A heatmap for expected cumulative live birth rate in preimplantation genetic testing for monogenic disorders and chromosomal structural rearrangements.

PURPOSE: Our objective is to predict the cumulative live birth rate (CLBR) and identify the specific subset within the population undergoing preimplantation genetic testing for monogenic disorders (PGT-M) and chromosomal structural rearrangements (PGT-SR) which is likely to exhibit a diminished expected CLBR based on various patient demographics. METHODS: We performed a single-centre retrospective cohort study including 1522 women undergoing 3130 PGT cycles at a referral centre for PGT. A logistic regression analysis was performed to predict the CLBR per ovarian stimulation in women undergoing PGT-M by polymerase chain reaction (PCR) or single-nucleotide polymorphism (SNP) array, and in women undergoing PGT-SR by SNP array, array comparative genomic hybridization (CGH) or next-generation sequencing (NGS). RESULTS: The mean age of women was 32.6 years, with a mean AMH of 2.75 µg/L. Female age and AMH significantly affected the expected CLBR irrespective of the inheritance mode or PGT technology. An expected CLBR < 10% was reached above the age of 42 years and AMH ≤ 1.25 µg/L. We found no significant difference in outcome per ovarian stimulation between the different PGT technologies, i.e. PCR, SNP array, array CGH and NGS. Whereas per embryo transfer, we noticed a significantly higher probability of live birth when SNP array, array CGH and NGS were used as compared to PCR. CONCLUSION: In a PGT-setting, couples with an unfavourable female age and AMH should be informed of the prognosis to allow other reproductive choices. The heatmap produced in this study can be used as a visual tool for PGT couples.

Effects of lactate, super-GDF9, and low oxygen tension during bi-phasic in vitro maturation on the bioenergetic profiles of mouse cumulus-oocyte complex†.

In vitro maturation (IVM) is an alternative assisted reproductive technology with reduced hormone-related side effects and treatment burden compared to conventional IVF. Capacitation (CAPA)-IVM is a bi-phasic IVM system with improved clinical outcomes compared to standard monophasic IVM. Yet, CAPA-IVM efficiency compared to conventional IVF is still suboptimal in terms of producing utilizable blastocysts. Previously, we have shown that CAPA-IVM leads to a precocious increase in cumulus cell (CC) glycolytic activity during cytoplasmic maturation. In the current study, considering the fundamental importance of CCs for oocyte maturation and cumulus-oocyte complex (COC) microenvironment, we further analyzed the bioenergetic profiles of maturing CAPA-IVM COCs. Through a multi-step approach, we (i) explored mitochondrial function of the in vivo and CAPA-IVM matured COCs through real-time metabolic analysis with Seahorse analyzer, and to improve COC metabolism (ii) supplemented the culture media with lactate and/or super-GDF9 (an engineered form of growth differentiation factor 9) and (iii) reduced culture oxygen tension. Our results indicated that the pre-IVM step is delicate and prone to culture-related disruptions. Lactate and/or super-GDF9 supplementations failed to eliminate pre-IVM-induced stress on COC glucose metabolism and mitochondrial respiration. However, when performing pre-IVM culture under 5% oxygen tension, CAPA-IVM COCs showed similar bioenergetic profiles compared to in vivo matured counterparts. This is the first study providing real-time metabolic analysis of the COCs from a bi-phasic IVM system. The currently used analytical approach provides the quantitative measures and the rational basis to further improve IVM culture requirements.

Nursing students' attitudes regarding euthanasia due to unbearable mental suffering: Cross-sectional study using the adapted and validated Euthanasia Attitude Scale.

AIM: To explore final year nursing students' attitudes towards euthanasia due to unbearable mental suffering by using the adapted and validated Euthanasia Attitude Scale. DESIGN: Cross-sectional survey. METHODS: Explorative, descriptive cross-sectional study conducted using an e-mail survey between October 2020 and March 2021 by a sample of final-year baccalaureate nursing students (n = 273) from eight of the eleven Flemish university colleges. The actual questionnaire contains 21 questions and was developed based on a consensus reached following independent translations. The psychometric properties of the Euthanasia Attitude Scale were assessed, including reliability and validity. Independent-sample Mann-Whitney U-test was used to investigate relation between demographic and education-related data, and domain and total score of the UMS-EAS-NL. This study received ethical approval from the Ethical Committee of the University Hospital Brussels, Belgium. RESULTS: McDonald's omega was 0.838 for the total Euthanasia Attitude Scale scores, supporting the validity of the questionnaire. A statistically significant difference in 'Naturalistic beliefs' score was found relating to the year of birth. There are clinically important results between those students who have been involved in euthanasia and those who have not. CONCLUSIONS: Most of the final-year nursing students supported the probability of patients' access to euthanasia due to unbearable mental suffering. To monitor adequate care, it is necessary to prepare nursing students adequately for this complex matter. IMPACT: To date, no large-scale study has examined nursing students' attitudes towards euthanasia because of unbearable mental suffering. It is expected that nursing students may be confronted with such a euthanasia request during an internship, or later in their professional career, in countries where euthanasia is legal. Students showed a high acceptability towards UMS-euthanasia. Clinically significant differences were found for students who had ever been involved in euthanasia.

Dialyzer Performance During Hemodialysis Without Systemic Anticoagulation Using a Heparin-Grafted Dialyzer Combined With a Citrate-Enriched Dialysate: Results of the Randomized Crossover Noninferiority EvoCit Study.

RATIONALE & OBJECTIVE: The EvoCit study was designed to evaluate performance of a heparin-grafted dialyzer during hemodialysis with and without systemic anticoagulation. STUDY DESIGN: Randomized, crossover, noninferiority trial. Noninferiority was defined as a difference of≤10% for the primary outcome. SETTING & PARTICIPANTS: Single hemodialysis center; 26 prevalent patients treated with 617 hemodialysis sessions. INTERVENTIONS: Hemodialysis using a heparin-grafted dialyzer combined with a 1.0mmol/L citrate-enriched dialysate ("EvoCit") without systemic anticoagulation compared with hemodialysis performed with a heparin-grafted dialyzer with systemic heparin ("EvoHep"). Patients were randomly allocated to a first period of 4 weeks and crossed over to the alternative strategy for a second period of 4 weeks. OUTCOMES: The primary end point was the difference in Kt/Vurea between EvoCit and EvoHep. Secondary end points were urea reduction ratio, middle molecule removal, treatment time, thrombin generation, and reduction in dialyzer blood compartment volume. RESULTS: The estimated difference in Kt/Vurea between EvoCit and EvoHep was-0.03 (95% CI, -0.06 to-0.007), establishing noninferiority with mean Kt/Vurea of 1.47±0.05 (SE) for EvoCit and 1.50±0.05 for EvoHep. Noninferiority was also established for reduction ratios of urea and ß2-microglobulin. Premature discontinuation of dialysis was required for 4.2% of sessions among 6 patients during EvoCit and no sessions during EvoHep. Effective treatment time was 236±5 minutes for EvoCit and 238±1 minutes for EvoHep. Thrombin generation was increased and there was greater reduction in dialyzer blood compartment volume after treatments with EvoCit compared with EvoHep. LIMITATIONS: The effects of avoiding systemic anticoagulation on clinical outcomes were not evaluated. CONCLUSIONS: EvoCit is noninferior to EvoHep with respect to solute clearance but results in a greater number of shortened treatments, more membrane clotting, and greater thrombin generation TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT03887468.

Non-invasive neurally adjusted ventilatory assist in preterm infants with RDS: effect of changing NAVA levels.

We aimed to examine the effect of changing levels of support (NAVA level) during non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in preterm infants with respiratory distress syndrome (RDS) on electrical diaphragm activity. This is a prospective, single-centre, interventional, exploratory study in a convenience sample. Clinically stable preterm infants supported with NIV-NAVA for RDS were eligible. Patients were recruited in the first 24 h after the start of NIV-NAVA. Following a predefined titration protocol, NAVA levels were progressively increased starting from a level of 0.5 cmH2O/µV and with increments of 0.5 cmH2O/µV every 3 min, up to a maximum level of 4.0 cmH2O/µV. We measured the evolution of peak inspiratory pressure and the electrical signal of the diaphragm (Edi) during NAVA level titration. Twelve infants with a mean (SD) gestational age at birth of 30.6 (3.5) weeks and birth weight of 1454 (667) g were enrolled. For all patients a breakpoint could be identified during the titration study. The breakpoint was on average (SD) at a level of 2.33 (0.58) cmH2O/µV. With increasing NAVA levels, the respiratory rate decreased significantly. No severe complications occurred.Conclusions: Preterm neonates with RDS supported with NIV-NAVA display a biphasic response to changing NAVA levels with an identifiable breakpoint. This breakpoint was at a higher NAVA level than commonly used in this clinical situation. Immature neural feedback mechanisms warrant careful monitoring of preterm infants when supported with NIV-NAVA.Trial registration: clinicaltrials.gov NCT03780842. Date of registration December 12, 2018. What is Known: • Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is a safe, feasible and effective way to support respiration in preterm infants. • Intact neural feedback mechanisms are needed to protect the lung from overdistension in neurally adjusted ventilatory assist. What is New: • Preterm infants with acute RDS have a similar pattern of respiratory unloading as previously described. • Neural feedback mechanisms seem to be immature with the risk of insufficient support and lung injury due to overdistension of the lung.

The mediating effect of pain catastrophizing and perceived injustice in the relationship of pain on health-related quality of life in breast cancer survivors.

BACKGROUND: The importance of cognitive appraisals in the effectiveness of pain coping is well established. Two key variables in these appraisal processes are pain catastrophizing (PC) and perceived injustice (PI), which are known to increase the risk of long-term disability and aggravate the pain-related distress through maladaptive behavioral responses. However, to date, the mediating effects of these appraisals have not been examined concurrently in the breast cancer survivor (BCS) population, nor have they been related to health-related quality of life (HRQoL). METHODS: Using cross-sectional data from 110 BCS, structural path analyses were used to examine the mediating effects of PC and PI in the relationship of pain on the HRQoL in BCS. RESULTS: Results demonstrated a significant direct effect of pain and PI on HRQoL combined with a significant indirect effect through PI, but not through PC. An increase in pain is suggested to result in a decrease in quality of life. On the other hand, an increase in pain also is suggested to increase the PI. A similar relation with PC was not retained as significant. CONCLUSION: The relative salience of PI as a mediator of HRQoL underscores the fact that PI is not only understudied but also underappreciated and undertreated in the BCS population. The results of our study warrant replication across longitudinal studies but continue to expand upon the evidence of the multifactorial nature of pain coping in BCS.

Functional impairment, symptom severity, and overall quality of life in patients with advanced lung or colorectal cancer in six European countries: baseline findings from the ACTION study.

BACKGROUND: People with advanced cancer often suffer from various symptoms, which can arise from the cancer itself and its treatment, the illness experience, and/or co-morbid conditions. Important patient-reported outcomes such as functional status, symptom severity, and quality of life (QoL) might differ between countries, as countries vary with regard to contextual factors such as their healthcare system. PURPOSE: To assess self-reported emotional functioning, physical functioning, symptoms, and overall QoL in patients with advanced lung or colorectal cancer from six European countries, particularly in relation to their country of residence. METHODS: We used baseline patient data from the ACTION trial, including socio-demographic and clinical data as well as patient-reported data regarding functioning, symptoms, and overall QoL (EORTC QLQ-C15-PAL). RESULTS: Data from 1117 patients (55% lung cancer stage III/IV, 45% colorectal cancer stage IV) were used. The highest (worst) average symptom score was found for fatigue. We found similarities but also important differences in the outcomes across countries. The best scores (the highest for emotional functioning and QoL, the lowest for symptoms) were reported by Dutch and Danish patients. Belgian patients reported relatively low emotional functioning. CONCLUSION: The optimization of functioning, symptom relief, and overall QoL should be important objectives of healthcare professionals who take care of patients with advanced cancer. There are similarities, but also substantial differences across countries in functional status, symptoms, and overall QoL. Policymakers should take these differences into account and invest in offering health care catered to the needs of their population.

Optimal timing to screen for asymptomatic bacteriuria during pregnancy: first vs. second trimester.

OBJECTIVES: Although current guidelines advice to screen for asymptomatic bacteriuria during pregnancy, little is known about the best moment of testing. The goal of this study is to analyze the optimal timing (first vs. second trimester) to screen for asymptomatic bacteriuria during pregnancy. METHODS: A retrospective cohort analysis, comparing patients that were screened for asymptomatic bacteriuria in the first vs. second trimester was performed. The main question was to compare the rate of positive urinary culture in both trimesters. Study included patients all followed a prenatal consultation at the University Hospital of Brussels between 2012 and 2017. Other outcomes considered were the nature of identified germs, treatments, possible risk and confounding factors (age, BMI, gravidity-parity-abortus [GPA], type of conception, ethnicity, education, prior urinary tract infection (UTI), diabetes, hypertension, prior preterm delivery and sickle cell disease) and complications (UTI, preterm delivery, preterm rupture of the membranes and chorio-amnionitis). RESULTS: A total of 2,005 consecutive files were reviewed, 655 concerned patients screened during the first trimester group and 1,350 in the second trimester group. Asymptomatic bacteriuria was present in only 71 cases (3.54%), 23 in the first trimester group (3.50%) and 48 in the second trimester group (3.55%). Escherichia coli was the most frequently identified germ (37 cases (1.8%), 14 in the first trimester group and 23 in the second trimester group). Our logistic regression analysis shows no statistical difference according to the moment the urinary culture was done for the presence of asymptomatic bacteriuria (E. coli or others), for its association with hospitalization for pyelonephritis, preterm contractions, preterm pre-labor rupture of the membranes (PPROM) and/or preterm delivery. CONCLUSIONS: If recommendations remain to screen for asymptomatic bacteriuria at least once during pregnancy, this study indicates that the moment of testing (first vs. second trimester) has no clinical impact on obstetrical outcomes.

Evolution of head-shaft angle and neck-shaft angle in childhood.

The current retrospective study investigates the natural evolution of head-shaft angle (HSA) and neck-shaft angle (NSA) in childhood. It is not known if a high HSA in early childhood leads to a high HSA in adulthood. This study aims to characterize the evolution of HSA and compares it with the more commonly known NSA in healthy children. We measured radiographs of 84 different healthy hips of children between 3 and 14.5 years old who underwent at least 2 radiographs of the pelvis, corresponding to 286 measurements. We used a linear mixed model to determine the covariance between random intercept and slope while allowing each individual hip to change over time. The covariance for HSA between random intercept and random slope was -4.262 (p < 0.001), corresponding to a high negative correlation of -0.717, for NSA -2.754 (p = 0.031) or a high negative correlation of -0.779. HSA and NSA were strongly correlated, a value of 0.736 (p < 0.001) was measured. The high negative correlation for random intercept and random slope means that the higher the initial value (intercept), the steeper the decline (slope). Therefore HSA decreases faster in hips with high HSA at an early age. Hips with high HSA in early childhood do not necessarily lead to hips with high HSA in adulthood. Our results may aid in future clinical decision making in patients with developmental dysplasia of the hip (DDH) with high HSA in particular.

Electrocardiographic Effects of Propofol versus Etomidate in Patients with Brugada Syndrome.

BACKGROUND: Brugada Syndrome is an inherited arrhythmogenic disease, characterized by the typical coved type ST-segment elevation in the right precordial leads from V1 through V3. The BrugadaDrugs.org Advisory Board recommends avoiding administration of propofol in patients with Brugada Syndrome. Since prospective studies are lacking, it was the purpose of this study to assess the electrocardiographic effects of propofol and etomidate on the ST- and QRS-segments. In this trial, it was hypothesized that administration of propofol or etomidate in bolus for induction of anesthesia, in patients with Brugada Syndrome, do not clinically affect the ST- and QRS-segments and do not induce arrhythmias. METHODS: In this prospective, double-blinded trial, 98 patients with established Brugada syndrome were randomized to receive propofol (2 to 3 mg/kg) or etomidate (0.2 to 0.3 mg/kg) for induction of anesthesia. The primary endpoints were the changes of the ST- and QRS-segment, and the occurrence of new arrhythmias upon induction of anesthesia. RESULTS: The analysis included 80 patients: 43 were administered propofol and 37 etomidate. None of the patients had a ST elevation greater than or equal to 0.2 mV, one in each group had a ST elevation of 0.15 mV. An ST depression up to -0.15mV was observed eleven times with propofol and five with etomidate. A QRS-prolongation of 25% upon induction was seen in one patient with propofol and three with etomidate. This trial failed to establish any evidence to suggest that changes in either group differed, with most percentiles being zero (median [25th, 75th], 0 [0, 0] vs. 0 [0, 0]). Finally, no new arrhythmias occurred perioperatively in both groups. CONCLUSIONS: In this trial, there does not appear to be a significant difference in electrocardiographic changes in patients with Brugada syndrome when propofol versus etomidate were administered for induction of anesthesia. This study did not investigate electrocardiographic changes related to propofol used as an infusion for maintenance of anesthesia, so future studies would be warranted before conclusions about safety of propofol infusions in patients with Brugada syndrome can be determined.

Is ovarian response associated with adverse perinatal outcomes in GnRH antagonist IVF/ICSI cycles?

RESEARCH QUESTION: Is there an association between ovarian response and perinatal outcomes? DESIGN: A retrospective, single-centre cohort study including all women undergoing their first ovarian stimulation cycle in a gonadotrophin releasing hormone antagonist protocol, with a fresh embryo transfer that resulted in a singleton live birth from January 2009 to December 2015. Patients were categorized into four groups according to the number of oocytes retrieved: one to three (category 1), four to nine (category 2), 10-15 (category 3), or over 15 oocytes (category 4). RESULTS: The overall number of patients analysed was 964. No relevant statistical difference was found among neonatal outcomes across the four ovarian response categories. Neonatal weight (in grams) was comparable between all groups (3222 ± 607 versus 3254 ± 537 versus 3235 ± 575 versus 3200 ± 622; P = 0.85, in categories 1, 2, 3 and 4, respectively). No statistically significant differences were found among the ovarian response categories for birth weight z-scores (taking into account neonatal sex and delivery term). The incidence of pre-term birth and low birth weight was comparable across the different ovarian response groups (P = 0.127 and P = 0.19, respectively). Finally, the occurrence of adverse obstetric outcomes did not differ among the ovarian response categories. Multivariate regression analysis revealed that the number of oocytes was not associated with neonatal birth weight. CONCLUSIONS: No association was found between ovarian response and adverse perinatal outcomes in antagonist IVF and intracytoplasmic sperm injection cycles. Future, larger scale and prospectively designed investigations are needed to validate these results.

Hyperprolactinemia in Acromegaly is Related to Prolactin Secretion by Somatolactotroph Tumours.

The aim of this study is to assess differences in patient characteristics, tumour characteristics and hormone levels between acromegalic patients with and without hyperprolactinemia. 44 patients of the University Hospital of Brussels, Belgium with acromegaly who were diagnosed between January 2007 and July 2018 were included in this study. Nineteen patients were classified in the hyperprolactinemia group and 25 patients were classified in the normoprolactinemia group. No significant differences between acromegalic patients with and without hyperprolactinemia were found in age at diagnosis, gender, presence of hyperprolactinemia symptoms, insulin-like growth factor 1, growth hormone and testosterone levels, tumour volume, tumour invasiveness, immunohistochemistry of growth hormone and prolactin, Ki-67 index and mitotic index. However, for a cut-off of 10% of prolactin-positive cells, there was a trend towards a higher percentage of prolactin-positive tumours in hyperprolactinemia patients (p=0.054) and higher mean prolactin level in case of positive prolactin immunostaining (p=0.007)). In our study there were no differences in characteristics between acromegaly patients with hyper- and normoprolactinemia. An association between the serum prolactin level and the positivity of prolactin immunohistochemistry of the adenoma tissue was found. The absence of a difference in tumour volume between patients with hyper- and normoprolactinemia suggests that the hyperprolactinemia is likely to be caused by the co-secretion of growth hormone and prolactin by the tumour. Finally, for the first time, the cut-off of 10% of prolactin cells was validated for the diagnosis of somatolactotroph tumours in acromegaly.

Forty years of neuromuscular monitoring and postoperative residual curarisation: a meta-analysis and evaluation of confidence in network meta-analysis.

BACKGROUND: The reported incidence of postoperative residual curarisation (PORC) is still unacceptably high. The capacity of intraoperative neuromuscular monitoring (NMM) to reduce the incidence of PORC has yet to be established from pooled clinical studies. We conducted a meta-analysis of data from 1979 to 2019 to reanalyse this relationship. METHODS: English language, peer-reviewed, and operation room adult anaesthesia setting articles published between 1979 and 2019 were searched for on PubMed, Cochrane Central Register of Controlled Trials, ISI-WoK, and Scopus. The primary outcome was PORC incidence as defined by an at- or post-extubation train-of-four ratio (TOFR) of lower than 0.7, 0.9, or 1.0. Additional collected variables included the duration of action of neuromuscular blocking agents (NMBAs) used, sugammadex or neostigmine use, and the technique of anaesthesia maintenance. RESULTS: Fifty-three studies (109 study arms, 12 664 patients) were included. The pooled PORC incidence associated with the use of intermediate duration NMBAs and quantitative NMM was 0.115 (95% confidence interval [CI], 0.057-0.188). This was significantly lower than the PORC rate for both qualitative NMM (0.306; 95% CI, 0.09-0.411) and no NMM (0.331; 95% CI, 0.234-0.435). Anaesthesia type did not significantly affect PORC incidence. Sugammadex use was associated with lower PORC rates. The GRADE global level of evidence was very low and the refined assessment of the network meta-analysis by means of a confidence in network meta-analysis raised concerns on within- and across-study bias. CONCLUSIONS: Quantitative NMM outperforms both subjective and no NMM monitoring in reducing PORC as defined by a TOFR of <0.9.

Nurses' self-efficacy, rather than their knowledge, is associated with their engagement in advance care planning in nursing homes: A survey study.

BACKGROUND: Considering social cognitive theory and current literature about successful advance care planning in nursing homes, sufficient knowledge and self-efficacy are important preconditions for staff to be able to carry out advance care planning in practice. AIM: Exploring to what extent nurses' knowledge about and self-efficacy is associated with their engagement in advance care planning in nursing homes. DESIGN: Survey study as part of a baseline measurement of a randomised controlled cluster trial (NCT03521206). SETTING/PARTICIPANTS: Nurses in a purposive sample of 14 nursing homes in Belgium. METHODS: A survey was distributed among nurses, evaluating knowledge (11 true/false items), self-efficacy (12 roles and tasks on 10-point Likert-type scale) and six advance care planning practices (yes/no), ranging from performing advance care planning conversations to completing advance directives. RESULTS: A total of 196 nurses participated (66% response rate). While knowledge was not significantly associated with advance care planning practices, self-efficacy was. One unit's increase in self-efficacy was statistically associated with an estimated 32% increase in the number of practices having carried out. CONCLUSIONS: Nurses' engagement in advance care planning practices is mainly associated with their self-efficacy rather than their knowledge. Further research is necessary to improve the evidence regarding the causal relationship between constructs. However, these results suggest that educational programmes that focus solely on knowledge might not lead to increasing uptake of advance care planning in nurses.

Vascular access type and mortality in haemodialysis: a retrospective cohort study.

BACKGROUND: Haemodialysis patients have a high mortality rate. Part of this can be attributed to vascular access complications. Large retrospective studies have shown a higher mortality in patients dialysed with a catheter, which is mostly ascribed to infectious complications. Since we observe very little infectious complications in our haemodialysis patients, the aim of our study was to assess if we could still detect a difference in survival according to vascular access type. METHODS: Patients that started chronic haemodialysis treatment between 1/1/2007 and 31/12/2016 at the 'Universitair Ziekenhuis Brussel' were retrospectively studied. The time to death was studied as a function of the two main vascular access types using survival analysis, considering the type of vascular access at the initiation of dialysis or as time varying, and accounting for the available baseline characteristics. RESULTS: Of 374 patients 309 (82.6%) initiated haemodialysis with a catheter, while 65 patients initiated with an arteriovenous access. Vascular access type during follow-up did not change in 74% of all patients. A Kaplan Meier plot did not suggest a survival dependent on the vascular access type at start. An extended cox proportional hazard analysis showed that vascular access type was not independently correlated with mortality. However, age, history of congestive heart failure and active cancer at initiation of dialysis were independently associated with mortality. CONCLUSIONS: In this retrospective cohort study, haemodialysis vascular access type was not independently correlated with patient survival, even after taking into account change of vascular access over time.

MultiSCED: A tool for (meta-)analyzing single-case experimental data with multilevel modeling.

The MultiSCED web application has been developed to assist applied researchers in behavioral sciences to apply multilevel modeling to quantitatively summarize single-case experimental design (SCED) studies through a user-friendly point-and-click interface embedded within R. In this paper, we offer a brief introduction to the application, explaining how to define and estimate the relevant multilevel models and how to interpret the results numerically and graphically. The use of the application is illustrated through a re-analysis of an existing meta-analytic dataset. By guiding applied researchers through MultiSCED, we aim to make use of the multilevel modeling technique for combining SCED data across cases and across studies more comprehensible and accessible.

Value of Relative Myocardial Perfusion at MRI for Fractional Flow Reserve-Defined Ischemia: A Pilot Study.

OBJECTIVE. Correcting the perfusion in areas distal to coronary stenosis (risk) according to that of normal (remote) areas defines the relative myocardial perfusion index, which is similar to the fractional flow reserve (FFR) concept. The aim of this study was to assess the value of relative myocardial perfusion by MRI in predicting lesion-specific inducible ischemia as defined by FFR. MATERIALS AND METHODS. Forty-six patients (33 men and 13 women; mean [± SD] age, 61 ± 9 years) who underwent adenosine perfusion MRI and FFR measurement distal to 49 coronary artery stenoses during coronary angiography were retrospectively evaluated. Subendocardial time-enhancement maximal upslopes, normalized by the respective left ventricle cavity upslopes, were obtained in risk and remote subendocardium during adenosine and rest MRI perfusion and were correlated to the FFR values. RESULTS. The mean FFR value was 0.84 ± 0.09 (range, 0.60-0.98) and was less than or equal to 0.80 in 31% of stenoses (n = 15). The relative subendocardial perfusion index (risk-to-remote upslopes) during hyperemia showed better correlations with the FFR value (r = 0.59) than the uncorrected risk perfusion parameters (i.e., both the upslope during hyperemia and the perfusion reserve index [stress-to-rest upslopes]; r = 0.27 and 0.29, respectively). A cutoff value of 0.84 of the relative subendocardial perfusion index had an ROC AUC of 0.88 to predict stenosis at an FFR of less than or equal to 0.80. CONCLUSION. Using adenosine perfusion MRI, the relative myocardial perfusion index enabled the best prediction of FFR-defined lesion-specific myocardial ischemia. This index could be used to noninvasively determine the need for revascularization of known coronary stenoses.

Systematic review and meta-analysis of the diagnostic value of optokinetic after-nystagmus in vestibular disorders.

Introduction: To date, no systematic review or meta-analysis has critically evaluated the relevance of using optokinetic after-nystagmus (OKAN) in diagnosis of vestibular disorders. To assess the role of OKAN in diagnosis of vestibular disorders, the OKAN time constant (TC) between patients with vestibular disorders and healthy participants will be compared. Methods: Automated search strategies were carried out in the Embase, Medline PubMed, Web of Science, and Scopus databases from inception to December 2023. The following inclusion criteria were applied: (1) evaluation of OKAN in individuals with vestibular disorders, (2) clinical trials, and (3) inclusion of healthy individuals as the control group. Exclusion criteria were: (1) animal studies, (2) non-clinical trial study designs, (3) assessment of non-vestibular disorders, (4) no examination of OKAN TC, (5) only examination of healthy participants, (6) studies published in a language other than English, (7) no healthy participants as control group, (8) case reports, and (9) only abstract available. The random-effects model was used to pool the data. The Joanna Briggs Institute (JBI) Critical Appraisal Tools was used to assess the risk of bias. The quality assessment was performed with the aid of the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, provided by NHLBI. The PRISMA guidelines were used as reporting guidelines. The main outcome of this study was the between-group mean difference (MDbetween) in OKAN TC and its 95% confidence interval between patients with vestibular disorders and healthy participants. Results: Seven out of 244 screened articles were included that studied 289 participants. The overall mean difference (MD = -7.08) with a 95% CI of [-10.18; -3.97] was significant (p = 0.014). The heterogeneity was significant (p = 0.02). Quality assessment was generally good (76%). The risk of bias was low in five studies and moderate in two studies. Conclusion: The results demonstrate that OKAN TC is significantly shorter in patients with vestibular disorders compared to healthy controls. This finding is important for future research, particularly with the emergence of novel clinical tools and diagnostic syndromes. Systematic Review: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=442695.

Exercise-Induced Hypoalgesia in Patients with Chronic Whiplash-Associated Disorders: Differences between Subgroups Based on the Central Sensitization Inventory.

BACKGROUND: Physical exercise is an important element in the rehabilitation of chronic whiplash-associated disorders, with the physiological process underlying pain reduction called exercise-induced hypoalgesia. In chronic whiplash-associated disorders, exercise-induced hypoalgesia appears impaired, and the research suggests a relationship with symptoms of dysfunctional nociceptive processing, such as central sensitization. This study improves our understanding of exercise-induced hypoalgesia in chronic whiplash-associated disorders by examining the differences between the extent of exercise-induced hypoalgesia in subgroups based on scores on the central sensitization inventory (CSI). METHODS: Data were collected from 135 participants with chronic whiplash-associated disorders who completed a set of questionnaires. Pain pressure thresholds and temporal summations were assessed before and after a submaximal aerobic bicycle exercise test. RESULTS: We observed no interaction effect between exercise-induced hypoalgesia and the CSI scores for both pain pressure threshold and temporal summation. No overall statistical effect was measured in the analysis of the effect of time. The pain pressure threshold significantly related to the CSI. The temporal summation showed no correlation. CONCLUSIONS: During this study, we did not find evidence for a difference in the presence of exercise-induced hypoalgesia when the subgroups were created based on the central sensitization cluster calculator. Limited evidence was found for the influence of CSI scores on the delta pain pressure threshold.