L-serine treatment in patients with GRIN-related encephalopathy: a phase 2A, non-randomized study.

GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18 years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12 months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3 months and 1 day before starting treatment and 1, 3, 6 and 12 months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8 years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes.

Infections following left ventricular assist device implantation and 1-year health-related quality of life.

BACKGROUND: Left ventricular assist device (LVAD) implantation leads to substantial and sustained improvement in health-related quality of life (HRQOL) among patients. Infection following device implantation remains an important and frequent complication and adversely affects patient-reported HRQOL. METHODS: Patients in The Society of Thoracic Surgeons' Interagency Registry for Mechanically Assisted Circulatory Support receiving a primary LVAD between April 2012 to October 2016 were included. The primary exposure was one-year post-implant infection, characterized by: (1) any infection; (2) total number of infections and (3) type (LVAD-specific, LVAD-related, non-LVAD). The association between infection and the primary composite adverse outcome (defined as EuroQoL Visual Analog Scale< 65, too sick to complete the survey, or death at 1-year) was estimated using inverse probability weighting and Cox regression. RESULTS: The study cohort included 11,618 patients from 161 medical centers with 4,768 (41.0%) patients developing an infection, and 2,282 (19.6%) patients having> 1 infection during the follow up period. The adjusted odds ratio for the primary composite adverse outcome was 1.22 (95% CI, 1.19-1.24, p < 0.001) for each additional infection. Each additional infection was associated with a 3.49% greater probability of the primary composite outcome and was associated with worse performance across multiple dimensions of HRQOL as assessed by the EQ-5D for patients who survived to 1 year. CONCLUSIONS: For patients undergoing LVAD implantation, each additional infection within the first post-implantation year was associated with an incremental negative effect on survival free of impaired HRQOL.

Association of Days Alive and Out of the Hospital After Ventricular Assist Device Implantation With Adverse Events and Quality of Life.

Importance: There is a need to better assess the cumulative effect on morbidity and mortality in patients undergoing durable left ventricular assist device (LVAD) implantation. This study evaluates a patient-centered performance metric (days alive and out of hospital [DAOH]) for durable LVAD therapy. Objective: To determine the incidence of percent of DAOH before and after LVAD implantation and (2) explore its association with established quality metrics (death, adverse events [AEs], quality of life). Design, Settings, and Participants: This was a retrospective national cohort study of Medicare beneficiaries implanted with a durable continuous-flow LVAD between April 2012 and December 2016. The data were analyzed from December 2021 to May 2022. Follow-up was 100% complete at 1 year. Data from The Society of Thoracic Surgeons Intermacs registry were linked to Medicare claims. Main Outcomes and Measures: The number of DAOH 180 days before and 365 days after LVAD implantation and daily patient location (home, index hospital, nonindex hospital, skilled nursing facility, rehabilitation center, hospice) were calculated. Percent of DAOH was indexed to each beneficiary's pre- (percent DAOH-BF) and postimplantation (percentage of DAOH-AF) follow-up time. The cohort was stratified by terciles of percentage of DAOH-AF. Results: Among the 3387 patients included (median [IQR] age: 66.3 [57.9-70.9] years), 80.9% were male, 33.6% and 37.1% were Interfaces Patient Profile 2 and 3, respectively, and 61.1% received implants as destination therapy. Median (IQR) percent of DAOH-BF was 88.8% (82.7%-93.8%) and 84.6% (62.1-91.5%) for percent of DAOH-AF. While DAOH-BF was not associated with post-LVAD outcomes, patients in the low tercile of percentage of DAOH-AF had a longer index hospitalization stay (mean, 44 days; 95% CI, 16-77), were less likely to be discharged home (mean. -46.4 days; 95% CI, 44.2-49.1), and spent more time in a skilled nursing facility (mean, 27 days; 95% CI, 24-29), rehabilitation center (mean, 10 days; 95% CI, 8-12), or hospice (mean, 6 days; 95% CI, 4-8). Increasing percentage of DAOH-AF was associated with patient risk, AEs, and indices of HRQoL. Patients experiencing non-LVAD-related AEs had the lowest percentage of DAOH-AF. Conclusions and Relevance: Significant variability existed in the percentage of DAOH within a 1-year time horizon and was associated with the cumulative AEs burden. This patient-centered measure may assist clinicians in informing patients about expectations after durable LVAD implantation. Validation of percentage DAOH as a quality metric for LVAD therapy across centers should be explored.

Mortality following durable left ventricular assist device implantation by timing and type of first infection.

OBJECTIVE: Although infections are common after left ventricular assist device implantation, the relationship between timing and type of first infection with regard to mortality is less well understood. METHODS: The Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support patients receiving a primary left ventricular assist device from April 2012 to May 2017 were included. The primary exposure was defined 3 ways: any infection, timing of first infection (early: ≤90 days; intermediate: 91-180 days; late: >180 days), and type (ventricular assist device specific, ventricular assist device related, non-ventricular assist device). The association between first infection and all-cause mortality was estimated using Cox regression. RESULTS: The cohort included 12,957 patients at 166 centers (destination therapy: 47.4%, bridge-to-transplant: 41.2%). First infections were most often non-ventricular assist device (54.2%). Rates of first infection were highest in the early interval (10.7/100 person-months). Patients with any infection had a significantly higher adjusted hazard of death (hazard ratio, 2.63; 2.46-2.86). First infection in the intermediate interval was associated with the largest increase in adjusted hazard of death (hazard ratio, 3.26; 2.82-3.78), followed by late (hazard ratio, 3.13; 2.77-3.53) and early intervals (hazard ratio, 2.37; 2.16-2.60). Ventricular assist device-related infections were associated with the largest increase in hazard of death (hazard ratio, 3.02; 2.69-3.40), followed by ventricular assist device specific (hazard ratio, 2.92; 2.57-3.32) and non-ventricular assist device (hazard ratio, 2.42; 2.20-2.65). CONCLUSIONS: Relative to those without infection, patients with any postimplantation infection had an increased risk of death. Ventricular assist device-related infections and infections occurring in the intermediate interval were associated with the largest increase in risk of death. After left ventricular assist device implantation, infection prevention strategies should target non-ventricular assist device infections in the first 90 days, then shift to surveillance/prevention of driveline infections after 90 days.

Care fragmentation predicts 90-day durable ventricular assist device outcomes.

OBJECTIVES: To examine whether fragmentation of care is associated with worse in-hospital and 90-day outcomes following durable ventricular assist device (VAD) implant. STUDY DESIGN: Cohort study. METHODS: This study was conducted using Medicare claims linked to the Society of Thoracic Surgeons (STS) Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) among patients undergoing VAD implant between July 2009 and April 2017. Medicare data were used to measure fragmentation of the multidisciplinary care delivery network for the treating hospital, based on providers' history of shared patients within the previous year. STS Intermacs data were used for risk adjustment and outcomes ascertainment. Hospitals were sorted into terciles based on the degree of network fragmentation, measured as the mean number of links separating providers in the network. Multivariable regression was used to associate network fragmentation with 90-day death or infection risk. RESULTS: The cohort included 5159 patients who underwent VAD implant, with 11.2% dying and 27.6% experiencing an infection within 90 days after implant. After adjustment, a 1-unit increase in network fragmentation was associated with an increase of 0.179 in the probability of in-hospital infection and an increase of 0.183 in the probability of 90-day infection (both P < .05). Similar results were observed in models of the numbers of in-hospital and 90-day infections. Network fragmentation was predictive of the probability of 90-day mortality, although this relationship was not significant after adjustment. CONCLUSIONS: Care delivery network fragmentation is associated with higher in-hospital and 90-day infection rates following durable VAD implant. These networks may serve as novel targets for enhancing outcomes for patients undergoing VAD implant.

Association Between Care Fragmentation and Total Spending After Durable Left Ventricular Device Implant: A Mediation Analysis of Health Care-Associated Infections Within a National Medicare-Society of Thoracic Surgeons Intermacs Linked Dataset.

BACKGROUND: Care fragmentation is associated with higher rates of infection after durable left ventricular assist device (LVAD) implant. Less is known about the relationship between care fragmentation and total spending, and whether this relationship is mediated by infections. METHODS: Total payments were captured from admission to 180 days post-discharge. Drawing on network theory, a measure of care fragmentation was developed based on the number of shared patients among providers (ie, anesthesiologists, cardiac surgeons, cardiologists, critical care specialists, nurse practitioners, physician assistants) caring for 4,987 Medicare beneficiaries undergoing LVAD implantation between July 2009 - April 2017. Care fragmentation was measured using average path length, which describes how efficiently information flows among network members; longer path length indicates greater fragmentation. Terciles based on the level of care fragmentation and multivariable regression were used to analyze the relationship between care fragmentation and LVAD payments and mediation analysis was used to evaluate the role of post-implant infections. RESULTS: The patient cohort was 81% male, 73% white, 11% Intermacs Profile 1 with mean (SD) age of 63.1 years (11.1). The mean (SD) level of care fragmentation in provider networks was 1.7 (0.2) and mean (SD) payment from admission to 180 days post-discharge was $246,905 ($109,872). Mean (SD) total payments at the lower, middle, and upper terciles of care fragmentation were $250,135 ($111,924), $243,288 ($109,376), and $247,290 ($108,241), respectively. In mediation analysis, the indirect effect of care fragmentation on total payments, through infections, was positive and statistically significant (ß=16032.5, p=0.008). CONCLUSIONS: Greater care fragmentation in the delivery of care surrounding durable LVAD implantation is associated with a higher incidence of infections, and consequently, higher payments for Medicare beneficiaries. Interventions to reduce care fragmentation may reduce the incidence of infections and in turn enhance the value of care for patients undergoing durable LVAD implantation.

Incompleteness of health-related quality of life assessments before left ventricular assist device implant: A novel quality metric.

BACKGROUND: Improved health-related quality of life (HRQOL) is an important outcome following durable left ventricular assist device (LVAD) implant. However, half of pre-implant HRQOL data are incomplete in The Society of Thoracic Surgeons' Intermacs registry. Pre-implant HRQOL incompleteness may reflect patient status or hospital resources to capture HRQOL data. We hypothesized that pre-implant HRQOL incompleteness predicts 90 day outcomes and serves as a novel quality metric. METHODS: Risk factors for pre-implant HRQOL (EQ-5D-5L visual analog scale; 12-item Kansas City Cardiomyopathy Questionnaire "KCCQ") incompleteness were examined by stepwise logistic modeling. Direct standardization method was used to calculate adjusted incompleteness rates using a mixed effects logistic model. Hospitals were dichotomized as low or high based on median adjusted incompleteness rates. Andersen-Gill models were used to associate pre-implant HRQOL adjusted incompleteness rate with adverse events within 90 day post-implant. RESULTS: The study cohort included 14,063 patients receiving a primary LVAD (4/2012-8/2017). HRQOL incompleteness at high-rate hospitals was more often due to administrative reasons (risk difference, EQ-5D: 10.1%; KCCQ-12: 11.6%) and less likely due to patient reasons (risk difference, EQ-5D: -8.9%; KCCQ-12: -11.4%). A 10% increase in the adjusted pre-implant EQ-5D incompleteness rate was significantly associated with higher risk of infection-related mortality (HR: 1.09), infection (HR: 1.05), and renal dysfunction (HR: 1.03). A 10% increase in the adjusted pre-implant KCCQ-12 incompleteness rate was significantly associated with higher risk of infection (HR: 1.04). CONCLUSIONS: Hospital adjusted pre-implant HRQOL incompleteness was predictive of 90-day post-implant outcomes and may serve as a novel quality metric.

Correction: Understanding and Addressing Variation in Health Care-Associated Infections After Durable Ventricular Assist Device Therapy: Protocol for a Mixed Methods Study.

[This corrects the article DOI: 10.2196/14701.].

Patient factors associated with left ventricular assist device infections: A scoping review.

Infections are widely prevalent in left ventricular assist device (LVAD) recipients and associated with adverse events including mortality and rehospitalizations. Current evidence examining factors associated with infections in this setting predominantly comprises single-center observational data. We performed a scoping review to systematically summarize all existing studies examining patient-related factors associated with infections after LVAD implantation. Studies published between 01/06 and 02/19 were identified through searching 5 bibliographic databases: PubMed, Scopus, EMBASE, CINAHL, and Web of Science Core Collection. Inclusion criteria required examination of patient-related factors associated with infections among recipients of contemporary implantable, continuous flow LVADs. Key study characteristics were extracted by four independent reviewers and current literature described narratively. All analyses took place between February 2019 and May 2021. A total of 31 studies met inclusion criteria. All included studies were observational, and most commonly focused on driveline infections (n = 17). Factors studied most commonly included body composition (n = 8), diabetes and other comorbidities (n = 8), and psychosocial/socio-economic factors (n = 6). Studies were frequently single-center with heterogeneity in definition of infectious outcomes as well as exposure variables. Patient race and sex did not correlate with infection risk. There was no consistent association noted between obesity, diabetes, or psychosocial/socio-economic factors and infections in LVAD recipients. Two studies reported a significant association between malnutrition and hypoalbuminemia and post implant infections. This review summarizes 31 studies that described patient-related factors associated with infection after LVAD implantation. Patient related comorbidities, especially body composition and diabetes, were most commonly evaluated, but were not consistently associated with infections after LVAD implantation.

Non-patient factors associated with infections in LVAD recipients: A scoping review.

BACKGROUND: Infections are the most common complication in recipients of durable left ventricular assist devices (LVAD) and are associated with increased morbidity, mortality, and expenditures. The existing literature examining factors associated with infection in LVAD recipients is limited and principally comprises single-center studies. This scoping review synthesizes all available evidence related to identifying modifiable, non-patient factors associated with infections among LVAD recipients. METHODS: Published studies were identified through searching 5 bibliographic databases: PubMed, Scopus, EMBASE, CINAHL, and Web of Science Core Collection. Inclusion criteria required examination of factors associated with infections among recipients of contemporary, implantable, continuous flow LVADs. Key study characteristics were extracted by 4 independent reviewers and current literature described narratively. The Systems Engineering Initiative for Patient Safety (SEIPS) model was used to develop a taxonomy for non-patient related factors (e.g., tasks, tools, technologies, organization, and environment) associated with infections following LVAD implantation. All analyses took place between February 2019 and May 2021. FINDINGS: A total of 43 studies met inclusion criteria. The majority of included studies were observational (n = 37), single-center (n = 29), from the U.S. (n = 38), and focused on driveline infections (n = 40). Among the 22 evaluated sub-domains of non-patient related factors, only two: increasing center experience and establishing a silicone-skin interface at the driveline exit site, were identified as consistently being associated with a lower risk of infection. CONCLUSION: This review identified 43 studies that described non-patient related factors associated with infection in LVAD recipients. Only two factors were consistently associated with lower infection risk in LVAD recipients: increasing experience and establishing a silicone-skin interface at driveline exit site. The large variability in reporting across multiple studied interventions limited the ability to discern their effectiveness.

Authorship Correction: Understanding and Addressing Variation in Health Care-Associated Infections After Durable Ventricular Assist Device Therapy: Protocol for a Mixed Methods Study.

[This corrects the article DOI: 10.2196/14701.].

Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer.

BACKGROUNDEpidemiologic studies suggest that metformin has antitumor effects. Laboratory studies indicate metformin impacts cancer stem-like cells (CSCs). As part of a phase II trial, we evaluated the impact of metformin on CSC number and on carcinoma-associated mesenchymal stem cells (CA-MSCs) and clinical outcomes in nondiabetic patients with advanced-stage epithelial ovarian cancer (EOC).METHODSThirty-eight patients with stage IIC (n = 1)/III (n = 25)/IV (n = 12) EOC were treated with either (a) neoadjuvant metformin, debulking surgery, and adjuvant chemotherapy plus metformin or (b) neoadjuvant chemotherapy and metformin, interval debulking surgery, and adjuvant chemotherapy plus metformin. Metformin-treated tumors, compared with historical controls, were evaluated for CSC number and chemotherapy response. Primary endpoints were (a) a 2-fold or greater reduction in aldehyde dehydrogenase-positive (ALDH+) CD133+ CSCs and (b) a relapse-free survival at 18 months of more than 50%.RESULTSMetformin was well tolerated. Median progression-free survival was 18.0 months (95% CI 14.0-21.6) with relapse-free survival at 18 months of 59.3% (95% CI 38.6-70.5). Median overall survival was 57.9 months (95% CI 28.0-not estimable). Tumors treated with metformin had a 2.4-fold decrease in ALDH+CD133+ CSCs and increased sensitivity to cisplatin ex vivo. Furthermore, metformin altered the methylation signature in CA-MSCs, which prevented CA-MSC-driven chemoresistance in vitro.CONCLUSIONTranslational studies confirm an impact of metformin on EOC CSCs and suggest epigenetic change in the tumor stroma may drive the platinum sensitivity ex vivo. Consistent with this, metformin therapy was associated with better-than-expected overall survival, supporting the use of metformin in phase III studies.TRIAL REGISTRATIONClinicalTrials.gov NCT01579812.

Orbital manifestations of granulomatosis with polyangiitis: 12-year experience in Mexico City.

PURPOSE: To present the clinical picture and radiological characteristics of orbital manifestations of granulomatosis with polyangiitis in a Mexican hospital and compare them with worldwide literature. METHODS: Retrospective, observational study from January 2007 to January 2019. An electronic file review was performed. All patients with the diagnosis of granulomatosis with polyangiitis (GPA) in the Oculoplastics department were included. Ophthalmological examination, biopsy, antibodies and tomographical results were included in the data collected. Descriptive statistics were obtained. RESULTS: One hundred and one patients in our institute had a diagnosis of GPA. Only 15 (14.8%) had orbital manifestations and were included in our study. 73.3% were female with a median age of 46.20 years (17-81). Diagnostic delay was on average 6 months. Only 6.7% had bilateral manifestations. No past medical history was found in 40%, 20% had a previous diagnosis of systemic GPA. Pain was reported in 73.3%. Increase of volume (proptosis or diffuse orbital mass) was present in 86.7%. C-ANCA antibodies were positive in seven patients (46.7%). In tomography, lacrimal gland involvement was present in 33.3% and diffuse orbital mass was present in 66.6%. Definite diagnosis was done with biopsy in 93.3%. One patient died from complications of GPA. CONCLUSIONS: Ophthalmologists should consider this rare disease as a differential diagnosis of orbital tumors, as it may have different clinical manifestations, even in non-Caucasian population. When in doubt, biopsy is always valuable. The statistics at our reference center correspond with statistics reported worldwide.

Evaluating the Impact of Pneumonia Prevention Recommendations After Cardiac Surgery.

BACKGROUND: Pneumonia is the most prevalent healthcare-associated infection after coronary artery bypass grafting (CABG), but the relative effectiveness of strategies to reduce its incidence remains unclear. We evaluated the relationship between healthcare-associated infection recommendations and risk of pneumonia after CABG. METHODS: Pneumonia prevention practice recommendations were developed based on literature review and analysis of semistructured interviews with key health care personnel across centers with low (<5.9%), medium (5.9%-6.1%), and high (>6.1%) rates of pneumonia. These practices were implemented among 2482 patients undergoing CABG from 2016 to 2017 across 18 centers. The independent effect of each practice in reducing pneumonia was assessed using multivariable logistic regression, adjusting for baseline risk and center. A composite (bundle) score was calculated as the number of practices (0 to 4) each patient received. RESULTS: Recommended pneumonia prevention practices included lung protective ventilation management, early extubation, progressive ambulation, and avoidance of postoperative bronchodilator therapy. Pneumonia occurred in 2.4% of patients. Lung protective ventilation (adjusted odds ratio [ORadj], 0.45; 95% confidence interval [CI], 0.22-0.92), ambulation (ORadj, 0.08; 95% CI, 0.04-0.17), and postoperative ventilation of less than 6 hours (ORadj, 0.47; 95% CI, 0.26-0.87) were significantly associated with lower odds of pneumonia. Postoperative bronchodilator therapy (ORadj, 4.83; 95% CI, 2.20-10.7) was significantly associated with higher odds. Risk-adjusted rates of pneumonia, operative mortality, and intensive care unit length of stay were lower in patients with higher bundle scores (all P-trend < .01). CONCLUSIONS: These pneumonia prevention recommendations may serve as effective targets for avoiding postoperative healthcare-associated infections.

Understanding and Addressing Variation in Health Care-Associated Infections After Durable Ventricular Assist Device Therapy: Protocol for a Mixed Methods Study.

BACKGROUND: Durable ventricular assist device (VAD) therapy is reserved for patients with advanced heart failure who have a poor estimated 1-year survival. However, despite highly protocolized management processes, patients are at a unique risk for developing a health care-associated infection (HAI). Few studies have examined optimal strategies for HAI prevention after durable VAD implantation, despite variability in rates across centers and their impact on short- and long-term outcomes. OBJECTIVE: The objective of this study is to develop recommendations for preventing the most significant HAIs after durable VAD implantation. The study has 3 specific aims: (1) identify determinants of center-level variability in HAI rates, (2) develop comprehensive understanding of barriers and facilitators for achieving low center-level HAI rates, and (3) develop and disseminate a best practices toolkit for preventing HAIs that accommodates various center contexts. METHODS: This is a sequential mixed methods study starting with a cross-sectional assessment of current practices. To address aim 1, we will conduct (1) a systematic review of HAI prevention studies and (2) in-depth quantitative analyses using administrative claims, in-depth clinical data, and organizational surveys of VAD centers. For aim 2, we will apply a mixed methods patient tracer assessment framework to conduct semistructured interviews, field observations, and document analysis informed by findings from aim 1 at 5 high-performing (ie, low HAIs) and 5 low-performing (ie, high HAI) centers, which will be examined using a mixed methods case series analysis. For aim 3, we will build upon the findings from the previous aims to develop and field test an HAI preventive toolkit, acquire stakeholder input at an annual cardiac surgical conference, disseminate the final version to VAD centers nationwide, and conduct follow-up surveys to assess the toolkit's adoption. RESULTS: The project was funded by the Agency for Healthcare Research and Quality in 2018 and enrollment for the overall project is ongoing. Data analysis is currently under way and the first results are expected to be submitted for publication in 2019. CONCLUSIONS: This mixed methods study seeks to quantitatively assess the determinants of HAIs across clinical centers and qualitatively identify the context-specific facilitators and barriers for attaining low HAI rates. The mixed data findings will be used to develop and disseminate a stakeholder-acceptable toolkit of evidence-based HAI prevention recommendations that will accommodate the specific contexts and needs of VAD centers. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/14701.

Posicionamiento del Comité de Medicamentos de la Asociación Española de Pediatría en relación con el uso de medicinas alternativas y seudociencias en niños / Position Statement From The Spanish Association Of Paediatrics Medicines Committee Concerning The Use Of Alternative Medicine And Pseudo-Science In Children

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[Position Statement From The Spanish Association Of Paediatrics Medicines Committee Concerning The Use Of Alternative Medicine And Pseudo-Science In Children]. / Posicionamiento del Comité de Medicamentos de la Asociación Española de Pediatría en relación con el uso de medicinas alternativas y seudociencias en niños.

Currently, there are some therapies that are being practiced without adjusting to the available scientific evidence. The terminology is confusing, encompassing terms such as "alternative medicine", "natural medicine", "complementary medicine", "pseudoscience" or "pseudo-therapies". The Medicines Committee of the Spanish Association of Paediatrics considers that no health professional should recommend treatments not supported by scientific evidence. Also, diagnostic and therapeutic actions should be always based on protocols and clinical practice guidelines. Health authorities and judicial system should regulate and regularize the use of alternative medicines in children, warning parents and prescribers of possible sanctions in those cases in which the clinical evolution is not satisfactory, as well responsibilities are required for the practice of traditional medicine, for health professionals who act without complying with the "lex artis ad hoc", and for the parents who do not fulfill their duties of custody and protection. In addition, it considers that, as already has happened, Professional Associations should also sanction, or at least reprobate or correct, those health professionals who, under a scientific recognition obtained by a university degree, promote the use of therapies far from the scientific method and current evidence, especially in those cases in which it is recommended to replace conventional treatment with pseudo-therapy, and in any case if said substitution leads to a clinical worsening that could have been avoided.

Clinical characterization and identification of five novel FOXL2 pathogenic variants in a cohort of 12 Mexican subjects with the syndrome of blepharophimosis-ptosis-epicanthus inversus.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant entity characterized by eyelid malformations and caused by mutations in the forkhead box L2 (FOXL2) gene. Clinical and genetic analyses of large cohorts of BPES patients from different ethnic origins are important for a better characterization of FOXL2 mutational landscape. The purpose of this study is to describe the phenotypic features and the causal FOXL2 variants in a Mexican cohort of BPES patients. A total of 12 individuals with typical facial findings were included. Clinical evaluation included palpebral measurements and levator function assessment. The complete coding sequence of FOXL2 was amplified by PCR and subsequently analyzed by Sanger sequencing. A total of 11 distinct FOXL2 pathogenic variants were identified in our cohort (molecular diagnostic rate of 92%), including 5 novel mutations. Our results broaden the BPES-related mutational spectrum and supports considerable FOXL2 allelic heterogeneity in our population.

Collaborative Quality Improvement Reduces Postoperative Pneumonia After Isolated Coronary Artery Bypass Grafting Surgery.

BACKGROUND: To date, studies evaluating outcome improvements associated with participation in physician-led collaboratives have been limited by the absence of a contemporaneous control group. We examined post cardiac surgery pneumonia rates associated with participation in a statewide, quality improvement collaborative relative to a national physician reporting program. METHODS AND RESULTS: We evaluated 911 754 coronary artery bypass operations (July 1, 2011, to June 30, 2017) performed across 1198 hospitals participating in a voluntary national physician reporting program (Society of Thoracic Surgeons [STS]), including 33 that participated in a Michigan-based collaborative (MI-Collaborative). Unlike STS hospitals not participating in the MI-Collaborative (i.e., STSnonMI) that solely received blinded reports, MI-Collaborative hospitals received a multi-faceted intervention starting November 2012 (quarterly in-person meetings showcasing unblinded data, webinars, site visits). Eighteen of the MI-Collaborative hospitals received additional support to implement recommended pneumonia prevention practices ("MI-CollaborativePlus"), whereas 15 did not ("MI-CollaborativeOnly"). We evaluated rates of postoperative pneumonia, adjusting for patient mix and hospital effects. Baseline patient characteristics were qualitatively similar between groups and time. During the preintervention period (Q3/2011 through Q3/2012), there was no statistically significant difference in the adjusted odds of pneumonia for STS hospitals participating in the MI-Collaborative compared to the STS non-MI hospitals. However, during the intervention period (Q4/2012 through Q2/2017), there was a significant 2% reduction per quarter in the adjusted odds of pneumonia for MI-Collaborative hospitals (n=33) relative to the STS-nonMI hospitals. There was a significant 3% per quarter reduction in the adjusted odds of pneumonia for the MI-CollaborativeOnly (n=15) hospitals relative to the STS-nonMI hospitals. Over the course of the overall study period, the STS-nonMI hospitals had a 1.96% reduction in risk-adjusted pneumonia (pre- vs. intervention periods), which was less than the MI-Collaborative (3.23%, P=0.011). Over the same time period, the MI-CollaborativePlus (n=18) reduced adjusted pneumonia rates by 10.29%, P=0.001. CONCLUSIONS: Participation in a physician-led collaborative was associated with significant reductions in pneumonia relative to a national quality reporting program. Interventions including collaborative learning may yield superior outcomes relative to solely using physician feedback reporting. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02068716.

Association Between Postoperative Pneumonia and 90-Day Episode Payments and Outcomes Among Medicare Beneficiaries Undergoing Cardiac Surgery.

Background Postoperative pneumonia is the most common healthcare-associated infection in cardiac surgical patients, yet their impact across a 90-day episode of care remains unknown. Our objective was to examine the relationship between pneumonia and 90-day episode payments and outcomes among Medicare beneficiaries undergoing cardiac surgery. Methods and Results Medicare claims were used to identify beneficiaries with episodes of coronary artery bypass grafting (CABG; n=56 728) and valve surgery (n=56 377) across 1045 centers between April 2014 and March 2015. Using a published diagnosis code-based algorithm, we identified pneumonia in 6.4% CABG episodes and 6.6% of valve surgery episodes. We compared price-standardized 90-day episode payments and outcome measures (postoperative length of stay, discharge to postacute care, mortality, and readmission) between beneficiaries with and without pneumonia using hierarchical regression models, adjusting for patient factors and hospital random effects. Pneumonia was associated with 24.5% higher episode payments for CABG ($46 723 versus $37 496; P<0.001) and 26.5% higher episode payments for valve surgery ($61 544 versus $48 549; P<0.001). For both cohorts, pneumonia was significantly associated with longer postoperative length of stay (CABG: +4.1 days, valve: +5.6 days), more frequent discharge to postacute care (CABG: odds ratio [OR]=1.99, valve: OR=2.17), and higher rates of 30-day mortality (CABG: OR=2.42, valve: OR=2.57) and 90-day readmission (CABG: OR=1.20, valve: OR=1.25), all P<0.001. We compared episode payments and outcomes across terciles of pneumonia rates and found that high pneumonia rate hospitals had higher episode payments and poorer outcomes compared with episodes at low pneumonia rate hospitals in both CABG and valve surgery cohorts. Conclusions Postoperative pneumonia was associated with significantly higher 90-day episode payments and inferior outcomes at the patient and hospital level. Future work should examine whether reducing pneumonia after cardiac surgery reduces episode spending and improves outcomes, which could facilitate hospital success in value-based reimbursement programs.