APOE3 Christchurch Heterozygosity and Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Variants in APOE and PSEN1 (encoding apolipoprotein E and presenilin 1, respectively) alter the risk of Alzheimer's disease. We previously reported a delay of cognitive impairment in a person with autosomal dominant Alzheimer's disease caused by the PSEN1 E280A variant who also had two copies of the apolipoprotein E3 Christchurch variant (APOE3 Ch). Heterozygosity for the APOE3 Ch variant may influence the age at which the onset of cognitive impairment occurs. We assessed this hypothesis in a population in which the PSEN1 E280A variant is prevalent. METHODS: We analyzed data from 27 participants with one copy of the APOE3 Ch variant among 1077 carriers of the PSEN1 E280A variant in a kindred from Antioquia, Colombia, to estimate the age at the onset of cognitive impairment and dementia in this group as compared with persons without the APOE3 Ch variant. Two participants underwent brain imaging, and autopsy was performed in four participants. RESULTS: Among carriers of PSEN1 E280A who were heterozygous for the APOE3 Ch variant, the median age at the onset of cognitive impairment was 52 years (95% confidence interval [CI], 51 to 58), in contrast to a matched group of PSEN1 E280A carriers without the APOE3 Ch variant, among whom the median age at the onset was 47 years (95% CI, 47 to 49). In two participants with the APOE3 Ch and PSEN1 E280A variants who underwent brain imaging, 18F-fluorodeoxyglucose positron-emission tomographic (PET) imaging showed relatively preserved metabolic activity in areas typically involved in Alzheimer's disease. In one of these participants, who underwent 18F-flortaucipir PET imaging, tau findings were limited as compared with persons with PSEN1 E280A in whom cognitive impairment occurred at the typical age in this kindred. Four studies of autopsy material obtained from persons with the APOE3 Ch and PSEN1 E280A variants showed fewer vascular amyloid pathologic features than were seen in material obtained from persons who had the PSEN1 E280A variant but not the APOE3 Ch variant. CONCLUSIONS: Clinical data supported a delayed onset of cognitive impairment in persons who were heterozygous for the APOE3 Ch variant in a kindred with a high prevalence of autosomal dominant Alzheimer's disease. (Funded by Good Ventures and others.).

Virtual Reality and Serious Videogame-Based Instruments for Assessing Spatial Navigation in Alzheimer's Disease: A Systematic Review of Psychometric Properties.

Over the past decade, research using virtual reality and serious game-based instruments for assessing spatial navigation and spatial memory in at-risk and AD populations has risen. We systematically reviewed the literature since 2012 to identify and evaluate the methodological quality and risk of bias in the analyses of the psychometric properties of VRSG-based instruments. The search was conducted primarily in July-December 2022 and updated in November 2023 in eight major databases. The quality of instrument development and study design were analyzed in all studies. Measurement properties were defined and analyzed according to COSMIN guidelines. A total of 1078 unique records were screened, and following selection criteria, thirty-seven studies were analyzed. From these studies, 30 instruments were identified. Construct and criterion validity were the most reported measurement properties, while structural validity and internal consistency evidence were the least reported. Nineteen studies were deemed very good in construct validity, whereas 11 studies reporting diagnostic accuracy were deemed very good in quality. Limitations regarding theoretical framework and research design requirements were found in most of the studies. VRSG-based instruments are valuable additions to the current diagnostic toolkit for AD. Further research is required to establish the psychometric performance and clinical utility of VRSG-based instruments, particularly the instrument development, content validity, and diagnostic accuracy for preclinical AD screening scenarios. This review provides a straightforward synthesis of the state of the art of VRSG-based instruments and suggests future directions for research.

Factors influencing living space utilization among older Afro-Colombian adults.

OBJECTIVES: Investigate the factors influencing life space utilization in older Afro-descendant adults residing in Tumaco, Colombia - a marginalized region of the country. DESIGN: This cross-sectional study included 388 Afro-descendant older adults. The study assessed living space using the Life Space Assessment (LSA) scale and collected demographic data. Cognitive levels were measured with the Mini-Mental State Examination (MMSE), and depressive symptoms were assessed using the Yesavage scale. Socio-emotional indicators were determined with the Medical Outcomes Study (MOS). The research employed linear and logistic regression models for data analysis. RESULTS: On average, participants scored 27.0 on the LSA scale. A lack of perceived income resulted in a 10.44-point decrease on the LSA scale. For each unit increase in the MOS-Instrumental Dimension score, the LSA score increased by 0.52 points (95% CI 0.17-0.87). As for cognitive performance (MMSE scale), each one-point increase resulted in a 0.69 decrease in the LSA score (95% CI -1.25 to -0.12). CONCLUSION: Socioeconomic disadvantages limit living space utilization, particularly in the Afro-descendant population. Yet, social support can enhance living space use despite environmental and economic constraints.

Nailing precision: a systematic review and meta-analysis of randomized controlled trials comparing piriformis and trochanteric entry points for femoral antegrade nailing.

INTRODUCTION: Entry point selection, a crucial aspect of femoral antegrade nailing, can impact nail fit and consequently fracture reduction. In adults, the standard entry portals used are the piriformis fossa and the tip of the greater trochanter. Previous systematic reviews comparing the two techniques have not been limited to Randomized Controlled Trials (RCTs) and have not consistently included the same available RCTs. MATERIALS AND METHODS: A systematic search of comparative studies regarding entry portal selection in femoral antegrade nailing was conducted on seven databases. Only Prospective RCTs comparing trochanteric and piriformis entry in the management of trochanteric or diaphyseal femur fractures were eligible for inclusion. RESULTS: Ultimately, only 6 RCTs were found eligible for inclusion. Five of the six included studies reported on operative time. The resulting mean difference (MD) illustrated a significant decrease in operative time by approximately 21.26 min (95% CI - 28.60 to - 13.92, p < 0.001) using trochanteric entry. Fluoroscopy exposure was reported on by four studies, however, only two studies were included in the analysis due to different reporting methods. Trochanteric entry used significantly less fluoroscopy than piriformis entry (MD -50.33 s, 95% CI - 84.441 to - 16.22, p = 0. 004). No significant difference in malalignment rates, delayed union rates, nonunion rates, pain scores, or complication rates was found. CONCLUSION: The significant differences found in operating time and fluoroscopy time align with those in other studies. While we were not able to pool the data on functional outcome scores, none of the included studies found a significant difference in scores by their last follow-up. Both approaches demonstrate comparable functional outcomes and safety profiles, indicating the choice of entry point should be at the discretion of the surgeon based on technique familiarity and fracture characteristics.

Expected impact of immunomodulatory agents during pregnancy: A newborn's perspective.

The neonatal immune ontogeny begins during pregnancy to ensure that the neonate is well-suited for perinatal life. It prioritizes Th2/M2 and regulatory responses over Th/M1 activity to avoid excessive inflammatory responses and to ensure immune tolerance and homeostasis. Newborns also present increased Th17/Th22 responses providing effective anti-fungal immunity and mucosal protection. Intrauterine exposure to immune modulatory drugs with the placental transfer may influence the natural course of the fetal immune development. The vertical transfer of both biological therapy and small molecules begins during the first trimester through neonatal Fc receptor or placental diffusion, respectively, reaching its maximum transfer potential during the third trimester of pregnancy. Most of the biological therapy have a prolonged half-life in newborn's blood, being detectable in infants up to 12 months after birth (usually 6-9 months). The use of immunomodulators during pregnancy is gaining global interest. Current evidence mainly reports birth-related outcomes without exhaustive analysis of the on-target side effect on the perinatal immune system ontogeny, the infection risk, or the immune dysregulation. The present review will focus on: (1) the main characteristics of the perinatal immune system to understand its specific features and vulnerabilities to immune modulation; (2) the mechanisms of placental transfer of immunomodulators; and (3) the immune changes reported to date in newborns exposed to immunomodulators with emphasis on the current concerns and gaps in knowledge.

Penguin: A tool for predicting pseudouridine sites in direct RNA nanopore sequencing data.

Pseudouridine is one of the most abundant RNA modifications, occurring when uridines are catalyzed by Pseudouridine synthase proteins. It plays an important role in many biological processes and has been reported to have application in drug development. Recently, the single-molecule sequencing techniques such as the direct RNA sequencing platform offered by Oxford Nanopore technologies have enabled direct detection of RNA modifications on the molecule being sequenced. In this study, we introduce a tool called Penguin that integrates several machine learning (ML) models to identify RNA Pseudouridine sites on Nanopore direct RNA sequencing reads. Pseudouridine sites were identified on single molecule sequencing data collected from direct RNA sequencing resulting in 723 K reads in Hek293 and 500 K reads in Hela cell lines. Penguin extracts a set of features from the raw signal measured by the Oxford Nanopore and the corresponding basecalled k-mer. Those features are used to train the predictors included in Penguin, which in turn, can predict whether the signal is modified by the presence of Pseudouridine sites in the testing phase. We have included various predictors in Penguin, including Support vector machines (SVM), Random Forest (RF), and Neural network (NN). The results on the two benchmark data sets for Hek293 and Hela cell lines show outstanding performance of Penguin either in random split testing or in independent validation testing. In random split testing, Penguin has been able to identify Pseudouridine sites with a high accuracy of 93.38% by applying SVM to Hek293 benchmark dataset. In independent validation testing, Penguin achieves an accuracy of 92.61% by training SVM with Hek293 benchmark dataset and testing it for identifying Pseudouridine sites on Hela benchmark dataset. Thus, Penguin outperforms the existing Pseudouridine predictors in the literature by 16 % higher accuracy than those predictors using independent validation testing. Employing penguin to predict Pseudouridine sites revealed a significant enrichment of "regulation of mRNA 3'-end processing" in Hek293 cell line and 'positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus' in Hela cell line. Penguin software and models are available on GitHub at https://github.com/Janga-Lab/Penguin and can be readily employed for predicting Ψ sites from Nanopore direct RNA-sequencing datasets.

Point of care ultrasound impact in acute heart failure hospitalization: A retrospective cohort study.

BACKGROUND: Acute decompensated heart failure (ADHF) is one of the most frequent causes of emergency department (ED) visits. Point-of-Care Ultrasound (POCUS) is a reliable, easy-to-use, and available tool for an accurate diagnosis of ADHF. We aimed to analyze the impact of introducing POCUS as an additional tool to clinical standard diagnosis in clinical times of hospitalized heart failure patients. METHODS: Retrospective cohort study comparing patients consulting to ED for heart failure acute decompensation previous to the rutinary use of POCUS versus patients who received an ultrasound-guided diagnosis at entrance. Ultrasound evaluation was additional to standard diagnosis (which included natriuretic peptides, images, etc). Cumulative incidence functions were calculated for time to treatment, time to disposition decision, and time to discharge. We used a flexible parametric model for estimate the time ratio (TR) in order to reflect the effect of POCUS. RESULTS: A total of 149 patients were included. The most frequent comorbid condition was hypertension (71.8%) followed by type 2 diabetes (36.2%). B type natriuretic peptide (BNP) was over 500 ng/ml. Most patients had Stevenson B profile (83.9%) at admission. In the cumulative incidence model (Fig. A), the TR (time ratio) for the outcome time to treatment was 1.539 (CI 95% 0.88 to 2.69). The TR for the outcome time to disposition decision was 0.665 (CI 95% 0.48 to 0.99). The TR for the outcome time to discharge (hospital length of stay) was 0.663 (CI 95% 0.49 to 0.90). CONCLUSION: In our study, the introduction of POCUS to ADHF patients decreases time to disposition decision and total length of hospital stay. Conversely, time to treatment augments. There is need for the evaluation of ultrasound as an intervention in clinical trials to confirm these findings.

Risk of radial head arthroplasty revision is correlated with radial head diameter: a multicenter analysis of 405 cases.

BACKGROUND: Radial head arthroplasty (RHA) is commonly used for the treatment of comminuted radial head fractures. Indications as well as implant types continue to evolve. RHA has had good outcomes with midterm longevity. The literature is limited to small case series with varying implant types, and larger studies are needed to determine the optimal implant type and radial head diameter. METHODS: A retrospective analysis of RHA cases performed by 75 surgeons at 14 medical centers in an integrated health care system between 2006 and 2017 was completed. Patient demographics, comorbidities, implant type and head diameter, and indications for revision were recorded. Patients' in-person clinical visit data were recorded. Patients were also contacted via telephone at a minimum of 2 years to obtain abbreviated Disabilities of the Arm, Shoulder, and Hand questionnaire and Oxford scores. Implant survivorship was also captured within our integrated system. RESULTS: 405 cases met our inclusion criteria. Mean age was 51.5 ± 15.5 years (range 16-88 years) and more common in females (62%). Chart review and telephone follow-up was performed at a mean of 68.9 ± 31.5 months (range 24-146 months). Our study found that revision rate was positively correlated with increasing radial head diameter. A 26-mm head had 7.7 odds of revision compared to a size 18-mm head (95% confidence interval 1.2-150.1). More than 95% of revision cases were performed within the first 36 months of the index procedure. Obese patients had a significantly lower mean postoperative Oxford score (35.5) compared to controls (38.3) (P = .02). There was a significantly higher overall reoperation rate for terrible triad (18.4%) vs. isolated injuries (10.4%) (P = .04). There was no difference between Acumed Anatomic and Evolve radial head implants in overall reoperation, implant revision, postoperative range of motion, or patient-reported outcomes. CONCLUSIONS: Risk of revision is directly correlated with implanted radial head diameter. There were no differences in outcomes and complications between the 2 main implants used. Individuals who did not undergo a revision by 3 years' time tend to retain the implant. Terrible triad injuries had a higher all-cause reoperation rate than isolated radial head fractures, but no difference in the rate of RHA revision. These data reinforce the practice of downsizing radial head implant diameter.

Predictive Factors of Hospital-Acquired Bacterial Infections in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: We aimed to identify the predictive factors of hospital-acquired bacterial infections in patients with systemic lupus erythematosus (SLE). METHODS: This chart review study included patients with SLE who were hospitalized between 2009 and 2020 for reasons other than infection. The outcome was defined as any infection confirmed using any bacterial isolation method or diagnosed by treating physicians and required treatment with intravenous antibiotics. For statistical analysis, logistic regression analyses were performed. RESULTS: In total, 1678 patients (87.6% women) were included. The median age was 33 years (interquartile range, 24-47 years). The incidence of hospital-acquired infections was 13.9% (233 infections). Age, Systemic Lupus Erythematosus Disease Activity Index score, Systemic Lupus International Collaborating Clinics damage score, blood urea nitrogen and C-reactive protein levels, dosage of steroid in the previous month, recent use of 1 or more immunosuppressants, admission with a central venous catheter (or dialysis catheter), and use of central venous catheter or bladder catheter in the first 5 days were the predictive factors of nosocomial infections. CONCLUSION: The patients' infection risk profile should be assessed to accurately determine the risk-benefit balance of any therapeutic intervention, minimize exposure to steroids and immunosuppressants, and maintain a low threshold for the early diagnosis of infections. Further studies should assess whether the modification of some identified factors could reduce the incidence of nosocomial infections.

Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer's Disease.

OBJECTIVE: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer's disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world's largest ADAD kindred and sex differences in the relationship between SCD and memory performance. METHODS: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. RESULTS: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. CONCLUSIONS: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

Symptomatology of attention deficit, hyperactivity and defiant behavior as predictors of academic achievement.

BACKGROUND: It is essential to understand the factors that affect the academic achievement of schoolchildren, both in general and in terms of the major subsectors of each grade. Although symptoms of Attention Deficit Hyperactivity Disorder (ADHD) and Negative Defiant Disorder (NDD-which are commonly recognized as externalizing problems in childhood and adolescence-have been associated with lower academic achievement in the international literature, few studies have addressed this problem in Latin America. This study aimed to analyze the possible predictive relationship of attention problems, hyperactivity, and defiant behavior on academic achievement. METHODS: We recruited a sample of 4580 schoolchildren (50.9% female, 1754 belonging to primary school, and 2826 to secondary school, ranging from 9 to 18 years old). This cross-sectional study used the scales pertaining to attention problems, hyperactivity, and challenging behavior from the Child and Adolescent Evaluation System. RESULTS: The analysis showed that attention problems significantly affected all academic achievement areas, while hyperactivity and challenging behavior affected only some of them. The regression models explained 24% of the variability in overall academic achievement in primary school and 17% in secondary school. Other predictors included sex, age, socioeconomic level, and school attendance. CONCLUSIONS: It is important to consider this symptomatology in the design of educational interventions.

Efficacy of high-intensity interval- or continuous aerobic-training on insulin resistance and muscle function in adults with metabolic syndrome: a clinical trial.

PURPOSE: We carried out a randomized, clinical trial in adults of both sexes with metabolic syndrome (MS) to assess the efficacy of high-intensity, low-volume interval training (HIIT) compared to moderate-intensity continuous training (MICT) on insulin resistance (IR), muscle mass, muscle activation, and serum musclin. METHODS: Fasting glycemia, insulinemia, and glycated haemoglobin were determined by conventional methods, IR by Homeostatic model assessment (HOMA), lean mass by Dual-Energy X-ray Absorptiometry, muscle activation through carnosine by Proton Magnetic Resonance Spectroscopy, and musclin by Enzyme-Linked ImmunoSorbent Assay before and after a supervised, three-times/week, 12-week treadmill programme. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). MICT (n = 31) trained at 60% of VO2peak for 30 min. RESULTS: Patients had a mean age of 50.8 ± 6.0 years, body mass index of 30.6 ± 4.0 kg/m2, and VO2peak of 29.0 ± 6.3 mL.kg-1.min-1. Compared to MICT, HIIT was not superior at reducing Ln HOMA-IR (adjusted mean difference: 0.083 [95%CI - 0.092 to 0.257]), carnosine or musclin or at increasing thigh lean mass. HIIT increased carnosine by 0.66 mmol/kg.ww (95% CI 0.08-1.24) after intervention. Both interventions reduced IR, body fat percentage and increased total lean mass/height2 and VO2peak. Musclin showed a non-significant reduction with a small effect size after both interventions. CONCLUSION: Compared to MICT, HIIT is not superior at reducing IR, carnosine or musclin or at increasing skeletal muscle mass in adults with MS. Both training types improved IR, muscle mass and body composition. NCT03087721, March 22nd, 2017. TRIAL REGISTRATION NUMBER: NCT03087721. Registered March 22nd, 2017.

[Predictive validity of a functional classification method in older adultsValidação preditiva de método de classificação funcional em idosos]. / Validación predictiva de un método de clasificación funcional en adultos mayores.

OBJECTIVE: Evaluate the predictive validity of a functional classification (FC) method for the use of emergency services and hospitalization, mortality, and health care costs among older adults. METHODS: Retrospective cohort study that included 2 168 older adults in a chronic noncommunicable disease (CNCD) care program in Medellin, Colombia. Patients were stratified according to a FC method based on functional status, presence of risk factors, and control of comorbidity. During one year of follow-up, the predictive validity of the FC method was assessed for the studied outcomes. Discrimination and calibration were measured with the C-statistic and Hosmer-Lemeshow (HL) test, respectively. RESULTS: The average age was 74.6 ± 7.9 years; 40.8% (n = 884) were men and 7.7% (n = 168) died. The risk of death (odds ratio [OR]: 1.767; 3.411; 8.525), hospitalization (OR: 1.397; 2.172; 3.540) and high cost of health care (OR: 1.703; 2.369; 5.073) increased in proportion to a deterioration in functional classification (classes 2B, 3, and 4, respectively). The predictive model for the outcome of death showed good capacity for discrimination (C-statistic = 0.721) and calibration (HL statistic 10.200; P = 0.251). CONCLUSION: There is a dose-response relationship between deterioration in FC and a higher risk of death, hospitalization, and high cost. FC has predictive validity for the mortality rate and could be used to stratify older adults in CNCD care programs with a view to guiding interventions.

OBJETIVO: Avaliar a validade preditiva de um método de classificação funcional (CF) para a utilização de serviços de emergência e internação hospitalar, mortalidade e custos da atenção de saúde em idosos. MÉTODOS: Estudo de coorte retrospectivo com 2 168 idosos atendidos em um programa de atenção de doenças crônicas não transmissíveis (DCNT) em Medellín, Colômbia. Um método de CF foi usado para estratificar os participantes segundo o estado funcional, presença de fatores de risco e controle de comorbidades. No período de acompanhamento de um ano, a validade preditiva da CF foi avaliada para os desfechos de interesse. A capacidade discriminatória (estatística C) e a calibração (teste de Hosmer-Lemeshow [H-L]) do modelo foram avaliadas. RESULTADOS: A média de idade dos participantes do estudo foi 74,6 ± 7,9 anos, 40,8% (n = 884) eram do sexo masculino e 7,7% (n = 168) vieram a óbito. Houve aumento do risco de óbito (odds ratio [OR] 1,767; 3,411­8,525), internação hospitalar (OR 1,397; 2,172-3,540) e custo elevado da atenção de saúde (OR 1,703; 2,369­5,073) com o declínio funcional ­ classes funcionais 2B, 3 e 4, respectivamente. O modelo preditivo para o desfecho de óbito demonstrou boa capacidade discriminatória (estatística C = 0,721) e calibração (estatística H-L = 10,200; P = 0,251). CONCLUSÃO: Há uma relação de dose-resposta entre o declínio da CF e risco maior de óbito, internação hospitalar e custo elevado da atenção. A CF tem validade preditiva para a taxa de mortalidade e poderia ser utilizada na estratificação de idosos em programas de atenção de DCNT para ajudar a direcionar as medidas de intervenção.

Prevalence, Incidence, and Clinical-Epidemiological Characterization of Amyotrophic Lateral Sclerosis in Antioquia: Colombia.

INTRODUCTION: The prevalence and incidence of amyotrophic lateral sclerosis (ALS) is not fully established, and this varies depending on the studied population. OBJECTIVE: To estimate the prevalence/incidence of ALS patients in Antioquia-Colombia. METHODOLOGY: Observational/descriptive study by reviewing clinical records from 2010 to 2014. Cases with possible, probable and definite ALS were included. To estimate the prevalence/incidence, capture-recapture method was used. RESULTS: Point prevalence in December 2014 was 4.9/100,000 (95% CI 2.0-7.8), and the incidence was 1.4/100,000/year (95% CI 0.5-2.2). The median survival was 4 years. Spinal-onset was observed in 62.4% of the included patients. CONCLUSION: Prevalence, incidence and clinical presentation of ALS in Antioquia are similar to most studies reported worldwide. However, prevalence in Antioquia seems to be slightly higher than in other studies from Latin -American countries. This may derive from the inclusion criteria and case detection methodology adopted, but sociodemographic and genetic factors should be considered.

Implementation of the clinical practice guideline for individuals with amputations in Colombia: a qualitative study on perceived barriers and facilitators.

BACKGROUND: The issue of lower extremity amputation has been in the Colombian political agenda for its relationship with the armed conflict and antipersonnel mines. In 2015 the Colombian Ministry of Health published a national clinical practice guideline (CPG) for amputee patients. However, there is a need to design implementation strategies that target end-users and the context in which the CPG will be used. This study aims to identify users' perceptions about the barriers and facilitators for implementing the guideline for the care of amputee patients in a middle-income country such as Colombia. METHODS: Semi-structured interviews were conducted with 38 users, including patients, health workers, and administrative staff of institutions of the health system in Colombia. Individuals were purposively selected to ensure different perspectives, allowing a balance of individual positions. RESULTS: According to participants' perceptions, barriers to implementation are classified as individual barriers (characteristics of the amputee patient and professionals), health system barriers (resource availability, timely care, information systems, service costs, and regulatory changes), and barriers related to clinical practice guidelines (utility, methodological rigour, implementation flexibility, and characteristics of the group developing the guidelines). CONCLUSIONS: Our study advances knowledge on the perceived individual and health system barriers and facilitators for the implementation of the CPG for amputee patients in Colombia. Importantly, the governance, financial, and service delivery arrangements of the Colombian health system are determining factors in implementing CPGs. For example, the financial arrangements between the insurance companies and the health care provider institutions were identified as barriers for the implementation of recommendations related to the continuity and opportunity of care of patients with amputations. The design of implementation strategies that successfully address the individual behaviours and the contextual health systems arrangements may significantly impact the health care process for amputee patients in Colombia.

Complications of Elbow Arthroscopy in a Community-Based Practice.

PURPOSE: The purpose of this study was to report the complications of elbow arthroscopy in a large community practice with multiple surgeons and to analyze potential risk factors for these complications. METHODS: Patient demographic information, surgical variables, surgeon variables, and complications were retrospectively reviewed for all elbow arthroscopies performed within the health network from 2006 to 2014. Inclusion criteria included patients of any age undergoing a primary and revision elbow arthroscopy, which may have been performed in conjunction with other procedures. Exclusion criteria included incorrectly coded procedures where arthroscopy was not performed and no postoperative follow-up. Statistical calculations were performed using a binary logistic regression analysis to fit a logistic regression model. RESULTS: 560 consecutive elbow arthroscopies in 528 patients performed between 2006 and 2014, by 42 surgeons at 14 facilities, were reviewed. 113 procedures were performed in pediatric patients under the age of 18. The average age was 38.6 years (range: 5-88). There were 444 males. The average length of follow-up was 375.8 days (2 to 2,739 days). Overall, heterotopic ossification occurred in 14 of 560 cases (2.5%) (all males), and 20 of 560 (3.5%) cases developed transient nerve palsies (8 ulnar, 8 radial, 1 median, 3 medial antebrachial cutaneous). There were 3 (0.5%) deep and 11 (2%) superficial infections. There were no vascular injuries, compartment syndrome, deep vein thrombosis, or pulmonary embolism. Elevated blood sugar was a significantly higher risk for infection (odds ratio [OR] 4.11, 95% confidence interval [CI] 1.337 to 12.645; P = .0136). Previous elbow surgery (OR 3.57, 95% CI 1.440 to 8.938; P = .006) and female sex (OR 4.05; 95% CI 1.642 to 9.970; P = .002) had a significantly higher risk for nerve injury. Relative to pediatric patients, there were higher odds in adults for nerve injury, infection, and heterotopic ossification, but none reached significance. CONCLUSIONS: Elbow arthroscopy is a safe procedure with low complication rates. Diabetes is a risk factor for infection. Prior surgery and female sex are risk factors for nerve injury. LEVEL OF EVIDENCE: Case series, level 4.

Individual, health system, and contextual barriers and facilitators for the implementation of clinical practice guidelines: a systematic metareview.

INTRODUCTION: Clinical practice guidelines (CPGs) are designed to improve the quality of care and reduce unjustified individual variation in clinical practice. Knowledge of the barriers and facilitators that influence the implementation of the CPG recommendations is the first step in creating strategies to improve health outcomes. The present systematic meta-review sought to explore the barriers and facilitators for the implementation of CPGs. METHODS: A search was conducted in the PubMed, Embase, Cochrane, Health System Evidence and International Guideline Library (G-I-N) databases. Systematic reviews of qualitative, quantitative or mixed-methods studies that identified barriers or facilitators for the implementation of CPGs were included. The selection of the title and abstract, the evaluation of the full text, extraction of the data and the quality assessment were carried out by two independent reviewers. To summarise the evidence, we grouped the barriers and facilitators according to the following contexts: political and social, health organisational system, guidelines, health professionals and patients. RESULTS: Overall, 25 systematic reviews were selected. The relevant barriers in the social-political context were the absence of a leader, difficulties with teamwork and a lack of agreement with colleagues. Relevant barriers in the health system were a lack of time, financial problems and a lack of specialised personnel. Barriers of the CPGs included a lack of clarity and a lack of credibility in the evidence. Regarding the health professional, a lack of knowledge about the CPG and confidence in oneself were relevant. Regarding patients, a negative attitude towards implementation, a lack of knowledge about the CPG and sociocultural beliefs played a role. Some of the most frequent facilitators were consistent leadership, commitment of the members of the team, administrative support of the institution, existence of multidisciplinary teams, application of technology to improve the practice and education regarding the guidelines. CONCLUSIONS: The barriers and facilitators described in this review are factors that influence the implementation of evidence in clinical practice. Knowledge of these factors should contribute to the development of a theoretical basis for the creation of CPG implementation strategies to improve professional practice and health outcomes for patients.

Functional outcomes of ulnar collateral ligament reconstruction with a novel double suspensory fixation.

BACKGROUND: Ulnar collateral ligament reconstruction (UCLR) has allowed the return of overhead athletes to throwing sports. We describe a new double suspensory (DS) technique using a single tunnel in the ulna and humerus, achieving fixation with adjustable loop buttons. METHODS: Inclusion criteria included skeletally mature baseball players with clinical and magnetic resonance imaging diagnosis of UCL insufficiency who failed a trial of structured nonoperative treatment. A total of 36 baseball players underwent DS UCLR, between 2011 and 2017, by 1 surgeon with minimum 2-year follow-up. The graft was fixated with an adjustable button loop on the humeral side and a tension slide technique with a button on the ulnar side. Pre- and postoperative Kerlan-Jobe Orthopaedic Clinic and Single Assessment Numerical Evaluation and postoperative Conway scores were obtained. RESULTS: The mean age was 19.8 ± 4.6 years (range, 14-35 years). All were male. Mean years played before surgery was 14.3 ± 4.6 years (range, 8-28 years). There were 32 (89%) pitchers and 4 (11%) position players. There were 13 (36%) high school, 20 (55%) college, 2 (6%) minor league, and 1 (3%) adult league athletes. The mean follow-up was 55.3 ± 23.7 months (range, 26-97 months). There was significant improvement in Kerlan-Jobe Orthopaedic Clinic (33.2 ± 19.9 to 89.7 ± 15.1, P < .0001) and Single Assessment Numerical Evaluation (20.7 ± 16.7 to 93.6 ± 11.9, P < .0001) scores. Using Conway scoring, 25 (69%) had excellent, 5 (14%) good, 3 (8%) fair, and 3 (8%) poor scores. Mean return to play was 9 ± 1.5 months (range, 6-16 months). Only 1 (3%) athlete required a revision surgery and ultimately returned to play and 1 (3%) hardware removal. None developed ulnar nerve symptoms. CONCLUSION: DS fixation for UCLR in baseball players can lead to excellent clinical results and early return to play.

Is there a difference in the acromiohumeral distances measured on radiographic and magnetic resonance images of the same shoulder with a massive rotator cuff tear?

BACKGROUND: The purpose of our study was to compare the acromiohumeral distance (AHD) between radiographic and magnetic resonance images (MRIs) of the same shoulder with massive rotator cuff tears (MRCTs). METHODS: Thirty-four shoulders with MRCTs that had an MRI and radiograph of the same shoulder within an average of 40.3 days (range: 8-109 days) were identified. AHD was measured digitally on radiograph and MRI by 3 examiners. Shoulders were grouped into Hamada grades <3 (group 1) and Hamada grades ≥3 (group 2). RESULTS: The mean age was 66.4 years (range: 51-89). There were 19 men (59%). The Kappa for inter-rater reliability was 0.982 (95% confidence interval [CI] 0.975, 0.988) for radiographs and 0.88 (95% CI 0.75, 0.94) for MRI. There was a significant difference in the mean AHD of group 1 on radiograph vs. MRI (7.9 mm vs. 2.5 mm, respectively; P < .0001), but no difference in group 2 (1.8 mm vs. 2.2 mm, respectively; P = .45). There was no difference in AHD in group 1 between shoulders with Goutallier stage <3 (8.1 ± 1.9 mm) and those with Goutallier stage ≥3 (7.3 ± 2.1 mm) (P = .3479). There was no difference in AHD in group 2 between shoulders with Goutallier stage <3 (3.0 ± 0.1 mm) and those with Goutallier stage ≥3 (1.5 ± 1.0 mm) (P = .079). CONCLUSION: There is a significant difference in AHD measurements between radiograph and MRI of the same shoulder with MRCT in early Hamada grades. AHDs measured on radiograph and MRI should not be used interchangeably in early Hamada grades to assess outcomes of superior capsule reconstruction and similar procedures.

Genetic origin of a large family with a novel PSEN1 mutation (Ile416Thr).

INTRODUCTION: A small percentage of Alzheimer's disease (AD) cases are caused by genetic mutations with autosomal dominant inheritance. We report a family with a novel variant in PSEN1. METHODS: We performed clinical and genetic evaluation of 93 related individuals from a Colombian admixed population. 31 individuals had whole-genome sequencing. RESULTS: Genetic analysis revealed a missense variant in PSEN1 (NM_000021.3: c.1247T>C p.Ile416Thr), which originated on an African haplotype and segregated with AD logarithm of the odds score of 6. Their clinical phenotype is similar to sporadic AD except for earlier age at onset: the mean age at onset for mild cognitive impairment was 47.6 years (standard deviation 5.83) and for dementia 51.6 years (standard deviation 5.03). DISCUSSION: Ile416Thr is a novel pathogenic variant that causes AD in the sixth decade of life. The history of the region that included slave importation and admixtures within a confined geographic locale represents a "mini-population bottleneck" and subsequent emergence of a rare dominant mutation.