Effect of antituberculosis drug resistance on response to treatment and outcome in adults with tuberculous meningitis

BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to 1 or more antituberculosis drugs is an increasingly common clinical problem, although the impact on outcome is uncertain. METHODS: We performed a prospective study of 180 Vietnamese adults admitted consecutively for TBM. M. tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and was tested for susceptibility to first-line antituberculosis drugs. Presenting clinical features, time to CSF bacterial clearance, clinical response to treatment, and 9-month morbidity and mortality were compared between adults infected with susceptible and those infected with drug-resistant organisms. RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1 antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and rifampicin. Isoniazid and/or streptomycin resistance was associated with slower CSF bacterial clearance but not with any differences in clinical response or outcome. Combined isoniazid and rifampicin resistance was strongly predictive of death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and was independently associated with human immunodeficiency virus infection. CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental effect on the outcome of TBM when patients are treated with first-line antituberculosis drugs, but combined isoniazid and rifampicin resistance is strongly predictive of death.     

Critical care trainees’ career goals and needs: A Canadian survey

Designing an effective training program requires information regarding the needs, capability and aspirations of its users. Prompted by the low career satisfaction levels shown by critical care medicine (CCM) clinicians in a previous survey, and a lack of data regarding the career goals of CCM trainees in Canadian training programs, this survey-based study, which had an exemplary response rate of 85%, examined career expectations, and the barriers and enablers to career goals among individuals from adult and pediatric CCM programs across Canada.

BACKGROUND:

For training programs to meet the needs of trainees, an understanding of their career goals and expectations is required.

OBJECTIVES:

Canadian critical care medicine (CCM) trainees were surveyed to understand their career goals in terms of clinical work, research, teaching, administration and management; and to identify their perceptions regarding the support they need to achieve their goals.

METHODS:

The online survey was sent to all trainees registered in a Canadian adult or pediatric CCM program. It documented the participants’ demographics; their career expectations; the perceived barriers and enablers to achieve their career goals; and their perceptions relating to their chances of developing a career in different areas.

RESULTS:

A response rate of 85% (66 of 78) was obtained. The majority expected to work in an academic centre. Only approximately one-third (31%) estimated their chances of obtaining a position in CCM as >75%. The majority planned to devote 25% to 75% of their time performing clinical work and <25% in education, research or administration. The trainees perceived that there were limited employment opportunities. Networking and having specialized expertise were mentioned as being facilitators for obtaining employment. They expressed a need for more protected time, resources and mentorship for nonclinical tasks during training.

CONCLUSION:

CCM trainees perceived having only limited support to help them to achieve their career goals and anticipate difficulties in obtaining successful employment. They identified several gaps that could be addressed by training programs, including more mentoring in the areas of research, education and administration.     

Patient selection and the volume effect in pancreatic surgery: unequal benefits?

Background

The volume effect in pancreatic surgery is well established. Regionalization to high-volume centres has been proposed. The effect of this proposal on practice patterns is unknown.

Methods

Retrospective review of pancreatectomy patients in the Nationwide Inpatient Sample 2004–2011. Inpatient mortality and complication rates were calculated. Patients were stratified by annual centre pancreatic resection volume (low <5, medium 5–18, high >18). Multivariable regression model evaluated predictors of resection at a high-volume centre.

Results

In total, 129 609 patients underwent a pancreatectomy. The crude inpatient mortality rate was 4.3%. 36.0% experienced complications. 66.5% underwent a resection at high-volume centres. In 2004, low-, medium- and high-volume centres resected 16.3%, 24.5% and 59.2% of patients, compared with 7.6%, 19.3% and 73.1% in 2011. High-volume centres had lower mortality (P < 0.001), fewer complications (P < 0.001) and a shorter median length of stay (P < 0.001). Patients at non-high-volume centres had more comorbidities (P = 0.001), lower rates of private insurance (P < 0.001) and more non-elective admissions (P < 0.001).

Discussion

In spite of a shift to high-volume hospitals, a substantial cohort still receives a resection outside of these centres. Patients receiving non-high-volume care demonstrate less favourable comorbidities, insurance and urgency of operation. The implications are twofold: already disadvantaged patients may not benefit from the high-volume effect; and patients predisposed to do well may contribute to observed superior outcomes at high-volume centres.     

Rankings versus reality in pancreatic cancer surgery: a real-world comparison

Background

Patients are increasingly confronted with systems for rating hospitals. However, the correlations between publicized ratings and actual outcomes after pancreatectomy are unknown.

Methods

The Massachusetts Division of Health Care Finance and Policy Hospital Inpatient Discharge Database was queried to identify pancreatic cancer resections carried out during 2005–2009. Hospitals performing fewer than 10 pancreatic resections in the 5-year period were excluded. Primary outcomes included mortality, complications, median length of stay (LoS) and a composite outcomes score (COS) combining primary outcomes. Ranks were determined and compared for: (i) volume, and (ii) ratings identified from consumer-directed hospital ratings including the US News & World Report (USN), Consumer Reports, Healthgrades and Hospital Compare. An inter-rater reliability analysis was performed and correlation coefficients (r) between outcomes and ratings, and between rating systems were calculated.

Results

Eleven hospitals in which a total of 804 pancreatectomies were conducted were identified. Surgical volume correlated with overall outcome, but was not the strongest indicator. The highest correlation referred to that between USN rank and overall outcome. Mortality was most strongly correlated with Healthgrades ratings (r = 0.50); however, Healthgrades ratings demonstrated poorer correlations with all other outcomes. Consumer Reports ratings showed inverse correlations.

Conclusions

The plethora of publicly available hospital ratings systems demonstrates heterogeneity. Volume remains a good but imperfect indicator of surgical outcomes. Further systematic investigation into which measures predict quality outcomes in pancreatic cancer surgery will benefit both patients and providers.     

Caffeine alters resting‐state functional connectivity measured by blood oxygenation level‐dependent MRI

This study aimed to investigate the pharmacological effect of caffeine on functional connectivity measured by resting‐state blood oxygenation level‐dependent (BOLD) MRI in the motor cortex, visual cortex and default mode network (DMN). The protocols and procedures of the study were reviewed and approved by the Institutional Review Board of our institution. On a 3‐T clinical MR system, 20 healthy volunteers underwent imaging before and after oral ingestion of a 200‐mg over‐the‐counter caffeine pill (data from three individuals were excluded from further analysis because of excessive motion). The demographics of the remaining participants were as follows: female/male, 8/9; age, 21–35 years; non‐habitual caffeine consumers over the past 6 months. Functional connectivity was calculated using the general linear model, assessed in terms of connected area (voxels) and statistical significance (Student t‐values), and correlated with changes in regional cerebral blood flow as measured by arterial spin labeling MRI. Per‐subject data analysis showed that caffeine decreased functional connectivity in the motor/visual cortices, but its effects on DMN varied among subjects. Correlation analysis of the changes in functional connectivity and regional blood flow suggested that the effect of caffeine on BOLD functional connectivity was predominantly neural (motor/visual cortices) and partly vascular (DMN). Group analysis showed that, after caffeine ingestion, DMN involved more attentional networks, and more extrastriate areas were integrated into the functional connectivity of the visual cortex, which may be associated with the known pharmacological effect of caffeine in elevating alertness. Caffeine consumption should thus be considered in the experimental design and data interpretation of functional connectivity studies using resting‐state BOLD MRI. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

The Role of Exercise and Physical Activity in Weight Loss and Maintenance

This review explores the role of physical activity (PA) and exercise training (ET) in the prevention of weight gain, initial weight loss, weight maintenance, and the obesity paradox. In particular, we will focus the discussion on the expected initial weight loss from different ET programs, and explore intensity/volume relationships. Based on the present literature, unless the overall volume of aerobic ET is very high, clinically significant weight loss is unlikely to occur. Also, ET also has an important role in weight regain after initial weight loss. Overall, aerobic ET programs consistent with public health recommendations may promote up to modest weight loss (~ 2 kg), however the weight loss on an individual level is highly heterogeneous. Clinicians should educate their patients on reasonable expectations of weight loss based on their physical activity program and emphasize that numerous health benefits occur from PA programs in the absence of weight loss.     

Regulation of memory CD4 T-cell pool size and function by natural killer T cells in vivo

To develop more effective vaccines and strategies to regulate chronic inflammatory diseases, it is important to understand the mechanisms of immunological memory. Factors regulating memory CD4⁺ T helper (Th)-cell pool size and function remain unclear, however. We show that activation of type I invariant natural killer T (iNKT) cells with glycolipid ligands and activation of type II natural killer T (NKT) cells with the endogenous ligand sulfatide induced dramatic proliferation and expansion of memory, but not naïve, CD4 T cells. NKT cell-induced proliferation of memory Th1 and Th2 cells was dependent largely on the production of IL-2, with Th2-cell proliferation also affected by loss of IL-4. Type II NKT cells were also required for efficient maintenance of memory CD4 T cells in vivo. Activation of iNKT cells resulted in up-regulation of IFN-γ expression by memory Th2 cells. These IFN-γ–producing memory Th2 cells showed a decreased capability to induce Th2 cytokines and eosinophilic airway inflammation. Thus, activated NKT cells directly regulate memory CD4 T-cell pool size and function via the production of cytokines in vivo.     

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

Background

In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial.

Design and Methods

Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression.

Results

Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis.

Conclusions

Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00020943","term_id":"NCT00020943"}}NCT00020943.