Deep Brain Stimulation of the Antero-Medial Globus Pallidus Interna for Tourette Syndrome

Background

We have previously reported the results of Deep Brain Stimulation (DBS) of the antero-medial globus pallidus interna (GPi) for severe Tourette Syndrome (TS) in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months.

Methods

17 patients (14 male; mean age 29.1 years, range 17–51 years) with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS). Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8–46 months) following surgery.

Results

Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6%) patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1), transient anxiety (2), dizziness (1), poor balance (1) and worsening of stuttering (1).

Conclusions

This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.     

Acute and Chronic Mood and Apathy Outcomes from a Randomized Study of Unilateral STN and GPi DBS

Objective

To study mood and behavioral effects of unilateral and staged bilateral subthalamic nucleus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for Parkinson''s disease (PD).

Background

There are numerous reports of mood changes following DBS, however, most have focused on bilateral simultaneous STN implants with rapid and aggressive post-operative medication reduction.

Methods

A standardized evaluation was applied to a subset of patients undergoing STN and GPi DBS and who were also enrolled in the NIH COMPARE study. The Unified Parkinson Disease Rating Scale (UPDRS III), the Hamilton depression (HAM-D) and anxiety rating scales (HAM-A), the Yale-Brown obsessive-compulsive rating scale (YBOCS), the Apathy Scale (AS), and the Young mania rating scale (YMRS) were used. The scales were repeated at acute and chronic intervals. A post-operative strategy of non-aggressive medication reduction was employed.

Results

Thirty patients were randomized and underwent unilateral DBS (16 STN, 14 GPi). There were no baseline differences. The GPi group had a higher mean dopaminergic dosage at 1-year, however the between group difference in changes from baseline to 1-year was not significant. There were no differences between groups in mood and motor outcomes. When combining STN and GPi groups, the HAM-A scores worsened at 2-months, 4-months, 6-months and 1-year when compared with baseline; the HAM-D and YMRS scores worsened at 4-months, 6-months and 1-year; and the UPDRS Motor scores improved at 4-months and 1-year. Psychiatric diagnoses (DSM-IV) did not change. No between group differences were observed in the cohort of bilateral cases.

Conclusions

There were few changes in mood and behavior with STN or GPi DBS. The approach of staging STN or GPi DBS without aggressive medication reduction could be a viable option for managing PD surgical candidates. A study of bilateral DBS and of medication reduction will be required to better understand risks and benefits of a bilateral approach.     

Bimanual Force Coordination in Parkinson’s Disease Patients with Bilateral Subthalamic Deep Brain Stimulation

Objective

Studies of bimanual actions similar to activities of daily living (ADLs) are currently lacking in evaluating fine motor control in Parkinson’s disease patients implanted with bilateral subthalamic deep brain stimulators. We investigated basic time and force characteristics of a bimanual task that resembles performance of ADLs in a group of bilateral subthalamic deep brain stimulation (DBS) patients.

Methods

Patients were evaluated in three different DBS parameter conditions off stimulation, on clinically derived stimulation parameters, and on settings derived from a patient-specific computational model. Model-based parameters were computed as a means to minimize spread of current to non-motor regions of the subthalamic nucleus via Cicerone Deep Brain Stimulation software. Patients were evaluated off parkinsonian medications in each stimulation condition.

Results

The data indicate that DBS parameter state does not affect most aspects of fine motor control in ADL-like tasks; however, features such as increased grip force and grip symmetry varied with the stimulation state. In the absence of DBS parameters, patients exhibited significant grip force asymmetry. Overall UPDRS-III and UPDRS-III scores associated with hand function were lower while patients were experiencing clinically-derived or model-based parameters, as compared to the off-stimulation condition.

Conclusion

While bilateral subthalamic DBS has been shown to alleviate gross motor dysfunction, our results indicate that DBS may not provide the same magnitude of benefit to fine motor coordination.     

Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia

Background

GPi (Internal globus pallidus) DBS (deep brain stimulation) is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.

Objectives

This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.

Methods

Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12–84)

Results

The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006). The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073). When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.

Conclusions

GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.     

Coordinate-Based Lead Location Does Not Predict Parkinson's Disease Deep Brain Stimulation Outcome

Background

Effective target regions for deep brain stimulation (DBS) in Parkinson''s disease (PD) have been well characterized. We sought to study whether the measured Cartesian coordinates of an implanted DBS lead are predictive of motor outcome(s). We tested the hypothesis that the position and trajectory of the DBS lead relative to the mid-commissural point (MCP) are significant predictors of clinical outcomes. We expected that due to neuroanatomical variation among individuals, a simple measure of the position of the DBS lead relative to MCP (commonly used in clinical practice) may not be a reliable predictor of clinical outcomes when utilized alone.

Methods

55 PD subjects implanted with subthalamic nucleus (STN) DBS and 41 subjects implanted with globus pallidus internus (GPi) DBS were included. Lead locations in AC-PC space (x, y, z coordinates of the active contact and sagittal and coronal entry angles) measured on high-resolution CT-MRI fused images, and motor outcomes (Unified Parkinson''s Disease Rating Scale) were analyzed to confirm or refute a correlation between coordinate-based lead locations and DBS motor outcomes.

Results

Coordinate-based lead locations were not a significant predictor of change in UPDRS III motor scores when comparing pre- versus post-operative values. The only potentially significant individual predictor of change in UPDRS motor scores was the antero-posterior coordinate of the GPi lead (more anterior lead locations resulted in a worse outcome), but this was only a statistical trend (p<.082).

Conclusion

The results of the study showed that a simple measure of the position of the DBS lead relative to the MCP is not significantly correlated with PD motor outcomes, presumably because this method fails to account for individual neuroanatomical variability. However, there is broad agreement that motor outcomes depend strongly on lead location. The results suggest the need for more detailed identification of stimulation location relative to anatomical targets.     

Using MDEFT MRI Sequences to Target the GPi in DBS Surgery

Objective

Recent advances in different MRI sequences have enabled direct visualization and targeting of the Globus pallidus internus (GPi) for DBS surgery. Modified Driven Equilibrium Fourier Transform (MDEFT) MRI sequences provide high spatial resolution and an excellent contrast of the basal ganglia with low distortion. In this study, we investigate if MDEFT sequences yield accurate and reliable targeting of the GPi and compare direct targeting based on MDEFT sequences with atlas-based targeting.

Methods

13 consecutive patients considered for bilateral GPi-DBS for dystonia or PD were included in this study. Preoperative targeting of the GPi was performed visually based on MDEFT sequences as well as by using standard atlas coordinates. Postoperative CT imaging was performed to calculate the location of the implanted leads as well as the active electrode(s). The coordinates of both visual and atlas based targets were compared. The stereotactic coordinates of the lead and active electrode(s) were calculated and projected on the segmented GPi.

Results

On MDEFT sequences the GPi was well demarcated in most patients. Compared to atlas-based planning the mean target coordinates were located significantly more posterior. Subgroup analysis showed a significant difference in the lateral coordinate between dystonia (LAT = 19.33 ± 0.90) and PD patients (LAT = 20.67 ± 1.69). Projected on the segmented preoperative GPi the active contacts of the DBS electrode in both dystonia and PD patients were located in the inferior and posterior part of the structure corresponding to the motor part of the GPi.

Conclusions

MDEFT MRI sequences provide high spatial resolution and an excellent contrast enabling precise identification and direct visual targeting of the GPi. Compared to atlas-based targeting, it resulted in a significantly different mean location of our target. Furthermore, we observed a significant variability of the target among the PD and dystonia subpopulation suggesting accurate targeting for each individual patient.     

Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome

Objective

Impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) are important behavioral problems that affect a subpopulation of patients with Parkinson''s disease (PD) and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN) and internal globus pallidus (GPi) deep brain stimulation (DBS) on ICD/DDS frequency and dopaminergic medication usage.

Methods

A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED), and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement) were examined.

Results

28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively.

Conclusions

Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.     

Comparative Effectiveness of Cognitive Therapies Delivered Face-to-Face or over the Telephone: An Observational Study Using Propensity Methods

Objectives

To compare the clinical and cost-effectiveness of face-to-face (FTF) with over-the-telephone (OTT) delivery of low intensity cognitive behavioural therapy.

Design

Observational study following SROBE guidelines. Selection effects were controlled using propensity scores. Non-inferiority comparisons assessed effectiveness.

Setting

IAPT (improving access to psychological therapies) services in the East of England.

Participants

39,227 adults referred to IAPT services. Propensity score strata included 4,106 individuals; 147 pairs participated in 1∶1 matching.

Intervention

Two or more sessions of computerised cognitive behavioural therapy (CBT).

Main outcome measures

Patient-reported outcomes: Patient Health Questionnaire (PHQ-9) for depression; Generalised Anxiety Disorder questionnaire (GAD-7); Work and Social Adjustment Scale (WSAS). Differences between groups were summarised as standardised effect sizes (ES), adjusted mean differences and minimally important difference for PHQ-9. Cost per session for OTT was compared with FTF.

Results

Analysis of covariance controlling for number of assessments, provider site, and baseline PHQ-9, GAD-7 and WSAS indicated statistically significantly greater reductions in scores for OTT treatment with moderate (PHQ-9: ES: 0.14; GAD-7: ES: 0.10) or small (WSAS: ES: 0.03) effect sizes. Non-inferiority in favour of OTT treatment for symptom severity persisted as small to moderate effects for all but individuals with the highest symptom severity. In the most stringent comparison, the one-to-one propensity matching, adjusted mean differences in treatment outcomes indicated non-inferiority between OTT versus FTF treatments for PHQ-9 and GAD-7, whereas the evidence was moderate for WSAS. The per-session cost for OTT was 36.2% lower than FTF.

Conclusions

The clinical effectiveness of low intensity CBT-based interventions delivered OTT was not inferior to those delivered FTF except for people with more severe illness where FTF was superior. This provides evidence for better targeting of therapy, efficiencies for patients, cost savings for services and greater access to psychological therapies for people with common mental disorders.     

Development of a One-Step Probe Based Molecular Assay for Rapid Immunodiagnosis of Infection with M. tuberculosis Using Dried Blood Spots

Background

Antigen specific release of IP-10 is the most promising alternative marker to IFN-γ for infection with M. tuberculosis. Compared to Interferon-γ release assays (IGRA), IP-10 is released in high levels enabling novel approaches such as field friendly dried blood spots (DBS) and molecular detection.

Aim

To develop a robust IP-10 based molecular assay for the diagnosis of infection with M. tubercuolsis from whole blood and DBS.

Method

We developed a one-step probe based multiplex RT-qPCR assay for detecting IP-10 and IFN-γ mRNA expression from whole blood and DBS samples. The assay was validated and applied for the diagnosis of M. tuberculosis infection in DBS samples from 43 patients with confirmed TB, 13 patients with latent TB and 96 presumed uninfected controls. In parallel, IP-10 and INF-γ levels were measured in Quantiferon (QFT-TB) plasma supernatants.

Results

IP-10 mRNA upregulation was detectable at 4 hours after stimulation (6 fold upregulation) peaking at 8 hours (108 fold upregulation). IFN-γ expression occurred in concert but levels were lower (peak 6.7 fold upregulation). IP-10 gene expression level was significantly higher in patients with tuberculosis (median 31.2, IQR 10.7–67.0) and persons with latent tuberculosis infection (LTBI) (41.2, IQR 9.8–64.9) compared to healthy controls (1.6, IQR 1.1–2.4; p<0.0001). The IP-10 mRNA and protein based tests had comparable diagnostic accuracy to QFT-TB, sensitivity (85% and 88% vs 85%) and specificity (96% and 96% vs 97%, p = ns.).

Conclusion

We developed a rapid, robust and accurate molecular immunodiagnostic test for M. tuberculosis infection. By combining DBS based sample acquisition, mail or currier based sample transport with centralized molecular detection, this immunodiagnostic test concept can reduce the local technological requirements everywhere and make it possible to offer highly accurate immunodiagnostic tests in low resource settings.     

Detection of Streptococcus pneumoniae and Haemophilus influenzae Type B by Real-Time PCR from Dried Blood Spot Samples among Children with Pneumonia: A Useful Approach for Developing Countries

Background

Dried blood spot (DBS) is a reliable blood collection method for storing samples at room temperature and easily transporting them. We have previously validated a Real-Time PCR for detection of Streptococcus pneumoniae in DBS. The objective of this study was to apply this methodology for the diagnosis of S. pneumoniae and Haemophilus influenzae b (Hib) in DBS samples of children with pneumonia admitted to two hospitals in Mozambique and Morocco.

Methods

Ply and wzg genes of S. pneumoniae and bexA gene of Hib, were used as targets of Real-Time PCR. 329 DBS samples of children hospitalized with clinical diagnosis of pneumonia were tested.

Results

Real-Time PCR in DBS allowed for a significant increase in microbiological diagnosis of S. pneumoniae and Hib. When performing blood bacterial culture, only ten isolates of S. pneumoniae and none of Hib were detected (3·0% positivity rate, IC95% 1·4-5·5%). Real-Time PCR from DBS samples increased the detection yield by 4x fold, as 30 S. pneumoniae and 11 Hib cases were detected (12·4% positivity rate, IC95% 9·0-16·5%; P<0·001).

Conclusion

Real-Time PCR applied in DBS may be a valuable tool for improving diagnosis and surveillance of pneumonia caused by S. pneumoniae or Hib in developing countries.     

Thirst Perception and Osmoregulation of Vasopressin Secretion Are Altered During Recovery From Septic Shock

Objective

Vasopressin (AVP) secretion during an osmotic challenge is frequently altered in the immediate post-acute phase of septic shock. We sought to determine if this response is still altered in patients recovering from septic shock.

Design

Prospective interventional study

Setting

Intensive care unit (ICU) at Raymond Poincaré and Etampes Hospitals.

Patients

Normonatremic patients at least 5 days post discontinuation of catecholamines given for a septic shock.

Intervention

Osmotic challenge involved infusing 500 mL of hypertonic saline solution (with cumulative amount of sodium not exceeding 24 g) over 120 minutes.

Measurements and main results

Plasma AVP levels were measured 15 minutes before the infusion and then every 30 minutes for two hours. Non-responders were defined as those with a slope of the relation between AVP and plasma sodium levels less than < 0.5 ng/mEq. Among the 30 included patients, 18 (60%) were non-responders. Blood pressure and plasma sodium and brain natriuretic peptide levels were similar in both responders and non-responders during the course of the test. Critical illness severity, hemodynamic alteration, electrolyte disturbances, treatment and outcome did not differ between the two groups. Responders had more severe gas exchange abnormality. Thirst perception was significantly diminished in non-responders. The osmotic challenge was repeated in 4 non-responders several months after discharge and the abnormal response persisted.

Conclusion

More than half of patients recovering from septic shock have an alteration of osmoregulation characterised by a dramatic decrease in vasopressin secretion and thirst perception during osmotic challenge. The mechanisms of this alteration but also of the relationship between haematosis and normal response remain to be elucidated.     

Gender Differences in Neuropsychological Performance across Psychotic Disorders – a Multi-Centre Population Based Case-Control Study

Background

Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance.

Methods

Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared.

Results

There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences.

Conclusions

Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients.     

Performance of DHI Score as a Predictor of Benign Paroxysmal Positional Vertigo in Geriatric Patients with Dizziness/Vertigo: A Cross-Sectional Study

Background

Dizziness/vertigo is one of the most common complaint and handicapping condition among patients aged 65 years and older (Geriatric patients). This study was conducted to assess the impact of dizziness/vertigo on the quality of life in the geriatric patients attending a geriatric outpatient clinic.

Settings and Design

A cross-sectional study was performed in a geriatric outpatient clinic of a rural teaching tertiary care hospital in central India.

Materials and Methods

In all consecutive geriatric patients with dizziness/vertigo attending geriatric outpatient clinic, DHI questionnaire was applied to assess the impact of dizziness/vertigo and dizziness associated handicap in the three areas of a patients’ life: physical, functional and emotional domain. Later, each patient was evaluated and underwent Dix-Hallpike maneuver by the physician who was blind of the DHI scoring of the patient.

Statistical Analysis Used

We compared means and proportions of variables across two categories of benign paroxysmal positional vertigo (BPPV) and non-BPPV. For these comparisons we used Student’s t-test to test for continuous variables, chi-square test for categorical variables and Fisher’s exact test in the case of small cell sizes (expected value<5).

Results

The magnitude of dizziness/vertigo was 3%. Of the 88 dizziness/vertigo patients, 19 (22%) and 69(78%) cases, respectively, were attributed to BPPV and non-BPPV group. The association of DHI score ≥50 with the BPPV was found to be statistically significant with x² value = 58.2 at P<0.01.

Conclusion

DHI Score is a useful tool for the prediction of benign paroxysmal positional vertigo. Correct diagnosis of BPPV is 16 times greater if the DHI Score is greater than or equal to 50. The physical, functional and emotional investigation of dizziness, through the DHI, has demonstrated to be a valuable and useful instrument in the clinical routine.     

Comparing Screening Instruments to Predict Posttraumatic Stress Disorder

Background

Following traumatic exposure, a proportion of trauma victims develops posttraumatic stress disorder (PTSD). Early PTSD risk screening requires sensitive instruments to identify everyone at risk for developing PTSD in need of diagnostic follow-up.

Aims

This study compares the accuracy of the 4-item SPAN, 10-item Trauma Screening Questionnaire (TSQ) and 22-item Impact of Event Scale-Revised (IES-R) in predicting chronic PTSD at a minimum sensitivity of 80%.

Method

Injury patients admitted to a level-I trauma centre (N = 311) completed the instruments at a median of 23 days and were clinically assessed for PTSD at 6 months. Areas under the curve and specificities at 80% sensitivity were compared between instruments.

Results

Areas under the curve in all instruments were adequate (SPAN: 0.83; TSQ: 0.82; IES-R: 0.83) with no significant differences. At 80% sensitivity, specificities were 64% for SPAN, 59% for TSQ and 72% for IES-R.

Conclusion

The SPAN, TSQ and IES-R show similar accuracy in early detection of individuals at risk for PTSD, despite differences in number of items. The modest specificities and low positive predictive values found for all instruments could lead to relatively many false positive cases, when applied in clinical practice.     

Retention and Risk Factors for Attrition in a Large Public Health ART Program in Myanmar: A Retrospective Cohort Analysis

Background

The outcomes from an antiretroviral treatment (ART) program within the public sector in Myanmar have not been reported. This study documents retention and the risk factors for attrition in a large ART public health program in Myanmar.

Methods

A retrospective analysis of a cohort of adult patients enrolled in the Integrated HIV Care (IHC) Program between June 2005 and October 2011 and followed up until April 2012 is presented. The primary outcome was attrition (death or loss-follow up); a total of 10,223 patients were included in the 5-year cumulative survival analysis. Overall 5,718 patients were analyzed for the risk factors for attrition using both logistic regression and flexible parametric survival models.

Result

The mean age was 36 years, 61% of patients were male, and the median follow up was 13.7 months. Overall 8,564 (84%) patients were retained in ART program: 750 (7%) were lost to follow-up and 909 (9%) died. During the 3 years follow-up, 1,542 attritions occurred over 17,524 person years at risk, giving an incidence density of 8.8% per year. The retention rates of participants at 12, 24, 36, 48 and 60 months were 86, 82, 80, 77 and 74% respectively. In multivariate analysis, being male, having high WHO staging, a low CD4 count, being anaemic or having low BMI at baseline were independent risk factors for attrition; tuberculosis (TB) treatment at ART initiation, a prior ART course before program enrollment and literacy were predictors for retention in the program.

Conclusion

High retention rate of IHC program was documented within the public sector in Myanmar. Early diagnosis of HIV, nutritional support, proper investigation and treatment for patients with low CD4 counts and for those presenting with anaemia are crucial issues towards improvement of HIV program outcomes in resource-limited settings.     

Identification of Differentially Expressed Transcripts and Pathways in Blood One Week and Six Months Following Implant of Left Ventricular Assist Devices

Introduction

Continuous-flow left ventricular assist devices (LVADs) are an established therapy for patients with end-stage heart failure. The short- and long-term impact of these devices on peripheral blood gene expression has not been characterized, and may provide insight into the molecular pathways mediated in response to left ventricular remodeling and an improvement in overall systemic circulation. We performed RNA sequencing to identify genes and pathways influenced by these devices.

Methods

RNA was extracted from blood of 9 heart failure patients (8 male) prior to LVAD implantation, and at 7 and 180 days postoperatively. Libraries were sequenced on an Illumina HiSeq2000 and sequences mapped to the human Ensembl GRCh37.67 genome assembly.

Results

A specific set of genes involved in regulating cellular immune response, antigen presentation, and T cell activation and survival were down-regulated 7 days after LVAD placement. 6 months following LVAD placement, the expression levels of these genes were significantly increased; yet importantly, remained significantly lower than age and sex-matched samples from healthy controls.

Conclusions

In summary, this genomic analysis identified a significant decrease in the expression of genes that promote a healthy immune response in patients with heart failure that was partially restored 6 months following LVAD implant.     

Retrospective Cohort Analysis of Chest Injury Characteristics and Concurrent Injuries in Patients Admitted to Hospital in the Wenchuan and Lushan Earthquakes in Sichuan,China

Background

The aim of this study was to compare retrospectively the characteristics of chest injuries and frequencies of other, concurrent injuries in patients after earthquakes of different seismic intensity.

Methods

We compared the cause, type, and body location of chest injuries as well as the frequencies of other, concurrent injuries in patients admitted to our hospital after the Wenchuan and Lushan earthquakes in Sichuan, China. We explored possible relationships between seismic intensity and the causes and types of injuries, and we assessed the ability of the Injury Severity Score, New Injury Severity Score, and Chest Injury Index to predict respiratory failure in chest injury patients.

Results

The incidence of chest injuries was 9.9% in the stronger Wenchuan earthquake and 22.2% in the less intensive Lushan earthquake. The most frequent cause of chest injuries in both earthquakes was being accidentally struck. Injuries due to falls were less prevalent in the stronger Wenchuan earthquake, while injuries due to burial were more prevalent. The distribution of types of chest injury did not vary significantly between the two earthquakes, with rib fractures and pulmonary contusions the most frequent types. Spinal and head injuries concurrent with chest injuries were more prevalent in the less violent Lushan earthquake. All three trauma scoring systems showed poor ability to predict respiratory failure in patients with earthquake-related chest injuries.

Conclusions

Previous studies may have underestimated the incidence of chest injury in violent earthquakes. The distributions of types of chest injury did not differ between these two earthquakes of different seismic intensity. Earthquake severity and interval between rescue and treatment may influence the prevalence and types of injuries that co-occur with the chest injury. Trauma evaluation scores on their own are inadequate predictors of respiratory failure in patients with earthquake-related chest injuries.     

Cost-Effectiveness of Alternative Strategies for Annual Influenza Vaccination among Children Aged 6 Months to 14 Years in Four Provinces in China

Background

To support policy making, we developed an initial model to assess the cost-effectiveness of potential strategies to increase influenza vaccination rates among children in China.

Methods

We studied on children aged 6 months to 14 years in four provinces (Shandong, Henan, Hunan, and Sichuan), with a health care system perspective. We used data from 2005/6 to 2010/11, excluding 2009/10. Costs are reported in 2010 U.S. dollars.

Results

In comparison with no vaccination, the mean (range) of Medically Attended Cases averted by the current self-payment policy for the two age groups (6 to 59 months and 60 months to 14 years) was 1,465 (23∼11,132) and 792 (36∼4,247), and the cost effectiveness ratios were $ 0 (-11-51) and $ 37 (6-125) per case adverted, respectively. In comparison with the current policy, the incremental cost effectiveness ratio (ICER) of alternative strategies, OPTION One-reminder and OPTION Two-comprehensive package, decreased as vaccination rate increased. The ICER for children aged 6 to 59 months was lower than that for children aged 60 months to 14 years.

Conclusions

The model is a useful tool in identifying elements for evaluating vaccination strategies. However, more data are needed to produce more accurate cost-effectiveness estimates of potential vaccination policies.     

Feasibility of Progressive Strength Training Implemented in the Acute Ward after Hip Fracture Surgery

Importance

Patients with a hip fracture lose more than 50% knee-extension strength in the fractured limb within one week of surgery. Hence, immediate progressive strength training following hip fracture surgery may be rational, but the feasibility unknown.

Objective

To examine the feasibility of in-hospital progressive strength training implemented in the acute ward following hip fracture surgery, based on pre-specified criteria for feasibility.

Design, Setting and Patients

A prospective cohort study conducted in an acute orthopedic hip fracture unit at a university hospital. A consecutive sample of 36 patients, 18 with a cervical and 18 with a trochanteric hip fracture (27 women and 9 men, mean (SD) age of 79.4 (8.3) years) were included between June and December 2012.

Intervention

A daily (on weekdays) program of progressive knee-extension strength training for the fractured limb, using ankle weight cuffs in 3 sets of 10 repetition maximum loadings.

Main outcomes and Measures

The primary outcome was the change in training load (kg) during the knee-extension strength training. The secondary outcomes were changes in hip fracture-related pain and maximal isometric knee-extension strength.

Results

The strength training was commenced at a mean of 2.4 (0.7) days after surgery. The training loads (kilograms lifted) increased from 1.6 (0.8) to 4.3 (1.7) kg over 4.3 (2.2) training sessions (P<.001). The maximal isometric knee-extension strength of the fractured limb increased from 0.37 (0.2) to 0.61 (0.3) Nm/kg (P<.001), while the average strength deficit in the fractured limb decreased from 50% to 32% (% non-fractured, P<.001). Only 3 of 212 sessions were not performed because of severe hip fracture-related pain.

Conclusion and Relevance

Progressive knee-extension strength training of the fractured limb commenced in the acute ward seems feasible, and may reduce strength asymmetry between limbs without hip pain interfering. The clinical efficacy needs confirmation in a randomized controlled design.

Trial Registration

ClinicalTrials.gov ID: NCT01616030