Community-based therapy for multidrug-resistant tuberculosis in Lima, Peru.

BACKGROUND: Despite the prevalence of multidrug-resistant tuberculosis in nearly all low-income countries surveyed, effective therapy has been deemed too expensive and considered not to be feasible outside referral centers. We evaluated the results of community-based therapy for multidrug-resistant tuberculosis in a poor section of Lima, Peru. METHODS: We describe the first 75 patients to receive ambulatory treatment with individualized regimens for chronic multidrug-resistant tuberculosis in northern Lima. We conducted a retrospective review of the charts of all patients enrolled in the program between August 1, 1996, and February 1, 1999, and identified predictors of poor outcomes. RESULTS: The infecting strains of Mycobacterium tuberculosis were resistant to a median of six drugs. Among the 66 patients who completed four or more months of therapy, 83 percent (55) were probably cured at the completion of treatment. Five of these 66 patients (8 percent) died while receiving therapy. Only one patient continued to have positive cultures after six months of treatment. All patients in whom treatment failed or who died had extensive bilateral pulmonary disease. In a multiple Cox proportional-hazards regression model, the predictors of the time to treatment failure or death were a low hematocrit (hazard ratio, 4.09; 95 percent confidence interval, 1.35 to 12.36) and a low body-mass index (hazard ratio, 3.23; 95 percent confidence interval, 0.90 to 11.53). Inclusion of pyrazinamide and ethambutol in the regimen (when susceptibility was confirmed) was associated with a favorable outcome (hazard ratio for treatment failure or death, 0.30; 95 percent confidence interval, 0.11 to 0.83). CONCLUSIONS: Community-based outpatient treatment of multidrug-resistant tuberculosis can yield high cure rates even in resource-poor settings. Early initiation of appropriate therapy can preserve susceptibility to first-line drugs and improve treatment outcomes

Time to Culture Conversion and Regimen Composition in Multidrug-Resistant Tuberculosis Treatment

Sputum cultures are an important tool in monitoring the response to tuberculosis treatment, especially in multidrug-resistant tuberculosis. There has, however, been little study of the effect of treatment regimen composition on culture conversion. Well-designed clinical trials of new anti-tuberculosis drugs require this information to establish optimized background regimens for comparison. We conducted a retrospective cohort study to assess whether the use of an aggressive multidrug-resistant tuberculosis regimen was associated with more rapid sputum culture conversion. We conducted Cox proportional-hazards analyses to examine the relationship between receipt of an aggressive regimen for the 14 prior consecutive days and sputum culture conversion. Sputum culture conversion was achieved in 519 (87.7%) of the 592 patients studied. Among patients who had sputum culture conversion, the median time to conversion was 59 days (IQR: 31–92). In 480 patients (92.5% of those with conversion), conversion occurred within the first six months of treatment. Exposure to an aggressive regimen was independently associated with sputum culture conversion during the first six months of treatment (HR: 1.36; 95% CI: 1.10, 1.69). Infection with human immunodeficiency virus (HR 3.36; 95% CI: 1.47, 7.72) and receiving less exposure to tuberculosis treatment prior to the individualized multidrug-resistant tuberculosis regimen (HR: 1.58; 95% CI: 1.28, 1.95) were also independently positively associated with conversion. Tachycardia (HR: 0.77; 95% CI: 0.61, 0.98) and respiratory difficulty (HR: 0.78; 95% CI: 0.62, 0.97) were independently associated with a lower rate of conversion. This study is the first demonstrating that the composition of the multidrug-resistant tuberculosis treatment regimen influences the time to culture conversion. These results support the use of an aggressive regimen as the optimized background regimen in trials of new anti-TB drugs

Retail ring-fencing of banks and its implications

Financial stability remains a key theme globally in view of the Euro zone debt crisis. The latest strategy by Germany and France is to ring-fence the crisis among the PIIGS countries (Portugal, Greece, Ireland, Italy and Spain). In the United Kingdom, the big four major banks have all responded to the Independent Commission of Bankings interim report key recommendation: ring-fencing retail operations into a separate subsidiary of any bank that wishes to operate in the United Kingdom. The report has clearly discussed the advantages and disadvantages of various types of subsidiarisation. Retail ring-fencing is considered a compromise as full subsidiarisation is too costly and operational subsidiarisation is too minimal. The Independent Commission of Banking published its final report on 12 September 2011. They recommended ring-fencing retail banking and a 10 per cent equity baseline. This article focuses on structural reforms of UK banks. It aims to address the question of financial stability from a wider European perspective. The first question is whether cross-border retail banking in the European Economic Area (EEA) is best served by branches or subsidiaries? The second question concerns the legality of setting up subsidiaries in the European Union (EU). Although there are no legal problems for UK-based banks setting up subsidiaries for their retail activities, there might be a legal hurdle for requiring foreign banks setting up subsidiaries in the United Kingdom. The third question concerns EU cross-border banking regulation and supervision. Are the passporting system and the home country supervisory approach still applicable in this post-financial crisis era? Many factors influence the choice of setting up branches or subsidiaries. However, the general position is that branches are more suited for wholesale/investment activities because of ease of funds transfer. Subsidiaries are more suitable for retail banking because of the limited liability principle and extensive local network. Effective cross-border banking must be accompanied by effective supervision and resolution regimes. The passporting concept under EU law and home country dominance are somewhat dated post-financial crisis. Host country control should play a dominant part in financial regulation, especially in the light of the importance of subsidiaries and the limited liability principle associated with them. The Icelandic bank crisis and collapse of Lehman Brothers International Europe illustrate the importance of host country control. Finally, the author argues that requiring banks to hold its retail activities in the form of subsidiaries in another European country is necessary to achieve financial stability. © 2012 Macmillan Publishers Ltd

Programmatic Management of Drug-Resistant Tuberculosis: An Updated Research Agenda.

There are numerous challenges in delivering appropriate treatment for multidrug-resistant tuberculosis (MDR-TB) and the evidence base to guide those practices remains limited. We present the third updated Research Agenda for the programmatic management of drug-resistant TB (PMDT), assembled through a literature review and survey

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

A genealogy of hacking

Hacking is now a widely discussed and known phenomenon, but remains difficult to define and empirically identify because it has come to refer to many different, sometimes incompatible, material practices. This paper proposes genealogy as a framework for understanding hacking by briefly revisiting Foucault’s concept of genealogy and interpreting its perspectival stance through the feminist materialist concept of the situated observer. Using genealogy as a theoretical frame a history of hacking will be proposed in four phases. The first phase is the ‘pre-history’ of hacking in which four core practices were developed. The second phase is the ‘golden age of cracking’ in which hacking becomes a self-conscious identity and community and is for many identified with breaking into computers, even while non-cracking practices such as free software mature. The third phase sees hacking divide into a number of new practices even while old practices continue, including the rise of serious cybercrime, hacktivism, the division of Open Source and Free Software and hacking as an ethic of business and work. The final phase sees broad consciousness of state-sponsored hacking, the re-rise of hardware hacking in maker labs and hack spaces and the diffusion of hacking into a broad ‘clever’ practice. In conclusion it will be argued that hacking consists across all the practices surveyed of an interrogation of the rationality of information techno-cultures enacted by each hacker practice situating itself within a particular techno-culture and then using that techno-culture to change itself, both in changing potential actions that can be taken and changing the nature of the techno-culture itself

Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

Background: Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.Result: An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner.Conclusions: Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis

Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

The clinical validity of drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line antituberculosis drugs is uncertain. In an individual patient data meta-analysis of 8955 patients with confirmed multidrug-resistant tuberculosis, DST results for these drugs were associated with treatment outcome

The Tuberculosis Network European Trials group (TBnet) ERS Clinical Research Collaboration: addressing drug-resistant tuberculosis through European cooperation

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