Neuropsychological and Socio-Occupational Functioning in Young Psychiatric Outpatients: A Longitudinal Investigation

Background

Clinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning.

Methods

At baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome.

Results

Good socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome.

Conclusions

Neuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches.     

Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis

Background

Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders.

Methods

We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics.

Results

Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A₂ (inPLA₂) activity, a marker of membrane lipid repair/remodelling.

Conclusions

Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.     

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     

Altered Fronto-Temporal Functional Connectivity in Individuals at Ultra-High-Risk of Developing Psychosis

Background

The superior temporal gyrus (STG) is one of the key regions implicated in psychosis, given that abnormalities in this region are associated with an increased risk of conversion from an at-risk mental state to psychosis. However, inconsistent results regarding the functional connectivity strength of the STG have been reported, and the regional heterogeneous characteristics of the STG should be considered.

Methods

To investigate the distinctive functional connection of each subregion in the STG, we parcellated the STG of each hemisphere into three regions: the planum temporale, Heschl’s gyrus, and planum polare. Resting-state functional magnetic resonance imaging was obtained from 22 first-episode psychosis (FEP) patients, 41 individuals at ultra-high-risk for psychosis (UHR), and 47 demographically matched healthy controls.

Results

Significant group differences (in seed-based connectivity) were demonstrated in the left planum temporale and from both the right and left Heschl’s gyrus seeds. From the left planum temporale seed, the FEP and UHR groups exhibited increased connectivity to the bilateral dorsolateral prefrontal cortex. In contrast, the FEP and UHR groups demonstrated decreased connectivity from the bilateral Heschl’s gyrus seeds to the dorsal anterior cingulate cortex. The enhanced connectivity between the left planum temporale and right dorsolateral prefrontal cortex was positively correlated with positive symptom severity in individuals at UHR (r = .34, p = .03).

Conclusions

These findings corroborate the fronto-temporal connectivity disruption hypothesis in schizophrenia by providing evidence supporting the altered fronto-temporal intrinsic functional connection at earlier stages of psychosis. Our data indicate that subregion-specific aberrant fronto-temporal interactions exist in the STG at the early stage of psychosis, thus suggesting that these aberrancies are the neural underpinning of proneness to psychosis.     

Genetic Variation at the BDNF Locus: Evidence for Association with Long-Term Outcome after Ischemic Stroke

Background and Purpose

Rates and extent of recovery after stroke vary considerably between individuals and genetic factors are thought to contribute to post-stroke outcome. Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair and has been shown to be involved in stroke severity, recovery, and outcome in animal models. Few clinical studies on BDNF genotypes in relation to ischemic stroke have been performed. The aims of the present study are therefore to investigate whether genetic variation at the BDNF locus is associated with initial stroke severity, recovery and/or short-term and long-term functional outcome after ischemic stroke.

Methods

Four BDNF tagSNPs were analyzed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS; 600 patients and 600 controls, all aged 18–70 years). Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke recovery was defined as the change in NIHSS over a 3-month period. Short- and long-term functional outcome post-stroke was assessed using the modified Rankin Scale at 3 months and at 2 and 7 years after stroke, respectively.

Results

No SNP was associated with stroke severity or recovery at 3 months and no SNP had an impact on short-term outcome. However, rs11030119 was independently associated with poor functional outcome 7-years after stroke (OR 0.66, 95% CI 0.46–0.92; P =  0.006).

Conclusions

BDNF gene variants were not major contributors to ischemic stroke severity, recovery, or short-term functional outcome. However, this study suggests that variants in the BDNF gene may contribute to poor long-term functional outcome after ischemic stroke.     

The Influence of the Patient-Clinician Relationship on Healthcare Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes.

Design

Systematic review and meta-analysis.

Data Sources

Electronic databases EMBASE and MEDLINE and the reference sections of previous reviews.

Eligibility Criteria for Selecting Studies

Included studies were randomized controlled trials (RCTs) in adult patients in which the patient-clinician relationship was systematically manipulated and healthcare outcomes were either objective (e.g., blood pressure) or validated subjective measures (e.g., pain scores). Studies were excluded if the encounter was a routine physical, or a mental health or substance abuse visit; if the outcome was an intermediate outcome such as patient satisfaction or adherence to treatment; if the patient-clinician relationship was manipulated solely by intervening with patients; or if the duration of the clinical encounter was unequal across conditions.

Results

Thirteen RCTs met eligibility criteria. Observed effect sizes for the individual studies ranged from d = −.23 to .66. Using a random-effects model, the estimate of the overall effect size was small (d = .11), but statistically significant (p = .02).

Conclusions

This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.     

Neurocognitive Outcome of Children Exposed to Perinatal Mother-to-Child Chikungunya Virus Infection: The CHIMERE Cohort Study on Reunion Island

Background

Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection.

Methods

The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ≤85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms.

Results

The mean DQ score was 86.3 (95%CI: 81.0–91.5) in infected children compared to 100.2 (95%CI: 98.0–102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45–5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <−2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas, predominant in the frontal lobes in these children.

Conclusions

The neurocognitive outcome of children exposed to perinatal mother-to-child CHIKV infection is poor. Severe CHIKV neonatal encephalopathy is associated with an even poorer outcome.     

Schizophrenia and Violence: Systematic Review and Meta-Analysis

Background

Although expert opinion has asserted that there is an increased risk of violence in individuals with schizophrenia and other psychoses, there is substantial heterogeneity between studies reporting risk of violence, and uncertainty over the causes of this heterogeneity. We undertook a systematic review of studies that report on associations between violence and schizophrenia and other psychoses. In addition, we conducted a systematic review of investigations that reported on risk of homicide in individuals with schizophrenia and other psychoses.

Methods and Findings

Bibliographic databases and reference lists were searched from 1970 to February 2009 for studies that reported on risks of interpersonal violence and/or violent criminality in individuals with schizophrenia and other psychoses compared with general population samples. These data were meta-analysed and odds ratios (ORs) were pooled using random-effects models. Ten demographic and clinical variables were extracted from each study to test for any observed heterogeneity in the risk estimates. We identified 20 individual studies reporting data from 18,423 individuals with schizophrenia and other psychoses. In men, ORs for the comparison of violence in those with schizophrenia and other psychoses with those without mental disorders varied from 1 to 7 with substantial heterogeneity (I ² = 86%). In women, ORs ranged from 4 to 29 with substantial heterogeneity (I ² = 85%). The effect of comorbid substance abuse was marked with the random-effects ORs of 2.1 (95% confidence interval [CI] 1.7–2.7) without comorbidity, and an OR of 8.9 (95% CI 5.4–14.7) with comorbidity (p<0.001 on metaregression). Risk estimates of violence in individuals with substance abuse (but without psychosis) were similar to those in individuals with psychosis with substance abuse comorbidity, and higher than all studies with psychosis irrespective of comorbidity. Choice of outcome measure, whether the sample was diagnosed with schizophrenia or with nonschizophrenic psychoses, study location, or study period were not significantly associated with risk estimates on subgroup or metaregression analysis. Further research is necessary to establish whether longitudinal designs were associated with lower risk estimates. The risk for homicide was increased in individuals with psychosis (with and without comorbid substance abuse) compared with general population controls (random-effects OR = 19.5, 95% CI 14.7–25.8).

Conclusions

Schizophrenia and other psychoses are associated with violence and violent offending, particularly homicide. However, most of the excess risk appears to be mediated by substance abuse comorbidity. The risk in these patients with comorbidity is similar to that for substance abuse without psychosis. Public health strategies for violence reduction could consider focusing on the primary and secondary prevention of substance abuse. Please see later in the article for Editors'' Summary     

Proteinuria Independently Predicts Unfavorable Outcome of Ischemic Stroke Patients Receiving Intravenous Thrombolysis

Background and Purpose

Patients with low estimated glomerular filtration rate (eGFR) and proteinuria may be at increased risk for stroke. This study investigated whether low eGFR and proteinuria are outcome predictors in stroke patients treated with intravenous thrombolysis.

Methods

We studied 432 consecutive stroke patients who received thrombolysis from January 2006 to December 2012, in Taiwan. Unfavorable outcome was defined as modified Rankin scale ≥2 at 3 months after stroke. Proteinuria was classified as negative or trace, mild, and moderate to severe. Using logistic regression analysis, we identified independent factors for unfavorable outcome after thrombolysis.

Results

Of all patients, 32.7% had proteinuria. Patients with proteinuria were older, had higher frequencies of diabetes mellitus, hyperlipidemia, atrial fibrillation, lower eGFR, and greater severity of stroke upon admission than those without proteinuria. Proteinuria, not low eGFR, was an independent predictor for unfavorable outcome for stroke (OR = 2.00 for mild proteinuria, p = 0.035; OR = 2.54 for moderate to severe proteinuria, p = 0.035). However, no clear relationship was found between proteinuria and symptomatic hemorrhage after thrombolysis.

Conclusions

Proteinuria is an independent predictor of unfavorable outcome for acute ischemic stroke in patients treated with intravenous thrombolysis, indicating the crucial role of chronic kidney disease on the effectiveness of thrombolysis.     

Indocyanine Green Video Angiography Predicts Outcome of Extravasation Injuries

Background

Extravasation of cytotoxic drugs is a serious complication of systemic cancer treatment. Still, a reliable method for early assessment of tissue damage and outcome prediction is missing. Here, we demonstrate that the evaluation of blood flow by indocyanine green (ICG) angiography in the extravasation area predicts for the need of surgical intervention.

Methods

Twenty-nine patients were evaluated by ICG angiography after extravasation of vesicant or highly irritant cytotoxic drugs administered by peripheral i.v. infusion. Tissue perfusion as assessed by this standardized method was correlated with clinical outcome.

Results

The perfusion index at the site of extravasation differed significantly between patients with reversible tissue damage and thus healing under conservative management (N = 22) versus those who needed surgical intervention due to the development of necrosis (N = 7; P = 0.0001). Furthermore, in patients benefiting from conservative management, the perfusion index was significantly higher in the central extravasation area denoting hyperemia, when compared with the peripheral area (P = 0.0001).

Conclusions

In this patient cohort, ICG angiography as indicator of local perfusion within the extravasation area was of prognostic value for tissue damage. ICG angiography could thus be used for the early identification of patients at risk for irreversible tissue damage after extravasation of cytotoxic drugs.     

HIV-1 Clade B pol Evolution following Primary Infection

Objective

Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals.

Design

Longitudinal cohort study of individuals enrolled during primary infection.

Methods

Eligible individuals were antiretroviral naïve participants enrolled in the cohort from December 1997-December 2005 and having at least two blood samples available with the first one collected within a year of their estimated date of infection. Population-based pol sequences were generated from collected blood samples and analyzed for genetic divergence over time in respect to dual infection status, HLA, CD4 count and viral load.

Results

93 participants were observed for a median of 1.8 years (Mean = 2.2 years, SD = 1.9 years). All participants classified as mono-infected had less than 0.7% divergence between any two of their pol sequences using the Tamura-Nei model (TN93), while individuals with dual infection had up to 7.0% divergence. The global substitution rates (substitutions/nucleotide/year) for mono and dually infected individuals were significantly different (p<0.001); however, substitution rates were not associated with HLA haplotype, CD4 or viral load.

Conclusions

Even after a maximum of almost 9 years of follow-up, all mono-infected participants had less than 1% divergence between baseline and longitudinal sequences, while participants with dual infection had 10 times greater divergence. These data support the use of HIV-1 pol sequence data to evaluate transmission events, networks and HIV-1 dual infection.     

Serum YKL-40 Levels Correlate with Infarct Volume,Stroke Severity,and Functional Outcome in Acute Ischemic Stroke Patients

Background and Purpose

YKL-40 is associated with various neurological disorders. However, circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS.

Methods

Serum YKL-40 and C-reactive protein (CRP) levels were monitored over time in AIS patients (n = 105) and compared with those of stroke-free controls (n = 34). Infarct volume and stroke severity (National Institutes of Health Stroke Scale; NIHSS) were measured within 48 hours of symptom onset, and functional outcome (modified Rankin Scale; mRS) was measured 3 months after AIS.

Results

Within 12 hours of symptom onset, levels of YKL-40 (251 vs. 41 ng/mL) and CRP (1.50 vs. 0.96 µg/mL) were elevated in AIS patients compared to controls. The power of YKL-40 for discriminating AIS patients from controls was superior to that of CRP (area under the curve 0.84 vs. 0.64) and YKL-40 (r = 0.26, P<0.001) but not CRP levels were correlated with mRS. On day 2 of admission (D2), YKL-40 levels correlated with infarct volume and NIHSS. High YKL-40 levels predicted poor functional outcome (odds ratio 5.73, P = 0.03). YKL-40 levels peaked on D2 and declined on D3, whereas CRP levels were highest on D3.

Conclusions

Our results demonstrate serial changes in serum YKL-40 levels immediately following AIS and provide the first evidence that it is a valid indicator of AIS extent and an early predictor of functional outcome.     

The Pretreatment Albumin to Globulin Ratio Has Predictive Value for Long-Term Mortality in Nasopharyngeal Carcinoma

Background

Low serum albumin is predictive of poor survival in nasopharyngeal carcinoma (NPC). We evaluated the ability of the pretreatment albumin/globulin ratio (AGR) to predict long-term mortality in patients with NPC.

Methods

This retrospective study examined an unselected cohort of 694 patients with NPC who had documented pretreatment total serum protein and serum albumin levels (ALB). AGR was calculated as [AGR = ALB/(total serum protein - ALB)]. Survival analysis was used to evaluate the predictive value of AGR.

Results

Multivariate analysis demonstrated that a low pretreatment serum AGR (<1.4) was an independent predictor of poor OS (P  = 0.029) and DMFS (P  = 0.033). A low AGR was significantly associated with advanced stage disease (P<0.001), high white blood cell count (P  = 0.033), high neutrophil count (P  = 0.047), high total serum protein (P<0.001) and low ALB (P<0.001).

Conclusion

The pretreatment AGR may represent a simple, potentially useful predictive biomarker for evaluating the long-term prognosis of patients with undifferentiated NPC.     

Phonatory Dysfunction as a Preclinical Symptom of Huntington Disease

Purpose

Although dysphonia has been shown to be a common sign of Huntington disease (HD), the extent of phonatory dysfunction in gene positive premanifest HD individuals remains unknown. The aim of the current study was to explore the possible occurrence of phonatory abnormalities in prodromal HD.

Method

Sustained vowel phonations were acquired from 28 premanifest HD individuals and 28 healthy controls of comparable age. Data were analysed acoustically for measures of several phonatory dimensions including airflow insufficiency, aperiodicity, irregular vibration of vocal folds, signal perturbations, increased noise, vocal tremor and articulation deficiency. A predictive model was built to find the best combination of acoustic features and estimate sensitivity/specificity for differentiation between premanifest HD subjects and controls. The extent of voice deficits according to a specific phonatory dimension was determined using statistical decision making theory. The results were correlated to global motor function, cognitive score, disease burden score and estimated years to disease onset.

Results

Measures of aperiodicity and increased noise were able to significantly differentiate between premanifest HD individuals and controls (p<0.01). The combination of these aspects of dysphonia led to a sensitivity of 91.5% and specificity of 79.2% to correctly distinguish speakers with premanifest HD from healthy individuals. Some form of disrupted phonatory function was revealed in 68% of our premanifest HD subjects, where 18% had one affected phonatory dimension and 50% showed impairment of two or more dimensions. A relationship between pitch control and cognitive score was also observed (r = −0.50, p = 0.007).

Conclusions

Phonatory abnormalities are detectable even the in premotor stages of HD. Speech investigation may have the potential to provide functional biomarkers of HD and could be included in future clinical trials and therapeutic interventions.     

Dietary Restriction and Exercise for Diabetic Patients with Chronic Kidney Disease: A Systematic Review

Background

Obesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD) have been conflicting.

Study Design

Systematic review.

Population

Diabetes patients with CKD stage 3 to 5.

Search Strategy and Sources

Medline, Embase and Central were searched to identify papers.

Intervention

Effect of a negative energy balance on hard outcomes in diabetics with CKD.

Outcomes

Death, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition.

Results

We retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from −0.66 to −1.77 g/24 h). Interventions with combined exercise and diet resulted in a slower decline of eGFR (−9.2 vs. −20.7 mL/min over two year observation; p<0.001). Aerobic and resistance exercise reduced HbA1c (−0.51 (−0.87 to −0.14); p = 0.007 and −0.38 (−0.72 to −0.22); p = 0.038, respectively). Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (−0.74% (−1.29 to −0.18); p = 0.009) and body weight (−2.2 kg (−3.9 to −0.6); p = 0.008). Resistance exercise reduces trunk fat mass (−0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001−0,005). In none of the studies did the intervention cause an increase in adverse events.

Limitations

All studies used a different intervention type and mixed patient groups.

Conclusions

There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful effects were observed.     

Salt-Restriction-Spoon Improved the Salt Intake among Residents in China

Objective

To evaluate the effect of an improved salt-restriction spoon on the attitude of salt-restriction, the using rate of salt-restriction-spoon, the actual salt intake, and 24-hour urinary sodium excretion (24HUNa).

Design

A community intervention study.

Setting

Two villages in Beijing.

Participants

403 local adult residents being responsible for home cooking.

Intervention

Participants were randomly assigned to the intervention group or the control group. Those in the intervention group were provided with an improved salt-restriction-spoon and health education, and were informed of their actual salt intake and 24HUNa. Not any intervention was given to those in the control group.

Main Outcome Measures

The scores on the variables of Health Belief Model, the using rate of salt-restriction-spoon, the actual salt intake, and 24HUNa.

Analysis

Covariance analyses, Chi-square tests, Student’s t tests, and repeated measures analyses of variance.

Results

After 6 months of intervention, the intervention group felt significantly less objective barriers, and got access to significantly more cues to action as compared to the control group. The using rate and the correctly using rate of salt-restriction-spoon were significantly higher in the intervention group. The daily salt intake decreased by 1.42 g in the intervention group and by 0.28 g in the control group, and repeated measures analysis of variance showed significant change over time (F = 7.044, P<0.001) and significant difference between groups by time (F = 2.589, P = 0.041). The 24HUNa decreased by 34.84 mmol in the intervention group and by 33.65 mmol in the control group, and repeated measures analysis of variance showed significant change over time (F = 14.648, P<0.001) without significant difference between groups by time (F = 0.222, P = 0.870).

Conclusions

The intervention effect was acceptable, therefore, the improved salt-restriction-spoon and corresponding health education could be considered as an alternative for salt reduction strategy in China and other countries where salt intake comes mainly from home cooking.     

Decreased Frequencies of Circulating CD4+ T Follicular Helper Cells Associated with Diminished Plasma IL-21 in Active Pulmonary Tuberculosis

Background

Circulating T follicular helper (Tfh) cells represent a distinct subset of CD4⁺ T cells and are important in immunity to infections. Although they have been shown to play a role in experimental models of tuberculosis infection, their role in human tuberculosis remains unexplored.

Aims/Methodology

To determine the distribution of circulating Tfh cells in human TB, we measured the frequencies of Tfh cells ex vivo and following TB - antigen or polyclonal stimulation in pulmonary TB (PTB; n = 30) and latent TB (LTB; n = 20) individuals, using the markers CXCR5, PD-1 and ICOS.

Results

We found that both ex vivo and TB - antigen induced frequencies of Tfh cell subsets was significantly lower in PTB compared to LTB individuals. Similarly, antigen induced frequencies of Tfh cells expressing IL-21 was also significantly lower in PTB individuals and this was reflected in diminished circulating levels of IL-21 and IFNγ. This was not accompanied by diminished frequencies of activated or memory B cell subsets. Finally, the diminution in frequency of Tfh cells in PTB individuals was dependent on IL-10, CTLA-4 and PD-L1 in vitro.

Conclusions

Thus, PTB is characterized by adiminution in the frequency of Tfh cell subsets.     

Evidence of the Innate Antiviral and Neuroprotective Properties of Progranulin

Background

Compelling data exist that show that normal levels of progranulin (PGRN) are required for successful CNS aging. PGRN production is also modulated by inflammation and infection, but no data are available on the production and role of PGRN during CNS HIV infection.

Methods

To determine the relationships between PGRN and HIV disease, neurocognition, and inflammation, we analyzed 107 matched CSF and plasma samples from CHARTER, a well-characterized HIV cohort. Levels of PGRN were determined by ELISA and compared to levels of several inflammatory mediators (IFNγ, IL-6, IL-10, IP-10, MCP-1, TNFα, IL-1β, IL-4 and IL-13), as well as clinical, virologic and demographic parameters. The relationship between HIV infection and PGRN was also examined in HIV-infected primary human microglial cultures.

Results

In plasma, PGRN levels correlated with the viral load (VL, p<0.001). In the CSF of subjects with undetectable VL, lower PGRN was associated with neurocognitive impairment (p = 0.046). CSF PGRN correlated with CSF IP-10, TNFα and IL-10, and plasma PGRN correlated with plasma IP-10. In vitro, microglial HIV infection increased PGRN production and PGRN knockdown increased HIV replication, demonstrating that PGRN is an innate antiviral protein.

Conclusions

We propose that PGRN plays dual roles in people living with HIV disease. With active HIV replication, PGRN is induced in infected macrophages and microglia and functions as an antiviral protein. In individuals without active viral replication, decreased PGRN production contributes to neurocognitive dysfunction, probably through a diminution of its neurotrophic functions. Our results have implications for the pathogenesis, biomarker studies and therapy for HIV diseases including HIV-associated neurocognitive dysfunction (HAND).     

Socioeconomic Status,Functional Recovery,and Long-Term Mortality among Patients Surviving Acute Myocardial Infarction

Objectives

To examine the relationship between socio-economic status (SES), functional recovery and long-term mortality following acute myocardial infarction (AMI).

Background

The extent to which SES mortality disparities are explained by differences in functional recovery following AMI is unclear.

Methods

We prospectively examined 1368 patients who survived at least one-year following an index AMI between 1999 and 2003 in Ontario, Canada. Each patient was linked to administrative data and followed over 9.6 years to track mortality. All patients underwent medical chart abstraction and telephone interviews following AMI to identify individual-level SES, clinical factors, processes of care (i.e., use of, and adherence, to evidence-based medications, physician visits, invasive cardiac procedures, referrals to cardiac rehabilitation), as well as changes in psychosocial stressors, quality of life, and self-reported functional capacity.

Results

As compared with their lower SES counterparts, higher SES patients experienced greater functional recovery (1.80 ml/kg/min average increase in peak V02, P<0.001) after adjusting for all baseline clinical factors. Post-AMI functional recovery was the strongest modifiable predictor of long-term mortality (Adjusted HR for each ml/kg/min increase in functional capacity: 0.91; 95% CI: 0.87–0.94, P<0.001) irrespective of SES (P = 0.51 for interaction between SES, functional recovery, and mortality). SES-mortality associations were attenuated by 27% after adjustments for functional recovery, rendering the residual SES-mortality association no longer statistically significant (Adjusted HR: 0.84; 95% CI:0.70–1.00, P = 0.05). The effects of functional recovery on SES-mortality associations were not explained by access inequities to physician specialists or cardiac rehabilitation.

Conclusions

Functional recovery may play an important role in explaining SES-mortality gradients following AMI.     

Recovery from Anemia in Patients with Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation – Prevalence,Predictors and Clinical Outcome

Introduction

Preoperative anemia is common in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and has been linked to a poorer outcome – including a higher 1-year mortality. The aim of this study was to investigate the impact of successful TAVI on baseline anemia.

Methods

A total of 253 patients who survived at least 1 year following TAVI were included in this study. The prevalence, predictors and clinical outcome of hemoglobin (Hb)-recovery were assessed.

Results

The prevalence of baseline anemia was 49% (n = 124) – recovery from anemia occurred in 40% of the anemic patients (n = 49) at 1 year after TAVI with an increase in mean Hb-level of 1.35 g/dL from baseline. This increase was not related to an improvement in renal function. At multivariate analysis, a high peak gradient (OR 4.82, P = 0.003) was shown to be an independent predictor for Hb-recovery, while blood transfusion (OR 0.31, P = 0.038) and chronic kidney disease (CKD, OR 0.33, P = 0.043) were identified as negative predictors at, respectively, one and two years after TAVI. When compared to patients without baseline anemia, those anemic patients with Hb-recovery had a similar functional improvement (OR 0.98, P = 0.975), whereas those without Hb-recovery had a significantly lower likelihood of functional improvement with ≧2 NYHA classes (OR 0.49, P = 0.034) and a higher likelihood of re-hospitalization within the first year after TAVI (OR 1.91, P = 0.024).

Conclusion

Recovery from anemia occurs in 40% of anemic patients at 1 year after TAVI – mainly in those with a high gradient and without CKD. Blood transfusion was found to have a transient adverse effect on this Hb-recovery. Finally, anemic patients without Hb-recovery experience less functional improvement and have a higher re-hospitalization rate within the first year after TAVI.