Factors associated with screening failure and study withdrawal in multidrug-resistant TB.

SETTING: Multidrug-resistant TB (MDR-TB) clinical trial in Lima, Peru and Cape Town, South Africa.OBJECTIVE: To identify baseline factors associated with screening failure and study withdrawal in an MDR-TB clinical trial.DESIGN: We screened patients for a randomized, blinded, Phase II trial which assessed culture conversion over the first 6 months of treatment with varying doses of levofloxacin plus an optimized background regimen (ClinicalTrials.gov: NCT01918397). We identified factors for screening failure and study withdrawal using Poisson regression to calculate prevalence ratios and Cox proportional hazard regression to calculate hazard ratios. We adjusted for factors with P < 0.2.RESULTS: Of the 255 patients screened, 144 (56.5%) failed screening. The most common reason for screening failure was an unsuitable resistance profile on sputum-based molecular susceptibility testing (n = 105, 72.9%). No significant baseline predictors of screening failure were identified in the multivariable model. Of the 111 who were enrolled, 33 (30%) failed to complete treatment, mostly for non-adherence and consent withdrawal. No baseline factors predicted study withdrawal in the multivariable model.CONCLUSION: No baseline factors were independently associated with either screening failure or study withdrawal in this secondary analysis of a MDR-TB clinical trial.

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil.

BACKGROUND: The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. METHODS: Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. RESULTS: Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). CONCLUSIONS: This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Effects of altitude versus economic status on birth weight and body shape at birth.

The compelling evidence linking small size at birth with later cardiovascular disease has renewed and amplified a clinical and scientific interest in the determinants of fetal growth. Although the effects of maternal nutrition on fetal growth have been extensively studied, comparatively little is known about the effects of maternofetal hypoxia. This study tested the hypothesis that in highland regions, high altitude rather than maternal economic status is associated with reduced and altered fetal growth by investigating the effects of high altitude versus economic status on birth weight and body shape at birth in Bolivia. Bolivia is geographically and socioeconomically unique. It contains several highland (>3500 m above sea level) and lowland (<500 m) cities that are inhabited by very economically divergent populations. Birth weight, body length, and head circumference were compared between a high- (n = 100) and low- (n = 100) income region of La Paz (3649 m; largest high-altitude city) and a high- (n = 100) and low- (n = 100) income region of Santa Cruz (437 m; largest low-altitude city). In addition, the frequency distribution across the continuum of birth weights was plotted for babies born from high- and low-income families in La Paz and Santa Cruz. Mean birth weights were lower in babies from La Paz than in babies from Santa Cruz in both high- and low-income groups. The cumulative frequency curve across all compiled birth weights was shifted to the left in babies from La Paz compared with those from Santa Cruz, regardless of economic status. The frequency of low birth weight (<2500 g) was higher in babies from La Paz than from Santa Cruz in both high- and low-income groups. In addition, at high altitude but not at low altitude, high income was associated with an increase in the head circumference:birth weight ratio. These findings suggest that high altitude rather than economic status is associated with low birth weight and altered body shape at birth in babies from Bolivia.

Prognostic signs in the surgical management of plexiform neurofibroma: the Children's Hospital of Philadelphia experience, 1974-1994.

OBJECTIVES: To estimate the rate of progression of plexiform neurofibroma after surgery and to identify prognostic factors that predict progression. STUDY DESIGN: A retrospective review of the inpatient and outpatient records of 121 patients, who had 302 procedures on 168 tumors over a 20-year period at a single large pediatric referral center. Data on age, location, indication for surgery, and extent of resection was analyzed for prognostic significance. RESULTS: The overall freedom from progression was 54%. Children < 10 years old had a shorter interval of tumor control than older children (p = 0.0004). Tumors of the head/neck/face fared worse than tumors of the extremities (p = 0.0003). Less extensive resection predicted shorter interval to progression (p < 0.0001). Indication for surgery was not of prognostic importance. In multivariable analysis older age and location in the extremities were predictors of a better outcome. CONCLUSIONS: Tumor progression is a serious problem for children with plexiform neurofibroma. Younger children, children with tumors of the head/neck/face, and tumors that cannot be nearly completely removed are at particular risk. These data may be useful in helping clinicians decide which patients and which tumors are most likely to benefit from surgical intervention.

Cognitive deficits in long-term survivors of childhood medulloblastoma and other noncortical tumors: age-dependent effects of whole brain radiation.

Twenty-four children, aged 1.5-20 yr at diagnosis, with noncortical brain tumors, primarily medulloblastoma, have been followed for 3-4 yr for intellectual status. All the children received craniospinal irradiation, and 19 of 24 received chemotherapy as well. For the group as a whole. Full Scale IQ fell from 104 at baseline to 91 at final follow-up. Children younger than 7 yr at diagnosis showed a significant decrease in IQ as early as year 1, and all changes from baseline to years 3 and 4 were significant. In contrast, children older than 7 yr at diagnosis did not show a significant IQ change from baseline to year 3 or 4. The Spearman correlation coefficient between IQ change and age at diagnosis from baseline to year 4 was 0.57 (P = 0.003). This study supports the hypothesis that children treated with whole brain radiation at a younger age have more severe cognitive impairment than those treated at a later age. Limitations in sample size and duration of observations do not permit us to identify whether a true plateau occurs 2-4 yr after irradiation versus a continued progressive decline in intellectual performance. Moreover, we cannot at this time distinguish between a true dementing process versus failure to acquire new cognitive skills at a rate comparable to age-matched peers.

Disruption of foraging by argentine ants,Iridomyrmex humilis (mayr) (hymenoptera: Formicidae), in citrus trees through the use of semiochemicals and related chemicals.

Foraging in trees by the Argentine ant,Iridomyrmex humilis (Mayr), was disrupted by a variety of synthetic chemicals, with the most effective chemical being farnesol. Testing of substrates for presentation of the disruptant chemicals gave some success with rubber or Tygon tubing, although best results were obtained through incorporation of the material into Stikem, which was then banded around tree trunks. Amounts of farnesol used for effective, long residual ant control were between 0.8 and 2 g per tree.