Critical Outcome Measures Research Articles

Bridging the Gap: Understanding Appalachian Patient Satisfaction in Cosmetic Rhinoplasty.

Rhinoplasty is a surgical procedure aimed at correcting both functional and aesthetic nasal deformities, addressing issues such as trauma-induced disfigurements and patient dissatisfaction with nasal appearance. Patient satisfaction is a critical outcome measure in rhinoplasty, reflecting the success of the procedure and the quality of care provided. This study investigates factors influencing patient satisfaction among Appalachian patients undergoing rhinoplasty for aesthetic reasons, considering the unique healthcare challenges faced by rural populations. A modified Rhinoplasty Outcome Evaluation questionnaire was utilized to assess patient satisfaction. Descriptive statistics and regression analyses were performed to analyze demographic characteristics, complications, re-operations, and satisfaction scores among rural and urban participants. While no significant differences were found in demographic characteristics, trends in satisfaction scores suggest potential disparities between rural and urban populations. Rural patients exhibited marginally lower satisfaction scores and higher rates of complications and re-operations, highlighting the need for targeted interventions in rural healthcare settings. Addressing geographic barriers, enhancing preoperative education and postoperative support, and fostering interdisciplinary collaboration are essential strategies to improve patient satisfaction and outcomes in rhinoplasty procedures, particularly in rural communities. Further research with larger sample sizes and qualitative methods is warranted to explore the underlying factors contributing to patient satisfaction disparities and to inform evidence-based interventions aimed at narrowing healthcare disparities and advancing health equity in rhinoplasty care.

Hospital-to-Home: logic model and theory of change exercise to identify outcomes arising from integrated health and social care.

Introduction: Although Canada boasts universal access to hospital-based services, bed capacity has been a challenge with long wait times for acute admissions to a hospital bed from the Emergency Department. The use of hospital beds by ‘alternate level of care’ (ALC) patients is a critical concern. These ALC patients exist because of a lack of an appropriate level of care in the community. Integrated health and social care (IHSC) can limit avoidable acute care utilization including in-patient stays in hospitals. CHATS--Community & Home Assistance to Seniors is a community-based agency that provides transportation, meals, in-home services, caregiver relief, education and support, community wellness, and 24/7 assisted living among other services, with the aim of supporting ageing in place. CHATS has partnered with several local hospitals and homecare providers to create a number of hospital-to-home programs (HTH) that provide seamless and coordinated care from hospital to home for older adults enabling safe and effective transitions. Hospital-based data has shown that ALC days and inpatient and ED hospital readmissions declined following implementation of HTH programs. Although hospital-based data is available, community-based health and social care outcome-based metrics have not been developed nor collected. Despite limited qualitative data showing high levels of client and caregiver satisfaction with its HTH services, the lack of outcome-based data makes it difficult for CHATS to articulate the benefits of the HTH programs from a community-based perspective that reflects both health and social care outcomes with the aim of informing policy and programming decisions in the future, including program scale and spread.
 Methodology: A logic model (LM) and theory of change (ToC) exercise was undertaken by a broad representation of CHATS staff at all levels of the organization to identify the theory of change for the HTH programs and critical activity-based and outcome-based metrics to support future measurement and evaluation work. The development of these models clarified the fundamental program theory behind community agency contributions to the HTH programs that enable their success.
 Results: The theory of change noted that the HTH program was able to achieve hospital to home transition success because it facilitates older adult clients to achieve greater self-determination that can support more independent living. The HTH program’s components, case management, personal support, transportation, training, counselling, and assessments ensure that the personal goals of clients and their caregivers are identified and addressed. Feelings of empowerment, improved mental health, health and social care navigation literacy, and reduced acute care readmissions are some of the outcomes perceived as being attributable to the HTH programs. These outcomes, in turn, allow for greater overall health and wellbeing, and sense of independence among older adult clients and their caregivers. Ultimately, the HTH programs contribute towards greater systems efficiency and enhanced quality of life for clients and their family/caregivers.
 Next steps: The results of the LM and ToC exercises have enabled CHATS to identify critical input, activity and outcome measures for the HTH programs that reflect the contributions of CHATS, and a towards a future summative evaluation of the HTH programs.

A Visual Analog Scale for Self-Reported Quality of Life: A Comparison of VAS and QoL-AD in Older Adults.

People with dementia (PWD) are one of the fastest-growing clinical populations for speech-language pathologists. Self-reported quality of life (QoL) assessments are critical patient-reported outcome measures that align with person-centered care principles. However, proxy-reporting is most often used due to assumptions that PWD cannot provide reliable self-report. Visual analog scales (VASs) have been successfully used with people with expressive and cognitive deficits to measure subjective constructs such as QoL, mood, and pain. The purpose of this project is to evaluate the feasibility and reliability of a VAS QoL assessment tool. Twenty older adults free of cognitive impairment were assessed using the quality of life in Alzheimer's disease (QoL-AD) and the QoL-AD in combination with a VAS (VAS QoL-AD). The construct validity, internal consistency, and test-retest reliability of the VAS QoL-AD were assessed by performing both assessments twice, 4 weeks apart. Significant correlations between the overall VAS QoL-AD and the QoL-AD scale ratings, between most of the QoL-AD and VAS QoL-AD subtests, and between the first and second assessment scores were observed. Results indicated strong construct validity, internal consistency, and test-retest reliability of the VAS QoL-AD in people without dementia. These results warrant further research into the development of a dementia-specific, self-reported VAS QoL scale for PWD.

Computational Structural Validation of CYP2C9 Mutations and Evaluation of Machine Learning Algorithms in Predicting the Therapeutic Outcomes of Warfarin.

The study aimed to identify the key pharmacogenetic variable influencing the therapeutic outcomes of warfarin using machine learning algorithms and bioinformatics tools. Warfarin, a commonly used anticoagulant drug, is influenced by cytochrome P450 (CYP) enzymes, particularly CYP2C9. MLAs have been identified to have great potential in personalized therapy. The purpose of the study was to evaluate MLAs in predicting the critical outcomes of warfarin therapy and validate the key predictor genotyping variable using bioinformatics tools. An observational study was conducted on adults receiving warfarin. Allele discrimination method was used for estimating the single nucleotide polymorphisms (SNPs) in CYP2C9, VKORC1, and CYP4F2. MLAs were used for identifying the significant genetic and clinical variables in predicting the poor anticoagulation status (ACS) and stable warfarin dose. Advanced computational methods (SNPs' deleteriousness and impact on protein destabilization, molecular dockings, and 200ns molecular dynamics simulations) were employed for examining the influence of CYP2C9 SNPs on structure and function. Machine learning algorithms revealed CYP2C9 to be the most important predictor for both outcomes compared to the classical methods. Computational validation confirmed the altered structural activity, stability, and impaired functions of protein products of CYP2C9 SNPs. Molecular docking and dynamics simulations revealed significant conformational changes with mutations R144C and I359L in CYP2C9. We evaluated various MLAs in predicting the critical outcome measures associated with warfarin and observed CYP2C9 as the most critical predictor variable. The results of our study provide insight into the molecular basis of warfarin and the CYP2C9 gene. A prospective study validating the MLAs is urgently needed.

Managing Critical Patient-Reported Outcome Measures in Oncology Settings: System Development and Retrospective Study.

Remote monitoring programs based on the collection of patient-reported outcome (PRO) data are being increasingly adopted in oncology practices. Although PROs are a great source of patient data, the management of critical PRO data is not discussed in detail in the literature. This first-of-its-kind study aimed to design, describe, and evaluate a closed-loop alerting and communication system focused on managing PRO-related alerts in cancer care. We designed and developed a novel solution using an agile software development methodology by incrementally building new capabilities. We evaluated these new features using participatory design and the Fit between Individuals, Task, and Technology framework. A total of 8 questionnaires were implemented using alerting features, resulting in an alert rate of 7.82% (36,838/470,841) with 13.28% (10,965/82,544) of the patients triggering at least one alert. Alerts were reviewed by 501 staff members spanning across 191 care teams. All the alerts were reviewed with a median response time of 1 hour (SD 185 hours) during standard business hours. The most severe (red) alerts were documented 56.83% (2592/4561) of the time, whereas unlabeled alerts were documented 27.68% (1298/4689) of the time, signaling clinician concordance with the alert thresholds. A PRO-based alert and communication system has some initial benefits in reviewing clinically meaningful PRO data in a reasonable amount of time. We have discussed key system design considerations, workflow integration, and the mitigation of potential impact on the burden of care teams. The introduction of a PRO-based alert and communication system provides a reliable mechanism for care teams to review and respond to patient symptoms quickly. The system was standardized across many different oncology settings, demonstrating system flexibility. Future studies should focus on formally evaluating system usability through qualitative methods.

PCR33 Real-World Symptom Severity Reported By Genomically-Tested Gastric Cancer Patients in the United States between 2014-2017

While recent advances in gastric cancer treatment have the potential to extend overall survival, patient reports of disease symptoms, treatment toxicities, and quality of life are critical outcome measures. This study sought to assess patient-reported symptoms in a real-world cancer treatment setting from 2014-2017 to serve as a comparator to patients receiving novel therapies after 2017.

Health-related quality of life for patients with chronic lymphocytic leukaemia - A critical outcome measure in the era of highly effective therapies.

Health-related quality of life for patients with chronic lymphocytic leukaemia - A critical outcome measure in the era of highly effective therapies.

Brazilian version of the Critical Care Functional Rehabilitation Outcome Measure: translation, cross-cultural adaptation and evaluation of clinimetric properties.

To translate, crossculturally adapt and evaluate the clinimetric properties of the Critical Care Functional Rehabilitation Outcome Measure for evaluating the functionality of patients admitted to intensive care units in Brazil. The process of translation and cross-cultural adaptation involved the following steps: initial translation, synthesis, back-translation, expert committee review and pretesting. The intra- and interrater reliability and agreement were analyzed between two physical therapists who evaluated the same group of patients (n = 35). The evaluations were performed by each therapist independently and blinded to the score assigned by the other professional. The qualitative analysis was performed by the review committee, and the experts adapted and synthesized the Portuguese translation of the Critical Care Functional Rehabilitation Outcome Measure. There was agreement between the initial Brazilian translations of the Critical Care Functional Rehabilitation Outcome Measure scale. The conceptual, idiomatic, semantic and experimental equivalences between the original and translated versions were assessed, resulting in the final Brazilian version of the scale, called the Medida de Resultado da Reabilitação Funcional em Cuidados Intensivos. The evaluation of the clinimetric properties showed evidence of a high degree of agreement and reliability, as all had an intraclass correlation coefficient above 0.75. The overall intraclass correlation coefficient was 0.89. The translated version of the Critical Care Functional Rehabilitation Outcome Measure scale for assessing the functionality of patients admitted to an intensive care unit can be used reliably in Brazil following translation and cross-cultural adaptation to Brazilian Portuguese and presents evidence of excellent interrater reliability.

Brazilian version of the Critical Care Functional Rehabilitation Outcome Measure: translation, cross-cultural adaptation and evaluation of clinimetric properties

ObjectiveTo translate, crossculturally adapt and evaluate the clinimetric properties of the Critical Care Functional Rehabilitation Outcome Measure for evaluating the functionality of patients admitted to intensive care units in Brazil.MethodsThe process of translation and cross-cultural adaptation involved the following steps: initial translation, synthesis, back-translation, expert committee review and pretesting. The intra- and interrater reliability and agreement were analyzed between two physical therapists who evaluated the same group of patients (n = 35). The evaluations were performed by each therapist independently and blinded to the score assigned by the other professional. The qualitative analysis was performed by the review committee, and the experts adapted and synthesized the Portuguese translation of the Critical Care Functional Rehabilitation Outcome Measure.ResultsThere was agreement between the initial Brazilian translations of the Critical Care Functional Rehabilitation Outcome Measure scale. The conceptual, idiomatic, semantic and experimental equivalences between the original and translated versions were assessed, resulting in the final Brazilian version of the scale, called the Medida de Resultado da Reabilitação Funcional em Cuidados Intensivos. The evaluation of the clinimetric properties showed evidence of a high degree of agreement and reliability, as all had an intraclass correlation coefficient above 0.75. The overall intraclass correlation coefficient was 0.89.ConclusionThe translated version of the Critical Care Functional Rehabilitation Outcome Measure scale for assessing the functionality of patients admitted to an intensive care unit can be used reliably in Brazil following translation and cross-cultural adaptation to Brazilian Portuguese and presents evidence of excellent interrater reliability.

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH). A large body of pre-clinical data has suggested the possibility of notable GSH-deficit in a subgroup of patients with schizophrenia. Nevertheless, studies of intracortical GSH are not conclusive in this regard. In this review, we highlight the recent ultra-high field magnetic resonance spectroscopic studies linking GSH to critical outcome measures across various stages of schizophrenia. We discuss the methodological steps required to conclusively establish or refute the persistence of GSH-deficit subtype and clarify the role of the central antioxidant system in disrupting the brain structure and connectivity in the early stages of schizophrenia. We propose in-vivo GSH quantification for patient selection in forthcoming antioxidant trials in psychosis. This review offers directions for a promising non-dopaminergic early intervention approach in schizophrenia.

Laser Doppler Perfusion Imaging in the Mouse Hindlimb.

Blood flow recovery is a critical outcome measure after experimental hindlimb ischemia or ischemia-reperfusion. Laser Doppler perfusion imaging (LDPI) is a common, noninvasive, repeatable method for assessing blood flow recovery. The technique calculates overall blood flow in the sampled tissue from the Doppler shift in frequency caused when a laser hits moving red blood cells. Measurements are expressed in arbitrary perfusion units, so the contralateral non-intervened upon leg is usually used to help control measurements. Measurement depth is in the range of 0.3-1 mm; for hindlimb ischemia, this means that dermal perfusion is assessed. Dermal perfusion is dependent on several factors-most importantly skin temperature and anesthetic agent, which must be carefully controlled to result in reliable readings. Furthermore, hair and skin pigmentation can alter the ability of the laser to either reach or penetrate to the dermis. This article demonstrates the technique of LDPI in the mouse hindlimb.

Extensive Variability in Platelet Count, Bleeding, and Quality of Life Outcome Measures in Adult and Pediatric Immune Thrombocytopenia: An Appraisal from a Critical Review of the Literature

Introduction: Despite publication of standardized platelet count response definitions by the immune thrombocytopenia (ITP) International Working Group (IWG) in 2009, there remains considerable variability in the definition of platelet count outcomes across ITP studies. Moreover, there is no widely-accepted bleeding scale, health-related quality of life (HRQoL) inventories, or definition of remission for use in ITP patients, all critical outcome measures not addressed in the IWG Report. This heterogeneity makes comparison of response rates and outcomes between studies challenging. Therefore, to better understand current practices and inform future standardization efforts, we performed a systematic review of ITP studies to characterize how these outcomes have been measured in the decade following publication of the IWG Report. Methods: We performed a systematic review of PubMed/MEDLINE-indexed manuscripts published from January 1, 2010 through December 31, 2019 that described a platelet count, bleeding, and/or HRQoL measure in reflection of treatment response in adult and pediatric ITP. Following initial search, two authors (H.A. and R.G.) screened each abstract for inclusion, then read each included full text manuscript to collect outcome measures. Interventional studies with ≥10 patients and observational studies with ≥50 patients were included; manuscripts without abstracts and non-English language manuscripts were excluded. Results: Studies. The PubMed/MEDLINE search revealed 1562 manuscripts; following abstract screening and manuscript review, 168 manuscripts met inclusion criteria for the study. Of the 168 studies, 110 studies evaluated adults, 41 evaluated children, and 17 evaluated both adults and children; 99 were prospective (including 32 randomized trials) and 69 were retrospective observational studies. Platelet Outcomes. 141 studies (including 28 randomized trials, 53 non-randomized prospective studies and 60 retrospective observational studies) reported platelet response outcomes and 11 reported platelet count remission definitions. Of the 141 reporting response outcomes, 61 (43%) used IWG definitions and 80 (57%) did not. Of these 80 studies, there were a total of 21 distinct platelet count outcome definition schemes (Figure 1). The majority of randomized trials (22/28, 79%) and other prospective studies (37/53, 70%) did not use IWG definitions; instead, a plurality of these studies used a Plt ≥50 × 109/L to define a treatment response, without definitions for complete, partial, or minor response. Most retrospective observational studies (39/60, 65%), however, used IWG definitions. Of the 11 studies reporting remission definitions, a platelet count of ≥100 × 109/L with or without treatment over a time period of ≥6 months was the most commonly used definition of remission, although a minority of studies used thresholds of ≥50 × 109/L or ≥150 × 109/L. Bleeding Outcomes. Bleeding outcomes were reported in a systematic fashion in only a minority of studies (67/168, 36%), which used a total of 21 distinct bleeding outcome reporting schemes. A plurality of adult studies used the WHO Bleeding Scale and a plurality of pediatric studies used the Buchanan and Adix Score, Figure 2. HRQoL Outcomes. HRQoL outcomes were reported in a small minority of studies (15/168, 9%), which used a total of 8 different HRQoL instruments (6 adult instruments and 2 pediatric instruments), Table. Conclusions: Despite prior attempts to standardize evaluation of platelet response to treatment in ITP, there remains wide variability in the definition of both treatment response and remission. In particular, most prospective and randomized studies published following release of the 2009 IWG report have used study-specific platelet count response thresholds, whereas retrospective observational studies were much more likely to adopt the IWG-recommended platelet response definitions. Despite the fact that ITP is a bleeding disorder and its impact on HRQoL has been well-documented, most ITP studies published in the past decade did not evaluate bleeding in any systematic way and fewer still evaluated the impact of treatment on HRQoL. Further standardization of platelet count, bleeding, and HRQoL outcomes in both pediatric and adult ITP is greatly needed, especially for future randomized trials, to allow for more meaningful comparison of response rates and efficacy between studies. Disclosures Al-Samkari: Agios: Consultancy, Research Funding; Argenx: Consultancy; Amgen: Research Funding; Dova: Consultancy, Research Funding; Rigel: Consultancy. Arnold:Novartis: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Principia: Consultancy. Grace:Novartis: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees; Pfizer: Research Funding; Agios: Research Funding.

An assessment of baseline risk factors for peripartum maternal critical care interventions

Background Maternal morbidity presents a growing challenge to the American healthcare system and increasing numbers of patients are requiring higher levels of care in pregnancy. Identifying patients at high risk for critical care interventions, including intensive care unit admission, during delivery hospitalizations may facilitate appropriate multidisciplinary planning and lead to improved maternal safety. Baseline risk factors for critical care in pregnancy have not been well-described previously. Objective This study assesses baseline factors associated with critical care interventions that were present at admission for delivery. Study design This is a secondary analysis of a multicenter observational registry of pregnancy after prior uterine surgery and primary cesarean delivery. All women with known gestational age were included. The primary outcome measure was a composite of critical care interventions that included postpartum intensive care unit admission, mechanical ventilation, central intravenous access, and arterial line placement. Risk for this critical care outcome measure was compared by selected baseline and obstetric characteristics known at the time of hospital admission, including maternal age, pre-pregnancy BMI, race, maternal co-morbidities, parity, and plurality. We evaluated these potential predictors and fit a multivariable logistic regression model to ascertain the most significant risk factors for critical care during a delivery hospitalization. Results 73,096 of 73,257 women in the parent trial met inclusion criteria, of whom 505 underwent a critical care intervention (0.7%). In the adjusted model, heart disease [aOR = 10.05, CI = 6.97 − 14.49], renal disease [aOR = 2.78, CI = 1.49 − 5.18], and connective tissue disease [aOR = 3.27, CI = 1.52 − 6.99], as well as hypertensive disorders of pregnancy [aOR = 2.04, CI = 1.31 − 3.17] were associated with the greatest odds of critical care intervention [p < .01] (Table 2). Other predictors associated with increased risk included maternal age, African American race, smoking, diabetes, asthma, anemia, nulliparity, and twin pregnancy. Conclusion In this cohort, women with cardiac disease, renal disease, connective tissue disease and preeclampsia spectrum disorders were at increased risk for critical care interventions. Obstetric providers should assess patient risk routinely, ensure appropriate maternal level of care, and create multidisciplinary plans to improve maternal safety and reduce risk.

The Quality Assurance and Quality Control Protocol for Neuropsychological Data Collection and Curation in the Ontario Neurodegenerative Disease Research Initiative (ONDRI) Study.

As large research initiatives designed to generate big data on clinical cohorts become more common, there is an increasing need to establish standard quality assurance (QA; preventing errors) and quality control (QC; identifying and correcting errors) procedures for critical outcome measures. The present article describes the QA and QC approach developed and implemented for the neuropsychology data collected as part of the Ontario Neurodegenerative Disease Research Initiative study. We report on the efficacy of our approach and provide data quality metrics. Our findings demonstrate that even with a comprehensive QA protocol, the proportion of data errors still can be high. Additionally, we show that several widely used neuropsychological measures are particularly susceptible to error. These findings highlight the need for large research programs to put into place active, comprehensive, and separate QA and QC procedures before, during, and after protocol deployment. Detailed recommendations and considerations for future studies are provided.

Determining the Rate of Educational Advancement of Associate Degree Nursing Graduates: A Replicable Method to Establish the ADN as a Pathway to the Baccalaureate in Nursing

This article reports on the initial analysis of a database constructed to track the educational advancement of graduates’ of a public associate degree nursing (ADN) consortium in the northeast United States. This study offers a valid, reliable, and replicable method for ADN programs to determine the frequency and rate of the educational advancement of graduates to demonstrate a critical program outcome measure and to show that these programs are contributing to the educational progression of the nation’s nursing workforce. In addition, this research represents a contribution to the body of evidence for a new paradigm of nursing education that demonstrates the ADN as a clear pathway to the BSN, essential to reach 80% BSN by 2020. The alignment of demographic and academic variables with educational advancement is a recommendation for further study.

Protocol for a feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients

IntroductionOxygen is the most commonly administered drug to mechanically ventilated critically ill adults, yet little is known about the optimum oxygen saturation (SpO2) target for these patients; the current standard...

Beyond Survival: Pediatric Critical Care Interventional Trial Outcome Measure Preferences of Families and Healthcare Professionals.

To identify, in addition to survival, preferred outcome measures of PICU family care providers and PICU healthcare professionals for interventional trials enrolling critically ill children, and to describe general attitudes of family care providers and healthcare professionals regarding research in the PICU. Cross-sectional survey examining subject experience with clinical research and personal preferences for outcome measures for a hypothetical interventional clinical trial. PICUs within four academic children's hospitals in the United States and Canada. Two cohorts including family members of critically ill children in PICUs (family care providers) and multidisciplinary staff working in the PICUs (healthcare professionals). Administration of a short, deidentified survey. Demographic data were collated for the two subject groups. Participants were queried regarding their attitudes related to research conducted in the PICU. In addition to survival, each group was asked to identify their three most important outcomes for an investigation examining whether or not an intervention helps seriously ill children recover. Demographics for family care providers (n = 40) and healthcare professionals (n = 53) were similarly distributed. Female respondents (79.8%) predominated. Participants (98.9%) ascertained the importance of conducting research in the PICU, but significant challenges associated with this goal in the high stress PICU environment. Both quality of life and functioning after leaving the hospital were chosen as the most preferred outcome measure, with 77.5% of family care providers and 84.9% of healthcare professionals indicating this choice. Duration of organ dysfunction was identified by 70.0% of family care providers and 40.7% of healthcare professionals as the second most preferred outcome measure. In addition to survival, long-term quality of life/functional status and duration of organ dysfunction represent important interventional trial outcome measures for both families of critically ill children, as well as the multidisciplinary team who provides critical care.

GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis.

The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm). CRD42016051091.

Bestrophinopathy: An RPE-photoreceptor interface disease.

Bestrophinopathies, one of the most common forms of inherited macular degenerations, are caused by mutations in the BEST1 gene expressed in the retinal pigment epithelium (RPE). Both human and canine BEST1-linked maculopathies are characterized by abnormal accumulation of autofluorescent material within RPE cells and bilateral macular or multifocal lesions; however, the specific mechanism leading to the formation of these lesions remains unclear. We now provide an overview of the current state of knowledge on the molecular pathology of bestrophinopathies, and explore factors promoting formation of RPE-neuroretinal separations, using the first spontaneous animal model of BEST1-associated retinopathies, canine Best (cBest). Here, we characterize the nature of the autofluorescent RPE cell inclusions and report matching spectral signatures of RPE-associated fluorophores between human and canine retinae, indicating an analogous composition of endogenous RPE deposits in Best Vitelliform Macular Dystrophy (BVMD) patients and its canine disease model. This study also exposes a range of biochemical and structural abnormalities at the RPE-photoreceptor interface related to the impaired cone-associated microvillar ensheathment and compromised insoluble interphotoreceptor matrix (IPM), the major pathological culprits responsible for weakening of the RPE-neuroretina interactions, and consequently, formation of vitelliform lesions. These salient alterations detected at the RPE apical domain in cBest as well as in BVMD- and ARB-hiPSC-RPE model systems provide novel insights into the pathological mechanism of BEST1-linked disorders that will allow for development of critical outcome measures guiding therapeutic strategies for bestrophinopathies.

Neuro-cognitive mechanisms of simultanagnosia in patients with posterior cortical atrophy.

Posterior cortical atrophy is dominated by progressive degradation of parieto-occipital grey and white matter, and represents in most cases a variant of Alzheimer's disease. Patients with posterior cortical atrophy are characterized by increasing higher visual and visuo-spatial impairments. In particular, a key symptom of posterior cortical atrophy is simultanagnosia i.e. the inability to perceive multiple visual objects at the same time. Two neuro-cognitive mechanisms have been suggested to underlie simultanagnosia, either reduced visual short-term memory capacity or decreased visual processing speed possibly resulting from white matter impairments over and above damage to cortical brain areas. To test these distinct hypotheses, we investigated a group of 12 patients suffering from posterior cortical atrophy with homogenous lesion sides in parieto-occipital cortices and varying severity of grey and white matter loss. More specifically, we (i) tested whether impaired short-term memory capacity or processing speed underlie symptoms of simultanagnosia; (ii) assessed the link to grey and white matter damage; and (iii) integrated those findings into a neuro-cognitive model of simultanagnosia in patients with posterior cortical atrophy. To this end, simultaneous perception of multiple visual objects was tested in patients with posterior cortical atrophy mostly with positive Alzheimer's disease biomarkers and healthy age-matched controls. Critical outcome measures were identification of overlapping relative to non-overlapping figures and visuo-spatial performance in tests sensitive to simultanagnosia. Using whole report of briefly presented letter arrays based on the mathematically formulated 'Theory of Visual Attention', we furthermore quantified parameters of visual short-term memory capacity and visual processing speed. Grey and white matter atrophy was assessed by voxel-based morphometry analyses of structural magnetic resonance data. All patients showed severe deficits of simultaneous perception. Compared to controls, we observed a specific slowing of visual processing speed, while visual short-term memory capacity was preserved. In a regression analysis, processing speed was identified as the only significant predictor of simultaneous perception deficits that explained a high degree of variance (70-82%) across simultanagnosia tasks. More severe slowing was also indicative for more severe impairments in reading and scene comprehension. Voxel-based morphometry yielded extensive reductions of grey and white matter in parieto-occipital and thalamic brain areas. Importantly, the degree of individual atrophy of white matter in left superior parietal lobe, but not of any grey matter region, was associated with processing speed. Based on these findings, we propose that atrophy of white matter commonly observed in posterior cortical atrophy leads to slowing of visual processing speed, which underlies the overt clinical symptoms of simultanagnosia.