Vitamin D supplementation has no major effect on pain or pain behavior in bedridden geriatric patients with advanced dementia

BACKGROUND AND AIMS: In a few, earlier, uncontrolled trials, alleviation of chronic pain has been documented by vitamin D supplementation. This randomized double-blind placebo controlled trial addressed the association between pain and vitamin D deficiency and the effects of vitamin D supplementation on pain in institutionalized aged patients. METHODS: 216 long-term care patients were enrolled in Helsinki, Finland. Pain was assessed by three tools: Resident Assessment Instrument (RAI), Discomfort Behavior Scale, and Pain Assessment in Advanced Dementia Scale. Scores for Cognitive Performance Scale (CPS) and other clinical assessments were also collected from the RAI-database. Levels of 25-hydroxyvitamin D (25- OHD) and parathyroid hormone were also determined. Patients in pain (n=202) were randomized into three treatment groups, each receiving 0, 400, or 1200 IU cholecalciferol per day, respectively. Assessments were repeated after six-month vitamin D supplementation. RESULTS: Patients were aged (84.5+/-7.5 yrs), demented (CPS= 4.9+/-1.4, range 1-6), and chronically bedridden. Pain was present in 38.4% to 83.8% of patients depending on assessment tool. Low 25-OHD levels (<50 nmol/L) were very common (98.1%). However, vitamin D deficiency was not associated with pain or pain behavior. The supplementation resulted in a marked increase in 25-OHD levels. However, neither prevalence of painlessness nor pain scores changed significantly after vitamin D supplementation. CONCLUSIONS: We were not able either to show an association between vitamin D deficiency and pain or to observe alleviation of pain by vitamin D supplementation. The independent role of vitamin D in the etiology of pain remains controversial.     

Perceptual reversals of Necker stimuli during intermittent presentation with limited attentional resources

During prolonged viewing of ambiguous stimuli, such as Necker cubes, sudden perceptual reversals occur from one perceptual interpretation to another. The role of attention in such reversals is not clear. We tested whether perceptual reversals depend on attentional resources by manipulating perceptual load and recording event‐related potentials (ERPs) during intermittent presentation of Necker stimuli. The results did not reveal any influence for perceptual load on the frequency of reversals. The ERPs showed that perceptual load influenced electrophysiological activity over parieto‐central areas in the P1 time window (110–140 ms), but load did not modify the early enhancements of positivity (30–140 ms), which correlated with perceptual reversals at occipito‐temporal sites. We conclude that disambiguation of ambiguous figures is based on early mechanisms that can work efficiently with only a minimal amount of attentional resources.     

Novel parameters indicate significant differences in severity of obstructive sleep apnea with patients having similar apnea–hypopnea index

Sleep apnea–hypopnea syndrome (SAHS) causes impairment of daytime functions and increases risk of cardiovascular diseases. Apnea–hypopnea index (AHI), currently used for the estimation of the severity of SAHS, does not contain information on the morphology or duration aspects of the breathing cessations and related oxygen desaturations. Longer breathing cessations and deeper desaturations may have more severe consequences than shorter and shallower ones. To address these issues, novel parameters containing information on the duration and morphology of breathing cessations and oxygen desaturations were calculated and evaluated on 160 male patients (40 patients in normal, mild, moderate and severe AHI severity categories). Obstruction and desaturation duration parameters consist of sum of event durations normalized with the total analysed time. Desaturation severity is a sum of desaturation event areas normalized with total analysed time and obstruction severity parameter is a sum of the products of apnea and hypopnea durations and related desaturation areas normalized with total analysed time. The median follow-up time of the patients was 183 months (range 154–215 months). The 40 patients in each category were further divided into subgroups A and B with lowest and highest novel parameter values, respectively. AHI showed no differences between the subgroups. Mortality was increased in subgroups B compared to subgroups A. The correlation of the novel parameters with AHI was only moderate and the parameter values were partially overlapping between the AHI severity categories. This suggests that patients with similar AHI may in fact suffer from SAHS of very different severity. Thus, the present results suggest that the novel parameters could bring new insight to the individual estimation of the severity of SAHS.     

Induction of Hyaluronan Cables and Monocyte Adherence in Epidermal Keratinocytes

Hyaluronan attached to cell surface can form at least two very different structures; a pericellular coat close to plasma membrane and hyaluronan chains coalesced into “cables” that can span several cell lengths. The hyaluronan in cables, induced by many inflammatory agents, can bind leukocytes, whereas that in the pericellular coat does not contribute to leukocyte binding. Therefore, this structural change seems to have a major role in inflammation. In the present study we checked whether cells of squamous epithelium, like epidermal keratinocytes, can form hyaluronan cables and bind leukocytes. In addition, we checked whether hyaluronan synthesis is affected during the induction of cables. Control keratinocytes expressed pericellular hyaluronan as small patches on plasma membrane. But when treated with inflammatory agents or stressful conditions (tunicamycin, interleukin-1β, tumor necrosis factor-α, and high glucose concentration), hyaluronan organization changed into cable-like structures that avidly bound monocytes. Simultaneously, the total amount of secreted hyaluronan was slightly decreased, and the expression levels of hyaluronan synthases (Has1–3) and CD44 were not significantly changed. The results show that epidermal keratinocytes can form cables and bind leukocytes under inflammatory provocation and that these effects are not dependent on stimulation of hyaluronan secretion.     

Cervical artery dissection goes frequently undiagnosed

Cervical artery dissection (CeAD) is a frequent cause of stroke among young patients. It is unclear how many CeADs occur asymptomatically or cause subtle and unspecific clinical symptoms. We hypothesize that CeAD remains often unrecognized. Accordingly, the incidence of CeAD might be higher and the stroke risk lower than generally assumed. Lack of CeAD-indicating clinical symptoms is regarded as the main cause of missed diagnoses. We further hypothesize that underrepresentation of asymptomatic and oligosymptomatic patients in CeAD studies may have biased the association between ischemia and local symptoms in CeAD patients as well as the associations of CeAD with risk factors or co-morbidities. We finally hypothesize that symptomatic CeAD may be preceded by an initial asymptomatic phase. According to this final hypothesis, the time of onset of CeAD should be considered uncertain. The issue of unrecognized CeAD is relevant, as it may affect the associations between CeAD and putative risk factors. Furthermore, the existence of clinically silent CeADs may explain why recurrent and familial CeAD have been rarely observed.     

Complex evolution and epidemiology of Dobrava-Belgrade hantavirus: definition of genotypes and their characteristics

Dobrava-Belgrade virus (DOBV) is a human pathogen that has evolved in, and is hosted by, mice of several species of the genus Apodemus. We propose a subdivision of the species Dobrava-Belgrade virus into four related genotypes – Dobrava, Kurkino, Saaremaa, and Sochi – that show characteristic differences in their phylogeny, specific host reservoirs, geographical distribution, and pathogenicity for humans.     

The severity of individual obstruction events is related to increased mortality rate in severe obstructive sleep apnea

Obstructive sleep apnea (OSA) is linked to an increased mortality rate. However, the severity of individual obstruction events is rarely considered quantitatively in clinical practice. We hypothesized that OSA with especially severe obstruction events would predispose a patient to greater health risks than OSA with a similar apnea–hypopnea index (AHI), but lower severity of individual events. This hypothesis was tested in a follow‐up (198.2 ± 24.7 months) of a population of 1068 men referred for ambulatory polygraphic recording due to suspected OSA. The recordings were analysed according to the guidelines of the American Academy of Sleep Medicine. Furthermore, a novel obstruction severity parameter was determined; this was defined as the product of duration of the individual obstruction event and area of the related desaturation event. Patients treated with continuous positive airway pressure (CPAP) were omitted. We identified 125 deceased patients from our original population and for 113 of these a matching alive patient with similar AHI, age, body mass index (BMI), smoking habits and follow‐up time could be found. The deceased patients with severe OSA (based on conventional AHI) showed higher obstruction severity values than their AHI‐matched alive controls. Based on the multivariate logistic regression analysis, obstruction severity was the only parameter which was related statistically significantly to mortality in the severe OSA category. Furthermore, 59% of all deceased patients and 83% of those who had severe OSA displayed higher obstruction severity than the AHI‐matched alive counterparts. To conclude, the obstruction severity parameter provided valuable prognostic information supplementing AHI. The obstruction severity parameter might improve recognition of the patients with the highest risk.