Treatment of paucibacillary leprosy with a regimen containing rifampicin, dapsone and prothionamide.

Ninety paucibacillary leprosy patients having indeterminate (I), tuberculoid (TT) and borderline tuberculoid (BT) type of leprosy with bacterial index (BI) of less than two on the Ridley scale were treated with rifampicin (RFM) 600 mg once a month, dapsone (DDS) 100 mg daily and prothionamide (PTH) 250 mg daily. Treatment was stopped at the end of six months. The patients tolerated the drugs fairly well and in only two patients the drugs had to be stopped (in one due to jaundice and in the other due to gastric intolerance). About 6% of patients had early reactions which subsided with additional steroid therapy. The inactivity rate was 60% at six months and this improved to 96% at 12 months. No cases of late reactions and relapses were encountered in the limited follow-up period of six months; and a longer follow-up is necessary for ascertaining the relapse rates. The preliminary results however suggest that the addition of prothionamide to the standard WHO paucibacillary regimen is well-tolerated with increased inactivity rate and fewer instances of late reactions.     

A comparative trial of single dose chemotherapy in paucibacillary leprosy patients with two to three skin lesions

A multicentric, double-blind, controlled, clinical trial was carried out to compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg (ROM) administered as single dose with that of standard WHO/MDT/PB six months regimen. The study subjects were 236 previously untreated, smear-negative patients, without nerve trunk involvement and having only two or three skin lesions. Randomization was done on individual patient basis. Results were analyzed for mean clinical score for improvement, marked clinical improvement and complete clinical cure at the time of release from treatment and at 12 months and 18 months of follow-up. Clinical improvement was seen in most patients in both regimens. Marked improvement (i.e., more than 90% reduction in clinical score) at 18 months was seen in 46.2% and 53.4% of the patients treated with ROM and standard regimens, respectively. But, significant difference in favour of standard PB regimen was seen in patients with three skin lesions and in patients in whom more than one body part was affected. Reversal reaction and adverse drug reactions were minimal in both groups.     

Treatment with corticosteroids of long-standing nerve function impairment in leprosy: a randomized controlled trial (TRIPOD 3)

Some leprosy patients with long-standing nerve function impairment (NFI) appear to have responded favourably to treatment with corticosteroids. This study investigated whether patients with untreated NFI between 6 and 24 months duration and who are given standard regimen corticosteroid therapy, will have a better treatment outcome than a placebo group. A multicentre, randomized, double-blind placebo-controlled trial was conducted in Nepal and Bangladesh. Subjects were randomised to either prednisolone treatment starting at 40 mg/day, tapered by 5 mg every 2 weeks, and completed after 16 weeks, or placebo. Outcome assessments were at 4, 6, 9, and 12 months from the start of treatment. 92 MB patients on MDT were recruited, of whom 40 (45%) received prednisolone and 52 (55%) placebo treatment. No demonstrable additional improvement in nerve function, or in preventing further leprosy reaction events was seen in the prednisolone group. Overall, improvement of nerve function at 12 months was seen in about 50% of patients in both groups. Analysis of subgroups according to nerve (ulnar and posterior tibial), duration of NFI, and sensory and motor function, also did not reveal any differences between the treatment and placebo groups. There was however, indication of less deterioration of nerve function in the prednisolone group. Finally, there was no difference in the occurrence of adverse events between both groups. The trial confirms current practice not to treat long-standing NFI with prednisolone. Spontaneous recovery of nerve function appears to be a common phenomenon in leprosy. Leprosy reactions and new NFI occurred in a third of the study group, emphasizing the need to keep patients under regular surveillance during MDT, and, where possible, after completion of MDT.     

Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group.

OBJECTIVE: To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. METHODS: 382 otherwise healthy patients with a history of frequently recurring genital HSV infection (eight recurrences per year) were randomly allocated to receive either oral valaciclovir (500 mg once daily) or placebo (3:1 ratio) for 16 weeks or until the first genital HSV recurrence, whichever occurred first. Patients were clinically assessed at regular intervals and also if they experienced a recurrence. Safety was evaluated through adverse experience reporting and monitoring of haematology and biochemistry variables. On completion of the double blind phase, patients were eligible for follow up to a maximum of 48 weeks' treatment with open label valaciclovir (500 mg once daily) for further safety monitoring. The results from the double blind phase of the study are reported here. RESULTS: A significant difference was detected between valaciclovir and placebo in the time to first recurrence of genital HSV infection. The hazard ratio [95% confidence interval] for valaciclovir v placebo was 0.155 [0.112, 0.214], p < 0.0001. Valaciclovir prevented or delayed 85% of the recurrences that would have occurred with placebo. After 16 weeks (day 112) with treatment, 69% of patients receiving valaciclovir were recurrence free compared with only 9.5% of patients assigned to placebo. The safety profiles of valaciclovir and placebo were comparable, with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that once daily valaciclovir (500 mg), is highly effective and well tolerated for the suppression of recurrent genital HSV infection. Once daily dosing with valaciclovir provides a more convenient dosing regimen than the more frequent aciclovir regimens.     

A comparison of interferon alfa-2a and podophyllin in the treatment of primary condylomata acuminata. The Condylomata International Collaborative Study Group.

OBJECTIVES--to compare the response to treatment and recurrence rate of condylomata accuminata using subcutaneous injection of interferon alfa 2a 1.5 million units three times weekly for four weeks, or podophyllin resin 25% applied to lesions twice weekly for up to six weeks. DESIGN--Randomised open study. SETTING--Multicentre European study in genitourinary medicine, dermatovenereology, and gynaecology departments. PATIENTS--87 males and 67 females with condylomata acuminata for less than six months and no history of previous treatment. MAIN OUTCOME MEASURES--Complete clearance of lesions and evidence of recurrence at three months and nine months after treatment commenced. RESULTS--A complete response was achieved at three months in 15 of 64 (23%) in the interferon treated group, and 31 of 69 (45%) in the podophyllin treated group (p = 0.003). At nine months 10 of 13 patients in the interferon group and 22 of 30 patients in the podophyllin group remained completely clear of lesions.     

A pragmatic randomized controlled trial on the effectiveness of low concentrated saline spa water baths followed by ultraviolet B (UVB) compared to UVB only in moderate to severe psoriasis

OBJECTIVE: To evaluate whether low concentrated saline spa water baths followed by ultraviolet B (LC-SSW-UVB) are superior to UVB alone in moderate to severe psoriasis. BACKGROUND: There is a lack of sufficiently large randomized controlled clinical trial evaluating the additional benefit of saltwater baths followed by UVB compared to UVB only in psoriasis. STUDY DESIGN: Partly evaluator blind, multicentre, pragmatic, randomized controlled trial. SETTING: Five German spa centres. SUBJECTS: One hundred and forty-three adults with stable psoriasis during the last month and a Psoriasis Area and Severity Index (PASI) of > 10 and/or an affected body surface area of > 15%. INTERVENTIONS: LC-SSW-UVB or UVB thrice a week until remission (PASI < 5) or for a maximum of 6 weeks. Sodium chloride concentrations of natural springs varied between 4.5% and 12%. Conventional UVB (broadband UVB or selective UVB phototherapy) was used as irradiation source. MAIN OUTCOME: Reduction of PASI and/or affected body surface area of 50% at the end of the intervention period (PASI-50). Only participants receiving at least one intervention were included in the primary analysis. RESULTS: Patients allocated to LC-SSP-UVB attained a statistically significantly higher rate of PASI-50 at the end of the intervention period than patients allocated to UVB [58/79 (73%) vs. 32/64 (50%); P = 0.01; NNT, 4.3, 95% CI, 2.4-18.1]. Benefit persisted until 3 months only for one of two secondary outcomes considered. CONCLUSIONS: In routine clinical practice balneophototherapy using conventional UVB is superior to conventional UVB only at the end of a 6-week treatment course.     

Safety and acceptability of vaginal disinfection with benzalkonium chloride in HIV infected pregnant women in west Africa: ANRS 049b phase II randomized, double blinded placebo controlled trial. DITRAME Study Group

OBJECTIVES: To study the tolerance and acceptability in Africa of a perinatal intervention to prevent vertical HIV transmission using benzalkonium chloride disinfection. DESIGN: A randomized, double blinded phase II trial. SETTING: Prenatal care units in Abidjan (Cote d''Ivoire) and Bobo-Dioulasso (Burkina Faso). PATIENTS: Women accepting testing and counselling who were seropositive for HIV-1 and under 37 weeks of pregnancy were eligible. A total of 108 women (54 in each group) enrolled from November 1996 to April 1997, with their informed consent. INTERVENTION: Women self administered daily a vaginal suppository of 1% benzalkonium chloride or matched placebo from 36 weeks of pregnancy, and a single intrapartum dose. The neonate was bathed with 1% benzalkonium chloride solution or placebo within 30 minutes after birth. MAIN OUTCOME MEASURES: Adverse events were recorded weekly, with a questionnaire and speculum examination in women through delivery, and examination of the neonate through day 30. The incidence of genital signs and symptoms in the women and cutaneous or ophthalmological events in newborns were compared between groups on an intent to treat basis. RESULTS: The median duration of prepartum treatment was 21 days (range 0-87 days). Compliance was 87% for prepartum and 69% for intrapartum treatment, and 88% for the neonatal bath, without differences between the two groups. In women, the most frequent event was leucorrhoea; the incidence of adverse events did not differ between treatment groups. In children, the incidence of dermatitis and conjunctivitis did not differ between the benzalkonium chloride and placebo groups (p = 0.16 and p = 0.29, respectively). CONCLUSION: Vaginal disinfection with benzalkonium chloride is a feasible and well tolerated intervention in west Africa. Its efficacy in preventing vertical HIV transmission remains to be demonstrated.


     

Costs and cost-effectiveness analysis of treatment in children with eczema by nurse practitioner vs. dermatologist: results of a randomized, controlled trial and a review of international costs

Background In a randomized, controlled trial (RCT) on childhood eczema we reported that substituting nurse practitioners (NPs) for dermatologists resulted in similar outcomes of eczema severity and in the quality of life, and higher patient satisfaction. Objectives To determine costs and cost‐effectiveness of care provided by NPs vs. dermatologists and to compare our results with those in studies from other countries. Methods We estimated the healthcare costs, family costs and the costs in other sectors alongside the RCT. All the costs were linked to quality of life [Infants’ Dermatitis Quality of Life Index (IDQOL), Children’s Dermatology Life Quality Index (CDLQI)] and to patient satisfaction (Client Satisfaction Questionnaire‐8) to determine the incremental cost‐effectiveness ratio (ICER). We also examined all the reported studies on the costs of childhood eczema. Results The mean annual healthcare costs, family costs and costs in other sectors were €658, €302 and €21, respectively, in the NP group and €801, €608 and €0·93, respectively, in the dermatologist group. The ICER in the NP group compared with the dermatologist group indicated €925 and €751 savings per one point less improvement in IDQOL and CDLQI, respectively, and €251 savings per one point more satisfaction in the NP group at 12 months. The mean annual healthcare costs and family costs varied considerably in the six identified studies. Conclusions Substituting NPs for dermatologists is both cost‐saving and cost‐effective. The treatment of choice is that provided by the NPs as it is similarly effective to treatment provided by a dermatologist with a higher parent satisfaction. International comparisons are difficult because the types of costs determined, the units and unit prices, and eczema severity all differ between studies.     

Open label randomized study comparing 3 months vs. 6 months treatment of actinic keratoses with 3% diclofenac in 2.5% hyaluronic acid gel: a trial of the German Dermatologic Cooperative Oncology Group

Background  Actinic keratoses (AK) are carcinomata in situ with the potential to develop into invasive carcinoma. Several studies have demonstrated that 3% diclofenac in 2.5% hyaluronic acid gel (HA) is effective and well tolerated in the treatment of AK. To date there are no large randomized multicentre trials with treatment durations longer than 90 days and histopathological control of treatment outcome. Objective  The aim of this study was to investigate whether a prolonged treatment with diclofenac in HA of 6 vs. 3 months adds to the efficacy in treatment for AK and if this will influence tolerability and quality of life (QoL). Methods  This was a multicentre, randomized open‐label study in which 418 patients with mild to moderate AKs were randomized into two treatment groups. Group A received diclofenac in HA for 3 months and group B for 6 months. Treatment efficacy was assessed by size measurement and a final biopsy of a defined marker AK. Quality of life was measured using the Dermatology Life Quality Index questionnaire. Results  Clinical complete clearance was observed in 40% in group A and in 45% in group B (P = 0.38). Histopathological clearance was confirmed in 30% in group A and in 40% in group B (P = 0.16). Treatment was well tolerated and QoL was significantly improved after treatment in both treatment groups. Conclusion  Treatment with diclofenac in HA is effective and well tolerated during a treatment period of 3 months as well as 6 months. Prolongation of the treatment duration did not significantly affect treatment outcome.