PCOM Library / Hot Topics in Research / Archive for "Internal Medicine"

Category: Internal Medicine

Hot Topics: Virtual Reality Used to Study How Memories Are Formed

katheride Biomedical Sciences, Hot Topics in Research, Neurology

CA1 and CA3 differentially support spontaneous retrieval of episodic contexts within human hippocampal subfields
Dimsdale-Zucker H, Ritchey M, Ekstrom AD, Yonelinas AP, Ranganath C. CA1 and CA3 differentially support spontaneous retrieval of episodic contexts within human hippocampal subfields. Nature Communications. 2018;9(1):294. https://doi.org/10.1038/s41467-017-02752-1.
The hippocampus plays a critical role in spatial and episodic memory. Mechanistic models predict that hippocampal subfields have computational specializations that differentially support memory. However, there is little empirical evidence suggesting differences between the subfields, particularly in humans. To clarify how hippocampal subfields support human spatial and episodic memory, we developed a virtual reality paradigm where participants passively navigated through houses (spatial contexts) across a series of videos (episodic contexts). We then used multivariate analyses of high-resolution fMRI data to identify neural representations of contextual information during recollection. Multi-voxel pattern similarity analyses revealed that CA1 represented objects that shared an episodic context as more similar than those from different episodic contexts. CA23DG showed the opposite pattern, differentiating between objects encountered in the same episodic context. The complementary characteristics of these subfields explain how we can parse our experiences into cohesive episodes while retaining the specific details that support vivid recollection.

Hot Topics: Flu May Be Spread By Breathing

katheride Hot Topics in Research, Infectious Disease

Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community
Yan J, Grantham M, Pantelic J, et al. Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community. Proc Natl Acad Sci USA. 2018. doi: 10.1073/pnas.1716561115
Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1–3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.

Hot Topics: CTE Caused by Head Impact, Not Concussions

katheride Hot Topics in Research, Neurology, Sports Medicine

Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model
Tagge C,A., Fisher A,M., Minaeva O,V., et al. Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model. Brain. 2018. doi: 10.1093/brain/awx350.
The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood–brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood–brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.

Hot Topics: Resistance to HIV Drugs in Low- and Middle-Income Countries Rising

katheride Hot Topics in Research, Infectious Disease

HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: a systematic review and meta-regression analysis
Gupta RK, Gregson J, Parkin N, et al. HIV-1 drug resistance before initiation or re-initiation of first-line antiretroviral therapy in low-income and middle-income countries: A systematic review and meta-regression analysis. The Lancet Infectious Diseases. http://dx.doi.org/10.1016/S1473-3099(17)30702-8.
Background
Pretreatment drug resistance in people initiating or re-initiating antiretroviral therapy (ART) containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) might compromise HIV control in low-income and middle-income countries (LMICs). We aimed to assess the scale of this problem and whether it is associated with the intiation or re-initiation of ART in people who have had previous exposure to antiretroviral drugs.
Methods
This study was a systematic review and meta-regression analysis. We assessed regional prevalence of pretreatment drug resistance and risk of pretreatment drug resistance in people initiating ART who reported previous ART exposure. We systematically screened publications and unpublished datasets for pretreatment drug-resistance data in individuals in LMICs initiating or re-initiating first-line ART from LMICs. We searched for studies in PubMed and Embase and conference abstracts and presentations from the Conference on Retroviruses and Opportunistic Infections, the International AIDS Society Conference, and the International Drug Resistance Workshop for the period Jan 1, 2001, to Dec 31, 2016. To assess the prevalence of drug resistance within a specified region at any specific timepoint, we extracted study level data and pooled prevalence estimates within the region using an empty logistic regression model with a random effect at the study level. We used random effects meta-regression to relate sampling year to prevalence of pretreatment drug resistance within geographical regions.
Findings
We identified 358 datasets that contributed data to our analyses, representing 56 044 adults in 63 countries. Prevalence estimates of pretreatment NNRTI resistance in 2016 were 11·0% (7·5–15·9) in southern Africa, 10·1% (5·1–19·4) in eastern Africa, 7·2% (2·9–16·5) in western and central Africa, and 9·4% (6·6–13·2) in Latin America and the Caribbean. There were substantial increases in pretreatment NNRTI resistance per year in all regions. The yearly increases in the odds of pretreatment drug resistance were 23% (95% CI 16–29) in southern Africa, 17% (5–30) in eastern Africa, 17% (6–29) in western and central Africa, 11% (5–18) in Latin America and the Caribbean, and 11% (2–20) in Asia. Estimated increases in the absolute prevalence of pretreatment drug resistance between 2015 and 2016 ranged from 0·3% in Asia to 1·8% in southern Africa.
Interpretation
Pretreatment drug resistance is increasing at substantial rate in LMICs, especially in sub-Saharan Africa. In 2016, the prevalence of pretreatment NNRTI resistance was near WHO’s 10% threshold for changing first-line ART in southern and eastern Africa and Latin America, underscoring the need for routine national HIV drug-resistance surveillance and review of national policies for first-line ART regimen composition.

Hot Topics: Antacids Taken During Pregnancy Linked to Asthma in Children

katheride Hot Topics in Research, Pediatrics, Pulmonary

Acid-Suppressive Drug Use During Pregnancy and the Risk of Childhood Asthma: A Meta-analysis
Lai T, Wu M, Liu J, et al. Acid-suppressive drug use during pregnancy and the risk of childhood asthma: A meta-analysis. Pediatrics. 2018. doi: 10.1542/peds.2017-0889.

CONTEXT: The association between acid-suppressive drug exposure during pregnancy and childhood asthma has not been well established.

OBJECTIVE: To conduct a systematic review and meta-analysis on this association to provide further justification for the current studies.

DATA SOURCES: We searched PubMed, Medline, Embase, the Cochrane Database of Systematic Reviews, EBSCO Information Services, Web of Science, and Google Scholar from inception until June 2017.

STUDY SELECTION: Observational studies in which researchers assessed acid-suppressive drug use during pregnancy and the risk of childhood asthma were included.

DATA EXTRACTION: Of 556 screened articles, 8 population-based studies were included in the final analyses.

RESULTS: When all the studies were pooled, acid-suppressive drug use in pregnancy was associated with an increased risk of asthma in childhood (relative risk [RR] = 1.45; 95% confidence interval [CI] 1.35–1.56; I2 = 0%; P < .00001). The overall risk of asthma in childhood increased among proton pump inhibitor users (RR = 1.34; 95% CI 1.18–1.52; I2 = 46%; P < .00001) and histamine-2 receptor antagonist users (RR = 1.57; 95% CI 1.46–1.69; I2 = 0%; P < .00001).

LIMITATIONS: None of the researchers in the studies in this meta-analysis adjusted for the full panel of known confounders in these associations.

CONCLUSIONS: The evidence suggests that prenatal, maternal, acid-suppressive drug use is associated with an increased risk of childhood asthma. This information may help clinicians and parents to use caution when deciding whether to take acid-suppressing drugs during pregnancy because of the risk of asthma in offspring.

Hot Topics: Virtual Reality Games Can Help Stroke Recovery

katheride Hot Topics in Research, Neurology, Physical Therapy

Virtual Reality Training for Upper Extremity in Subacute Stroke (VIRTUES): A multicenter RCT
Brunner, I., Skouen, J. S., Hofstad, H., Aßmus, J., Becker, F., Sanders, A., . . . Verheyden, G. (2017). Virtual reality training for upper extremity in subacute stroke (VIRTUES). Neurology, doi:10.1212/WNL.0000000000004744
Objective: To compare the effectiveness of upper extremity virtual reality rehabilitation training
(VR) to time-matched conventional training (CT) in the subacute phase after stroke.
Methods: In this randomized, controlled, single-blind phase III multicenter trial, 120 participants
with upper extremity motor impairment within 12 weeks after stroke were consecutively included
at 5 rehabilitation institutions. Participants were randomized to either VR or CT as an adjunct to
standard rehabilitation and stratified according to mild to moderate or severe hand paresis,
defined as $20 degrees wrist and 10 degrees finger extension or less, respectively. The training
comprised a minimum of sixteen 60-minute sessions over 4 weeks. The primary outcome measure
was the Action Research Arm Test (ARAT); secondary outcome measures were the Box and
Blocks Test and Functional Independence Measure. Patients were assessed at baseline, after
intervention, and at the 3-month follow-up.
Results: Mean time from stroke onset for the VR group was 35 (SD 21) days and for the CT group
was 34 (SD 19) days. There were no between-group differences for any of the outcome measures.
Improvement of upper extremity motor function assessed with ARAT was similar at the
postintervention (p 5 0.714) and follow-up (p 5 0.777) assessments. Patients in VR improved
12 (SD 11) points from baseline to the postintervention assessment and 17 (SD 13) points from
baseline to follow-up, while patients in CT improved 13 (SD 10) and 17 (SD 13) points, respectively.
Improvement was also similar for our subgroup analysis with mild to moderate and severe
upper extremity paresis.
Conclusions: Additional upper extremity VR training was not superior but equally as effective as
additional CT in the subacute phase after stroke. VR may constitute a motivating training alternative
as a supplement to standard rehabilitation.

Hot Topics: Adolescent Athletes with Limited Hip Range of Motion at Risk for Osteoarthritis

katheride Hot Topics in Research, Pediatrics, Rheumatology

Cam Deformities and Limited Hip Range of Motion Are Associated With Early Osteoarthritic Changes in Adolescent Athletes: A Prospective Matched Cohort Study
Wyles, C. C., Norambuena, G. A., Howe, B. M., Larson, D. R., Levy, B. A., Yuan, B. J., . . . Sierra, R. J. (2017). Cam deformities and limited hip range of motion are associated with early osteoarthritic changes in adolescent athletes: A prospective matched cohort study. Am J Sports Med, 45(13), 3036-3043. doi:10.1177/0363546517719460
Background:
The natural history of femoroacetabular impingement (FAI) remains incompletely understood. In particular, there is limited documentation of joint damage in adolescent patients with limited range of motion (LROM) of the hip, which is commonly associated with FAI.
Purpose:
To evaluate changes in magnetic resonance imaging (MRI), radiographs, and clinical examinations over 5 years in a group of athletes from a wide variety of sports with asymptomatic LROM of the hip compared with matched controls.
Study Design:
Cohort study (prognosis); Level of evidence, 2.
Methods:
The authors screened 226 male and female athletes aged 12 to 18 years presenting for preparticipation sports physical examinations. Using a goniometer, we identified 13 participants with at least one hip having internal rotation <10° with the hip flexed to 90°. Overall, 21 of 26 hips (81%) had internal rotation <10°. These participants were age- and sex-matched to 13 controls with internal rotation >10°. At the time of enrollment, all participants were asymptomatic and underwent a complete hip examination and radiographic imaging with radiographs (anteroposterior [AP] and von Rosen views) and non-arthrogram MRI. Participants returned at 5-year follow-up and underwent repeat hip examinations, imaging (AP and lateral radiographs and non-arthrogram MRI), and hip function questionnaires. MRI scans were classified as “normal” versus “abnormal” based on the presence of any of 13 scored chondral, labral, or osseous abnormalities. Comparisons between the LROM group and control group were performed using generalized linear models (either linear, logistic, or log-binomial regression as appropriate for the outcome) with generalized estimating equations to account for the within-participant correlation due to patients having both hips included. Relative risk (RR) estimates are reported with 95% CIs.
Results:
At the time of study enrollment, 16 of 26 hips (62%) in the LROM group had abnormal MRI findings within the acetabular labrum or cartilage compared with 8 of 26 hips (31%) in the control group (RR, 2.0; 95% CI, 0.95-4.2; P = .067). The mean alpha angle measured from radial MRI sequences was 58° in the LROM group versus 44° in the control group (P < .0001). In the LROM group, 13 of 26 hips (50%) had a positive anterior impingement sign, whereas 0 of 26 hips (0%) had a positive anterior impingement sign in the control group. At 5-year follow-up, 18 of 19 hips (95%) in the LROM group had abnormal MRI findings compared with 14 of 26 hips (54%) in the control group (RR, 1.7; 95% CI, 1.1-2.7; P = .014). New or progressive findings were documented on MRI in 15 of 20 hips in the LROM group compared with 8 of 26 hips in the control group (RR, 2.4; 95% CI, 1.2-4.8; P = .011). Six of 22 hips (27%) in the LROM group progressed from Tönnis grade 0 to Tönnis grade 1 in degenerative changes, whereas all 26 hips in the control group remained at Tönnis grade 0 on hip radiographs. In the LROM group, 11 of 22 hips (50%) had a positive anterior impingement sign, whereas 1 of 26 hips (4%) had a positive anterior impingement sign in the control group. A cam deformity (alpha angle >55° on lateral radiographs) was present in 20 of 22 hips (91%) in the LROM group and 12 of 26 hips (46%) in the control group (P = .0165). The following variables at baseline were associated with an increased risk of degenerative changes at 5-year follow-up for the entire cohort: decreased hip internal rotation, positive anterior impingement sign, decreased hip flexion, increased alpha angle, and presence of a cam lesion.
Conclusion:
At 5 years, young athletes with LROM of the hip showed increased progressive degenerative changes on MRI and radiographs compared with matched controls. Although the majority of these participants remained asymptomatic, those with features of FAI had radiographic findings consistent with early osteoarthritis. These outcomes suggest that more aggressive screening and counseling of young active patients may be helpful to prevent hip osteoarthritis in those with FAI.

Hot Topics: New Guidelines Lower Threshold for High Blood Pressure

katheride Cardiology, Hot Topics in Research
Potential U.S. Population Impact of the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline
Muntner, P., Carey, R. M., Gidding, S., Jones, D. W., Taler, S. J., Wright, J. T., & Whelton, P. K. (2017). Potential U.S. population impact of the 2017 American Ccollege of Cardiology/American Heart Association high blood pressure guideline. Journal of the American College of Cardiology. doi: 10.1016/j.jacc.2017.10.073

Background The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults provides recommendations for the definition of hypertension, systolic and diastolic blood pressure (BP) thresholds for initiation of antihypertensive medication and BP target goals.

Objective Determine the prevalence of hypertension, implications of recommendations for antihypertensive medication and prevalence of BP above the treatment goal among US adults using criteria from the 2017 ACC/AHA and the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC7) guidelines.

Methods We analyzed data from the 2011-2014 National Health and Nutrition Examination Survey (N=9,623). NHANES participants completed study interviews and an examination. For each participant, blood pressure was measured three times following a standardized protocol and averaged. Results were weighted to produce US population estimates.

Results According to the 2017 ACC/AHA and JNC7 guidelines, the overall crude prevalence of hypertension among US adults was 45.6% (95% confidence interval [CI] 43.6%,47.6%) and 31.9% (95%CI 30.1%, 33.7%), respectively, and antihypertensive medication was recommended for 36.2% (95%CI 34.2%, 38.2%) and 34.3% (32.5%, 36.2%) of US adults, respectively. Compared to US adults recommended antihypertensive medication by JNC7, those recommended treatment by the 2017 ACC/AHA guideline but not JNC7 had higher CVD risk. Non-pharmacological intervention is advised for the 9.4% of US adults with hypertension according to the 2017 ACC/AHA guideline who are not recommended antihypertensive medication. Among US adults taking antihypertensive medication, 53.4% (95%CI 49.9%, 56.8%) and 39.0% (95%CI 36.4%, 41.6%) had BP above the treatment goal according to the 2017 ACC/AHA and JNC7 guidelines, respectively. Overall, 103.3 (95%CI 92.7, 114.0) million US adults had hypertension according to the 2017 ACC/AHA guideline of whom 81.9 (95%CI 73.8, 90.1) million were recommended antihypertensive medication.

Conclusion Compared with the JNC 7 guideline, the 2017 ACC/AHA guideline results in a substantial increase in the prevalence of hypertension but a small increase in the percentage of U.S. adults recommended antihypertensive medication. A substantial proportion of US adults taking antihypertensive medication is recommended more intensive BP lowering under the 2017 ACC/AHA guideline.

Hot Topics: Wristband Devices Detect Dangerous Epileptic Seizures

katheride Central Nervous System Disorders, Hot Topics in Research, Neurology

Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors
Onorati, F., Regalia, G., Caborni, C., Migliorini, M., Bender, D., et al. (2017), Multicenter clinical assessment of improved wearable multimodal convulsive seizure detectors. Epilepsia. doi:10.1111/epi.13899
Objective
New devices are needed for monitoring seizures, especially those associated with sudden unexpected death in epilepsy (SUDEP). They must be unobtrusive and automated, and provide false alarm rates (FARs) bearable in everyday life. This study quantifies the performance of new multimodal wrist-worn convulsive seizure detectors.
Methods
Hand-annotated video-electroencephalographic seizure events were collected from 69 patients at six clinical sites. Three different wristbands were used to record electrodermal activity (EDA) and accelerometer (ACM) signals, obtaining 5,928 h of data, including 55 convulsive epileptic seizures (six focal tonic–clonic seizures and 49 focal to bilateral tonic–clonic seizures) from 22 patients. Recordings were analyzed offline to train and test two new machine learning classifiers and a published classifier based on EDA and ACM. Moreover, wristband data were analyzed to estimate seizure-motion duration and autonomic responses.
Results
The two novel classifiers consistently outperformed the previous detector. The most efficient (Classifier III) yielded sensitivity of 94.55%, and an FAR of 0.2 events/day. No nocturnal seizures were missed. Most patients had <1 false alarm every 4 days, with an FAR below their seizure frequency. When increasing the sensitivity to 100% (no missed seizures), the FAR is up to 13 times lower than with the previous detector. Furthermore, all detections occurred before the seizure ended, providing reasonable latency (median = 29.3 s, range = 14.8–151 s). Automatically estimated seizure durations were correlated with true durations, enabling reliable annotations. Finally, EDA measurements confirmed the presence of postictal autonomic dysfunction, exhibiting a significant rise in 73% of the convulsive seizures.
Significance
The proposed multimodal wrist-worn convulsive seizure detectors provide seizure counts that are more accurate than previous automated detectors and typical patient self-reports, while maintaining a tolerable FAR for ambulatory monitoring. Furthermore, the multimodal system provides an objective description of motor behavior and autonomic dysfunction, aimed at enriching seizure characterization, with potential utility for SUDEP warning.

Hot Topics: Shortened Tuberculosis Treatment As Effective as Current Recommended Treatment

katheride Hot Topics in Research, Infectious Disease

Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials.
Moodley, R., Godec, T. R., & STREAM Trial Team. (2016). Short-course treatment for multidrug-resistant tuberculosis: The STREAM trials. European Respiratory Review : An Official Journal of the European Respiratory Society, 25(139), 29-35. doi:10.1183/16000617.0080-2015
Multidrug-resistant (MDR) tuberculosis (TB) is a threat to global TB control, as suboptimal and poorly tolerated treatment options have resulted in largely unfavourable outcomes for these patients. The last of six cohort studies conducted in Bangladesh which assessed a new shorter regimen using currently available TB drugs showed promising results and offered the possibility of a more acceptable and more effective regimen than the one recommended by the World Health Organization (WHO). The aims of stage 1 of the STREAM (Evaluation of a Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) trial are to evaluate the efficacy and safety of this regimen, compared to the current WHO-recommended standard of care. Stage 2 evaluates two new bedaquiline-containing regimens: one an all-oral regimen and the second a further shortened and simplified version of the stage 1 study regimen, comparing the efficacy and safety of each to that of the stage 1 study regimen and also to the WHO-recommended standard of care. Success of the stage 1 study regimen would in all probability provide a new standard of care for MDR-TB patients, while positive results from the bedaquiline-containing regimens in stage 2 may allow for even greater progress in the management of this difficult population.