Targeted Drug-Resistance Testing Strategy for Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008

Running head: Targeted Drug-Resistance Testing Strategy for MDR T

Scale-up of Multidrug-Resistant Tuberculosis Laboratory Services, Peru

One-sentence summary for table of contents: Strategic design and implementation of these services is feasible in resource-poor settings

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

Implementing Evidence-Based Alcohol Interventions in a Resource-Limited Setting: Novel Delivery Strategies in Tomsk, Russia

Effective implementation of evidence-based interventions in “real-world” settings can be challenging. Interventions based on externally valid trial findings can be even more difficult to apply in resource-limited settings, given marked differences—in provider experience, patient population, and health systems—between those settings and the typical clinical trial environment. Under the auspices of the Integrated Management of Physician-Delivered Alcohol Care for Tuberculosis Patients (IMPACT) study, a randomized, controlled effectiveness trial, and as an integrated component of tuberculosis treatment in Tomsk, Russia, we adapted two proven alcohol interventions to the delivery of care to 200 patients with alcohol use disorders. Tuberculosis providers performed screening for alcohol use disorders and also delivered naltrexone (with medical management) or a brief counseling intervention either independently or in combination as a seamless part of routine care. We report the innovations and challenges to intervention design, training, and delivery of both pharmacologic and behavioral alcohol interventions within programmatic tuberculosis treatment services. We also discuss the implications of these lessons learned within the context of meeting the challenge of providing evidence-based care in resource-limited settings. (Harv Rev Psychiatry 2012;20:58–67.

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

Immune and hemorheological changes in Chronic Fatigue Syndrome

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients. METHODS: Flow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56(dim)CD16(+ )and CD56(bright)CD16(-)) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed. RESULTS: CFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56(bright)CD16(- )NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56(dim)CD16(+ )NK cells were similar between the two groups. CONCLUSION: These results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Long-term Follow-up for Multidrug-resistant Tuberculosis

Patients treated in Peru for multidrug-resistant tuberculosis (MDR-TB) were followed-up for a median of 67 months. Among 86 patients considered cured after completion of treatment, 97 % remain healthy; 1 patient relapsed. Employment increased from 34 % before treatment to 71%. We observed favorable long-term outcomes among MDR-TB patients. Increasing awareness of the rising global rates of multidrug-resistant tuberculosis (MDR-TB) has led to a concerted international effort to confront this disease, particularly in countries with a high incidence of TB (1–3). Nonetheless, despite cure rates>80 % in some programs, MDR-TB patients tend to have chronic disease and require prolonged therapy. Little is known about the long-term follow-up of patients treated for MDR-TB, including rates of relapse and chronic disability among cured persons. Among patients treated for pansusceptible TB, chronic disability caused by pulmonary sequelae and malnutrition can be substantial (4). Given the prolonged nature of MDR-TB, one might expect higher rates of chronic disability among patients with drugresistant TB compared with those with pansusceptible TB. To explore these questions, we conducted long-term follow-up, defined as follow-up for a minimum of 4 years after treatment was initiated, of MDR-TB patients who received individualized therapy in Lima, Peru (1). The Study We performed a retrospective study among all patients who initiated individualized, community-based MDR-TB therapy from August 1, 1996, to March 1, 2000. The details of patient identification, enrollment, and treatment are described elsewhere (5). Patients were resistant to a median of 5 drugs (range 2–9). Regimens generally included at least 5 drugs to which the infecting isolate was susceptible, and treatment duration was 18–24 months. Routine follow-up after completion of MDR-TB therap

Long-term Follow-up for Multidrug-resistant Tuberculosis

Patients treated in Peru for multidrug-resistant tuberculosis (MDR-TB) were followed-up for a median of 67 months. Among 86 patients considered cured after completion of treatment, 97% remain healthy; 1 patient relapsed. Employment increased from 34% before treatment to 71%. We observed favorable long-term outcomes among MDR-TB patients