A multicentre, randomised, double-blind, placebo controlled study of cryotherapy versus cryotherapy and podophyllotoxin cream as treatment for external anogenital warts.

OBJECTIVES: To compare the efficacy and safety of combination therapy with cryotherapy and podophyllotoxin 0.15% cream versus cryotherapy alone in the treatment of anogenital warts. METHODS: A randomised, double-blind, multicentre controlled trial. Patients received podophyllotoxin cream or placebo twice daily for 3 days/week for up to 4 weeks, with weekly cryotherapy continued to week 12 if required. Further treatment from week 12 to 24 was discretionary. Patients were stratified by sex and history of warts. HIV positivity, warts treated in the past 4 months, or warts with a combined area of less than 10 mm(2) were exclusion criteria. Primary endpoints were clearance at weeks 4 and 12. RESULTS: 70 patients per group were randomly assigned and started treatment; 101 first-episode warts, 91 male. No treatment-related serious adverse events were reported. Follow-up at week 12 was 85%. By intention-to-treat analysis, clearances at 4 and 12 weeks were higher in the combination group (60.0% and 60.0%, respectively) than with cryotherapy alone (45.7%, 45.7%) although not statistically significant (RR 1.31, 95% CI 0.95 to 1.81). By week 24 there was no difference between the groups (68.6% and 64.3%, respectively; RR 1.07, CI 0.84 to 1.35). At week 4, wart clearance was higher in men (p = 0.001) and those with a past history of warts (p = 0.009), but these differences were not detected at week 12. There was some evidence for a higher relapse rate in the group receiving cryotherapy alone. CONCLUSIONS: Initial combination therapy with podophyllotoxin/cryotherapy was well tolerated and may have resulted in earlier clearance in some patients, compared with cryotherapy alone; however, overall differences in clearance rates were not statistically significant.

Grommets in otitis media with effusion: an individual patient data meta-analysis.

AIMS: To identify subgroups of children with otitis media with effusion (OME) that might benefit more than others from treatment with ventilation tubes. METHODS: An individual patient data (IPD) meta-analysis on seven randomised controlled trials (n = 1234 children in all), focusing on interactions between treatment and baseline characteristics--hearing level (HL), history of acute otitis media, common colds, attending day-care, gender, age, socioeconomic status, siblings, season, passive smoking, and history of breast feeding. Outcome measures that could be studied were mean time spent with effusion (n = 557), mean hearing levels (n = 557 in studies that randomised children, and n = 180 in studies that randomised ears), and language development (n = 381). RESULTS: In the trials that treated both ears the only significant interaction was between day-care and surgery, occurring where mean hearing level was the outcome measure. None of the other baseline variables showed an interaction effect with treatment that would justify subgrouping. In the trials that treated only one ear, the baseline hearing level showed a significant but not pervasive interaction with treatment-that is, only with a cut-off of 25 dB HL. CONCLUSIONS: The effects of conventional ventilation tubes in children studied so far are small and limited in duration. Observation (watchful waiting) therefore seems to be an adequate management strategy for most children with OME. Ventilation tubes might be used in young children that grow up in an environment with a high infection load (for example, children attending day-care), or in older children with a hearing level of 25 dB HL or greater in both ears persisting for at least 12 weeks.

Patient assessment of anogenital warts and the success of treatment with home applied therapy.

Home treatment with podophyllotoxin or imiquimod are commonly prescribed therapies for anogenital warts. It is important to ascertain if patients are locating all lesions for treatment and if they know when they are clear of them. We set out to assess patients' ability to determine the number and location of their genital warts and compare their observation with that of their examining doctor or nurse. Following instruction on the use of home treatment and being given an instruction leaflet patients were reviewed in four weeks' time. One hundred and fifty-five patients enrolled in the study--31% (48) male, 69% (107) female. At initial assessment 62.5% (30) of male patients and 59.8% (64) of female patients underestimated the extent of their disease: 10.5% (5) of male patients and 10.3% (11) of female patients overestimated their disease burden with some mistaking skin tags for genital warts. At review 29.4% (5) of male patients and 44.4% (20) of female patients still underestimated the extent of their infection. Patients undertaking home treatment for warts not only need detailed instruction on its use but should be reviewed to assess the success of treatment.

Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts.

OBJECTIVES: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. METHODS: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. RESULTS: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. CONCLUSIONS: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin.

Post-exposure prophylaxis for non-occupational exposure to HIV: current clinical practice and opinions in the UK.

OBJECTIVES: To assess the frequency and nature of requests for post-exposure prophylaxis following nonoccupational exposure (NONOPEP) to HIV and to describe variations in practice and opinions on the need for its administration at UK genitourinary medicine (GUM) clinics. METHOD: A retrospective survey was carried out of physicians representative of all UK GUM clinics using self completed questionnaires requesting information for January to December 1999. The number of requests for NONOPEP, reasons for the requests, the number prescribed, and physician opinions regarding the justification for its administration were noted. RESULTS: The number of requests and prescriptions for NONOPEP increased fourfold and sevenfold respectively in comparison with a survey from 1997. Of 242 requests, 130 people were prescribed NONOPEP. Half the requests followed sexual exposures between known HIV discordant couples. Requests for NONOPEP were received by 56 of 132 (42%) clinics, with nine clinics receiving over half of them (145/242, 60%). Similarly, over half the prescriptions for NONOPEP (83/130, 64%) were given by six of 39 prescribing clinics. Most physicians thought that post-exposure prophylaxis (PEP) was justified for people exposed to a known HIV positive source patient resulting from sexual assault or unprotected receptive anal or penovaginal sex. CONCLUSION: The use of NONOPEP has increased since the last survey and there is considerable variation between GUM clinics in practice and beliefs regarding administration of NONOPEP.

Imiquimod 5% cream is an acceptable treatment option for external anogenital warts in uncircumcised males.

OBJECTIVES: To determine the safety and efficacy of imiquimod (Aldara) 5% cream in the treatment of prepuce-associated warts in uncircumcised males. METHODS: An open-label study in six UK medical centres with 35 uncircumcised males with prepuce-associated warts treated with imiquimod 5% cream three times per week for up to 16 weeks. Other anogenital warts were also treated. RESULTS: Three times weekly application of imiquimod was found to be safe, with erythema as the most commonly reported local skin reaction. Forty per cent of patients had complete clearance of anogenital warts within 16 weeks. CONCLUSIONS: Imiquimod cream at a dosing regimen of three times per week, is effective and has an acceptable safety profile in the treatment of prepuce associated warts and other external anogenital warts in uncircumcised males.

Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts--results of an open-label, multicentre Phase IIIB trial.

Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.

Genital schistosomiasis.

Schistosomiasis is the most serious helminthic infection in the United Kingdom. Female genital schistosomiasis affects 9-13 million women worldwide, mainly in areas where Schistosoma haematobium is endemic. With increasing tourism to these areas, this diagnosis is being encountered more frequently in the West. We present 2 cases of vulval schistosomiasis that were presented to our department in 1999 and 2000.

Randomised controlled trial of early surgery versus watchful waiting for glue ear: the effect on behavioural problems in pre-school children.

This trial was designed to compare early surgery with watchful waiting for persistent bilateral otitis media with effusion (OME) in terms of hearing loss and behavioural problems in pre-school children. A randomised controlled trial compared the effects of early treatment with ventilation tubes versus watchful waiting for 9 months. Results were analysed by intention-to-treat. One hundred and eighty-two pre-school children (date of birth between 1 April 1991 and 31 December 1992), mean age of 2.9 years (SD 0.85) with at least a 3-month history of bilateral OME and hearing loss of greater than 25 dB were treated in Bristol Children's Hospital between November 1993 and January 1996. Bilateral ventilation tubes were inserted within 6 weeks of randomisation or within 6 weeks of reassessment after 9 months of watchful waiting, with a final assessment at 18 months. The main outcome measures were behavioural problems, measured by the Richman Behaviour Checklist, and hearing loss at 4000 Hz in the better hearing ear. Early surgical intervention significantly reduced behavioural problems by 17% (95% CI, 2% - 33%). This difference was largely mediated by concurrent hearing loss. After 18 months, there was no longer a significant difference (95% Cl, -19% to +10%). However, the majority (85%) of the Watchful Waiting group had required surgery and 22% of all children still had behavioural problems.

An audit of patients who have received imiquimod cream 5% for the treatment of anogenital warts.

With the licensing of the new drug Imiquimod cream 5% (Aldara 3M Health Care) for the treatment of anogenital warts and its inclusion into clinic guidelines, a case note review audit was performed of its use. The treatment of 52 patients was audited. Results showed that clinic guidelines were being followed and that patient outcomes in terms of clearance were at least as good as the quoted rates in the literature. Significant issues included firstly patient education-especially for those who had previously received ablative therapy. Secondly the length of time that therapy would be continued before a patient was deemed to be a non-responder to Imiquimod cream 5%, and if this was the case should the frequency of application be amended from the manufacturer's recommended regime of 3 times a week.

Surgical treatment of chronic otitis media with effusion.

Otitis media with effusion is the most frequent reason for admission to hospital for surgery in children. There are worldwide differences in the management of the condition. Recent studies have evaluated indications for surgery, surgical treatment methods, outcome measures following surgery and sequelae. The present report defines the increased risk of behavioural problems in pre-school children with persistent disease. Factors affecting the outcome of surgery with ventilation tubes are discussed. Assessment is made of the complications due to the disease and those resulting from treatment with ventilation tubes. Finally, a review is made of the various international guidelines for the management of persistent disease as a basis for good clinical practice.

Early surgery compared with watchful waiting for glue ear and effect on language development in preschool children: a randomised trial.

BACKGROUND: Otitis media with effusion (OME) is the most common cause of hearing loss in children and is generally treated by elective surgery. We compared in children with persistent OME the effect on speech and language development of immediate surgery (ventilation-tube insertion) and watchful waiting before surgery. METHODS: We did a randomised controlled trial with masked outcome assessment in Bristol Children's Hospital, Bristol, UK. We included 186 children born between April 1, 1991, and Dec 31, 1992, who had confirmed bilateral OME and bilateral hearing impairment of 25-70 dB of at least 3 months' duration. Children were randomly assigned surgery within 6 weeks (n=92), or 9 months of watchful waiting (n=90), after which bilateral tube insertion was done if required. We assessed hearing loss, expressive language, and verbal comprehension at 9 months and 18 months. FINDINGS: At 9 months, standardised scores for expressive language and verbal comprehension differed between groups with marginal significance after adjustment for baseline differences (p=0.04 and p=0.028, respectively). At 9 months, verbal comprehension and expressive language skills in the watchful-waiting group were 3.24 months behind those in the early-surgery group. The watchful-waiting group was delayed on these two measures compared with their age-expected levels. 18 months after randomisation, 85% of children in the watchful-waiting group had received surgery and groups did not differ significantly. INTERPRETATION: There is some benefit from ventilation-tube insertion for expressive language and verbal comprehension but the timing of surgery is not critical.

An international survey of patients with genital warts: perceptions regarding treatment and impact on lifestyle.

Our aim was to determine country-specific attitudes and perceptions of patients with genital warts and to understand the psychosexual impact of the disease and its treatment. We used a standardized discussion guide to interview patients with genital warts in Canada, France, Germany, the UK, and the USA about their perceptions and concerns regarding the diagnosis, treatment, and psychosexual impact of the disease. Interviews were conducted in person and lasted approximately 30 min. The study group included 80 men and 86 women with genital warts. Forty-seven per cent were currently undergoing treatment. Overall, 49% of the men had first consulted a general or family practitioner, and 52% of the women had first consulted a gynaecologist. Although all the patients eventually consulted a physician about their warts, one-third delayed seeing a doctor because they thought the condition would resolve on its own or that the problem was not serious. Most patients reported that treatment was associated with pain, discomfort, and embarrassment. Sixty per cent of patients experienced a recurrence after initial clearance with treatment. More than 80% stated that they had had little or no involvement in the selection of treatment. Globally, 52% of men and 61% of women were 'quite concerned' or 'very concerned' about having genital warts, although there were significant variations by country. Approximately two-thirds of patients had made lifestyle changes regarding sexual relationships. In addition, two-thirds believed that there were risks associated with having genital warts; the most common risk identified was a link to cancer (cervical and unspecified). A high level of anxiety is associated with the diagnosis and treatment of genital warts. Patients with genital warts require understanding and an acknowledgement of their concerns. A better understanding of the psychosexual aspect of the disease by health-care providers is pivotal to effective disease management and patient counselling.