Association between genetic polymorphisms and risk of adolescent idiopathic scoliosis in case-control studies: a systematic review.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a structural lateral spinal curvature of ≥10° with rotation. Approximately 2%-3% of children across populations are affected with AIS, and this condition is responsible for ~$3 billion in costs within the USA. Although AIS is believed to have a strong genetic contribution, clinical translation of identified genetic variants has stalled. METHODS: The databases MEDLINE (via PubMed), Embase, Google Scholar and Ovid MEDLINE were searched and limited to articles in English. Title and abstract, full-text and data extraction screening was conducted through Covidence, followed by data transfer to a custom REDCap database. Studies containing variant-level data using genome-wide methodology as well as validation studies of genome-wide methods were considered. Quality assessment was conducted using Q-Genie. RESULTS: 33 studies were included, including 9 genome-wide association studies, 4 whole exome sequencing and 20 validation studies. Combined, these studies included data from >35,000 cases and >67,000 controls, not including validation cohorts. Additionally, results from six meta-analyses containing novel cohorts were also reported. All included study cohorts were from populations of primarily East Asian or Caucasian descent. Quality assessment found that overall study quality was high and control group selection was moderate. The highest number of reported associations were in single nucleotide polymorphisms (SNPs) in or near LBX1, LBX1-AS1, GPR126/ADGRG6 or BNC2. CONCLUSION: AIS risk may be influenced by specific SNPs, particularly those in/near LBX1 and GPR126. Translatability of study findings is unknown due to an underrepresentation of most ethnic groups as well as few identified genome-wide studies. Further studies may benefit from increased cohort diversity and thorough evaluation of control cohort groups.

The Impact of Complementary and Integrative Medicine Following Traumatic Brain Injury: A Scoping Review.

OBJECTIVE: To examine the evidence levels, study characteristics, and outcomes of nonpharmacologic complementary and integrative medicine (CIM) interventions in rehabilitation for individuals with traumatic brain injury (TBI). DATA SOURCES: MEDLINE (OvidSP), PubMed (NLM), EMBASE ( Embase.com ), CINAHL (EBSCO), PsycINFO (OvidSP), Cochrane Library (Wiley), and National Guidelines Clearinghouse databases were evaluated using PRISMA guidelines. The protocol was registered in INPLASY (protocol registration: INPLASY202160071). DATA EXTRACTION: Quantitative studies published between 1992 and 2020 investigating the efficacy of CIM for individuals with TBI of any severity, age, and outcome were included. Special diets, herbal and dietary supplements, and counseling/psychological interventions were excluded, as were studies with mixed samples if TBI data could not be extracted. A 2-level review comprised title/abstract screening, followed by full-text assessment by 2 independent reviewers. DATA SYNTHESIS: In total, 90 studies were included, with 57 001 patients in total. This total includes 2 retrospective studies with 17 475 and 37 045 patients. Of the 90 studies, 18 (20%) were randomized controlled trials (RCTs). The remainder included 20 quasi-experimental studies (2-group or 1-group pre/posttreatment comparison), 9 retrospective studies, 1 single-subject study design, 2 mixed-methods designs, and 40 case study/case reports. Guided by the American Academy of Neurology evidence levels, class II criteria were met by 61% of the RCTs. Included studies examined biofeedback/neurofeedback (40%), acupuncture (22%), yoga/tai chi (11%), meditation/mindfulness/relaxation (11%), and chiropractic/osteopathic manipulation (11%). The clinical outcomes evaluated across studies included physical impairments (62%), mental health (49%), cognitive impairments (39%), pain (31%), and activities of daily living/quality of life (28%). Additional descriptive statistics were summarized using narrative synthesis. Of the studies included for analyses, 97% reported overall positive benefits of CIM. CONCLUSION: Rigorous and well experimentally designed studies (including RCTs) are needed to confirm the initial evidence supporting the use of CIM found in the existing literature.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

Global rural health disparities in Alzheimer's disease and related dementias: State of the science.

INTRODUCTION: Individuals living in rural communities are at heightened risk for Alzheimer's disease and related dementias (ADRD), which parallels other persistent place-based health disparities. Identifying multiple potentially modifiable risk factors specific to rural areas that contribute to ADRD is an essential first step in understanding the complex interplay between various barriers and facilitators. METHODS: An interdisciplinary, international group of ADRD researchers convened to address the overarching question of: "What can be done to begin minimizing the rural health disparities that contribute uniquely to ADRD?" In this state of the science appraisal, we explore what is known about the biological, behavioral, sociocultural, and environmental influences on ADRD disparities in rural settings. RESULTS: A range of individual, interpersonal, and community factors were identified, including strengths of rural residents in facilitating healthy aging lifestyle interventions. DISCUSSION: A location dynamics model and ADRD-focused future directions are offered for guiding rural practitioners, researchers, and policymakers in mitigating rural disparities. HIGHLIGHTS: Rural residents face heightened Alzheimer's disease and related dementia (ADRD) risks and burdens due to health disparities. Defining the unique rural barriers and facilitators to cognitive health yields insight. The strengths and resilience of rural residents can mitigate ADRD-related challenges. A novel "location dynamics" model guides assessment of rural-specific ADRD issues.

National Institute on Aging Butler-Williams Scholars Program: The first 30 years.

The development of a skilled research workforce in aging is fundamental to understanding conditions associated with growing older and extending healthy, active years of life. The National Institutes of Health (NIH) supports the training of health scientists, and its National Institute on Aging (NIA) prioritizes the professional development of investigators with an interest in aging. Since 1987, NIA's Summer Institute on Aging Research, renamed the Butler-Williams (B-W) Scholars Program in 2013, has offered an intensive one-week experience on issues, opportunities, and challenges of research on aging, with emphasis on disparities and health equity. The first 30 years of the Program are described in this report, including its history, selected curriculum highlights, Scholar outcomes, and qualitative data from faculty, and the program's impact on the training, growth, and development of scientists in aging research. Questions raised over a decade ago by the Committee on the Future Health Care Workforce for Older Americans Board on Health Care Services are revisited, and recommendations for the future are provided. This important Program remains an exemplar for the training and development of health scientists for careers that advance biomedical research and emphasize an equitable understanding of factors related to extending healthy years of life.

Walking speed and patient-reported outcomes in young adults with cerebral palsy.

AIM: To examine the relationship between quantitative gait measurements and self-reported physical, psychological, cognitive, and social function status in young adults with cerebral palsy (CP). METHOD: Seventy-two adults with CP (range 18-48y; median age 23y [interquartile range 21-27y]; 34 males, 38 females), in Gross Motor Function Classification System levels I to IV, who previously underwent an instrumented gait analysis (IGA) at our center as children were recruited. Participants underwent a repeated IGA. National Institutes of Health Patient-Reported Outcomes Information System (PROMIS) instruments including the PROMIS-57, Applied Cognition - General Concerns (Short Form), and Applied Cognition - Executive Function (Short Form) were administered. Data derived from current and prior IGA were compared via non-parametric correlation analysis with PROMIS subscores. RESULTS: Subscores for anxiety, depression, sleep, and fatigue did not significantly correlate with any IGA data. Walking speed, adjusted for stature, correlated strongly with multiple subscores: physical function (p<0.001, rs =0.708); participation in social roles (p=0.007, rs =0.319); executive function (p=0.005, rs =0.335). Pain interference correlated with longitudinal change in adjusted walking speed (p=0.032, rs =-0.259). The Applied Cognition - General Concerns (Short Form) correlated with prior absolute walking speed, but not adjusted values. INTERPRETATION: This study underscores the importance of walking speed and its association with a variety of functional domains in adults with CP. WHAT THIS PAPER ADDS: Patient-Reported Outcomes Information System measures provide useful clinical data in young adults with cerebral palsy. Temporospatial gait parameters have wide-reaching functional influence in this population. Walking speed is strongly correlated with physical, social, and executive function.

International Practice Recommendations for the Recognition and Management of Hearing and Vision Impairment in People with Dementia.

INTRODUCTION: Hearing, vision, and cognitive impairment commonly co-occur in older people. However, the rate of recognition and appropriate management of combined hearing and vision impairment in people with dementia impairment is low. The aim of this work was to codevelop internationally relevant, multidisciplinary practice recommendations for professionals involved in the diagnosis, care, and management of older people with these concurrent conditions. METHODS: We applied consensus methods with professional and lay expert stakeholders, using an adapted version of the World Health Organization Handbook for Guideline Development. The development involved 4 phases and included: (1) collating existing evidence, (2) filling the gaps in evidence, (3) prioritising evidence, and (4) refining the final list of recommendations. Each phase encompassed various methodologies including a review of existing guidelines within the 3 clinical domains, systematic reviews, qualitative studies, a clinical professional consortium, surveys, and consensus meetings with interdisciplinary domain experts. RESULTS: The task force evaluated an initial list of 26 recommendations, ranking them in the order of priority. A consensus was reached on 15 recommendations, which are classified into 6 domains of "awareness and knowledge," "recognition and detection," "evaluation," "management," "support," and "services and policies." Pragmatic options for implementation for each domain were then developed. CONCLUSION: This is the first set of international, interdisciplinary practice recommendations that will guide the development of multidisciplinary services and policy to improve the lives of people with dementia and hearing and vision impairment.

An overview of systematic reviews on the pharmacological randomized controlled trials for reducing intracranial pressure after traumatic brain injury.

BACKGROUND: There is a need for an overview of systematic reviews (SRs) examining randomized clinical trials (RCTs) of pharmacological interventions in the treatment of intracranial pressure (ICP) post-TBI. OBJECTIVES: To summarize pharmacological effectiveness in decreasing ICP in SRs with RCTs and evaluate study quality. METHODS: Comprehensive literature searches were conducted in MEDLINE, PubMed, EMBASE, PsycINFO, and Cochrane Library databases for English SRs through October 2020. Inclusion criteria were SRs with RCTs that examined pharmacological interventions to treat ICP in patients post-TBI. Data extracted were participant characteristics, pharmacological interventions, and ICP outcomes. Study quality was assessed with AMSTAR-2. RESULTS: Eleven SRs between 2003 and 2020 were included. AMSTAR-2 ratings revealed 3/11 SRs of high quality. Pharmacological interventions included hyperosmolars, neuroprotectives, anesthetics, sedatives, and analgesics. Study samples ranged from 7 to 1282 patients. Hyperosmolar agents and sedatives were beneficial in lowering elevated ICP. High bolus dose opioids had a more deleterious effect on ICP. Neuroprotective agents did not show any effects in ICP management. CONCLUSIONS: RCT sample sizes and findings in the SRs varied. A lack of detailed data syntheses was noted. AMSTAR-2 analysis revealed moderate to high quality in most SRs. Future SRs may focus on streamlined reporting of dosing and clearer clinical recommendations. PROSPERO-Registration: CRD42015017355.

Prevalence of metabolic syndrome and cardiovascular disease risk factors in adults with cerebral palsy.

AIM: To investigate the prevalence of metabolic syndrome and cardiovascular disease (CVD) risk factors and the association between common metabolic markers and Gross Motor Function Classification System (GMFCS) levels in ambulatory adults with cerebral palsy (CP). METHOD: Metabolic markers and GMFCS levels were evaluated in a cross-sectional study of 70 ambulatory adults with CP (34 males, 36 females; mean age 24y 5mo [SD 5y 4mo], range 18y 6mo-48y 8mo) to determine the prevalence of metabolic syndrome and CVD risk factors, and were compared to age-matched, population norms from the National Health and Nutrition Examination Survey (NHANES) registry. The Framingham Heart Study (FHS) CVD risk estimation was also used to evaluate an individual's risk for CVD. RESULTS: Metabolic syndrome was identified in 17.1% of the cohort, higher than the 10% in the NHANES registry. The FHS CVD 30-year lipid and body mass index (BMI)-based risk factor results showed that 20% to 40% of the cohort was at greater risk of developing CVD (BMI-based: 39.7% 'full' CVD risk factor; lipid-based: 26.5% 'full' CVD risk factor) as compared to the FHS normative population data. There was a positive correlation between GMFCS level, waist circumference (r=0.28, p=0.02), and waist-to-hip ratio (r=0.28, p=0.02). INTERPRETATION: Adults with CP are at higher risk of CVD and metabolic syndrome compared to the general population, which is probably because of impaired mobility.

Overview of pharmacological interventions after traumatic brain injuries: impact on selected outcomes.

The purpose of this study was to conduct an overview of systematic reviews (SRs) to appraise the published evidence related to pharmacological interventions after traumatic brain injury (TBI). Searches were conducted with Medline, Embase, PsycINFO, Web of Science, PubMed. 780 retrieved SRs underwent a two-level screening to determine inclusion. Data extracted included participant characteristics, TBI severity, study design, pharmacological interventions, and outcomes. SRs were assessed for methodological quality by using the AMSTAR measurement tool. After removing duplicates, 166/780 SRs published between 1990-2017 were reviewed, 62 of which met inclusion criteria. More than 90 drugs and 22 substance-classes were extracted. Most medications were administered during the acute stage. Mild TBI was included in 3% of the SRs. Physiological outcomes comprised 45% of the SRs, primarily mortality. Activities of daily living (ADLs) outcomes constituted 22% of the SRs followed by cognition (13%) and psychological/behavioral outcomes (13%). Only 7% of the SRs assessed adverse events. Inconsistencies in definitions, methods, and heterogeneity of instruments used to measure treatment response were noted. Only a third of the SRs had high methodological quality. Most SRs had heterogeneous TBI samples, outcomes, or methodologies making it difficult to synthesize findings into recommended guidelines. This study demonstrated a need for adequately powered and rigorous randomized clinical trials (RCTs) to provide generalizable evidence on the effectiveness of pharmacologic interventions for TBI. PROSPERO Registration: CRD42015017355.