Cognitive Factors Mediate Placebo Responses in Patients with House Dust Mite Allergy

Background

Placebo effects have been reported in type I allergic reactions. However the neuropsychological mechanisms steering placebo responses in allergies are largely unknown. The study analyzed whether and to what extend a conditioned placebo response is affecting type I allergic reactions and whether this response can be reproduced at multiple occasions.

Methods

62 patients with house dust mite allergy were randomly allocated to either a conditioned (n = 25), sham-conditioned (n = 25) or natural history (n = 12) group. During the learning phase (acquisition), patients in the conditioned group received the H₁-receptor antagonist desloratadine (5mg) (unconditioned stimulus/US) together with a novel tasting gustatory stimulus (conditioned stimulus/CS). Patients in the sham-conditioned control group received the CS together with a placebo pill. After a wash out time of 9 days patients in the conditioned and sham-conditioned group received placebo pills together with the CS during evocation. Allergic responses documented by wheal size after skin prick test and symptom scores after nasal provocation were analyzed at baseline, after last desloratadine treatment and after the 1^st and 5^th CS re-exposure.

Results

Both conditioned and sham-conditioned patients showed significantly decreased wheal sizes after the 1^st CS-evocation and significantly decreased symptom scores after the 1^st as well as after the 5^th evocation compared to the natural history control group.

Conclusions

These results indicate that placebo responses in type I allergy are not primarily mediated by learning processes, but seemed to be induced by cognitive factors such as patients’ expectation, with these effects not restricted to a single evocation.     

Respiratory Gating during Stereotactic Body Radiotherapy for Lung Cancer Reduces Tumor Position Variability

Purpose

We evaluated the effects of respiratory gating on treatment accuracy in lung cancer patients undergoing lung stereotactic body radiotherapy by using electronic portal imaging device (EPID) images.

Materials and Methods

Our study population consisted of 30 lung cancer patients treated with stereotactic body radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with- (group A) and 16 without gating (group B); typically the patients whose tumors showed three-dimensional respiratory motion ≧5 mm were selected for gating. Tumor respiratory motion was estimated using four-dimensional computed tomography images acquired during treatment simulation. Tumor position variability during all treatment sessions was assessed by measuring the standard deviation (SD) and range of tumor displacement on EPID images. The two groups were compared for tumor respiratory motion and position variability using the Mann-Whitney U test.

Results

The median three-dimensional tumor motion during simulation was greater in group A than group B (9 mm, range 3–30 mm vs. 2 mm, range 0–4 mm; p<0.001). In groups A and B the median SD of the tumor position was 1.1 mm and 0.9 mm in the craniocaudal- (p = 0.24) and 0.7 mm and 0.6 mm in the mediolateral direction (p = 0.89), respectively. The median range of the tumor position was 4.0 mm and 3.0 mm in the craniocaudal- (p = 0.21) and 2.0 mm and 1.5 mm in the mediolateral direction (p = 0.20), respectively.

Conclusions

Although patients treated with respiratory gating exhibited greater respiratory tumor motion during treatment simulation, tumor position variability in the EPID images was low and comparable to patients treated without gating. This demonstrates the benefit of respiratory gating.     

Prevention of Contrast-Induced Acute Kidney Injury: Is Simple Oral Hydration Similar To Intravenous? A Systematic Review of the Evidence

Background

Pre-procedural intravenous fluid administration is an effective prophylaxis measure for contrast-induced acute kidney injury. For logistical ease, the oral route is an alternative to the intravenous. The objective of this study was to compare the efficacy of the oral to the intravenous route in prevention of contrast-induced acute kidney injury.

Study Design

A systematic review and meta-analysis of randomised trials with a stratified analysis and metaregression. Databases included MEDLINE (1950 to November 23 2011), EMBASE (1947 to week 47 2011), Cochrane CENTRAL (3^rd quarter 2011). Two reviewers identified relevant trials and abstracted data.

Settings and Population

Trials including patients undergoing a contrast enhanced procedure.

Selection Criteria

Randomised controlled trial; adult (>18 years) population; comparison of oral versus intravenous volume expansion.

Intervention

Oral route of volume expansion compared to the intravenous route.

Outcomes

Any measure of acute kidney injury, need for renal replacement therapy, hospitalization and death.

Results

Six trials including 513 patients met inclusion criteria. The summary odds ratio was 1.19 (95% CI 0.46, 3.10, p = 0.73) suggesting no difference between the two routes of volume expansion. There was significant heterogeneity (Cochran’s Q = 11.65, p = 0.04; I² = 57). In the stratified analysis, inclusion of the five studies with a prespecified oral volume expansion protocol resulted in a shift towards oral volume expansion (OR 0.75, 95% CI 0.37, 1.50, p = 0.42) and also resolved the heterogeneity (Q = 3.19, P = 0.53; I² = 0).

Limitations

Small number of studies identified; lack of hard clinical outcomes.

Conclusion

The oral route may be as effective as the intravenous route for volume expansion for contrast-induced acute kidney injury prevention. Adequately powered trials with hard endpoints should be done given the potential advantages of oral (e.g. reduced patient burden and cost) over intravenous volume expansion.     

Identification of an Abbreviated Test Battery for Detection of HIV-Associated Neurocognitive Impairment in an Early-Managed HIV-Infected Cohort

Background

HIV-associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral treatment (ART), and it is essential to have a sensitive and specific HAND screening tool.

Methods

Participants were 200 HIV-infected US military beneficiaries, managed early in the course of HIV infection, had few comorbidities, and had open access to ART. Participants completed a comprehensive, seven-domain (16-test), neuropsychological battery (∼120 min); neurocognitive impairment (NCI) was determined using a standardized score derived from demographically adjusted T-scores (global deficit score ≥0.5). Restricting the estimated administration time of the screening battery to < = 20 minutes, we examined the sensitivity and specificity of detecting NCI for all possible combinations of 2-, 3-, and 4- tests from the comprehensive battery.

Results

Participants were relatively healthy (median CD4 count: 546 cells/mm³) with 64% receiving ART. Prevalence of NCI was low (19%). The best 2-test screener included the Stroop Color Test and the Hopkins Verbal Learning Test-Revised (11 min; sensitivity = 73%; specificity = 83%); the best 3-test screener included the above measures plus the Paced Auditory Serial Addition Test (PASAT; 16 min; sensitivity = 86%; specificity = 75%). The addition of Action Fluency to the above three tests improved specificity (18 min; sensitivity = 86%; specificity = 87%).

Conclusions

Combinations of widely accepted neuropsychological tests with brief implementation time demonstrated good sensitivity and specificity compared to a time intensive neuropsychological test battery. Tests of verbal learning, attention/working memory, and processing speed are particularly useful in detecting NCI. Utilizing validated, easy to administer, traditional neuropsychological tests with established normative data may represent an excellent approach to screening for NCI in HIV.     

Moving in an Environment of Induced Sensorimotor Incongruence Does Not Influence Pain Sensitivity in Healthy Volunteers: A Randomised Within-Subject Experiment

Objectives

It has been proposed that in the same way that conflict between vestibular and visual inputs leads to motion sickness, conflict between motor commands and sensory information associated with these commands may contribute to some chronic pain states. Attempts to test this hypothesis by artificially inducing a state of sensorimotor incongruence and assessing self-reported pain have yielded equivocal results. To help clarify the effect sensorimotor incongruence has on pain we investigated the effect of moving in an environment of induced incongruence on pressure pain thresholds (PPT) and the pain experienced immediately on completion of PPT testing.

Methods

Thirty-five healthy subjects performed synchronous and asynchronous upper-limb movements with and without mirror visual feedback in random order. We measured PPT over the elbow and the pain evoked by testing. Generalised linear mixed-models were performed for each outcome. Condition (four levels) and baseline values for each outcome were within-subject factors.

Results

There was no effect of condition on PPT (p = 0.887) or pressure-evoked pain (p = 0.771). A sensitivity analysis using only the first PPT measure after each condition confirmed the result (p = 0.867).

Discussion

Inducing a state of movement related sensorimotor incongruence in the upper-limb of healthy volunteers does not influence PPT, nor the pain evoked by testing. We found no evidence that sensorimotor incongruence upregulates the nociceptive system in healthy volunteers.     

Dynamic Eye Tracking Based Metrics for Infant Gaze Patterns in the Face-Distractor Competition Paradigm

Objective

To develop new standardized eye tracking based measures and metrics for infants’ gaze dynamics in the face-distractor competition paradigm.

Method

Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants’ initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus).

Results

The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants.

Conclusion

The results suggest that eye tracking based assessments of infants’ cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals.

Significance

Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development.     

Influence of Body Mass Index (BMI) on Functional Improvements at 3 Years Following Total Knee Replacement: A Retrospective Cohort Study

Background

The number of patients presenting for total knee replacement who are classified as obese is increasing. The functional benefits of performing TKR in these patients are unclear.

Aim

To assess the influence pre-operative body mass index has upon knee specific function, general health status and patient satisfaction at 3 years following total knee replacement.

Design

Retrospective comparative cohort study using prospectively collected data from an institutional arthroplasty register.

Methods

1367 patients were assessed using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Medical Outcomes Trust Short Form-36 (SF-36) scores supplemented by a validated measure of satisfaction pre-operatively and subsequently at 1,2 and 3 year post-operatively. Comparisons were made by dividing the cohort into 4 groups based on body mass index (BMI) 18.5–25.0 kg/m² (n = 253);>25.0–30.0 kg/m² (n = 559);>30.0−35.0 kg/m² (n = 373);>35.0 kg/m² (n = 182).

Results

Despite lower pre-operative, 1 and 3 year WOMAC and SF-36 scores patients with the highest BMIs >35.0 kg/m² experienced similar improvements to patients with a ‘normal‘ BMI (18.5–25.0 kg/m²) at 1 year (Difference in WOMAC improvement = 0.0 (95%CI −5.2 to 5.2), p = 1.00) and this improvement was sustained at up to 3 years (Difference in 1 year to 3 year improvement = 2.2 (95%CI: −2.1 to 6.5), p = 1.00). This effect was also observed for the SF-36 mental and physical component scores. Despite equivalent functional improvements levels of satisfaction in the >35.0 kg/m² group were lower than for any other BMI group (>35.0 kg/m² = 84.6% satisfied versus 18.5–5.0 kg/m² = 93.3% satisfied,p = 0.01) as was the proportion of patients who stated they would have the operation again (>35.0 kg/m² = 69.6% versus 18.5–25.0 kg/m² = 82.2%,p = 0.01).

Conclusion

Obese and morbidly obese patients gain as much functional benefit from total knee replacement as patients with lesser body mass indexes. This benefit is maintained for up to 3 years following surgery. However, these patients are less satisfied with their knee replacement and almost a third would not have the operation again.     

Cortisol Patterns Are Associated with T Cell Activation in HIV

Objective

The level of T cell activation in untreated HIV disease is strongly and independently associated with risk of immunologic and clinical progression. The factors that influence the level of activation, however, are not fully defined. Since endogenous glucocorticoids are important in regulating inflammation, we sought to determine whether less optimal diurnal cortisol patterns are associated with greater T cell activation.

Methods

We studied 128 HIV-infected adults who were not on treatment and had a CD4⁺ T cell count above 250 cells/µl. We assessed T cell activation by CD38 expression using flow cytometry, and diurnal cortisol was assessed with salivary measurements.

Results

Lower waking cortisol levels correlated with greater T cell immune activation, measured by CD38 mean fluorescent intensity, on CD4⁺ T cells (r = −0.26, p = 0.006). Participants with lower waking cortisol also showed a trend toward greater activation on CD8⁺ T cells (r = −0.17, p = 0.08). A greater diurnal decline in cortisol, usually considered a healthy pattern, correlated with less CD4⁺ (r = 0.24, p = 0.018) and CD8⁺ (r = 0.24, p = 0.017) activation.

Conclusions

These data suggest that the hypothalamic-pituitary-adrenal (HPA) axis contributes to the regulation of T cell activation in HIV. This may represent an important pathway through which psychological states and the HPA axis influence progression of HIV.     

Paradoxical Interventricular Septal Motion as a Major Determinant of Late Gadolinium Enhancement in Ventricular Insertion Points in Pulmonary Hypertension

Background

This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH).

Methods

Forty-six consecutive PH patients (mean pulmonary artery pressure ≥25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index.

Results

Mean pulmonary arterial pressure (MPAP) of PH patients was 38±9 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47–2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = −0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001).

Conclusions

LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.     

Effect of Tree Nuts on Glycemic Control in Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Dietary Trials

Background

Tree nut consumption has been associated with reduced diabetes risk, however, results from randomized trials on glycemic control have been inconsistent.

Objective

To provide better evidence for diabetes guidelines development, we conducted a systematic review and meta-analysis of randomized controlled trials to assess the effects of tree nuts on markers of glycemic control in individuals with diabetes.

Data Sources

MEDLINE, EMBASE, CINAHL, and Cochrane databases through 6 April 2014.

Study Selection

Randomized controlled trials ≥3 weeks conducted in individuals with diabetes that compare the effect of diets emphasizing tree nuts to isocaloric diets without tree nuts on HbA1c, fasting glucose, fasting insulin, and HOMA-IR.

Data Extraction and Synthesis

Two independent reviewer’s extracted relevant data and assessed study quality and risk of bias. Data were pooled by the generic inverse variance method and expressed as mean differences (MD) with 95% CI’s. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I²).

Results

Twelve trials (n = 450) were included. Diets emphasizing tree nuts at a median dose of 56 g/d significantly lowered HbA1c (MD = −0.07% [95% CI:−0.10, −0.03%]; P = 0.0003) and fasting glucose (MD = −0.15 mmol/L [95% CI: −0.27, −0.02 mmol/L]; P = 0.03) compared with control diets. No significant treatment effects were observed for fasting insulin and HOMA-IR, however the direction of effect favoured tree nuts.

Limitations

Majority of trials were of short duration and poor quality.

Conclusions

Pooled analyses show that tree nuts improve glycemic control in individuals with type 2 diabetes, supporting their inclusion in a healthy diet. Owing to the uncertainties in our analyses there is a need for longer, higher quality trials with a focus on using nuts to displace high-glycemic index carbohydrates.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01630980","term_id":"NCT01630980"}}NCT01630980     

Interventions to Reduce and Prevent Obesity in Pre-Conceptual and Pregnant Women: A Systematic Review and Meta-Analysis

Background

The increasing prevalence of obesity in pregnant women is associated with adverse maternal and neonatal outcomes, and increased costs to healthcare, the economy and broader society.

Objectives

To assess the efficacy of behavioural interventions for managing gestational weight gain (GWG) in the pre-conceptual and pregnancy period in overweight, obese and morbidly obese women.

Search Methods

A search was performed for published studies in the English language, from date? 2000–31 December 2012 in five electronic databases; PubMed, Scopus, Cochrane Library, CINAHL and PsycINFO.

Selection criteria

Studies were included if they compared the efficacy or effectiveness of a particular behavioural intervention in pregnant or pre-conceptual women with standard maternity care. Studies that included women with co-morbid conditions such as diabetes mellitus and polycystic ovarian syndrome were excluded to help isolate the effect of the intervention.

Results

Fifteen studies involving 3,426 participants were included. One study (n = 692) focused on the pre-conceptual period and the remaining 14 (n = 2,734) in the pregnancy period. Pooled mean difference for GWG indicated a lower GWG in the intervention groups when compared to standard maternity care groups (n = 1771, mean difference (MD) −1.66 kg, 95% CI −3.12 to −0.21 kg). With respect to the types of participants, considerable heterogeneity between studies was shown in the obese subgroup [Tau² = 15.61; Chi² = 40.80, df = 3 (P<0.00001); I² = 93%].

Conclusions

Behavioural interventions in pregnancy may be effective in reducing GWG in obese women without comorbid conditions, but not overweight or morbidly obese women. Behavioural interventions had no effect on postpartum weight loss or retention, gestation week of delivery and infant birth weight in overweight, obese and morbidly obese women.     

Anatomic Distribution of Nerves and Microvascular Density in the Human Anterior Vaginal Wall: Prospective Study

Background

The presence of the G-spot (an assumed erotic sensitive area in the anterior wall of the vagina) remains controversial. We explored the histomorphological basis of the G-spot.

Methods

Biopsies were drawn from a 12 o’clock direction in the distal- and proximal-third areas of the anterior vagina of 32 Chinese subjects. The total number of protein gene product 9.5–immunoreactive nerves and smooth muscle actin–immunoreactive blood vessels in each specimen was quantified using the avidin-biotin-peroxidase assay.

Results

Vaginal innervation was observed in the lamina propria and muscle layer of the anterior vaginal wall. The distal-third of the anterior vaginal wall had significantly richer small-nerve-fiber innervation in the lamina propria than the proximal-third (p = 0.000) and in the vaginal muscle layer (p = 0.006). There were abundant microvessels in the lamina propria and muscle layer, but no small vessels in the lamina propria and few in the muscle layer. Significant differences were noted in the number of microvessels when comparing the distal- with proximal-third parts in the lamina propria (p = 0.046) and muscle layer (p = 0.002).

Conclusions

Significantly increased density of nerves and microvessels in the distal-third of the anterior vaginal wall could be the histomorphological basis of the G-spot. Distal anterior vaginal repair could disrupt the normal anatomy, neurovascular supply and function of the G-spot, and cause sexual dysfunction.     

Phospholipid Metabolites in Recurrent Glioblastoma: In Vivo Markers Detect Different Tumor Phenotypes before and under Antiangiogenic Therapy

Purpose

Metabolic changes upon antiangiogenic therapy of recurrent glioblastomas (rGBMs) may provide new biomarkers for treatment efficacy. Since in vitro models showed that phospholipid membrane metabolism provides specific information on tumor growth we employed in-vivo MR-spectroscopic imaging (MRSI) of human rGBMs before and under bevacizumab (BVZ) to measure concentrations of phosphocholine (PCho), phosphoethanolamine (PEth), glycerophosphocholine (GPC), and glyceroethanolamine (GPE).

Methods

¹H and ³¹P MRSI was prospectively performed in 32 patients with rGBMs before and under BVZ therapy at 8 weeks intervals until tumor progression. Patients were dichotomized into subjects with long overall survival (OS) (>median OS) and short OS (<median OS) survival time from BVZ-onset. Metabolite concentrations from tumor tissue and their ratios were compared to contralateral normal-appearing tissue (control).

Results

Before BVZ, ¹H-detectable choline signals (total GPC and PCho) in rGBMs were elevated but significance failed after dichotomizing. For metabolite ratios obtained by ³¹P MRSI, the short-OS group showed higher PCho/GPC (p = 0.004) in rGBMs compared to control tissue before BVZ while PEth/GPE was elevated in rGBMs of both groups (long-OS p = 0.04; short-OS p = 0.003). Under BVZ, PCho/GPC and PEth/GPE in the tumor initially decreased (p = 0.04) but only PCho/GPC re-increased upon tumor progression (p = 0.02). Intriguingly, in normal-appearing tissue an initial PEth/GPE decrease (p = 0.047) was followed by an increase at the time of tumor progression (p = 0.031).

Conclusion

An elevated PCho/GPC ratio in the short-OS group suggests that it is a negative predictive marker for BVZ efficacy. These gliomas may represent a malignant phenotype even growing under anti-VEGF treatment. Elevated PEth/GPE may represent an in-vivo biomarker more sensitive to GBM infiltration than MRI.     

External Validation of the Simple Clinical Score and the HOTEL Score,Two Scores for Predicting Short-Term Mortality after Admission to an Acute Medical Unit

Background

Clinical scores can be of aid to predict early mortality after admission to a medical admission unit. A developed scoring system needs to be externally validated to minimise the risk of the discriminatory power and calibration to be falsely elevated. We performed the present study with the objective of validating the Simple Clinical Score (SCS) and the HOTEL score, two existing risk stratification systems that predict mortality for medical patients based solely on clinical information, but not only vital signs.

Methods

Pre-planned prospective observational cohort study.

Setting

Danish 460-bed regional teaching hospital.

Findings

We included 3046 consecutive patients from 2 October 2008 until 19 February 2009. 26 (0.9%) died within one calendar day and 196 (6.4%) died within 30 days. We calculated SCS for 1080 patients. We found an AUROC of 0.960 (95% confidence interval [CI], 0.932 to 0.988) for 24-hours mortality and 0.826 (95% CI, 0.774–0.879) for 30-day mortality, and goodness-of-fit test, χ² = 2.68 (10 degrees of freedom), P = 0.998 and χ² = 4.00, P = 0.947, respectively. We included 1470 patients when calculating the HOTEL score. Discriminatory power (AUROC) was 0.931 (95% CI, 0.901–0.962) for 24-hours mortality and goodness-of-fit test, χ² = 5.56 (10 degrees of freedom), P = 0.234.

Conclusion

We find that both the SCS and HOTEL scores showed an excellent to outstanding ability in identifying patients at high risk of dying with good or acceptable precision.     

Cognitive Functioning in Patients with Bipolar Disorder: Association with Depressive Symptoms and Alcohol Use

Background

Cognitive dysfunction is clearly recognized in bipolar patients, but the degree of impairment varies due to methodological factors as well as heterogeneity in patient populations. The goal of this study was to evaluate cognitive functioning in bipolar patients and to assess its association with depressive symptoms. Post hoc the relationship with lifetime alcohol use disorder was explored.

Methodology/Principal Findings

The study included 110 bipolar patients and 75 healthy controls. Patients with severe depressive symptoms, (hypo)manic symptoms and current severe alcohol use disorder were excluded. Diagnoses were evaluated via the Mini-International Neuropsychiatric Interview. Cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating. Patients were euthymic (n = 46) or with current mild (n = 38) or moderate (n = 26) depressive symptoms. Cognitive impairment was found in 26% (z-score 2 or more above reference control group for at least one domain) of patients, most prominent in executive functioning (effect size; ES 0.49) and speed of information processing (ES 0.47). Depressive symptoms were associated with dysfunction in psychomotor speed (adjusted beta 0.43; R² 7%), speed of information processing (adjusted beta 0.36; R² 20%), attentional switching (adjusted beta 0.24; R² 16%) and the mean score (adjusted beta 0.23; R² 24%), but not with verbal and visual memory and executive functioning. Depressive symptoms explained 24% of the variance in the mean z-score of all 6 cognitive domains. Comorbid lifetime alcohol use (n = 21) was not associated with cognitive dysfunction.

Conclusions/Significance

Cognitive dysfunction in bipolar disorder is more severe in patients with depressive symptoms, especially regarding speed and attention. Therefore, interpretation of cognitive functioning in patients with depressive symptoms should be cautious. No association was found between cognitive functioning and lifetime comorbid alcohol use disorder.     

Determinants and Improvement of Electrocardiographic Diagnosis of Left Ventricular Hypertrophy in a Black African Population

Background

Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor. The electrocardiogram (ECG) has been shown to be a poor tool in detecting LVH due to cardiac and extracardiac factors. We studied the determinants and possibility of improving the test performance of the ECG in a group of Black Africans.

Methods

We studied echocardiograms and electrocardiograms of 182 Cameroonian patients among whom 113 (62.1%) were having an echocardiographic LVH. Echocardiographic LVH was defined as Left Ventricular Mass Indexed to height ^2.7(LVMI)>48 g/m^2.7 in men, and >44 g/m ^2.7 in women or Body Surface Area ≥116 g/m² in men, and ≥96 g/m² in women. Test performances were calculated for 6 classic ECG criteria Sokolow-Lyon, Cornell, Cornell product, Gubner-Ungerleiger, amplitudes of R in aVL, V₅ and V₆.

Results

The most sensitive criteria were Cornell (37.2%) and Sokolow-Lyon index (26.5%). The most specific criteria were Gubner (98.6%), RaVL (97.1%), RV₅/V₆ (95.7%) and Cornell product (94.2%). The performance of the ECG in diagnosing LVH significantly increased with the severity of LVH for Cornell index (r = 0.420, p<0.0001) and Sokolow index (r = 0.212, p = 0.002). It decreased with body habitus (r = −0.248, p = 0.001) for Sokolow-Lyon index. Cornell index was less affected (age p = 0.766; body habitus: p = 0.209). After sex-specific adjustment for BMI, Cornell BMI sensitivity increased from 37.2% to 69% (r = 0.472, p<0.0001), and Sokolow-Lyon BMI sensitivity increased from 26.5% to 58.4% (r = 0.270, p<0.001).

Conclusion

The test performance of the ECG in diagnosing LVH is low in this Black African population, due to extracardiac factors such as age, sex, body habitus, and cardiac factors such as LVH severity and geometry. However, this performance is improved after adjustment for extracardiac factors.     

Decreases in Molecular Diffusion,Perfusion Fraction and Perfusion-Related Diffusion in Fibrotic Livers: A Prospective Clinical Intravoxel Incoherent Motion MR Imaging Study

Purpose

This study was aimed to determine whether pure molecular-based diffusion coefficient (D) and perfusion-related diffusion parameters (perfusion fraction f, perfusion-related diffusion coefficient D*) differ in healthy livers and fibrotic livers through intra-voxel incoherent motion (IVIM) MR imaging.

Material and Methods

17 healthy volunteers and 34 patients with histopathologically confirmed liver fibrosis patients (stage 1 = 14, stage 2 = 8, stage 3& 4 = 12, METAVIR grading) were included. Liver MR imaging was performed at 1.5-T. IVIM diffusion weighted imaging sequence was based on standard single-shot DW spin echo-planar imaging, with ten b values of 10, 20, 40, 60, 80, 100, 150, 200, 400, 800 sec/mm² respectively. Pixel-wise realization and regions-of-interest based quantification of IVIM parameters were performed.

Results

D, f, and D* in healthy volunteer livers and patient livers were 1.096±0.155 vs 0.917±0.152 (10⁻³ mm²/s, p = 0.0015), 0.164±0.021 vs 0.123±0.029 (p<0.0001), and 13.085±2.943 vs 9.423±1.737 (10⁻³ mm²/s, p<0.0001) respectively, all significantly lower in fibrotic livers. As the fibrosis severity progressed, D, f, and D* values decreased, with a trend significant for f and D*.

Conclusion

Fibrotic liver is associated with lower pure molecular diffusion, lower perfusion volume fraction, and lower perfusion-related diffusion. The decrease of f and D* in the liver is significantly associated liver fibrosis severity.     

Significant Improvement in Dynamic Visual Acuity after Cataract Surgery: A Promising Potential Parameter for Functional Vision

Purpose

Dynamic visual acuity (DVA) is a relatively independent parameter for evaluating the ability to distinguish details of a moving target. The present study has been designed to discuss the extent to which age-related cataract impacts DVA in elderly individuals and to determine whether it could be restored after bilateral phacoemulsification combined with intraocular lens implantation surgery.

Methods

Twenty-six elderly cataract patients scheduled for binocular cataract surgery and 30 elderly volunteers without cataract were enrolled in the study. DVA at 15, 30, 60 and 90 degree per second (dps) was assessed, and velocity-dependent visual acuity decreases between consecutive speed levels were calculated.

Results

Compared with the control group, the patient group exhibited significantly worse DVA performance at all speed levels (p<0.001), and the decreases in velocity-dependent visual acuity were more serious in the patient group at the intervals of 0–15 dps (p<0.001), 15–30 dps (p = 0.007) and 30–60 dps (p = 0.008). Postoperatively, DVA performance at every speed level in the patient group clearly improved (p<0.001) and recovered to levels compatible to the control group. The decrease in visual acuity with increasing speed was less pronounced than during the preoperative phase (p_{0–15 dps} = 0.001, p_{15–30 dps}<0.001 and p_{30–60 dps} = 0.001) and became similar to that of the control group. The postoperative visual benefit regarding DVA was more pronounced than the improvement in static visual acuity (p_{15 dps} = 0.001 and p<0.001 at 30 dps, 60 dps and 90 dps).

Conclusions

The impact of age-related cataract on DVA was more severe than its effects on static visual acuity. After cataract surgery, not only static vision of the patients was restored markedly, but also the dynamic vision. DVA could be an important adjunct to the current evaluation system of functional vision, thereby meriting additional attention in clinical assessment.     

Left Ventricular Hypertrophy and Insulin Resistance in Adults from an Urban Community in the Gambia: Cross-Sectional Study

Objective

To determine the association between left ventricular hypertrophy and insulin resistance in Gambians.

Design

Cross-sectional study.

Setting

Outpatient clinics of Royal Victoria Teaching Hospital and Medical Research Council Laboratories in Banjul.

Participants

Three hundred and sixteen consecutive patients were enrolled from outpatient clinics. The data of 275 participants (89 males) were included in the analysis with a mean (± standard deviation) age of 53.7 (±11.9) years.

Interventions

A questionnaire was filled and anthropometric measurements were taken. 2-D guided M-mode echocardiography, standard 12-1ead electrocardiogram, fasting insulin and the oral glucose tolerance test were performed.

Main Outcome Measures

The Penn formula was used to determine the left ventricular mass index, 125 g/m² in males and 110 g/m² in females as the cut-off for left ventricular hypertrophy. Using the fasting insulin and fasting glucose levels, the insulin resistance was estimated by the homeostatic model assessment formula. Logistic regression analysis was used to determine the association between left ventricular hypertrophy and insulin resistance.

Results

The mean Penn left ventricular mass index was 119.5 (±54.3) and the prevalence of Penn left ventricular mass index left ventricular hypertrophy was 41%. The mean fasting glucose was 5.6 (±2.5) mmol/l, fasting insulin was 6.39 (±5.49) μU/ml and insulin resistance was 1.58 (±1.45). There was no association between Penn left ventricular mass index left ventricular hypertrophy and log of insulin resistance in univariate (OR = 0.98, 95% CI = 0.80 – 1.19, p = 0.819) and multivariate logistic regression (OR = 0.93, 95% CI = 0.76–1.15, p = 0.516) analysis.

Conclusion

No association was found in this study between left ventricular hypertrophy and insulin resistance in Gambians and this does not support the suggestion that insulin is an independent determinant of left ventricular hypertrophy in hypertensives.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036