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.     

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.     

Score for Neonatal Acute Physiology–II and Neonatal Pain Predict Corticospinal Tract Development in Premature Newborns

Premature infants are at risk for adverse motor outcomes, including cerebral palsy and developmental coordination disorder. The purpose of this study was to examine the relationship of antenatal, perinatal, and postnatal risk factors for abnormal development of the corticospinal tract, the major voluntary motor pathway, during the neonatal period. In a prospective cohort study, 126 premature neonates (24-32 weeks' gestational age) underwent serial brain imaging near birth and at term-equivalent age. With diffusion tensor tractography, mean diffusivity and fractional anisotropy of the corticospinal tract were measured to reflect microstructural development. Generalized estimating equation models examined associations of risk factors on corticospinal tract development. The perinatal risk factor of greater early illness severity (as measured by the Score for Neonatal Acute Physiology–II [SNAP-II]) was associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.02), even after correcting for gestational age at birth and postnatal risk factors (P = 0.009). Consistent with previous findings, neonatal pain adjusted for morphine and postnatal infection were also associated with a slower rise in fractional anisotropy of the corticospinal tract (P = 0.03 and 0.02, respectively). Lessening illness severity in the first hours of life might offer potential to improve motor pathway development in premature newborns.     

Planning and implementation of community oral health programs for caries management in children

Tooth decay or cavities (dental caries) can have a significant impact on children's quality of life, causing pain, infection, and other problems in the oral environment. Good oral health is a fundamental element of good general health for children, yet dental caries is still prevalent among children in many countries. Dental caries is well-understood, and effective prevention is an attainable goal. Dental professionals should actively engage with communities--in particular, the underprivileged--to identify dental caries problems and implement appropriate and effective community oral health programs (COHPs) to improve oral health and reduce oral health inequalities. This paper discusses COHPs as well as the steps involved in caries prevention for children. These steps cannot ensure the success of every COHP, but they are helpful for developing, integrating, expanding, and enhancing them. The effectiveness of COHPs for the prevention of caries in children varies from country to country, according to cultural, social, economic, and health care settings. Careful consideration of the local situation is required when selecting the elements of COHPs.     

Complex karyotypes confer a poor survival in adult acute myeloid leukemia with unfavorable cytogenetic abnormalities

Cytogenetics represents the most valuable predictor for a poor outcome in patients with acute myeloid leukemia (AML), but it encompasses a heterogeneous patient population who might have diverse pathogenesis and clinical courses. In particular, the significance of complex chromosome aberrations within this cohort has seldom been addressed before. We analyzed 48 AML patients with adverse-risk cytogenetics in this study. The complex karyotype (three or more numerical/structural cytogenetic changes; 29 patients) was found to occur more frequently among the elderly than a noncomplex adverse karyotype (19 patients; median age, 71 vs. 48; P = 0.005). The patients' performance status was the sole independent factor determining the complete remission rate among patients receiving standard induction chemotherapy. On survival analysis, two factors independently predicted a longer overall survival: noncomplex karyotypes [vs. complex karyotypes, hazard ratio (HR) 0.434, 95% confidence interval (CI) 0.189-0.994, P = 0.048] and achievement of complete remission [(CR) vs. CR not reached, HR 0.170, 95% CI 0.051-0.572, P = 0.004)]. In conclusion, among AML patients with adverse cytogenetics, complex chromosomal aberrations occurred more frequently among the elderly and predicted a poor outcome. These patients should be considered as a unique entity and be separated from those with a noncomplex adverse cytogenetic change. Exploring the underlying mechanisms of leukemogenesis could improve the therapeutic outcome for this group of patients.     

High levels of the p53 inhibitor MDM4 in head and neck squamous carcinomas

The p53 tumor suppressor is mutated in most human tumors. MDM2, a well-known inhibitor of p53, is overexpressed in a large number of tumors, suggesting that increased levels of MDM2 also contribute to tumorigenesis. A novel p53 inhibitor, MDM4, was more recently identified. The role of MDM4 in cancer development is not well understood. We set out to examine the levels of MDM4 by immunohistochemistry in head and neck squamous carcinomas (HNSC) to ask whether high MDM4 levels could contribute to its development and progression. In addition, MDM2 and p53 levels were examined to identify overlapping expression patterns. MDM4 is present at high levels in 50% of HNSC. In addition, overexpression of MDM2 was detected in 80% of tumors, many of which were also positive for MDM4. A subset of tumors displayed high levels of all 3 proteins. Sequencing of the p53 gene revealed that tumors with positive immunoreactivity for MDM2 or MDM4, some of which also had high levels of p53, did not carry mutations in this gene. Thus, the detection of p53 by immunohistochemistry was not synonymous with the presence of p53 mutations. Expression of both MDM2 and MDM4 in tumors without p53 mutations strongly suggests that MDM2 and MDM4 inhibit the activity of this tumor suppressor in HNSC.