Patterns of care and burden of chronic idiopathic thrombocytopenic purpura in Brazil.

AIMS: Although several therapeutic options are available for chronic immune thrombocytopenic purpura (cITP), little is known about the treatment of cITP in Brazil. MATERIALS AND METHODS: A multi-center, retrospective chart review, observational study was designed to describe the treatment patterns, clinical burden, resources use, and associated costs for adult patients diagnosed with cITP and treated in public and private institutions in Brazil. Patient charts were screened in reverse chronological order based on their last visit post January 1, 2012. (All costs were calculated using 1.00 USD = 3.9571 BRL, from February 2016.) Results: Of 340 patient charts screened, 50 patients were eligible for inclusion in the study. Single-drug therapy (prednisone, dexamethasone, or dapsone) was the most commonly used treatment, followed by combination therapies (azathioprine + prednisone, azathioprine + prednisone + danazol, and prednisone + dapsone). Splenectomy was performed in 22% of patients after at least first-line treatment. Platelet count and number of bleeding episodes at diagnosis were 31,561.1/mm3 (SD = ±26,396.1) and 40 episodes, respectively; in first-line, 92,631.1/mm3 (SD = ±79,955.3) and 19 episodes, respectively; in second-line, 96,950.0/mm3 (SD = ±76,476.4) and 17 episodes, respectively. Private system patients had a higher median cost compared to public system patients (USD 17.49/month, range = 0-2,020.77 vs USD 9.51/month, range = 0-192.64, respectively). LIMITATIONS: This study does not allow conclusions for causal explanations due to the cohort study design, and treatment patterns represent only the practices of physicians who have agreed to participate in the study. CONCLUSIONS: The data indicate that available therapeutic strategies for second- and third-line therapies appear to be limited.

Prophylaxis for human immunodeficiency virus-related Pneumocystis carinii pneumonia: using simulation modeling to inform clinical guidelines.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) have experienced a dramatic decrease in Pneumocystis carinii pneumonia (PCP), necessitating reassessment of clinical guidelines for prophylaxis. METHODS: A simulation model of HIV infection was used to estimate the lifetime costs and quality-adjusted life expectancy (QALE) for alternative CD4 cell count criteria for stopping primary PCP prophylaxis in patients with CD4 cell count increases receiving HAART and alternative agents for second-line PCP prophylaxis in those intolerant of trimethoprim-sulfamethoxazole (TMP/SMX). The target population was a cohort of HIV-infected patients in the United States with initial CD4 cell counts of 350/microL who began PCP prophylaxis after their first measured CD4 lymphocyte count less than 200/microL. Data were from randomized controlled trials and other published literature. RESULTS: For patients with CD4 cell count increases during HAART, waiting to stop prophylaxis until the first observed CD4 cell count was greater than 300/microL prevented 9 additional cases per 1000 patients and cost $9400 per quality-adjusted life year (QALY) gained compared with stopping prophylaxis at 200/microL. For patients intolerant of TMP/SMX, using dapsone increased QALE by 2.7 months and cost $4500 per QALY compared with no prophylaxis. Using atovaquone rather than dapsone provided only 3 days of additional QALE and cost more than $1.5 million per QALY. CONCLUSIONS: Delaying discontinuation of PCP prophylaxis until the first observed CD4 cell count greater than 300/microL is cost-effective and provides an explicit "PCP prophylaxis stopping criterion." In TMP/SMX-intolerant patients, dapsone is more cost-effective than atovaquone.

Chlorproguanil-dapsone (LAPDAP) for uncomplicated falciparum malaria.

The synergistic antifolate combination of chlorproguanil with dapsone (CPG-DDS; LAPDAP) is being developed by a public-private partnership as a low-cost treatment for uncomplicated falciparum malaria. LAPDAP is rapidly eliminated from the body, giving it low selection pressure for drug resistance. Clinical cases with sulphadoxine-pyrimethamine (SP)-resistant infections acquired in Africa have been predicted to be responsive to LAPDAP, and clinical evidence is available to support this. A regulatory dossier is being prepared for simultaneous submission to the UK Medicines Control Agency and African licencing authorities. The team working on LAPDAP has also started to develop the triple combination of chlorproguanil-dapsone-artesunate (CDA) as a low-cost combination therapy for uncomplicated falciparum malaria. Although LAPDAP does not have regulatory approval (and development of CDA is at an early stage), the development team is keen to communicate with public health scientists to try to anticipate the policy and implementation hurdles that lie ahead. This short paper outlines the current stages that LAPDAP and CDA have reached, and sketches the anticipated public health issues.

Use of dapsone in the prevention and treatment of Pneumocystis carinii pneumonia: a review.

Dapsone, with or without trimethoprim or pyrimethamine, has strong anti-Pneumocystis carinii activity, as demonstrated by in vitro methods, animal studies, and clinical trials. The drug blocks folic acid synthesis of P. carinii by inhibition of dihydropteroate synthetase activity. Dapsone is efficiently absorbed (70%-80%) from the gastrointestinal tract, reaches peak serum concentration in 2-6 hours, and is adequately distributed to the fluid of the alveolar spaces. Synergistic effects against P. carinii are noted when trimethoprim is combined with dapsone. This combination is recommended for therapeutic use for P. carinii pneumonia (PCP) as an alternative for patients who cannot take trimethoprim-sulfamethoxazole (TMP-SMZ). Evidence from more than 40 studies of dapsone as prophylaxis for PCP in AIDS patients shows that dapsone, either alone or in combination with pyrimethamine, is as effective as aerosolized pentamidine or atovaquone but slightly less effective than TMP-SMZ. Adverse effects include rash, anemia, methemoglobinemia, agranulocytosis, and hepatic dysfunction. Desensitization can be accomplished with many cases. Dapsone is the most cost-effective prophylaxis currently available for PCP.

Controlled trial of lambda-cyhalothrin impregnated bed nets and Maloprim chemosuppression to control malaria in children living in a holoendemic area of Sierra Leone, west Africa. Study design and preliminary results.

The effect of lambda-cyhalothrin impregnated bed nets and maloprim/placebo was studied in approximately 1,500 children living in 17 villages in a rural area of Sierra Leone, approximately 150 miles south east of Freetown, 30 miles north of the town of Bo. Villages were selected randomly amongst villages with impregnated bed nets and villages with no nets at all. Within these villages, children with ages ranging between 3 months to 6 years were chosen to receive maloprim or a double-blind distributed placebo fortnightly. In the villages randomised to receive nets, all beds have received nets. Malaria morbidity is estimated from weekly active case detection, and the impact on the Anopheles vector is being estimated by indoor spray catching, exit trap catching, human night landing catches and light trap catches. During the first 8 weeks of the intervention there was a significant reduction in slide positive rates, reported fever rates and children with temperature > or = 37.5 degrees C in the villages with impregnated bed nets.

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, west Africa. 8. Cost-effectiveness of bed net impregnation alone or combined with chemoprophylaxis in preventing mortality and morbidity from malaria in Gambian children.

In The Gambia, insecticide impregnation of bed nets, used alone or combined with Maloprim, reduced morbidity and mortality from malaria amongst children between one and 4 years of age. Taking expenditure of both time and money by public authorities and village volunteers into account, the costs and cost-effectiveness of each intervention were estimated. Bed net impregnation alone and the combined strategy cost US $5.65 and US $7.49 per child-year protected respectively (1990 figures). Insecticide (and drugs) accounted for more than 80% of the costs of each intervention strategy. They were both highly cost-effective. Estimated costs per death and per clinical episode of malaria averted were US $188 and US $28 for bed net impregnation and $257 and $19 for impregnation combined with chemoprophylaxis. Estimated costs per healthy year of life saved, discounted at 3%, were US $7.90 and US $10.84.

The cost-effectiveness of chemoprophylaxis with Maloprim administered by primary health care workers in preventing death from malaria amongst rural Gambian children aged less than five years old.

In recent trials in The Gambia, mass chemoprophylaxis with Maloprim administered over several years by primary health care workers to children aged 3-59 months has reduced both mortality and morbidity without inducing impairment of natural immunity or significant development of drug resistance. Taking expenditure of both time and money, by both public authorities and village volunteers, into account, the costs and the cost effectiveness of such mass chemoprophylaxis are estimated here. The cost per child protected per season was (1990 US) $2.84; the cost per childhood death averted was $143. Both costs compare favourably with those of permethrin bed net impregnation. So in some circumstances where malaria is holoendemic, control of childhood malaria by chemoprophylaxis may be more economically efficient than provision of impregnated bed nets.