Controversy on the CONVINCE study findings: the PRO take / Controvérsia sobre os achados do estudo CONVINCE: a perspectiva PRO

ABSTRACT The CONVINCE study, recently published in the New England Journal of Medicine, reveals a groundbreaking 23% reduction in the relative risk of all-cause mortality among end-stage kidney patients undergoing high convective volume hemodiafiltration. This significant finding challenges the conventional use of high-flux hemodialysis and offers hope for improving outcomes in chronic kidney disease patients. While some controversies surround the study's findings, including concerns about generalizability and the causes of death, it is essential to acknowledge the study's design and its main outcomes. The CONVINCE study, part of the HORIZON 2020 project, enrolled 1360 patients and demonstrated the superiority of hemodiafiltration in reducing all-cause mortality overall, as well as in specific patient subgroups (elderly, short vintage, non-diabetic, and those without cardiac issues). Interestingly, it was shown that hemodiafiltration had a protective effect against infection, including COVID-19. Future research will address sustainability, dose scaling effects, identification of subgroups especially likely to benefit and cost-effectiveness. However, for now, the findings strongly support a broader adoption of hemodiafiltration in renal replacement therapy, marking a significant advancement in the field.

RESUMO O estudo CONVINCE, publicado recentemente no New England Journal of Medicine, revela uma redução inovadora de 23% no risco relativo de mortalidade por todas as causas entre pacientes renais em estágio terminal submetidos à hemodiafiltração de alto volume de convecção. Esse achado significativo desafia o uso convencional da hemodiálise de alto fluxo e oferece esperança de melhoria dos desfechos em pacientes com doença renal crônica. Embora algumas controvérsias cerquem os achados do estudo, incluindo preocupações sobre a generalização e as causas de óbito, é essencial reconhecer o desenho do estudo e seus principais desfechos. O estudo CONVINCE, parte do projeto HORIZON 2020, inscreveu 1.360 pacientes e demonstrou a superioridade da hemodiafiltração na redução da mortalidade por todas as causas em geral, bem como em subgrupos específicos de pacientes (idosos, HD de curta duração, não diabéticos e aqueles sem problemas cardíacos). Curiosamente, demonstrou-se que a hemodiafiltração teve um efeito protetor contra infecções, incluindo a COVID-19. Pesquisas futuras abordarão sustentabilidade, efeitos de escalonamento da dose, identificação de subgrupos especialmente propensos a se beneficiar e a relação custo-benefício. No entanto, por ora, os achados apoiam fortemente uma adoção mais ampla da hemodiafiltração na terapia renal substitutiva, marcando um avanço significativo na área.

Management of left atrial myxoma in pregnant women: a case series.

BACKGROUND: Left atrial myxoma during pregnancy is rare. We present three cases in order to aid in the management. CASE PRESENTATION: Three cases of left atrial myxoma during pregnancy were presented in this article. Three patients all received multidisciplinary team work and acquired good outcomes. The case 1 had no symptoms and delivered before traditional cardiac surgery. The case 2 and case 3 undergone totally endoscopic minimally invasive cardiac surgery during pregnancy. The case 3 maintained pregnancy to term and gave birth to a healthy baby via vaginal delivery. No relapse of the tumor was observed. CONCLUSIONS: The management of left atrial myxoma during pregnancy ought to be individualized and combined with the gestational age. If the diagnosis was made in the first two trimesters of pregnancy, totally endoscopic minimally invasive cardiac surgery during pregnancy would be an optimal choice. The patients can benefit from the multidisciplinary team work.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Mechanisms of Injury Leading to Concussions in Collegiate Soccer Players: A CARE Consortium Study.

BACKGROUND: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes. PURPOSE: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The Concussion Assessment, Research and Education (CARE) Consortium database was used. The mechanism of injury was categorized into head-to-ball, head-to-head, head-to-body, and head-to-ground/equipment. Baseline/acute injury characteristics-including Sports Concussion Assessment Tool-3 total symptom severity (TSS), loss of consciousness (LOC), and altered mental status (AMS); descriptive data; and recovery (RTP and URTP)-were compared. Multivariable regression and Weibull models were used to assess the predictive value of the mechanism of injury on TSS and RTP/URTP, respectively. RESULTS: Among 391 soccer SRCs, 32.7% were attributed to a head-to-ball mechanism, 27.9% to a head-to-body mechanism, 21.7% to a head-to-head mechanism, and 17.6% to a head-to-ground/equipment mechanism. Event type was significantly associated with injury mechanism [χ2(3) = 63; P < .001), such that more head-to-ball concussions occurred in practice sessions (n = 92 [51.1%] vs n = 36 [17.1%]) and more head-to-head (n = 65 [30.8%] vs n = 20 [11.1]) and head-to-body (n = 76 [36%] vs n = 33 [18.3%]) concussions occurred in competition. The primary position was significantly associated with injury mechanism [χ2(3) = 24; P < .004], with goalkeepers having no SRCs from the head-to-head mechanism (n = 0 [0%]) and forward players having the least head-to-body mechanism (n = 15 [19.2%]). LOC was also associated with injury mechanism (P = .034), with LOC being most prevalent in head-to-ground/equipment. Finally, AMS was most prevalent in head-to-ball (n = 54 [34.2%]) and head-to-body (n = 48 [30.4%]) mechanisms [χ2(3) = 9; P = .029]. In our multivariable models, the mechanism was not a predictor of TSS or RTP; however, it was associated with URTP (P = .044), with head-to-equipment/ground injuries resulting in the shortest mean number of days (14 ± 9.1 days) to URTP and the head-to-ball mechanism the longest (18.6 ± 21.6 days). CONCLUSION: The mechanism of injury differed by event type and primary position, and LOC and AMS were different across mechanisms. Even though the mechanism of injury was not a significant predictor of acute symptom burden or time until RTP initiation, those with head-to-equipment/ground injuries spent the shortest time until URTP, and those with head-to-ball injuries had the longest time until URTP.

Construct validity, responsiveness and minimal important difference of the cumulated ambulation score in older adults with hip fracture in sub-acute rehabilitation facility.

OBJECTIVE: To assess the construct validity, responsiveness and minimal important difference of the cumulated ambulation score in patients with hip fracture in sub-acute rehabilitation facility. DESIGN: Observational, prospective, monocenter, cohort study. SETTING: Rehabilitation Institute. PARTICIPANTS: 456 older adults with hip fracture (≥65 years) admitted for inpatient rehabilitation. MAIN OUTCOME MEASURES: Cumulated ambulation score, functional independence measure and functional ambulation category were collected at admission and discharge. Construct validity and responsiveness were assessed through hypothesis testing and minimal important difference was determined using the anchor-based method; floor and ceiling effects were also assessed. RESULTS: The cumulated ambulation score showed strong correlations with the functional independence measure and functional ambulation category scores at both admission and discharge, satisfying all the hypotheses for construct validity. The effect size of cumulated ambulation score was 1.63. Changes in cumulated ambulation score had a moderate-to-strong correlation with changes of other instruments and were able to discriminate patients improved from those not-improved, and patients classified as independent ambulators from those dependent. A ceiling effect was found only at discharge. The estimated minimal important difference was 2 points. CONCLUSIONS: The cumulated ambulation score showed high levels of construct validity and responsiveness according to the hypothesis testing. A two points improvement at the end of rehabilitation was found to be clinically important in people with hip fracture in the sub-acute phase. The ceiling effect found at discharge suggested the limitation of the scale in assessing people with a partially recovered autonomy in performing postural changes and gait.

Understanding the influence of different proxy perspectives in explaining the difference between self-rated and proxy-rated quality of life in people living with dementia: a systematic literature review and meta-analysis.

PURPOSE: Proxy assessment can be elicited via the proxy-patient perspective (i.e., asking proxies to assess the patient's quality of life (QoL) as they think the patient would respond) or proxy-proxy perspective (i.e., asking proxies to provide their own perspective on the patient's QoL). This review aimed to identify the role of the proxy perspective in explaining the differences between self-rated and proxy-rated QoL in people living with dementia. METHODS: A systematic literate review was conducted by sourcing articles from a previously published review, supplemented by an update of the review in four bibliographic databases. Peer-reviewed studies that reported both self-reported and proxy-reported mean QoL estimates using the same standardized QoL instrument, published in English, and focused on the QoL of people with dementia were included. A meta-analysis was conducted to synthesize the mean differences between self- and proxy-report across different proxy perspectives. RESULTS: The review included 96 articles from which 635 observations were extracted. Most observations extracted used the proxy-proxy perspective (79%) compared with the proxy-patient perspective (10%); with 11% of the studies not stating the perspective. The QOL-AD was the most commonly used measure, followed by the EQ-5D and DEMQOL. The standardized mean difference (SMD) between the self- and proxy-report was lower for the proxy-patient perspective (SMD: 0.250; 95% CI 0.116; 0.384) compared to the proxy-proxy perspective (SMD: 0.532; 95% CI 0.456; 0.609). CONCLUSION: Different proxy perspectives affect the ratings of QoL, whereby adopting a proxy-proxy QoL perspective has a higher inter-rater gap in comparison with the proxy-patient perspective.

Further psychometric evaluation of the WOUND-Q: A responsiveness study.

The WOUND-Q is a modular patient-reported outcome measure (PROM) with 13 scales measuring constructs across 4 domains (i.e., wound characteristics, health related quality of life, experience of care and wound treatment). The psychometrics of the WOUND-Q were previously assessed and the 13 scales evidenced good validity and reliability. However, the responsiveness (i.e., ability to detect clinical change) of the WOUND-Q has yet to be assessed. The objective of this study was to evaluate responsiveness for 9 WOUND-Q scales that assess outcomes, in a sample of people 18 years of age or older with chronic wounds that were present for at least 3 months. This study conducted a 4 month follow-up of 421 participants who completed the WOUND-Q as part of a previous psychometric study. Participants completed an online survey answering questions about their current wound state (e.g., number, type, size, smell, drainage), anchor questions about change, as well as the WOUND-Q scales that they had completed in their initial assessment. Pre-defined hypotheses were tested with a 75% acceptance threshold indicating sufficient evidence of responsiveness. Minimally important differences (MIDs) were also calculated using both anchor-based and distribution-based methods. Of 390 invited participants, 320 provided responses, ranging in age from 19 to 84 years. Acceptance of hypotheses ranged from 60% to 100%, with only the Symptom scale not meeting the 75% threshold. The findings of this study provide evidence that the WOUND-Q can validly measure clinical change in patients with chronic wounds.

Perinatal outcome in anti-NMDAr encephalitis during pregnancy-a systematic review with individual patients' data analysis.

INTRODUCTION: Anti-N-methyl-D-aspartate receptor (NMDAr) antibody encephalitis is an autoimmune disorder characterized by synaptic NMDAr current disruption and receptor hypofunction, often affecting women during pregnancy. Clinical manifestations associated with anti-NMDAr encephalitis can occur both in the mother and fetus. METHODS: We generated a systematic search of the literature to identify epidemiological, clinical, and serological data related to pregnant women with anti-NMDAr encephalitis and their children, analyzing the fetal outcomes. We examined the age and neurologic symptoms of the mothers, the presence of an underlying tumor, immunotherapies used during pregnancy, duration of the pregnancy, and type of delivery. RESULTS: Data from 41 patients were extrapolated from the included studies. Spontaneous interruption of pregnancy, premature birth, and cesarean section were reported in pregnant women with NMDAr encephalitis. Several fetal and neonatal symptoms (e.g., movement disorders, spina bifida, poor sucking, respiratory distress, cardiac arrhythmias, infections, icterus, hypoglycemia, and low birth weight) depending on the mother's serum anti-NR1 concentration were also reported. CONCLUSIONS: We characterized the outcomes of children born from mothers with anti-NMDAr encephalitis, analyzing the pivotal risk factors related to pregnancy and maternal disorder. Neuropsychiatric involvement seems strictly related to pathogenic NMDAr antibodies detected in maternal and/or neonatal serum. These findings clarify a complex condition to manage, outlining the risks associated with pregnant women with anti-NMDAr encephalitis and also providing a concrete guide for therapeutic strategies to prevent potential harm to the fetus and the child's neurodevelopment.

Endovascular thrombectomy for treatment of isolated posterior cerebral artery occlusion: a real-world analysis of hospitalizations in the United States.

BACKGROUND: Despite renewed interest and recently demonstrated efficacy for endovascular thrombectomy (EVT) for treatment of acute ischemic stroke (AIS) of the posterior circulation, to date, no randomized clinical trials have been conducted to evaluate EVT for isolated occlusions of the posterior cerebral artery (IPCA). METHODS: Hospitalizations for adult patients with primary admission diagnoses of IPCA occlusion were identified in the National Inpatient Sample registry during the period of 2016-2020. The study exposure was treatment with EVT, and primary clinical endpoints included favorable functional outcome (defined as discharge disposition to home without services, previously shown to have high concordance with modified Rankin scale scores 0-2), in-hospital mortality, and any intracranial hemorrhage (ICH). Inverse probability of treatment weighting (IPTW) was performed to balance baseline clinical characteristics between those receiving EVT or medical management (MM). RESULTS: This analysis identified 34,880 IPCA occlusion hospitalizations, 730 (2.1%) of which documented treatment with EVT. Following IPTW adjustment, EVT was associated with favorable outcome in IPCA patients presenting with mild deficits (M-D) (NIHSS < 6) [adjusted odds ratio (aOR) 2.36, 95% confidence interval (CI) 2.27, 2.45; p < 0.001] and in those presenting with moderate-to-severe deficits (M-S-D) (NIHSS 6-42) (aOR 2.00, 95% CI 1.86, 2.15; p < 0.001). Mortality rates did not differ among those with M-S-D [EVT 4.8% vs. MM 4.7%, p = 0.742], while ICH rates were lower. CONCLUSION: Retrospective analysis of a large administrative registry in the Unites States demonstrates an association of EVT with favorable outcomes following IPCA occlusion, without concomitant risk of hemorrhagic transformation or mortality.

Remote Symptom Monitoring Using Patient-Reported Outcomes in Patients With Chronic Kidney Disease: Process Evaluation of a Randomized Controlled Trial.

BACKGROUND: In Denmark, outpatient follow-up for patients with chronic kidney disease (CKD) is changing from in-hospital visits toward more remote health care delivery. The nonuse of remote patient-reported outcomes (PROs) is a well-known challenge, and it can be difficult to explain which mechanisms of interventions influence the outcome. Process evaluation may, therefore, be used to answer important questions on how and why interventions work, aiming to enhance the implications for clinical practice. OBJECTIVE: This study aimed to provide insight into the intervention process by evaluating (1) the representativity of the study population, (2) patient and physician use patterns, (3) patient adherence to the intervention, and (4) clinical engagement. METHODS: A process evaluation determining the reach, dose, fidelity, and clinical engagement was carried out, alongside a multicenter randomized controlled trial (RCT). We developed and implemented an intervention using PRO measures to monitor outpatients remotely. Data were collected for the PRO intervention arms in the RCT from 4 sources: (1) PRO data from the participants to determine personal factors, (2) the web-based PRO system to identify key usage intervention patterns, (3) medical records to identify clinical factors relating to the use of the intervention, and (4) semistructured interviews conducted with involved physicians. RESULTS: Of the 320 patients invited, 152 (47.5%) accepted to participate. The study population reflected the target population. The mean adherence rate to the PRO intervention arms was 82% (95% CI 76-87). The questionnaire response rate was 539/544 (99.1%). A minority of 13 (12.9%) of 101 patients needed assistance to complete study procedures. Physicians assessed 477/539 (88.5%) of the questionnaires. Contact was established in 417/539 (77.4%) of the cases, and 122/539 (22.6%) of the patients did not have contact. Physicians initiated 288/417 (69.1%) and patients requested 129/417 (30.9%) of all the contacts. The primary causes of contact were clinical data (242/417, 58%), PRO data (92/417, 22.1%), and medication concerns and precautionary reasons (83/417, 19.9%). Physicians found the use of PRO measures in remote follow-up beneficial for assessing the patient's health. The inclusion of self-reported clinical data in the questionnaire motivated physicians to assess patient responses. However, some barriers were emphasized, such as loss of a personal relationship with the patient and the risk of missing important symptoms in the absence of a face-to-face assessment. CONCLUSIONS: This study demonstrates the importance and practical use of remote monitoring among patients with CKD. Overall, the intervention was implemented as intended. We observed high patient adherence rates, and the physicians managed most questionnaires. Some physicians worried that distance from the patients made it unfeasible to use their "clinical glance," posing a potential risk of overlooking crucial patients' symptoms. These findings underscore key considerations for the implementation of remote follow-up. Introducing a hybrid approach combining remote and face-to-face consultations may address these concerns. TRIAL REGISTRATION: ClinicalTrials.gov NCT03847766; https://clinicaltrials.gov/study/NCT03847766.

The Impact of Digital Self-Monitoring of Weight on Improving Diabetes Clinical Outcomes: Quasi-Randomized Study.

BACKGROUND: The management of type 2 diabetes (T2D) and obesity, particularly in the context of self-monitoring, remains a critical challenge in health care. As nearly 80% to 90% of patients with T2D have overweight or obesity, there is a compelling need for interventions that can effectively manage both conditions simultaneously. One of the goals in managing chronic conditions is to increase awareness and generate behavioral change to improve outcomes in diabetes and related comorbidities, such as overweight or obesity. There is a lack of real-life evidence to test the impact of self-monitoring of weight on glycemic outcomes and its underlying mechanisms. OBJECTIVE: This study aims to assess the efficacy of digital self-monitoring of weight on blood glucose (BG) levels during diabetes management, investigating whether the weight changes may drive glucose fluctuations. METHODS: In this retrospective, real-world quasi-randomized study, 50% of the individuals who regularly used the weight monitoring (WM) feature were propensity score matched with 50% of the users who did not use the weight monitoring feature (NWM) based on demographic and clinical characteristics. All the patients were diagnosed with T2D and tracked their BG levels. We analyzed monthly aggregated data 6 months before and after starting their weight monitoring. A piecewise mixed model was used for analyzing the time trajectories of BG and weight as well as exploring the disaggregation effect of between- and within-patient lagged effects of weight on BG. RESULTS: The WM group exhibited a significant reduction in BG levels post intervention (P<.001), whereas the nonmonitoring group showed no significant changes (P=.59), and both groups showed no differences in BG pattern before the intervention (P=.59). Furthermore, the WM group achieved a meaningful decrease in BMI (P<.001). Finally, both within-patient (P<.001) and between-patient (P=.008) weight variability was positively associated with BG levels. However, 1-month lagged back BMI was not associated with BG levels (P=.36). CONCLUSIONS: This study highlights the substantial benefits of self-monitoring of weight in managing BG levels in patients with diabetes, facilitated by a digital health platform, and advocates for the integration of digital self-monitoring tools in chronic disease management. We also provide initial evidence of testing the underlying mechanisms associated with BG management, underscoring the potential role of patient empowerment.

Internet-delivered transdiagnostic psychological treatments for individuals with depression, anxiety or both: a systematic review with meta-analysis of randomised controlled trials.

OBJECTIVE: Depression and anxiety are major public health problems. This study evaluated the effects of internet-delivered transdiagnostic psychological treatments for individuals with depression, anxiety, or both. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Medline (Ovid), Cochrane Library (Wiley), the Web of Science Core Collection (Clarivate), and PsycInfo (EBSCO) were searched on 24 May 2021, with an update on 6 February 2023. ELIGIBILITY CRITERIA: Randomised controlled trials of internet-delivered transdiagnostic psychological treatments, open to both participants with primary depression and participants with primary anxiety. This review concerned all treatment frameworks, both guided and unguided formats and all age groups. DATA EXTRACTION AND SYNTHESIS: In random-effects meta-analysis, we estimated pooled effects on depression symptoms and anxiety in terms of Hedges' g with 95% CIs. Absolute and relative heterogeneity was quantified as the τ2 and I 2. RESULTS: We included 57 trials with 21 795 participants. Nine trials (16%) recruited exclusively from routine care, and three (5%) delivered treatment via video. For adults, large within-group reductions were seen in depression (g=0.90; 95% CI 0.81 to 0.99) and anxiety (g=0.87; 95% CI 0.78 to 0.96). Compared with rudimentary passive controls, the added effects were moderate (depression: g=0.52; 95% CI 0.42 to 0.63; anxiety: g=0.45; 95% CI 0.34 to 0.56) and larger in trials that required all participants to meet full diagnostic criteria for depression or an anxiety disorder. Compared with attention/engagement controls, the added effects were small (depression: g=0.30; 95% CI 0.07 to 0.53; anxiety: g=0.21; 95% CI 0.01 to 0.42). Heterogeneity was substantial, and the certainty of the evidence was very low. Two trials concerned adolescents and reported mixed results. One trial concerned older adults and reported promising results. CONCLUSION: Internet-delivered transdiagnostic treatments for depression and anxiety show small-to-moderate added effects, varying by control condition. Research is needed regarding routine care, the video format, children and adolescents and older adults. PROSPERO REGISTRATION NUMBER: CRD42021243172.

Reliability and Responsiveness of Clinical and Endoscopic Outcome Measures in Crohn's Disease.

BACKGROUND: Regulatory guidance for Crohn's disease trials recommends coprimary efficacy end points that evaluate both symptoms and mucosal inflammation. We aimed to characterize the operating properties of commonly used disease activity assessments alone and in combination. METHODS: Endoscopic and clinical data were available for 129 participants from the Study of Biologic and Immunomodulator Naïve Patients in Crohn's Disease trial. Readers scored the Simple Endoscopic Score for Crohn's Disease and the Crohn's Disease Endoscopic Index of Severity using standardized conventions. Index reliability was determined using intraclass correlation coefficients. Index responsiveness was assessed using standardized effect sizes based upon treatment assignment. Outcomes were evaluated for optimal sensitivity to treatment effect. RESULTS: Substantial inter-rater reliability was observed when the Simple Endoscopic Score for Crohn's Disease and Crohn's Disease Endoscopic Index of Severity were used as continuous measures (intraclass correlation coefficient, 0.64; 95% confidence interval [CI], 0.50-0.73; and 0.62 95% CI, 0.36-0.77) compared with moderate reliability when dichotomized (0.46; 95% CI, 0.26-0.65; and 0.51; 95% CI, 0.00-0.78). The Simple Endoscopic Score for Crohn's Disease, Crohn's Disease Endoscopic Index of Severity, patient-reported outcome-2, and Crohn's Disease Activity Index were similarly responsive (standardized effect size, 0.43, 95% CI, 0.05-0.81; 0.38, 95% CI, 0.0-0.76; 0.53, 95% CI, 0.15-0.91). A composite outcome of Crohn's Disease Activity Index score <150 and Crohn's Disease Endoscopic Index of Severity score <6 was most sensitive to treatment effect (28.9%; 95% CI, 11.0%-46.8%; P = .003). CONCLUSION: Endoscopic indices were more reliable as continuous measures. Composite outcomes including endoscopy improved sensitivity to treatment effect.

This study largely supports current regulatory guidance for Crohn's disease trials recommending coprimary efficacy end points evaluating both symptoms and mucosal inflammation. Continuous endoscopic measures are most reliable and improve sensitivity to treatment effect when employed in composite outcomes.

Psychological Predictors of Mental Health Difficulties after Pediatric Concussion.

Children often experience mental health difficulties after a concussion. Yet, the extent to which a concussion precipitates or exacerbates mental health difficulties remains unclear. This study aimed to examine psychological predictors of mental health difficulties after pediatric concussion. Children (aged 5 to <18 years, M=11.7, SD=3.3) with concussion were recruited in a single-site longitudinal prospective cohort study conducted at a tertiary children's hospital (n=115, 73.9% male). The primary outcomes included internalizing (anxious, depressed, withdrawn behaviors), externalizing (risk-taking, aggression, attention difficulties), and total mental health problems, as measured by the Child Behavior Checklist at two weeks (acute) and three months (post-acute) after concussion. Predictors included parents' retrospective reports of premorbid concussive symptoms (Post-Concussion Symptom Inventory; PCSI), the child and their family's psychiatric history, child-rated perfectionism (Adaptive-Maladaptive Perfectionism Scale), and child-rated resilience (Youth Resilience Measure). Higher premorbid PCSI ratings consistently predicted acute and post-acute mental health difficulties. This relationship was significantly moderated by child psychiatric history. Furthermore, pre-injury learning difficulties, child psychiatric diagnoses, family psychiatric history, lower resilience, previous concussions, female sex, and older age at injury were associated with greater mental health difficulties after concussion. Pre-injury factors accounted for 23.4-39.9% of acute mental health outcomes, and 32.3-37.8% of post-acute mental health outcomes. When acute mental health was factored into the model, a total of 47.0%-68.8% of variance was explained by the model. Overall, in this sample of children, several pre-injury demographic and psychological factors were observed to predict mental health difficulties after a concussion. These findings need to be validated in future research involving larger, multi-site studies that include a broader cohort of children after concussion.

Echocardiographic findings and pregnancy outcomes for fetuses with complete closure of the ductus arteriosus.

OBJECTIVE: We aimed to analyze the echocardiographic characteristics and pregnancy outcomes for fetuses with premature complete closure of the fetal ductus arteriosus. METHODS: A retrospective analysis was performed for eight cases of premature ductus arteriosus closure diagnosed by prenatal ultrasonography in the Hunan Maternal and Child Health Hospital from July 2019 to August 2022, and the characteristics of fetal echocardiography and pregnancy outcomes of the eight cases were analyzed and summarized. RESULTS: In all cases, the intima of the ductus arteriosus was thickened and occluded, the ductus arteriosus could be seen with slightly hyperechogenic, and no blood flow signal was found in the ductus arteriosus by Doppler ultrasonography. The right heart was enlarged in seven cases, and the whole heart was enlarged in one case. Tricuspid valve regurgitation was observed to different degrees, of which seven cases were severe and one case was moderate. The pulmonary arteries of eight patients had varying degrees of widening. All eight cases were delivered by cesarean section, and one newborn died after follow-up. The prognosis of the other newborns was good. CONCLUSION: The parameters of prenatal echocardiography are helpful for the prognosis of fetuses with premature closure of the ductus arteriosus. Early prenatal detection, close observation, and clinical guidance can be used to select the right time of delivery.

Comparison of minimally invasive to standard temporal lobectomy approaches to epilepsy surgery: Seizure relief and visual confrontation naming outcomes.

The purpose of this study was to systematically examine three different surgical approaches in treating left medial temporal lobe epilepsy (mTLE) (viz., subtemporal selective amygdalohippocampectomy [subSAH], stereotactic laser amygdalohippocampotomy [SLAH], and anterior temporal lobectomy [ATL]), to determine which procedures are most favorable in terms of visual confrontation naming and seizure relief outcome. This was a retrospective study of 33 adults with intractable mTLE who underwent left temporal lobe surgery at three different epilepsy surgery centers who also underwent pre-, and at least 6-month post-surgical neuropsychological testing. Measures included the Boston Naming Test (BNT) and the Engel Epilepsy Surgery Outcome Scale. Fisher's exact tests revealed a statistically significant decline in naming in ATLs compared to SLAHs, but no other significant group differences. 82% of ATL and 36% of subSAH patients showed a significant naming decline whereas no SLAH patient (0%) had a significant naming decline. Significant postoperative naming improvement was seen in 36% of SLAH patients in contrast to 9% improvement in subSAH patients and 0% improvement in ATLs. Finally, there were no statistically significant differences between surgical approaches with regard to seizure freedom outcome, although there was a trend towards better seizure relief outcome among the ATL patients. Results support a possible benefit of SLAH in preserving visual confrontation naming after left TLE surgery. While result interpretation is limited by the small sample size, findings suggest outcome is likely to differ by surgical approach, and that further research on cognitive and seizure freedom outcomes is needed to inform patients and providers of potential risks and benefits with each.

Patient-reported outcomes after personalised dose-escalation for stage II-III non-small-cell lung cancer patients: Results from the randomised ARTFORCE PET-Boost trial.

BACKGROUND AND PURPOSE: The ultimate challenge in dose-escalation trials lies in finding the balance between benefit and toxicity. We examined patient-reported outcomes (PROs), including health-related quality of life (HRQoL) in patients with locally advanced non-small cell lung cancer (LA-NSCLC), treated with dose-escalated radiotherapy. MATERIALS AND METHODS: The international, randomised, phase 2 ARTFORCE PET-Boost study (NCT01024829) aimed to improve 1-year freedom from local failure rates in patients with stage II-III NSCLC, with a ≥ 4 cm primary tumour. Treatment consisted of an individualised, escalated fraction dose, either to the primary tumour as a whole or to its most FDG-avid subvolume (24 x 3.0-5.4 Gy). Patients received sequential or concurrent chemoradiotherapy, or radiotherapy only. Patients were asked to complete the EORTC QLQ-C30, QLQ-LC13, and the EuroQol-5D at eight timepoints. We assessed the effect of dose-escalation on C30 sum score through mixed-modelling and evaluated clinically meaningful changes for all outcomes. RESULTS: Between Apr-2010 and Sep-2017, 107 patients were randomised; 102 were included in the current analysis. Compliance rates: baseline 86.3%, 3-months 85.3%, 12-months 80.3%; lowest during radiation treatment 35.0%. A linear mixed-effect (LME) model revealed no significant change in overall HRQoL over time, and no significant difference between the two treatment groups. Physical functioning showed a gradual decline in both groups during treatment and at 18-months follow-up, while clinically meaningful worsening of dyspnoea was seen mainly at 3- and 6-months. CONCLUSION: In patients with LA-NSCLC treated with two dose-escalation strategies, the average patient-reported HRQoL remained stable in both groups, despite frequent patient-reported symptoms, including dyspnoea, dysphagia, and fatigue.

Aetiology and predictors of major bleeding events in patients with heart failure with reduced ejection fraction undergoing percutaneous coronary intervention.

OBJECTIVES: We sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI). DESIGN: This was an observational retrospective cohort analysis. Patients who underwent PCI from 2009 to 2017 were identified from our institutional National Cardiovascular Disease Registry (NCDR) CathPCI database. Patients were stratified by pre-PCI LVEF: preserved (≥50%), mildly reduced (41%-49%) and reduced (≤40%) LVEF. PRIMARY OUTCOME MEASURES: The outcome was major bleeding, defined by NCDR criteria. Events were classified based on bleeding aetiology and analysed by multivariable logistic regression. RESULTS: Among 13 537 PCIs, there were 817 bleeding events (6%). The rate of bleeding due to any cause, blood transfusion, gastrointestinal bleeding and coronary artery perforation or tamponade each increased in a stepwise fashion comparing preserved, mildly reduced and reduced LVEF reduction (p<0.05 for all comparisons). However, there were no differences in bleeding due to asymptomatic drops in haemoglobin, access site haematoma or retroperitoneal bleeding. After multivariable adjustment, mildly reduced and reduced LVEF remained independent predictors of bleeding events (OR 1.36, 95% CI 1.06 to 1.74, p<0.05 and OR 1.73, 95% CI 1.45 to 2.06, p<0.0001). CONCLUSIONS: The degree of LV dysfunction is an independent predictor of post-PCI major bleeding events. Patients with mildly reduced or reduced LVEF are at greatest risk of post-PCI bleeding, driven by an increased need for blood transfusion, major GI bleeding events and coronary artery perforation or tamponade. Pre-PCI LV dysfunction does not predict asymptomatic declines in haemoglobin, access site haematoma or retroperitoneal bleeding.

Identifying prehospital trauma patients from ambulance patient care records; comparing two methods using linked data in New South Wales, Australia.

BACKGROUND: Linked datasets for trauma system monitoring should ideally follow patients from the prehospital scene to hospital admission and post-discharge. Having a well-defined cohort when using administrative datasets is essential because they must capture the representative population. Unlike hospital electronic health records (EHR), ambulance patient-care records lack access to sources beyond immediate clinical notes. Relying on a limited set of variables to define a study population might result in missed patient inclusion. We aimed to compare two methods of identifying prehospital trauma patients: one using only those documented under a trauma protocol and another incorporating additional data elements from ambulance patient care records. METHODS: We analyzed data from six routinely collected administrative datasets from 2015 to 2018, including ambulance patient-care records, aeromedical data, emergency department visits, hospitalizations, rehabilitation outcomes, and death records. Three prehospital trauma cohorts were created: an Extended-T-protocol cohort (patients transported under a trauma protocol and/or patients with prespecified criteria from structured data fields), T-protocol cohort (only patients documented as transported under a trauma protocol) and non-T-protocol (extended-T-protocol population not in the T-protocol cohort). Patient-encounter characteristics, mortality, clinical and post-hospital discharge outcomes were compared. A conservative p-value of 0.01 was considered significant RESULTS: Of 1 038 263 patient-encounters included in the extended-T-population 814 729 (78.5 %) were transported, with 438 893 (53.9 %) documented as a T-protocol patient. Half (49.6 %) of the non-T-protocol sub-cohort had an International Classification of Disease 10th edition injury or external cause code, indicating 79644 missed patients when a T-protocol-only definition was used. The non-T-protocol sub-cohort also identified additional patients with intubation, prehospital blood transfusion and positive eFAST. A higher proportion of non-T protocol patients than T-protocol patients were admitted to the ICU (4.6% vs 3.6 %), ventilated (1.8% vs 1.3 %), received in-hospital transfusion (7.9 vs 6.8 %) or died (1.8% vs 1.3 %). Urgent trauma surgery was similar between groups (1.3% vs 1.4 %). CONCLUSION: The extended-T-population definition identified 50 % more admitted patients with an ICD-10-AM code consistent with an injury, including patients with severe trauma. Developing an EHR phenotype incorporating multiple data fields of ambulance-transported trauma patients for use with linked data may avoid missing these patients.

Comparison of two surgical protocols for the treatment of unilateral cleft lip and palate: a multidisciplinary systematic review and meta-analysis.

There is still no unanimous agreement on the optimal surgical protocol(s) for the treatment of unilateral cleft lip and palate (UCLP), and a huge variety of protocols are employed by cleft centres across the world. The aim of this systematic review and meta-analysis was to compare reported patient outcomes of the Oslo protocol (and modifications) (OP) and delayed hard palate closure protocols (DHPCP) from a multidisciplinary perspective. A systematic search of multiple databases was conducted until September 2023. Studies reporting any patient outcomes of these protocols were included. Random-effects meta-analyses were performed for evidence synthesis, including comparisons of results between the types of protocol. The quality of evidence was evaluated using the ROBINS-I tool. In total, 62 articles (42 studies) reporting patients with UCLP were reviewed, involving 1281 patients following the OP and 655 following DHPCP. Equally poor long-term sagittal maxillofacial growth was found, and similar results for velopharyngeal insufficiency and nasolabial appearance. In contrast, OP was associated with a lower rate of oronasal fistulas. Disregarding the scarcity of comparable evidence for some domains, the results of this review, overall, favour OP over DHPCP. However, caution should be taken when interpreting the results on velopharyngeal insufficiency and oronasal fistulas, since the possibility of confounding and other biases remains.