Hyperbaric Oxygen Therapy Can Improve Post Concussion Syndrome Years after Mild Traumatic Brain Injury - Randomized Prospective Trial

Background

Traumatic brain injury (TBI) is the leading cause of death and disability in the US. Approximately 70-90% of the TBI cases are classified as mild, and up to 25% of them will not recover and suffer chronic neurocognitive impairments. The main pathology in these cases involves diffuse brain injuries, which are hard to detect by anatomical imaging yet noticeable in metabolic imaging. The current study tested the effectiveness of Hyperbaric Oxygen Therapy (HBOT) in improving brain function and quality of life in mTBI patients suffering chronic neurocognitive impairments.

Methods and Findings

The trial population included 56 mTBI patients 1–5 years after injury with prolonged post-concussion syndrome (PCS). The HBOT effect was evaluated by means of prospective, randomized, crossover controlled trial: the patients were randomly assigned to treated or crossover groups. Patients in the treated group were evaluated at baseline and following 40 HBOT sessions; patients in the crossover group were evaluated three times: at baseline, following a 2-month control period of no treatment, and following subsequent 2-months of 40 HBOT sessions. The HBOT protocol included 40 treatment sessions (5 days/week), 60 minutes each, with 100% oxygen at 1.5 ATA. “Mindstreams” was used for cognitive evaluations, quality of life (QOL) was evaluated by the EQ-5D, and changes in brain activity were assessed by SPECT imaging. Significant improvements were demonstrated in cognitive function and QOL in both groups following HBOT but no significant improvement was observed following the control period. SPECT imaging revealed elevated brain activity in good agreement with the cognitive improvements.

Conclusions

HBOT can induce neuroplasticity leading to repair of chronically impaired brain functions and improved quality of life in mTBI patients with prolonged PCS at late chronic stage.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00715052","term_id":"NCT00715052"}}NCT00715052     

Development of a Melanoma Risk Prediction Model Incorporating MC1R Genotype and Indoor Tanning Exposure: Impact of Mole Phenotype on Model Performance

Background

Identifying individuals at increased risk for melanoma could potentially improve public health through targeted surveillance and early detection. Studies have separately demonstrated significant associations between melanoma risk, melanocortin receptor (MC1R) polymorphisms, and indoor ultraviolet light (UV) exposure. Existing melanoma risk prediction models do not include these factors; therefore, we investigated their potential to improve the performance of a risk model.

Methods

Using 875 melanoma cases and 765 controls from the population-based Minnesota Skin Health Study we compared the predictive ability of a clinical melanoma risk model (Model A) to an enhanced model (Model F) using receiver operating characteristic (ROC) curves. Model A used self-reported conventional risk factors including mole phenotype categorized as “none”, “few”, “some” or “many” moles. Model F added MC1R genotype and measures of indoor and outdoor UV exposure to Model A. We also assessed the predictive ability of these models in subgroups stratified by mole phenotype (e.g. nevus-resistant (“none” and “few” moles) and nevus-prone (“some” and “many” moles)).

Results

Model A (the reference model) yielded an area under the ROC curve (AUC) of 0.72 (95% CI = 0.69, 0.74). Model F was improved with an AUC = 0.74 (95% CI = 0.71–0.76, p<0.01). We also observed substantial variations in the AUCs of Models A & F when examined in the nevus-prone and nevus-resistant subgroups.

Conclusions

These results demonstrate that adding genotypic information and environmental exposure data can increase the predictive ability of a clinical melanoma risk model, especially among nevus-prone individuals.     

MRI Evidence for Altered Venous Drainage and Intracranial Compliance in Mild Traumatic Brain Injury

Purpose

To compare venous drainage patterns and associated intracranial hydrodynamics between subjects who experienced mild traumatic brain injury (mTBI) and age- and gender-matched controls.

Methods

Thirty adult subjects (15 with mTBI and 15 age- and gender-matched controls) were investigated using a 3T MR scanner. Time since trauma was 0.5 to 29 years (mean 11.4 years). A 2D-time-of-flight MR-venography of the upper neck was performed to visualize the cervical venous vasculature. Cerebral venous drainage through primary and secondary channels, and intracranial compliance index and pressure were derived using cine-phase contrast imaging of the cerebral arterial inflow, venous outflow, and the craniospinal CSF flow. The intracranial compliance index is the defined as the ratio of maximal intracranial volume and pressure changes during the cardiac cycle. MR estimated ICP was then obtained through the inverse relationship between compliance and ICP.

Results

Compared to the controls, subjects with mTBI demonstrated a significantly smaller percentage of venous outflow through internal jugular veins (60.9±21% vs. controls: 76.8±10%; p = 0.01) compensated by an increased drainage through secondary veins (12.3±10.9% vs. 5.5±3.3%; p<0.03). Mean intracranial compliance index was significantly lower in the mTBI cohort (5.8±1.4 vs. controls 8.4±1.9; p<0.0007). Consequently, MR estimate of intracranial pressure was significantly higher in the mTBI cohort (12.5±2.9 mmHg vs. 8.8±2.0 mmHg; p<0.0007).

Conclusions

mTBI is associated with increased venous drainage through secondary pathways. This reflects higher outflow impedance, which may explain the finding of reduced intracranial compliance. These results suggest that hemodynamic and hydrodynamic changes following mTBI persist even in the absence of clinical symptoms and abnormal findings in conventional MR imaging.     

Shannon and Renyi entropies to classify effects of Mild Traumatic Brain Injury on postural sway

Background

Mild Traumatic Brain Injury (mTBI) has been identified as a major public and military health concern both in the United States and worldwide. Characterizing the effects of mTBI on postural sway could be an important tool for assessing recovery from the injury.

Methodology/Principal Findings

We assess postural sway by motion of the center of pressure (COP). Methods for data reduction include calculation of area of COP and fractal analysis of COP motion time courses. We found that fractal scaling appears applicable to sway power above about 0.5 Hz, thus fractal characterization is only quantifying the secondary effects (a small fraction of total power) in the sway time series, and is not effective in quantifying long-term effects of mTBI on postural sway. We also found that the area of COP sensitively depends on the length of data series over which the COP is obtained. These weaknesses motivated us to use instead Shannon and Renyi entropies to assess postural instability following mTBI. These entropy measures have a number of appealing properties, including capacity for determination of the optimal length of the time series for analysis and a new interpretation of the area of COP.

Conclusions

Entropy analysis can readily detect postural instability in athletes at least 10 days post-concussion so that it appears promising as a sensitive measure of effects of mTBI on postural sway.

Availability

The programs for analyses may be obtained from the authors.     

Combining Biochemical and Imaging Markers to Improve Diagnosis and Characterization of Mild Traumatic Brain Injury in the Acute Setting: Results from a Pilot Study

Background

Mild traumatic brain injury (mTBI) is a significant healthcare burden and its diagnosis remains a challenge in the emergency department. Serum biomarkers and advanced magnetic resonance imaging (MRI) techniques have already demonstrated their potential to improve the detection of brain injury even in patients with negative computed tomography (CT) findings. The objective of this study was to determine the clinical value of a combinational use of both blood biomarkers and MRI in mTBI detection and their characterization in the acute setting (within 24 hours after injury).

Methods

Nine patients with mTBI were prospectively recruited from the emergency department. Serum samples were collected at the time of hospital admission and every 6 hours up to 24 hours post injury. Neuronal (Ubiquitin C-terminal Hydrolase-L1 [UCH-L1]) and glial (glial fibrillary acidic protein [GFAP]) biomarker levels were analyzed. Advanced MRI data were acquired at 9±6.91 hours after injury. Patients’ neurocognitive status was assessed by using the Standard Assessment of Concussion (SAC) instrument.

Results

The median serum levels of UCH-L1 and GFAP on admission were increased 4.9 folds and 10.6 folds, respectively, compared to reference values. Three patients were found to have intracranial hemorrhages on SWI, all of whom had very high GFAP levels. Total volume of brain white matter (WM) with abnormal fractional anisotropy (FA) measures of diffusion tensor imaging (DTI) were negatively correlated with patients’ SAC scores, including delayed recall. Both increased and decreased DTI-FA values were observed in the same subjects. Serum biomarker level was not correlated with patients’ DTI data nor SAC score.

Conclusions

Blood biomarkers and advanced MRI may correlate or complement each other in different aspects of mTBI detection and characterization. GFAP might have potential to serve as a clinical screening tool for intracranial bleeding. UCH-L1 complements MRI in injury detection. Impairment at WM tracts may account for the patients’ neurocognitive symptoms.     

Cost-Effectiveness of a Community Pharmacist-Led Sleep Apnea Screening Program – A Markov Model

Background

Despite the high prevalence and major public health ramifications, obstructive sleep apnea syndrome (OSAS) remains underdiagnosed. In many developed countries, because community pharmacists (CP) are easily accessible, they have been developing additional clinical services that integrate the services of and collaborate with other healthcare providers (general practitioners (GPs), nurses, etc.). Alternative strategies for primary care screening programs for OSAS involving the CP are discussed.

Objective

To estimate the quality of life, costs, and cost-effectiveness of three screening strategies among patients who are at risk of having moderate to severe OSAS in primary care.

Design

Markov decision model.

Data Sources

Published data.

Target Population

Hypothetical cohort of 50-year-old male patients with symptoms highly evocative of OSAS.

Time Horizon

The 5 years after initial evaluation for OSAS.

Perspective

Societal.

Interventions

Screening strategy with CP (CP-GP collaboration), screening strategy without CP (GP alone) and no screening.

Outcomes measures

Quality of life, survival and costs for each screening strategy.

Results of base-case analysis

Under almost all modeled conditions, the involvement of CPs in OSAS screening was cost effective. The maximal incremental cost for “screening strategy with CP” was about 455€ per QALY gained.

Results of sensitivity analysis

Our results were robust but primarily sensitive to the treatment costs by continuous positive airway pressure, and the costs of untreated OSAS. The probabilistic sensitivity analysis showed that the “screening strategy with CP” was dominant in 80% of cases. It was more effective and less costly in 47% of cases, and within the cost-effective range (maximum incremental cost effectiveness ratio at €6186.67/QALY) in 33% of cases.

Conclusions

CP involvement in OSAS screening is a cost-effective strategy. This proposal is consistent with the trend in Europe and the United States to extend the practices and responsibilities of the pharmacist in primary care.     

Early Detection of Ventilation-Induced Brain Injury Using Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: An In Vivo Study in Preterm Lambs

Background and Aim

High tidal volume (V_T) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs.

Methods

Newborn lambs (0.85 gestation) were stabilized with a “protective ventilation” strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, V_T 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH₂O) or an initial 15 minutes of “injurious ventilation” (INJ, n = 10: V_T 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm³, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman''s correlations.

Results

No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups.

Conclusion

Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury.     

Diffusion Tensor Magnetic Resonance Imaging of the Brain in APP Transgenic Mice: A Cohort Study

Introduction

Fast in-vivo high resolution diffusion tensor imaging (DTI) of the mouse brain has recently been shown to enable cohort studies by the combination of appropriate pulse sequences and cryogenically cooled resonators (CCR). The objective of this study was to apply this DTI approach at the group level to β-amyloid precursor protein (APP) transgenic mice.

Methods

Twelve mice (5 wild type, 7 APP transgenic tg2576) underwent DTI examination at 156²×250 µm³ spatial resolution with a CCR at ultrahigh field (11.7 T). Diffusion images were acquired along 30 gradient directions plus 5 references without diffusion encoding with a total acquisition time of 35 minutes. Fractional anisotropy (FA) maps were statistically compared by whole brain-based spatial statistics (WBSS) at the group level vs. wild type controls.

Results

FA-map comparison showed characteristic regional patterns of differences between the groups with localizations associated with Alzheimer’s disease in humans, such as the hippocampus, the entorhinal cortex, and the caudoputamen.

Conclusion

In this proof-of-principle study, regions associated with amyloid-β deposition could be identified by WBSS of FA maps in APP transgenic mice vs. wild type mice. Thus, DTI in the mouse brain acquired at 11.7 T by use of a CCR was demonstrated to be feasible for cohort studies.     

Tractography of the Brainstem in Major Depressive Disorder Using Diffusion Tensor Imaging

Background

The brainstem is the main region that innervates neurotransmitter release to the Hypothalamic-Pituitary Adrenal (HPA) axis and fronto-limbic circuits, two key brain circuits found to be dysfunctional in Major Depressive Disorder (MDD). However, the brainstem’s role in MDD has only been evaluated in limited reports. Using Diffusion Tensor Imaging (DTI), we investigated whether major brainstem white matter tracts that relate to these two circuits differ in MDD patients compared to healthy controls.

Methods

MDD patients (n = 95) and age- and gender-matched controls (n = 34) were assessed using probabilistic tractography of DTI to delineate three distinct brainstem tracts: the nigrostriatal tract (connecting brainstem to striatum), solitary tract (connecting brainstem to amygdala) and corticospinal tract (connecting brainstem to precentral cortex). Fractional anisotropy (FA) was used to measure the white matter integrity of these tracts, and measures were compared between MDD and control participants.

Results

MDD participants were characterized by a significant and specific decrease in white matter integrity of the right solitary tract (p<0.009 using independent t-test), which is a “bottom up” afferent pathway that connects the brainstem to the amygdala. This decrease was not related to symptom severity.

Conclusions

The results provide new evidence to suggest that structural connectivity between the brainstem and the amygdala is altered in MDD. These results are interesting in light of predominant theories regarding amygdala-mediated emotional reactivity observed in functional imaging studies of MDD. The characterization of altered white matter integrity in the solitary tract in MDD supports the possibility of dysfunctional brainstem-amygdala connectivity impacting vulnerable circuits in MDD.     

Brainstem Involvement as a Cause of Central Sleep Apnea: Pattern of Microstructural Cerebral Damage in Patients with Cerebral Microangiopathy

Background

The exact underlying pathomechanism of central sleep apnea with Cheyne-Stokes respiration (CSA-CSR) is still unclear. Recent studies have demonstrated an association between cerebral white matter changes and CSA. A dysfunction of central respiratory control centers in the brainstem was suggested by some authors. Novel MR-imaging analysis tools now allow far more subtle assessment of microstructural cerebral changes. The aim of this study was to investigate whether and what severity of subtle structural cerebral changes could lead to CSA-CSR, and whether there is a specific pattern of neurodegenerative changes that cause CSR. Therefore, we examined patients with Fabry disease (FD), an inherited, lysosomal storage disease. White matter lesions are early and frequent findings in FD. Thus, FD can serve as a "model disease" of cerebral microangiopathy to study in more detail the impact of cerebral lesions on central sleep apnea.

Patients and Methods

Genetically proven FD patients (n = 23) and age-matched healthy controls (n = 44) underwent a cardio-respiratory polysomnography and brain MRI at 3.0 Tesla. We applied different MR-imaging techniques, ranging from semiquantitative measurement of white matter lesion (WML) volumes and automated calculation of brain tissue volumes to VBM of gray matter and voxel-based diffusion tensor imaging (DTI) analysis.

Results

In 5 of 23 Fabry patients (22%) CSA-CSR was detected. Voxel-based DTI analysis revealed widespread structural changes in FD patients when compared to the healthy controls. When calculated as a separate group, DTI changes of CSA-CSR patients were most prominent in the brainstem. Voxel-based regression analysis revealed a significant association between CSR severity and microstructural DTI changes within the brainstem.

Conclusion

Subtle microstructural changes in the brainstem might be a neuroanatomical correlate of CSA-CSR in patients at risk of WML. DTI is more sensitive and specific than conventional structural MRI and other advanced MR analyses tools in demonstrating these abnormalities.     

Linear Associations between Clinically Assessed Upper Motor Neuron Disease and Diffusion Tensor Imaging Metrics in Amyotrophic Lateral Sclerosis

Objective

To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI).

Methods

This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates.

Results

For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003).

Conclusions

Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination.     

Fast Diffusion Tensor Magnetic Resonance Imaging of the Mouse Brain at Ultrahigh-Field: Aiming at Cohort Studies

Introduction

In-vivo high resolution diffusion tensor imaging (DTI) of the mouse brain is often limited by the low signal to noise ratio (SNR) resulting from the required small voxel sizes. Recently, cryogenically cooled resonators (CCR) have demonstrated significant increase of the effective SNR. It is the objective of this study to enable fast DTI of the mouse brain. In this context, CCRs appear attractive for SNR improvement.

Methods

Three mice underwent a DTI examination at 156²×250 µm³ spatial resolution with a CCR at ultrahigh field (11.7T). Diffusion images were acquired along 30 gradient directions plus 5 references without diffusion encoding, resulting in a total acquisition time of 35 minutes. For comparison, mice additionally underwent a standardized 110 minutes acquisition protocol published earlier. Fractional anisotropy (FA) and fiber tracking (FT) results including quantitative tractwise fractional anisotropy statistics (TFAS) were qualitatively and quantitatively compared.

Results

Qualitative and quantitative assessment of the calculated fractional anisotropy maps and fibre tracking results showed coinciding outcome comparing 35 minute scans to the standardized 110 minute scan. Coefficients of variation for ROI-based FA-comparison as well as for TFAS revealed comparable results for the different scanning protocols.

Conclusion

Mouse DTI at 11.7 T was performed with an acquisition time of approximately 30 minutes, which is considered feasible for cohort studies. The rapid acquisition protocol reveals reliable and reproducible FA-values and FT reconstructions, thus allowing an experimental setup for in-vivo large scale whole brain murine DTI cohort studies.     

The Value of Diffusion Tensor Imaging in Differentiating High-Grade Gliomas from Brain Metastases: A Systematic Review and Meta-Analysis

Purpose

Differentiation of high-grade gliomas and solitary brain metastases is an important clinical issue because the treatment strategies differ greatly. Our study aimed to investigate the potential value of diffusion tensor imaging (DTI) in differentiating high-grade gliomas from brain metastases using a meta-analytic approach.

Materials and Methods

We searched Pubmed, Embase and the Cochrane Library for relevant articles published in English. Studies that both investigated high-grade gliomas and brain metastases using DTI were included. Random effect model was used to compare fractional anisotropy (FA) and mean diffusivity (MD) values in the two tumor entities.

Results

Nine studies were included into the meta-analysis. In the peritumoral region, compared with brain metastases, high-grade gliomas had a significant increase of FA (SMD  = 0.47; 95% CI, 0.22–0.71; P<0.01) and a significant decrease of MD (SMD  = −1.49; 95% CI, −1.91 to −1.06; P<0.01). However, in the intratumoral area, no significant change in FA (SMD  = 0.16; 95% CI, −0.49 to 0.82; P = 0.73) or MD (SMD  = 0.34; 95% CI, −0.91 to 1.60; P = 0.59) was detected between gliomas and metastases.

Conclusions

High-grade gliomas may be distinguished from brain metastases by comparing the peritumoral FA and MD values. DTI appears to be a promising tool in diagnosing solitary intracranial lesions.     

Levels of State and Trait Anxiety in Patients Referred to Ophthalmology by Primary Care Clinicians: A Cross Sectional Study

Purpose

There is a high level of over-referral from primary eye care leading to significant numbers of people without ocular pathology (false positives) being referred to secondary eye care. The present study used a psychometric instrument to determine whether there is a psychological burden on patients due to referral to secondary eye care, and used Rasch analysis to convert the data from an ordinal to an interval scale.

Design

Cross sectional study.

Participants and Controls

322 participants and 80 control participants.

Methods

State (i.e. current) and trait (i.e. propensity to) anxiety were measured in a group of patients referred to a hospital eye department in the UK and in a control group who have had a sight test but were not referred. Response category analysis plus infit and outfit Rasch statistics and person separation indices were used to determine the usefulness of individual items and the response categories. Principal components analysis was used to determine dimensionality.

Main Outcome Measure

Levels of state and trait anxiety measured using the State-Trait Anxiety Inventory.

Results

State anxiety scores were significantly higher in the patients referred to secondary eye care than the controls (p<0.04), but similar for trait anxiety (p>0.1). Rasch analysis highlighted that the questionnaire results needed to be split into “anxiety-absent” and “anxiety-present” items for both state and trait anxiety, but both subscales showed the same profile of results between patients and controls.

Conclusions

State anxiety was shown to be higher in patients referred to secondary eye care than the controls, and at similar levels to people with moderate to high perceived susceptibility to breast cancer. This suggests that referral from primary to secondary eye care can result in a significant psychological burden on some patients.     

A Prospective Study of LINE-1DNA Methylation and Development of Adiposity in School-Age Children

Background

Repetitive element DNA methylation is related to prominent obesity-related chronic diseases including cancer and cardiovascular disease; yet, little is known of its relation with weight status. We examined associations of LINE-1 DNA methylation with changes in adiposity and linear growth in a longitudinal study of school-age children from Bogotá, Colombia.

Methods

We quantified methylation of LINE-1 elements from peripheral leukocytes of 553 children aged 5–12 years at baseline using pyrosequencing technology. Anthropometric characteristics were measured periodically for a median of 30 months. We estimated mean change in three age-and sex-standardized indicators of adiposity: body mass index (BMI)-for-age Z-score, waist circumference Z-score, and subscapular-to-triceps skinfold thickness ratio Z-score according to quartiles of LINE-1 methylation using mixed effects regression models. We also examined associations with height-for-age Z-score.

Results

There were non-linear, inverse relations of LINE-1 methylation with BMI-for-age Z-score and the skinfold thickness ratio Z-score. After adjustment for baseline age and socioeconomic status, boys in the lowest quartile of LINE-1 methylation experienced annual gains in BMI-for-age Z-score and skinfold thickness ratio Z-score that were 0.06 Z/year (P = 0.04) and 0.07 Z/year (P = 0.03), respectively, higher than those in the upper three quartiles. The relation of LINE-1 methylation and annual change in waist circumference followed a decreasing monotonic trend across the four quartiles (P trend = 0.02). DNA methylation was not related to any of the adiposity indicators in girls. There were no associations between LINE-1 methylation and linear growth in either sex.

Conclusions

Lower LINE-1 DNA methylation is related to development of adiposity in boys.     

Task Shifting for Non-Communicable Disease Management in Low and Middle Income Countries – A Systematic Review

Background

One potential solution to limited healthcare access in low and middle income countries (LMIC) is task-shifting- the training of non-physician healthcare workers (NPHWs) to perform tasks traditionally undertaken by physicians. The aim of this paper is to conduct a systematic review of studies involving task-shifting for the management of non-communicable disease (NCD) in LMIC.

Methods

A search strategy with the following terms “task-shifting”, “non-physician healthcare workers”, “community healthcare worker”, “hypertension”, “diabetes”, “cardiovascular disease”, “mental health”, “depression”, “chronic obstructive pulmonary disease”, “respiratory disease”, “cancer” was conducted using Medline via Pubmed and the Cochrane library. Two reviewers independently reviewed the databases and extracted the data.

Findings

Our search generated 7176 articles of which 22 were included in the review. Seven studies were randomised controlled trials and 15 were observational studies. Tasks performed by NPHWs included screening for NCDs and providing primary health care. The majority of studies showed improved health outcomes when compared with usual healthcare, including reductions in blood pressure, increased uptake of medications and lower depression scores. Factors such as training of NPHWs, provision of algorithms and protocols for screening, treatment and drug titration were the main enablers of the task-shifting intervention. The main barriers identified were restrictions on prescribing medications and availability of medicines. Only two studies described cost-effective analyses, both of which demonstrated that task-shifting was cost-effective.

Conclusions

Task-shifting from physicians to NPHWs, if accompanied by health system re-structuring is a potentially effective and affordable strategy for improving access to healthcare for NCDs. Since the majority of study designs reviewed were of inadequate quality, future research methods should include robust evaluations of such strategies.     

Assessing the Impact of the National Smoking Ban in Indoor Public Places in China: Evidence from Quit Smoking Related Online Searches

Background

Despite the tremendous economic and health costs imposed on China by tobacco use, China lacks a proactive and systematic tobacco control surveillance and evaluation system, hampering research progress on tobacco-focused surveillance and evaluation studies.

Methods

This paper uses online search query analyses to investigate changes in online search behavior among Chinese Internet users in response to the adoption of the national indoor public place smoking ban. Baidu Index and Google Trends were used to examine the volume of search queries containing three key search terms “Smoking Ban(s),” “Quit Smoking,” and “Electronic Cigarette(s),” along with the news coverage on the smoking ban, for the period 2009–2011.

Findings

Our results show that the announcement and adoption of the indoor public place smoking ban in China generated significant increases in news coverage on smoking bans. There was a strong positive correlation between the media coverage of smoking bans and the volume of “Smoking Ban(s)” and “Quit Smoking” related search queries. The volume of search queries related to “Electronic Cigarette(s)” was also correlated with the smoking ban news coverage.

Interpretation

To the extent it altered smoking-related online searches, our analyses suggest that the smoking ban had a significant effect, at least in the short run, on Chinese Internet users’ smoking-related behaviors. This research introduces a novel analytic tool, which could serve as an alternative tobacco control evaluation and behavior surveillance tool in the absence of timely or comprehensive population surveillance system. This research also highlights the importance of a comprehensive approach to tobacco control in China.     

Relative Influence of Genetics and Shared Environment on Child Mental Health Symptoms Depends on Comorbidity

Background

Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes.

Methods

The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%).

Results

Latent class models delineated groups of children according to symptom profiles–not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a “Low Symptom” class to a “Moderately Internalizing & Severely Externalizing” class. In addition, a “Moderately Anxious” class was identified for girls but not boys, and a “Severely Impulsive & Inattentive” class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the “Low Symptom” and “Moderately Internalizing & Severely Externalizing” classes, and small to zero for other classes.

Conclusions

We conclude that symptom classes are largely similar across sexes in middle childhood. Heritability was moderate for all classes, but shared environment played a greater role for classes in which no one type of symptom predominated.