Validation of an Magnetic Resonance Imaging Acquisition and Review Protocol for Alzheimer's Disease and Related Disorders

PurposeMagnetic resonance imaging (MRI) of the brain allows for the identification of structural lesions typical of Alzheimer's disease (AD), the main cause of dementia. However, to have a clinical impact, it is imperative that acquisition and reporting of this MRI-based evidence be standardized, ensuring the highest possible reliability and reproducibility. Our objective was to validate a systematic radiological MRI acquisition and review process in the context of AD.MethodsWe included 100 individuals with a suspicion of dementia due to AD for whom MRI were acquired using our proposed protocol of clinically achievable acquisitions and used a unified reading grid to gather semi-quantitative evidence guiding diagnostic. MRIs were read by 3 raters with different experience levels. Interrater reliability was measured using Cohen's kappa statistic.ResultsInterrater reliability average for lesions occupying space, hemorrhage, or ischemia, was respectively 0.754, 0.715, and 0.501. Average reliability of white matter hyperintensity burden (Fazekas), global cortical atrophy, and temporal lobe atrophy (Scheltens) scales was 0.687, 0.473, and 0.621 (right)/0.599 (left), respectively. The kappas for regional cortical atrophy (frontal, parietal, occipital, temporal, and posterior cingulum) varied from 0.281–0.678. The average MRI reading time varied between 1.43-5.22 minutes.ConclusionsThe presence of space occupying lesions, hemorrhagic or ischemic phenomena, and radiological scales have a good interrater reproducibility in MRI. Coupled with standardized acquisitions, such a protocol should be used when evaluating possible dementias, especially those due to probable AD.     

Implementation of human biomonitoring in the Dehcho region of the Northwest Territories,Canada (2016–2017)

Background

Human biomonitoring represents an important tool for health risk assessment, supporting the characterization of contaminant exposure and nutrient status. In communities where country foods (locally harvested foods: land animals, fish, birds, plants) are integrated in the daily diet, as is the case in remote northern regions where food security is a challenge, such foods can potentially be a significant route of contaminant exposure. To assess this issue, a biomonitoring project was implemented among Dene/Métis communities of the Dehcho region of the Northwest Territories, Canada.

Methods

Participants completed dietary surveys (i.e., a food frequency questionnaire and 24-h recall) to estimate food consumption patterns as well as a Health Messages Survey to evaluate the awareness and perception of contaminants and consumption notices. Biological sampling of hair, urine and blood was conducted. Toxic metals (e.g., mercury, lead, cadmium), essential metals (e.g., copper, nickel, zinc), fatty acids, and persistent organic pollutants (POPs) were measured in samples.

Results

The levels of contaminants in blood, hair and urine for the majority of participants were below the available guidance values for mercury, cadmium, lead and uranium. However, from the 279 participants, approximately 2% were invited to provide follow up samples, mainly for elevated mercury level. Also, at the population level, blood lead (GM: 11 μg/L) and blood cadmium (GM: 0.53 μg/L) were slightly above the Canadian Health Measures Survey data. Therefore, although country foods occasionally contain elevated levels of particular contaminants, human exposures to these metals remained similar to those seen in the Canadian general population. In addition, dietary data showed the importance and diversity of country foods across participating communities, with the consumption of an average of 5.1% of total calories from wild-harvested country foods.

Conclusion

This project completed in the Mackenzie Valley of the Northwest Territories fills a data gap across other biomonitoring studies in Canada as it integrates community results, will support stakeholders in the development of public health strategies, and will inform environmental health issue prioritization.

     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Attention Deficits and Divorce

Objective:

Building on previous work on the role of attention deficits associated with the regulation of executive control in psychiatric disorders, we examine whether these attention deficits are related to an interpersonal disturbance, the experience of divorce.

Method:

Attentional capacities of 95 randomly selected couples from the general population were measured with a well-established task, the Attentional Network Task, which assesses the efficiency of 3 attention networks (that is, alerting, orienting, and executive control). Among the 190 participants, 32 had experienced a divorce in the past. ANCOVAs were used to compare divorced people in marital or cohabiting unions with people in first unions in their performance on this purely cognitive task.

Results:

Our findings indicate that divorced people who are currently living in a cohabiting relationship show significantly lower executive control than other adults living as couples, after controlling for sex, age, income, and education. This subgroup of divorced people not only exhibit greater difficulty in responding to some stimuli while ignoring irrelevant ones but also manifest cognitive deficits in conflict resolution.

Conclusions:

This study highlights the links between attention and the long-term maintenance of intimate relationships. Our results may have important implications for the identification of people at risk for divorce.     

Gonadotropin-releasing hormone pulsatile administration restores luteinizing hormone pulsatility and normal testosterone levels in males with hyperprolactinemia

Hyperprolactinemia in men is frequently associated with hypogonadism. Normalization of serum PRL levels is generally associated with an increase in serum testosterone (T) to normal. To determine the mechanism of the inhibitory effect of hyperprolactinemia on the hypothalamic-pituitary-gonadal axis, we studied the effect of intermittent pulsatile GnRH administration on LH pulsatility and T levels in four men with prolactinomas. All patients had high PRL values (100-3000 ng/ml), low LH (mean +/- SEM, 2.2 +/- 0.1 mIU/ml), and low T values (2.3 +/- 0.3 ng/ml), with no other apparent abnormality of pituitary function. GnRH was administered iv using a pump delivering a bolus dose of 10 micrograms every 90 min for 12 days. No LH pulses were detected before treatment. Pulsatile GnRH administration resulted in a significant increase in basal LH levels (6.7 +/- 0.6 mIU/ml; P less than 0.001) and restored LH pulsatility. In addition, T levels increased significantly to normal values in all patients (7.8 +/- 0.4 ng/ml; P less than 0.001) and were normal or supranormal as long as the pump was in use, although PRL levels remained elevated. These data, therefore, suggest that hyperprolactinemia produces hypogonadism primarily by interfering with pulsatile GnRH release.     

Clinical features and outcome in childhood T-cell leukemia-lymphoma according to stage of thymocyte differentiation: a Pediatric Oncology Group Study

The immunophenotypes of lymphoblasts from children with newly diagnosed T-cell acute lymphoid leukemia (T-ALL, n = 101) or T-cell non-Hodgkin lymphoma (T-NHL, n = 31) were analyzed to correlate stage of thymocyte differentiation with clinical features and outcome. The 67 boys and 34 girls with T-ALL were 1 month to 18 years old (median, 8 years) with leukocyte counts ranging from 2 to 810 x 10(9)/L (median, 55 x 10(9)/L). Eighteen of these patients were black, and 70 had a mediastinal mass. Twenty-six boys and five girls with a median age of 9 years (range, 1 to 20 years) had T-NHL. Seven of these patients were black, and 24 had a mediastinal mass. The distributions of thymocyte developmental stages (early [CD7+], intermediate [CD1+ and/or CD4+ and/or CD8+], and mature [CD3+]) in cases of T-ALL and T-NHL were significantly different: 34%, 43%, and 23% v 6%, 62%, and 32% (P = .02). A comparison of the patients' clinical features according to the maturational stage of thymocytes failed to disclose significant differences in the majority of characteristics studied. However, patients with mature-stage T-NHL, with or without the addition of subjects with mature-stage T-ALL, were less likely to have a mediastinal mass (P = .02 for both comparisons). Those with intermediate-stage T-cell malignancy (T-ALL and T-NHL combined) were the subgroup most likely to have a mediastinal mass (P = .01). Response to remission induction therapy was significantly worse in the T-ALL subgroup with an early-stage phenotype: a failure rate of 21% v 0% and 6% for the two more differentiated phenotypic subgroups (P = .007). Event-free survival was not affected by thymocyte maturational stage in cases of either T-ALL or T-NHL. Despite evidence of clinical heterogeneity among the maturational stages of T-cell malignancies in children, these developmental subdivisions do not appear to be critical determinants of outcome once remission is achieved. We conclude that such phenotypes need not be included in the stratification plans for clinical trials using common induction treatment.     

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady- state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.