Drug dispensing practices during implementation of artemisinin-based combination therapy at health facilities in rural Tanzania, 2002-2005.

OBJECTIVE: To assess the degree to which policy changes to artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria translate into effective ACT delivery. METHODS: Prospective observational study of drug dispensing practices at baseline and during the 3 years following introduction of ACT with sulfadoxine-pyrimethamine (SP) plus artesunate (AS) in Rufiji District, compared with two neighbouring districts where SP monotherapy remained the first-line treatment, was carried out. Demographic and dispensing data were collected from all patients at the dispensing units of selected facilities for 1 month per quarter, documenting a total of 271, 953 patient encounters in the three districts. RESULTS: In Rufiji, the proportion of patients who received a clinical diagnosis of malaria increased from 47.6% to 57.0%. A majority (75.9%) of these received SP + AS during the intervention period. Of patients who received SP + AS, 94.6% received the correct dose of both. Among patients in Rufiji who received SP, 14.2% received SP monotherapy, and among patients who received AS, 0.3% received AS monotherapy. CONCLUSIONS: The uptake of SP + AS in Rufiji was rapid and sustained. Although some SP monotherapy occurred, AS monotherapy was rare, and most received the correct dose of both drugs. These results suggest that implementation of an artemisinin combination therapy, accompanied by training, job aids and assistance in stock management, can rapidly increase access to effective antimalarial treatment.

Central bone grafting for nonunion of fractures of the tibia: a retrospective series.

Nonunion of the tibia associated with bone loss, previous infection, obliteration of the intramedullary canal or located in the distal metaphysis poses a challenge to the surgeon and significant morbidity to patients. We retrospectively reviewed the records of 24 patients who were treated by central bone grafting and compared them to those of 20 who were treated with a traditional posterolateral graft. Central bone grafting entails a lateral approach, anterior to the fibula and interosseous membrane which is used to create a central space filled with cancellous iliac crest autograft. Upon consolidation, a tibiofibular synostosis is formed that is strong enough for weight-bearing. This procedure has advantages over other methods of treatment for selected nonunions. Of the 24 patients with central bone grafting, 23 went on to radiographic and clinical union without further intervention. All healed within a mean of 20 weeks (10 to 48). No further bone grafts were required, and few complications were encountered. These results were comparable to those of the 20 patients who underwent posterolateral bone grafting who united at a mean of 31.3 weeks (16 to 60) but one of whom required below-knee amputation for intractable sepsis. Central bone grafting is a safe and effective treatment for difficult nonunions of the tibia.

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya.

OBJECTIVES: To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. METHODS: Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6-59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. RESULTS: The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrollment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. CONCLUSION: Although artemether-lumefantrine (Coartem) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardize the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy.

The perception of respiratory work and effort can be independent of the perception of air hunger.

Dyspnea in patients could arise from both an urge to breathe and increased effort of breathing. Two qualitatively different sensations, "air hunger" and "respiratory work and effort," arising from different afferent sources are hypothesized. In the laboratory, breathing below the spontaneous level may produce an uncomfortable sensation of air hunger, and breathing above it a sensation of work or effort. Measurement of a single sensory dimension cannot distinguish these as separate sensations; we therefore measured two sensory dimensions and attempted to vary them independently. In five normal subjects we obtained simultaneous ratings of air hunger and of work and effort while independently varying PCO(2) or the level of targeted voluntary breathing. We found a difference in response to the two stimulus dimensions: air hunger ratings changed more steeply when PCO(2) was altered and ventilation was constant; work or effort ratings changed more steeply when ventilation was altered and PCO(2) was constant. We conclude that "air hunger" is qualitatively different from "work and effort" and arises from different afferent sources.