Advice to use topical or oral ibuprofen for chronic knee pain in older people: randomised controlled trial and patient preference study.

OBJECTIVE: To determine whether older patients with chronic knee pain should be advised to use topical or oral non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: Randomised controlled trial and patient preference study. SETTING: 26 general practices. PARTICIPANTS: People aged > or =50 with knee pain: 282 in randomised trial and 303 in preference study. INTERVENTIONS: Advice to use topical or oral ibuprofen. Primary outcome measures WOMAC (Western Ontario and McMaster Universities) osteoarthritis index, major and minor adverse effects. RESULTS: Changes in global WOMAC scores at 12 months were equivalent. In the randomised trial the difference (topical minus oral) was two points (95% confidence interval -2 to 6); in the preference study, it was one point (-4 to 6). There were no differences in major adverse effects in the trial or study. The only significant differences in secondary outcomes were in the randomised trial. The oral group had more respiratory adverse effects (17% v 7%,95% confidence interval for difference -17% to -2%), the change in serum creatinine was 3.7 mmol/l less favourable (0.9 micromol/l to 6.5 micromol/l); and more participants changed treatments because of adverse effects (16% v 1%, -16% to -5%). In the topical group more participants had chronic pain grade III or IV at three months, and more participants changed treatment because of ineffectiveness. CONCLUSIONS: Advice to use oral or topical preparations has an equivalent effect on knee pain over one year, and there are more minor side effects with oral NSAIDs. Topical NSAIDs may be a useful alternative to oral NSAIDs. TRIAL REGISTRATION: ISRCTN 79353052.

The risk factors for relapse among patients with African trypanosomiasis in Daloa, Cote d'Ivoire.

We describe rates of follow-up and the risk factors for relapse in a cohort of adult patients treated for Trypanosoma brucei gambiense African trypanosomiasis. 812 patients were discharged from hospital between 6 January 1983 and 16 January 1992. The numbers who did not attend a scheduled follow-up appointment at 6,12,18 and 24 months were 383 (47%), 467 (58%), 536 (66%) and 533 (66%), respectively. Thirty-two patients relapsed over the 2 years follow-up: 24 (75%) before the 12-month follow-up appointment. The presence of antibody to trypanosomes in the cerebrospinal fluid (CSF) at discharge from hospital was associated significantly with the risk of relapse at any time. When the analysis was restricted to a follow-up of 1 year, a protein level in the CSF above the median and the presence of antibody in the CSF (both at discharge) were associated in univariate analysis with relapse. A high number of patients were lost to follow-up, which may have resulted in bias. From the data available, the majority of the relapses were recorded within 12 months and the presence of antibody in the CSF at hospital discharge was identified as an independent predictor of future relapse at any time.

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN: Systematic review and meta-analysis of longitudinal studies. METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

TOIB Study. Are topical or oral ibuprofen equally effective for the treatment of chronic knee pain presenting in primary care: a randomised controlled trial with patient preference study. [ISRCTN79353052].

BACKGROUND: Many older people have chronic knee pain. Both topical and oral non- steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat this. Oral NSAIDS are effective, at least in the short term, but can have severe adverse effects. Topical NSAIDs also appear to be effective, at least in the short term. One might expect topical NSAIDs both to be less effective and to have fewer adverse effects than oral NSAIDs. If topical NSAIDs have fewer adverse effects this may outweigh both the reduction in effectiveness and the higher cost of topical compared to oral treatment. Patient preferences may influence the comparative effectiveness of drugs delivered via different routes. METHODS: TOIB is a randomised trial comparing topical and oral ibuprofen, with a parallel patient preference study. We are recruiting people aged 50 or over with chronic knee pain, from 27 MRC General Practice Research Framework practices across the UK. We are seeking to recruit 283 participants to the RCT and 379 to the PPS. Participants will be followed up for up to two years (with the majority reaching one year). Outcomes will be assessed by postal questionnaire, nurse examination, laboratory tests and medical record searches at one and two years or the end of the study. DISCUSSION: This study will provide new evidence on the overall costs and benefits of treating chronic knee pain with either oral or topical ibuprofen. The use of a patient preference design is unusual, but will allow us to explore how preference influences response to a medication. In addition, it will provide more information on adverse events. This study will provide evidence to inform primary care practitioners, and possibly influence practice.