Analgesic treatments in people with dementia - how safe are they? A systematic review

Introduction: People with dementia may be unable to verbally express pain and suffer from untreated pain. Use of analgesics in people with dementia has increased during the last decade, in particular opioid analgesics with high potential for adverse effects.

Areas covered: This article presents a systematic review of the current evidence for safety and tolerability of analgesic drugs from randomized controlled trials in people with dementia. Relevant trials were identified by a literature search in the EMBASE, MEDLINE, and Cochrane databases from inception to November 2018. The search included the main terms ‘dementia’ and ‘analgesic’ or their subterms, and was filtered to limit results to clinical trials.

Expert opinion: Although pain treatment is increasingly recognized as an important clinical issue in people with advanced dementia, there is currently a lack of evidence to support safety evaluations of commonly used analgesics in this group. To inform treatment decisions and enable care providers to appropriately monitor patients at risk of adverse effects, it is necessary to conduct well-designed clinical trials to investigate the relative efficacy and safety of analgesics in people with dementia, with particular emphasis on harmful effects of long-term opioid use as well as short-term use of nonsteroidal anti-inflammatory drugs.     

Can a threshold for 11‐nor‐9‐carboxy‐Δ9 ‐tetrahydrocannabinol in hair be derived when its respective concentration in blood serum indicates regular use?

A 100 μg/L or higher concentration of 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinol (THC‐COOH) in blood serum is generally assumed to be associated with regular and/or heavy use of cannabis. At present, determination of the extent of cannabis use by means of the concentration of THC‐COOH in hair has not been assessed. Therefore, we aimed at establishing a threshold for THC‐COOH concentrations in hair to prove frequent consumption by comparing THC‐COOH concentrations in 129 corresponding serum and hair samples, respectively. The concentration of THC‐COOH in the serum was analyzed by gas chromatography–mass spectrometry and in the hair by liquid chromatography–tandem mass spectrometry. Data were statistically evaluated using receiver operating characteristic curves and contingency tables. Our results suggest that a THC‐COOH concentration of ≥4.2 pg/mg in hair was always accompanied by a THC‐COOH concentration of at least 100 μg/L in blood serum. Should this be confirmed by further studies of a larger study population, a hair concentration of 4.2 pg/mg THC‐COOH can be set as a threshold to predict regular and/or heavy consumption of cannabis even if no corresponding blood sample is available for analysis.     

Automated morphometric magnetic resonance imaging analysis for the detection of periventricular nodular heterotopia

Purpose: To describe a novel magnetic resonance imaging (MRI) postprocessing technique for the detection of periventricular nodular heterotopia (PNH) and to evaluate its diagnostic value. The method is a further development of voxel‐based morphometric analysis with focus on a region of interest around the lateral ventricles to increase the sensitivity and specificity for automated detection of abnormally located gray matter in this area. Methods: T₁‐weighted MRI volume data sets were normalized and segmented in statistical parametric mapping (SPM 5 software), and the distribution of gray matter was compared to a normal database. As a new approach, individual masks derived from segmentation of the lateral ventricles were used to restrict the search for ectopic gray matter to the periventricular area. PNH were automatically detected by localizing the maximum deviation from the normal database in this area, provided that the z‐score exceeded a certain threshold. The optimal z‐score threshold for maximum sensitivity and specificity was determined by a receiver operating characteristic (ROC) curve analysis. The method was applied in 40 patients with PNH and 400 controls. Key Findings: PNH were detected in 37 of 40 patients, and false positives were found in 34 of 400 controls, amounting to 92.5% sensitivity and 91.5% specificity. In 17 of the patients in whom PNH could be identified, these lesions had been overlooked in the past, and in 8 patients even in the high‐resolution MRI subsequently used for postprocessing. Significance: The results suggest that automated morphometric MRI analysis with focus on ectopic gray matter in the periventricular areas facilitates the evaluation of MRI data and increases the sensitivity for the detection of PNH.     

Clinical,histological and immunpathological findings in 32 patients with dermatitis herpetiformis Duhring

Background: Dermatitis herpetiformis is a chronic severely pruritic dermatosis. It is a cutaneous manifestation of celiac disease. The aim of our study was to collect clinical, histological and immunopathological data on patients who were treated in the University Departments of Dermatology in Würzburg and Lübeck from 1996 to 2008. Patients and Methods: We retrospectively analyzed 32 patients. Only patients with positive findings on direct immunofluorescence microscopy were included in this study. Results: All patients demonstrated skin lesions in the predilection areas of knees, elbows, gluteal region and scalp. The male to female ratio was 1.5 : 1 and the average age was 43 years. The interval between the first symptoms and diagnosis ranged from 6 weeks to 20 years. Direct immunofluorescence microscopy showed that granular IgA deposits were more often found continuously along the dermal‐epidermal junction rather than focally in the tips of the dermal papillae. Results of small intestinal biopsies were available from 29 patients and confirmed the presence of celiac disease in all cases. None of the patients reported gastrointestinal symptoms. IgA antibodies against tissue transglutaminase and epidermal transglutaminase were found in 88% and 94% of patient sera, respectively. Conclusions: The detection of IgA autoantibodies against epidermal transglut‐aminase is the most sensitive serological test in the diagnosis of dermatitis herpetiformis. Our observations confirm that patients with dermatitis herpetiformis usually do not demonstrate apparent gastrointestinal symptoms.     

Racism,Health Status,and Birth Outcomes: Results of a Participatory Community-Based Intervention and Health Survey

Many community-based participatory research (CBPR) partnerships address social determinants of health as a central consideration. However, research studies that explicitly address racism are scarce in the CBPR literature, and there is a dearth of available community-generated data to empirically examine how racism influences health disparities at the local level. In this paper, we provide results of a cross-sectional, population-based health survey conducted in the urban areas of Genesee and Saginaw Counties in Michigan to assess how a sustained community intervention to reduce racism and infant mortality influenced knowledge, beliefs, and experiences of racism and to explore how perceived racism is associated with self-rated health and birth outcomes. We used ANOVA and regression models to compare the responses of intervention participants and non-participants as well as African Americans and European Americans (N = 629). We found that intervention participants reported greater acknowledgment of the enduring and differential impact of racism in comparison to the non-intervention participants. Moreover, survey analyses revealed that racism was associated with health in the following ways: (1) experiences of racial discrimination predicted self-rated physical health, mental health, and smoking status; (2) perceived racism against one’s racial group predicted lower self-rated physical health; and (3) emotional responses to racism-related experiences were marginally associated with lower birth-weight births in the study sample. Our study bolsters the published findings on perceived racism and health outcomes and highlights the usefulness of CBPR and community surveys to empirically investigate racism as a social determinant of health.     

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef’s influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef’s ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor.