UK. CONCLUSIONS: We estimate that 126 669 people were living with MS in the UK in 2010 (203.4 per 100 000 population) and that 6003 new cases were diagnosed that year (9.64 per 100 000/year). There is an increasing population living longer with MS, which has important implications for resource allocation for MS in the UK.

Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD.

BACKGROUND: Influenza and pneumococcal vaccination are recommended in patients with chronic obstructive pulmonary disease (COPD). A recent study from Tayside found a reduced risk of all-cause mortality with vaccination in patients with COPD. The Health Improvement Network (THIN) database was used to test this hypothesis in a different data source. METHODS: The THIN database was searched for patients with COPD. Vaccination status against Pneumococcus and the annual influenza vaccination status were determined. Mortality rates were calculated in the periods December to March and April to November. Relative risks for the effect of vaccination on all-cause mortality were estimated by Poisson regression, adjusting for age, sex, year and serious co-morbidities. RESULTS: 177,120 patients with COPD (mean age 65 years) were identified, with a mean follow-up of 6.8 years between 1988 and 2006. Vaccination rates against influenza rose from <30% before 1995 to >70% in 2005 in patients aged 60 years or more. The cumulative vaccination rate against pneumonia rose from almost zero to 70% in patients aged 70 years or more over the same period. For all-cause mortality the adjusted relative risks associated with influenza vaccination were 0.59 (95% CI 0.57 to 0.61) during the influenza season and 0.97 (95% CI 0.94 to 1.00) outside the season in patients not vaccinated against pneumonia, and 0.30 (95% CI 0.28 to 0.32) and 0.98 (95% CI 0.96 to 1.11), respectively, in patients vaccinated against pneumonia. The relative risk associated with pneumococcal vaccination was >1 at all times of the year. CONCLUSIONS: Influenza but not pneumococcal vaccination was associated with a reduced risk of all-cause mortality in COPD.

Diagnosis and treatment of lower urinary tract symptoms suggestive of overactive bladder and bladder outlet obstruction among men in general practice in the UK.

OBJECTIVE: To assess the epidemiology and treatment of storage symptoms suggestive of overactive bladder (OAB) and voiding symptoms suggestive of bladder outlet obstruction (BOO) because of benign prostatic hyperplasia in UK general practice. PATIENTS AND METHODS: This was a retrospective analysis of data collected between 2000 and 2006 and entered in The Health Improvement Network general practice database, containing medical records for > 1 million men (aged >or= 18 years) in the UK. Using Read codes, we analysed the prevalence of storage and voiding lower urinary tract symptoms (LUTS) as well as prescribing trends for 5alpha-reductase inhibitors (5ARIs) and alpha-blockers for LUTS secondary to BOO and antimuscarinics for OAB. RESULTS: In 2006, the prevalence of diagnosed LUTS/OAB was only 0.3% and the recorded prevalence of LUTS/BOO was only 2.2%. Treatment rates also remained low throughout the study period. In the 12 months before 1 January 2006, only 25% of men diagnosed with OAB and 6-7% of men with storage LUTS received antimuscarinics, whereas 36% of men with a record of LUTS/BOO received alpha-blockers and/or 5ARIs. Alpha-blockers were prescribed to approximately 10% of men diagnosed with OAB or storage LUTS who did not have any recorded BOO diagnosis or symptoms. CONCLUSION: Diagnosis of both storage and voiding LUTS occurs at much lower rates than indicated by prevalence estimates. Despite the availability of effective prescription therapies, many men with storage and/or voiding LUTS may not be receiving appropriate treatment in UK general practice.

Treatment patterns of hypertension and dyslipidaemia in hypertensive patients at higher and lower risk of cardiovascular disease in primary care in the United Kingdom.

Few studies have investigated the presence of dyslipidaemia in hypertensive individuals. In addition, few data exist on the concurrent treatment of both conditions for the prevention of cardiovascular disease (CVD). This retrospective cohort study examined treatment patterns for hypertension and dyslipidaemia among hypertensive patients in UK primary care. We defined a population of patients aged > or =40 years from the UK General Practice Research Database. Hypertensive individuals with > or =3 additional cardiovascular risk factors (ARFs) were compared with a cohort comprising hypertensive patients with < or =2 ARFs. We analysed the prevalence of risk factors and the prevalence and incidence of treatment for hypertension, dyslipidaemia and for both conditions between January 1997 and December 2001. A total of 117 840 hypertensive patients were identified (23 655 with > or =3 ARFs, 94 185 with < or =2 ARFs) in 1997; in 2001, the number diagnosed as hypertensive was 133 683 (40 248 > or =3 ARFs, 93 435 < or =2 ARFs). The prevalence of antihypertensive treatment in the hypertensive patients with > or =3 ARFs increased during the study. In 2001, approximately one-third of hypertensive patients with > or =3 ARFs were not receiving antihypertensives. Among those patients who received such treatment, the majority received > or =2 separate agents in accordance with current guidelines. Treatment for concurrent hypertension and dyslipidaemia was initiated in <8% of patients with hypertension and > or =3 ARFs in each year. These findings demonstrate the under-recognition/undertreatment of cardiovascular risk factors in UK primary care among patients at risk of CVD.

Application of a propensity score to adjust for channelling bias with NSAIDs.

PURPOSE: To compare the relative risks of upper GI haemorrhage (UGIH) in users of Newer versus Older, non-specific NSAIDs when adjusted for channelling bias by regression on individual covariates, a propensity score and both. METHODS: Cohort study of patients prescribed NSAIDs between June 1987 and January 2000. Exposure to Newer and Older non-specific NSAIDs was identified, and risk factors evaluated for each patient. Results of multiple covariate analyses and the propensity scoring technique to assess potential channelling bias in comparisons between Newer and Older non-specific NSAIDs were compared. RESULTS: This study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to Older non-specific NSAIDs. Patients receiving Newer NSAIDs were older, more likely to have a history of GI symptoms, and at higher risk for GI complications. Adjusting for these risk factors reduced the relative risks of UGIH on meloxicam and coxibs versus Older non-specific NSAIDs to 0.84 (95%CI 0.60, 1.17) and 0.36 (0.14, 0.97) respectively. CONCLUSIONS: Channelling towards high GI risk patients occurred in the prescribing of Newer NSAIDs. Propensity scores highlighted the markedly different risk profiles of users of Newer and Older non-specific NSAID. Correcting for channelling bias, coxib exposure, but not meloxicam exposure, was associated with less UGIH than Older non-specific NSAID exposure. In the present study, corrections made by regression on a propensity score and on individual covariates were similar.

Cardiovascular prophylaxis with aspirin: costs of supply and management of upper gastrointestinal and renal toxicity.

AIMS: To determine the cost to the NHS of prescribed low-dose aspirin. METHODS: This was a population based observational cohort study. Patients from Tayside Scotland (17 244 new users of dispensed aspirin each with 10 matched comparators) were included. A pragmatic analysis totalled costs from the start to end of the study and compared these with a matched cohort of aspirin nonusers to estimate excess costs. Fastidious analyses were done of subjects with no prior history of upper gastrointestinal (UGI) or renal disease where the cost that occurred during aspirin exposure, the 30 days following aspirin exposure and subsequent nonexposure was calculated adjusting for risk factors in each period. RESULTS: Subjects took aspirin for only 1.18 of the 2.53 years follow-up (47% compliance). Aspirin use cost an additional 49.86 UK pounds per year (pragmatic analysis) made up of 1.96 UK pounds for aspirin tablets (4%), 5.49 UK pounds for dispensing costs (11%), 24.60 UK pounds for UGI complications (49%) and 17.81 UK pounds for renal complications (36%). The costs for managing complications were substantially lower in the fastidious analysis (2.66 UK pounds for UGI complications and 2.92 UK pounds for renal complications). Assuming that the antiplatelet trial meta-analysis is an accurate assessment of the benefits of aspirin, the costs of preventing one vascular event lay between 62 500 UK pounds (primary prevention, pragmatic analysis) and 867 UK pounds (secondary prevention, fastidious analysis). These costs may be underestimates due to the low compliance observed. CONCLUSIONS: Compliance with aspirin was poor. Serious adverse events were uncommon but despite this aspirin cost the NHS between 6 and 25 times the cost of aspirin tablets due to dispensing costs and the cost of managing adverse effects.

Rates of production of acetate, propionate, and butyrate in the rumen of lactating dairy cows given normal and low-roughage diets.

Five lactating dairy cows with a permanent cannula in the rumen were given (kg DM/d) a normal diet (7.8 concentrates, 5.1 hay) or a low-roughage (LR) diet (11.5 concentrates, 1.2 hay) in two meals daily in a two-period crossover design. Milk fat (g/kg) was severely reduced on diet LR. To measure rates of production of individual volatile fatty acids (VFA) in the rumen, 0.5 mCi 1-(14)C-acetic acid, 2-(14)C-propionic acid, or 1-(14)C-n-butyric acid were infused into the rumen for 22 h at intervals of 2 to 6 d; rumen samples were taken over the last 12 h. To measure rumen volume, we infused Cr-EDTA into the rumen continuously, and polyethylene glycol was injected 2 h before the morning feed. Results were very variable, so volumes measured by rumen emptying were used instead. Net production of propionic acid more than doubled on LR, but acetate and butyrate production was only numerically lower. Net production rates pooled across both diets were significantly related to concentrations for each VFA. Molar proportions of net production were only slightly higher than molar proportions of concentrations for acetate and propionate but were lower for butyrate. The net energy value (MJ/d) of production of the three VFA increased from 89.5 on normal to 109.1 on LR, equivalent to 55 and 64% of digestible energy, respectively. Fully interchanging, three-pool models of VFA C fluxes are presented. It is concluded that net production rates of VFA can be measured in non-steady states without the need to measure rumen volumes.

Channelling bias and the incidence of gastrointestinal haemorrhage in users of meloxicam, coxibs, and older, non-specific non-steroidal anti-inflammatory drugs.

BACKGROUND: Although clinical trial results suggest that meloxicam has less gastrointestinal toxicity than most other non-steroidal anti-inflammatory drugs (NSAIDs), in practice it has been associated with a large number of yellow card reports of gastrointestinal complications. AIMS: To estimate whether meloxicam and the coxibs, rofecoxib and celecoxib, have been channelled towards high risk patients, and to estimate the risk of hospitalisation for gastrointestinal haemorrhage associated with the use of these drugs, allowing for the effects of channelling. PATIENTS: Using the UK General Practice Research Database, this study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to older non-specific NSAIDs. METHODS: Cohort study of patients who received a prescription for an NSAID between June 1987 and January 2001. Exposure to newer NSAIDs (meloxicam, rofecoxib, celecoxib) and to older non-specific NSAIDs was identified. Channelling was assessed on factors including: demographic variables; diagnosis of arthritis; history of NSAID use or gastrointestinal events, including gastrointestinal haemorrhage; and use of ulcer healing drugs. RESULTS: Most risk factors for gastrointestinal haemorrhage were more prevalent among patients prescribed the newer NSAIDs. Adjusting for these risk factors reduced the relative risks of gastrointestinal haemorrhage on meloxicam and coxibs versus older non-specific NSAIDs to 0.84 (95% confidence interval 0.60, 1.17) and 0.36 (0.14, 0.97), respectively. CONCLUSIONS: Channelling towards high risk gastrointestinal patients occurred in the prescribing of newer NSAIDs. After attempting to correct for channelling bias, coxib exposure, but not meloxicam exposure, was associated with a significantly lower risk of gastrointestinal haemorrhage than older non-specific NSAID exposure.

A pharmacoeconomic comparison of misoprostol/diclofenac with diclofenac.

OBJECTIVES: To estimate the economic impact of misoprostol/diclofenac in a fixed combination tablet compared with diclofenac. DESIGN: Cohort study with a prospectively constructed, population-based, record-linkage database containing details of exposure to all community dispensed NSAIDs and all admissions to hospital for upper gastrointestinal (GI) diagnoses. Costs associated with each study drug exposure were analysed using generalized linear models. SETTING: The population of Tayside, Scotland. SUBJECTS: Subjects aged 20 years and over who received misoprostol/diclofenac or any other NSAID between January 1989 and 31 December 1995. MAIN OUTCOME MEASURES: Total costs for the number of days of exposure to diclofenac and misoprostol/diclofenac, plus costs of concomitant ulcer healing drug therapy plus endoscopy procedures plus costs of admissions to hospital for upper GI diagnoses. RESULTS: The rate of hospitalization with gastrointestinal events was 30% higher among patients receiving diclofenac than that for patients receiving misoprostol/diclofenac. Among patients who received diclofenac and an ulcer-healing drug (UHD), the event rate was more than twice that for patients receiving misoprostol/diclofenac. In patients with a prior GI history, switching from diclofenac to misoprostol/diclofenac would reduce the costs of hospitalization. The resulting savings would more than offset the extra prescription costs. In patients without a prior GI history, the greatest potential saving would arise due to reduced use of UHDs and net savings would occur in subjects aged between 60 and 70 years of age or more. CONCLUSION: Use of misoprostol/diclofenac instead of diclofenac can produce cost savings due to reduced hospitalization rates and decreased use of UHDs in subjects with a prior history of GI disease and in older subjects without prior GI disease. These findings have implications for the management of patients who require treatment with NSAIDs.

A randomized, double-blind, crossover clinical trial of diclofenac plus misoprostol versus acetaminophen in patients with osteoarthritis of the hip or knee.

OBJECTIVE: To perform a randomized, double-blind, crossover clinical trial of diclofenac + misoprostol versus acetaminophen in ambulatory patients with osteoarthritis of the hip or knee. METHODS: Patients in 12 ambulatory care settings were eligible if they were age >40 years and if they had Kellgren/Lawrence radiographic grade 2-4 osteoarthritis of the knee or hip and a score of > or =30 mm on a 100-mm visual analog pain scale. Patients were randomized to one of two groups, 75 mg diclofenac + 200 microg misoprostol twice daily or 1,000 mg acetaminophen 4 times daily (each for 6 weeks), and were then crossed over to the other treatment for 6 weeks. A placebo was included in each treatment regimen to enable double blinding. The primary outcome measures were the Western Ontario and McMaster Universities Osteoarthritis Index and the visual analog pain scale of the Multidimensional Health Assessment Questionnaire. Safety was assessed using a standard form to review adverse events. RESULTS: We enrolled 227 patients, of whom 218 provided data for the first treatment period and 181 provided data for both treatment periods. Significantly higher levels of improvement in the primary outcomes were seen for diclofenac + misoprostol than for acetaminophen (P < 0.001). Adverse events were more common when patients took diclofenac + misoprostol (P = 0.046). Diclofenac + misoprostol was rated as "better" or "much better" by 57% of the 174 patients who provided such ratings for both treatment periods, while acetaminophen was rated as "better" or "much better" by 20% of these patients, and 22% reported no difference (P < 0.001). Differences favoring diclofenac + misoprostol over acetaminophen were greater in patients with more severe osteoarthritis according to baseline pain scores, radiographs, or number of involved joints. CONCLUSION: Patients with osteoarthritis of the hip or knee had significantly greater improvements in pain scores over 6 weeks with diclofenac + misoprostol than with acetaminophen, although patients with mild osteoarthritis had similar improvements with both drugs. Acetaminophen was associated with fewer adverse events.

[Thrombolytic delay in myocardial infarction and primary care]. / Retraso trombolítico del infarto de miocardio y atención primaria.

OBJECTIVES: To analyse the effect of a primary care consultation at a health centre or at home and to determine the effect of the use of the pre-hospital electrocardiogram on thrombolytic delay. DESIGN: Analytical cross-sectional study. SETTING: La Safor county (136,000 inhabitants), Valencia, Spain. PATIENTS: Sample of 137 patients from the area admitted for acute myocardial infarction. INTERVENTION: None. MEASUREMENTS AND RESULTS: Multivariate analysis through Cox regression models of the thrombolytic delay, comparing the patients who attended a primary care centre (40, 29.2%) and those who called out a doctor to their home (26, 19.0%) with those who attended hospital (71, 51.8%). The thrombolysis proportions in the groups were analysed with logistic regression. Patients referred from primary care arrived at hospital later than those who attended directly, although a greater thrombolytic delay was only seen in those visited at home (RR 0.25, 95% CI 0.09-0.71). A primary care electrocardiogram (14 patients, 10.2%) reduced the thrombolytic delay (RR 8.81, 95% CI 1.20-64.91) by reducing intra-hospital delay. There were no differences between the groups for the thrombolysis proportion (67 patients, 48.9%). CONCLUSIONS: Patients with infarction seen in primary care reach hospital later. Calling and waiting for the doctor at home increases the thrombolytic delay. An electrocardiogram on the infarction patients who attend a health centre reduces thrombolytic delay by reducing intra-hospital delay.

Low-dose misoprostol for the prevention of low-dose aspirin-induced gastroduodenal injury.

INTRODUCTION: The harmful effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the gastric mucosa and the prophylactic effects of misoprostol are both dose-dependent. AIM: To investigate whether a low-dose of misoprostol is sufficient to prevent gastric mucosal injury caused by low-dose aspirin. METHODS: We conducted a double-blind placebo controlled parallel group endoscopic study in 32 evaluable volunteers. The main outcome measure was erosive injury (ulcers and superficial erosions) in the gastric mucosa over 28 days. RESULTS: Most subjects developed erosions on aspirin 300 mg daily. This was significantly reduced by misoprostol 100 microg daily. (Odds ratio 0.18, 95% CI: 0.07-0.48). There were no drug-related or gastrointestinal adverse events in subjects receiving misoprostol. CONCLUSION: Misoprostol 100 microg daily can prevent low-dose aspirin induced gastric mucosal injury without causing identifiable adverse effects.

Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study.

OBJECTIVES: To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with, and after cessation of, non-steroidal anti-inflammatory drugs. DESIGN: Cohort study with a prospectively constructed, population based, record linkage database containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses. SETTING: The population of Tayside, Scotland. SUBJECTS: 52,293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73,792 subjects who did not receive one during the same period (controls). MAIN OUTCOME MEASURES: Admission to hospital for upper gastrointestinal bleeding and perforation, and admission for other upper gastrointestinal diagnoses. RESULTS: About 2% of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4% of controls. The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure. The results were similar for admissions for all upper gastrointestinal events. CONCLUSION: This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure. There seems to be carryover toxicity after the end of prescribing. These findings have implications for the management of patients requiring non-steroidal anti-inflammatory drugs.

Emergency admissions for upper gastrointestinal disease and their relation to NSAID use.

BACKGROUND: There are considerable variations in estimates of the number of emergency upper gastrointestinal admissions per annum which are attributable to nonsteroidal anti-inflammatory drug (NSAID) use. AIM: To obtain a more accurate estimate of the number of these emergency admissions per annum in UK. METHODS: A retrospective survey of the case notes of all emergency admissions for upper gastrointestinal disease ('Cases') to two English District General Hospitals with a combined catchment population of 550,000. Records of all community deaths attributed to upper gastrointestinal diagnoses (with the same ICD codes) were also surveyed. Matched controls were identified from emergency admissions not caused by upper gastrointestinal diagnoses. The proportions of patients taking NSAIDs on admission to hospital (or at the time of death at home) and the outcome following admission to hospital were analysed. RESULTS: 620 emergency upper gastrointestinal admissions were identified and matched with 460 controls. Cases were more likely to be NSAID users than Controls (31% vs. 16%, OR 2.4, 95% CI: 1.8, 3.3: P < 0.001). Case NSAID use was higher in females and with increasing age. As severity of mode of presentation worsened, the probability of NSAID use increased (e.g. OR relative to controls for peptic pain 1.9, for perforation 5.9). Blood transfusion requirements were significantly higher (P < 0.0001) in Cases taking NSAIDs, although NSAID use did not influence mortality. Extrapolation from these data indicate that there are 65,000 emergency upper gastrointestinal admissions per annum in UK; 12,000 of these admissions (including 2230 deaths) are attributable to NSAID use. A further 330 attributable deaths occur in the community. CONCLUSIONS: There is a strong association between NSAID use and propensity for upper gastrointestinal emergency admission; NSAID use is associated with significant morbidity and mortality each year in UK.

Evaluation of intravenous tramadol for use in the prehospital situation by ambulance paramedics.

INTRODUCTION: An evaluation of the opioid analgesic tramadol (Zydol, Searle United Kingdom) was carried-out by ambulance paramedics to assess its efficacy in providing pain relief in the prehospital situation. METHOD: Type of subjects--Patients suffering severe pain from any cause uncontrolled by other simple methods. Number of subjects--101 patients received tramadol and 41 patients served as a control. Study design--Random, open study. Statistical tests--Pain score at scene and on arrival at hospital were compared using Fisher's exact tests (2 sides). Logistic regression analyses also were applied to other factors. RESULTS: Pain scores improved for 93.1% of the tramadol treated patients and for 44.0% of the controls. A total of 30.7% of patients treated with tramadol complained of nausea after treatment compared with 17.1% before treatment and with 12.2% of the control patients. CONCLUSIONS: Pain was significantly decreased by the administration of tramadol. It was safe with only minimal side effects, the major one being nausea. Suggestions are made for areas of further study.

The prevention and healing of acute non-steroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol.

This double-blind study assessed the acute development of NSAID-associated gastroduodenal (GD) damage and its prevention by misoprostol. Patients requiring chronic NSAID therapy were stratified into two groups depending on initial endoscopic appearance, Group I: normal (n = 223); Group II: non-ulcer lesions (n = 78). After 2 weeks of therapy with NSAID and either misoprostol 400-800 micrograms daily or placebo the incidence of severe mucosal damage (including ulcers) was significantly reduced by misoprostol (odds ratio; 95% CI). Group I: 4.52; 1.94, 10.51 (P = 0.018); Group II: 10.93; 1.09, 109.60 (P = 0.014); Groups I and II combined: 5.95; 3.23, 10.94 (P = 0.0003). Misoprostol exerted a significant protective effect against progression of minor to severe damage in Group II (P < 0.001). Endoscopic findings did not correlate significantly with gastrointestinal symptoms and misoprostol did not interfere with the NSAID efficacy. Significant GD damage occurs early in the course of NSAID treatment and misoprostol significantly reduces the incidence of such damage.