Intervention Trial Research Articles

How far has diabetes-related foot disease research progressed in Australia? A bibliometric review (1970-2023).

Diabetes-related foot disease (DFD) is a leading cause of the Australian and global disease burdens and requires proportionate volumes of research to address. Bibliometric analyses are rigorous methods for exploring total research publications in a field to help identify volume trends, gaps and emerging areas of need. This bibliometric review aimed to explore the volume, authors, institutions, journals, collaborating countries, research types and funding sources of Australian publications investigating DFD over 50years. A systematic search of the Scopus® database was conducted by two independent authors to identify all Australian DFD literature published between 1970 and 2023. Bibliometric meta-data were extracted from Scopus®, analyzed in Biblioshiny, an R Statistical Software interface, and publication volumes, authors, institutions, journals and collaborative countries were described. Publications were also categorised for research type and funding source. Overall, 332 eligible publications were included. Publication volume increased steadily over time, with largest volumes (78%) and a 7-fold increase over the last decade. Mean co-authors per publication was 5.6, mean journal impact factor was 2.9 and median citation was 9 (IQR2-24). Most frequent authors were Peter Lazzarini (14%), Vivienne Chuter (8%) and Jonathon Golledge (7%). Most frequent institutions affiliated were Queensland University Technology (33%), University Sydney (30%) and James Cook University (25%). Most frequent journals published in were Journal Foot and Ankle Research (17%), Diabetic Medicine (7%), Journal Diabetes and its Complications (4%) and International Wound Journal (4%). Most frequent collaborating countries were the United Kingdom (9%), the Netherlands (6%) and the United States (5%). Leading research types were etiology (38%), treatment evaluation (25%) and health services research (13%). Leading funding sources were no funding (60%), internal institution (16%) and industry/philanthropic/international (10%). Australian DFD research increased steadily until more dramatic increases were seen over the past decade. Most research received no funding and mainly investigated etiology, existing treatments or health services. Australian DFD researchers appear to be very productive, particularly in recent times, despite minimal funding indicating their resilience. However, if the field is to continue to rapidly grow and address the very large national DFD burden, much more research funding is needed in Australia, especially targeting prevention and clinical trials of new treatments in DFD.

Effects of a plant-based high energy and protein enteral tube feed in home enterally tube fed patients: results from a 6-month single-arm intervention trial

Effects of a plant-based high energy and protein enteral tube feed in home enterally tube fed patients: results from a 6-month single-arm intervention trial

Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials.

According to the new AASLD Practice Guidance, all patients with primary sclerosing cholangitis (PSC) should be considered for participation in clinical trials. However, PSC's rarity has posed challenges to characterizing patient interest in trial participation and identifying predictors of patient willingness to participate in drug trials. PSC Partners Seeking a Cure developed the "Our Voices" survey to inform the development of the Externally-Led Patient-Focused Drug Development Forum, an FDA initiative to capture patient experiences and perspectives on drug development. Of 797 survey respondents from over 30 countries, 536 (67%) identified slowing disease progression as the most important outcome. Eighty-nine percent identified their hepatologist/gastroenterologist as someone they would approach for advice about trials. Although 61% reported being willing to participate in drug trials, only 26% had ever been asked to participate. Notable barriers to trial involvement included unknown long-term risks (71%), long travel times to the study center (32%), and a liver biopsy requirement (27%). On multivariable logistic regression, pruritus (OR 1.62, 95% CI: 1.09-2.40, p = 0.017) was positively associated with willingness to participate in disease-modifying therapy trials, while jaundice (OR 0.34, 95% CI: 0.19-0.61, p < 0.001) and inflammatory bowel disease (OR 0.64, 95% CI: 0.42-0.98, p = 0.038) were negatively associated. Pruritus (OR 2.25, 95% CI: 1.50-3.39, p < 0.001) was also independently associated with willingness to participate in symptom treatment trials. Most patients with PSC report interest in participating in clinical trials, but few have been asked to participate. Referral of patients with PSC by their hepatologist/gastroenterologist to clinical trials and patient education on trial participation are vital to closing the gap between trial interest and participation. Pruritus may serve as a key indicator of patient interest in trial participation.

A plain language summary of the perspectives of women who were interviewed about their experiences with uterine fibroids.

This summary describes what researchers learned during interviews of women with uterine fibroids and heavy menstrual bleeding (or period bleeding). At this time, little is known about how women perceive the impact of uterine fibroids on their lives and more information is needed. The goal of this study was to provide new information about the symptoms women have and how these symptoms affect their everyday lives. These interviews were done to better understand how uterine fibroid symptoms affect the lives of women in their own words. Thirty women from the United States, who had completed a clinical trial for a new treatment for heavy menstrual bleeding and uterine fibroids, agreed to be interviewed. The women described what their experiences with uterine fibroids were and the impact these experiences with uterine fibroids had on their lives before participating in the clinical trial. The most common symptoms of uterine fibroids the women described were heavy bleeding with their menstrual periods, pain in the pelvis or groin area, the passing of blood clots, and anemia (or low hemoglobin in red blood cells). Women said their symptoms affected them physically, emotionally, socially, and financially. They also said their symptoms made it hard to do daily activities, sleep, have a sex life, and go to work or school. Women who have heavy menstrual bleeding and uterine fibroids experience various uterine fibroid symptoms, and these symptoms affect most parts of the their lives.

A randomized controlled intervention trial to study the effect of a personalized lifestyle program on cancer-related fatigue among colorectal cancer survivors: protocol for the SoFiT study.

Observational studies suggest that a healthy diet in combination with ample physical activity is associated with a lower prevalence of cancer-related fatigue. The SoFiT trial (SoFiT: Study on Fatigue: a lifestyle intervention among colorectal cancer survivors) will assess the effect of a personalized lifestyle program on cancer-related fatigue in a randomised study.We designed a program that aims to increase adherence to lifestyle recommendations on diet and physical activity. The program was person-centred with regards to the lifestyle and personal characteristics of participants, to the determinants of behaviour of that participant, and to the preference, opportunities, and barriers of the participant.The effect of the program was tested in the SoFiT trial: a two-armed, parallel, randomized controlled trial among adult stage I-III colorectal cancer survivors, who experience cancer-related fatigue after treatment completion; intended sample size n=184. Participants randomized to the intervention group received the personalized lifestyle program. During six months, participants in the intervention group had individual sessions with a lifestyle coach of which four sessions were face-to-face and eight sessions were remote. After six months, participants randomized to the control group had access to two lifestyle coaching sessions and to the same materials that the intervention group also received.The primary endpoint of the trial is cancer-related fatigue. Secondary endpoints are: sleep quality and duration, health-related quality of life, physical performance, depression and anxiety, skeletal muscle echo intensity and cross-sectional area, and gut microbiota composition.This trial will show the effects of a personalized lifestyle program on cancer-related fatigue, and on an extensive set of secondary outcomes.

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study

IntroductionCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. MethodsParticipants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. DiscussionAusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Virologic Response and Reinfection Following HCV Treatment among Hospitalized People Who Inject Drugs: Follow-up Data from the OPPORTUNI-C Trial

Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50–70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46–66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08–2.22]; p = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR &gt; 4 (OR 12.7 [95% CI 4.3–37.8]; p &lt; 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0–9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.

Cascading Effects of the Family Check-Up on Mothers' and Fathers' Observed and Self-Reported Parenting and Young Adult Antisocial Behavior: a 12-Year Longitudinal Intervention Trial.

Over a 12-year period, this study examined the effects of the Family Check-Up preventive intervention model on both observed and self-reported parenting behaviors of mothers and fathers as well as how those parenting behaviors were associated with young adult antisocial behavior. Teachers identified 641 early adolescent youth from school settings to be at elevated risk for the development of externalizing behavior and/or substance use. These youth and their families were randomly assigned to the Family Check-Up intervention model (consisting of an adaptive, multi-tiered model of support, including a school-based family resource room, the Family Check-Up, and targeted follow-up services) or a control condition. Using an intent-to-treat approach, the Family Check-Up intervention model positively impacted mothers' observed parenting approximately 5years later in middle adolescence but was not associated with changes in fathers' observed or self-reported parenting. Mothers' observed adaptive parenting and fathers' self-reported adaptive parenting in middle adolescence were associated with lower risk for young adult antisocial behavior. The cascading effects of brief, family-focused interventions are discussed along with implications for the measurement of parenting in mothers and fathers in the context of preventive intervention trials.

From lab bench to hope: a review of gene therapies in clinical trials for Parkinson's disease and challenges.

Parkinson's disease (PD) is a chronic neurological disorder that is identified by a characteristic combination of symptoms such as bradykinesia, resting tremor, rigidity, and postural instability. It is the second most common neurodegenerative disease after Alzheimer's disease and is characterized by the progressive loss of dopamine-producing neurons in the brain. Currently, available treatments for PD are symptomatic and do not prevent the disease pathology. There is growing interest in developing disease-modifying therapy that can reduce disease progression and improve patients' quality of life. One of the promising therapeutic approaches under evaluation is gene therapy utilizing a viral vector, adeno-associated virus (AAV), to deliver transgene of interest into the central nervous system (CNS). Preclinical studies in small animals and nonhuman primates model of PD have shown promising results utilizing the gene therapy that express glial cell line-derived neurotrophic factor (GDNF), cerebral dopamine neurotrophic factor (CDNF), aromatic L-amino acid decarboxylase (AADC), and glutamic acid decarboxylase (GAD). This study provides a comprehensive review of the current state of the above-mentioned gene therapies in various phases of clinical trials for PD treatment. We have highlighted the rationale for the gene-therapy approach and the findings from the preclinical and nonhuman primates studies, evaluating the therapeutic effect, dose safety, and tolerability. The challenges associated with gene therapy for heterogeneous neurodegenerative diseases, such as PD, have also been described. In conclusion, the review identifies the ongoing promising gene therapy approaches in clinical trials and provides hope for patients with PD.

The use of biologics and JAK inhibitors in the management of moderate to severe Hidradenitis Suppurativa treatment: a scoping review.

This scoping review aims to characterize the use of biologics and Janus Kinase inhibitors (JAKi) in the treatment of Hidradenitis Suppurativa (HS), which is a chronic inflammatory condition. A comprehensive literature search was conducted in PubMed/NCBI, Embase, Web of Science databases, and the Clinicaltrials.gov register. The search included interventional trials assessing the use of biologics or JAKi in HS, with no geographic or time restrictions. Secukinumab and adalimumab were identified as the only two drugs approved by the FDA for treating moderate to severe HS in adults. Several other drug classes showed promising results based on clinical studies reviewed. IL-12/23 inhibitor ustekinumab demonstrated improvements in disease severity scores and HiSCR rates in small trials. IL-17 inhibitors such as brodalumab, bimekizumab, and CJM112 showed preliminary positive responses in early-phase clinical studies and case reports. While evidence was mixed, some TNF-α inhibitors such as infliximab provided benefits according to a randomized controlled trial, though etanercept trials yielded non-significant or inconsistent findings. Larger, well-designed studies are required to further establish their efficacy and safety, but biologics and JAKis show potential as alternative treatment options for moderate to severe HS. The findings of this review contribute to the growing interest among patients and to enhancing the understanding of physician's regarding potential alternative therapeutic options for HS and provide a basis for further research in this field.

Comparative efficacy of psychological interventions on anxiety and depression in patients with cancer: A systematic review and network meta-analysis.

Numerous studies have demonstrated that psychological interventions are effective in alleviating anxiety and depression in patients with cancer. However, the optimal psychological intervention to alleviate anxiety and depression in patients with cancer remains unknown. This study was carried out to compare and rank the comparative effectiveness of various psychological interventions on anxiety and depression in patients with cancer. Databases, namely PubMed, Embase, Cochrane Library, Web of Science, PsycINFO, CNKI, WanFang, VIP and CBM were systematically searched from their inception dates to December 2023 for randomized controlled trials of psychological interventions for anxiety and depression in patients with cancer. Utilizing the Cochrane Review Manager 5.4, we evaluated the risk of bias in the studies included in the current study based on the Cochrane Handbook 5.1.0 Methodological Quality Evaluation Criteria. The NMA was conducted using STATA 15.0. This study did not involve human participants and therefore did not require ethical approval. Thirty-one randomized controlled trials involving 3471 participants were included. MT [SMD = 1.35, 95% CI (0.76, 1.93)] and cognitive behavioral therapy (CBT) [SMD = 0.97, 95% CI (0.53, 1.42)] were superior to usual care in alleviating anxiety. Besides, interpersonal psychotherapy (IPT) [SMD = 1.17, 95% CI (0.06, 2.28)], CBT [SMD = 0.97, 95 % CI (0.63, 1.30)], and MT [SMD = 0.93, 95% CI (0.35, 1.50)] were superior to usual care in alleviating depression. In addition, CBT was superior to family therapy in alleviating depression [SMD = 0.73, 95% CI (0.08, 1.38)]. The MT, CBT, and IPT ranked in the top three in alleviating anxiety, while IPT, CBT, and MT ranked in the top three in alleviating depression. MT and IPT would be a more appropriate option in alleviating anxiety and depression in patients with cancer, respectively. This study also suggested that CBT had a significant effect in alleviating negative emotions in patients with cancer. However, the results need to be validated by high-quality and large-sample studies.

The neuropathobiology of multiple sclerosis.

Chronic low-grade inflammation and neuronal deregulation are two components of a smoldering disease activity that drives the progression ofdisability in people with multiple sclerosis (MS). Although several therapies exist to dampen the acute inflammation that drives MS relapses, therapeutic options to halt chronic disability progression are a major unmet clinical need. The development of such therapies is hindered by our limited understanding of the neuron-intrinsic determinants of resilience or vulnerability to inflammation. In this Review, we provide a neuron-centric overview of recent advances in deciphering neuronal response patterns that drive the pathology of MS. We describethe inflammatory CNS environment thatinitiates neurotoxicity by imposing ion imbalance, excitotoxicity and oxidative stress, and by direct neuro-immune interactions, which collectively lead to mitochondrial dysfunction and epigenetic dysregulation. The neuronal demise is further amplified by breakdown of neuronal transport, accumulation ofcytosolic proteins and activation of cell death pathways. Continuous neuronal damage perpetuates CNS inflammation by activating surrounding glia cells and by directly exerting toxicity on neighbouring neurons. Further, we explore strategies to overcome neuronal deregulation in MS and compile a selection of neuronal actuators shown to impact neurodegeneration in preclinical studies. We conclude by discussing the therapeutic potential of targeting such neuronal actuators in MS, including some that have already been tested in interventional clinical trials.

Genetic counselling for at-risk family members with hereditary transthyretin amyloidosis: data from a single-centre study

Background Hereditary transthyretin-related amyloidosis is an autosomal dominant disorder. Recently, disease-modifying therapies (DMTs) have been developed. For at-risk individuals, genetic analysis aids in the early administration of medical care; however, few studies have evaluated the current status of genetic counselling and management of presymptomatic carriers of amyloidogenic variants. Methods We retrospectively evaluated the medical records of 202 consecutive participants. Results A total of 103 clients who received genetic counselling for predictive testing were at-risk, and 83 underwent predictive testing. Genetic testing results were positive in 33 patients, 11 of whom had confirmed amyloid deposition and were administered DMTs. For presymptomatic V30M (p.V50M) carriers, 32.0 ± 2.4 years (median ± standard error) was the age when amyloid deposition was first identified (95% confidence interval 27.4–36.6). Serum transthyretin (TTR) levels decreased serially with an estimated slope of −1.2 mg/dL/year. Conclusions Our study suggests the clinical utility of management using a combination of predictive testing and monitoring methods. Psychosocial support should be considered with collaboration between geneticists/genetic counsellors and psychologists. For a more optimised protocol for monitoring and designing future interventional trials in presymptomatic carriers, prospective cohort studies are necessary to clarify the natural history, particularly in the early stages of the disease.

Substance Use Within Trials of Psychological Interventions for Psychosis: Sample Inclusion, Secondary Measures, and Intervention Effectiveness.

Current clinical guidelines recommend that patients with co-occurring psychosis and alcohol or substance use disorders (A/SUD) receive evidenced-based treatment for both disorders, including psychological intervention for psychosis. However, the efficacy of such treatments for individuals with co-occurring psychosis and A/SUD is unclear. Randomized controlled trials (RCTs) of psychological interventions for psychosis were systematically reviewed, to investigate how alcohol and substance use has been accounted for across sample inclusion and secondary measures. Findings from trials including individuals with co-occurring alcohol or substance use issues were then narratively summarized using the Synthesis Without Meta-Analysis guidelines, to indicate the overall efficacy of psychological interventions for psychosis, for this comorbid population. Across the 131 trials identified, 60.3% of trials excluded individuals with alcohol or substance use issues. Additionally, only 6.1% measured alcohol or substance use at baseline, while only 2.3% measured alcohol or substance use as a secondary outcome. Across trials explicitly including individuals with alcohol or substance use issues, insufficient evidence was available to conclude the efficacy of any individual psychological intervention. However, preliminary findings suggest that psychoeducation (PE) and metacognitive therapy (MCT) may be proposed for further investigation. Overall, co-occurring alcohol and substance use issues have been largely neglected across the recent RCTs of psychological interventions for psychosis; highlighting the challenges of making treatment decisions for these individuals using the current evidence base.

#2437 Association between iron deficiency and risk of major events in chronic kidney disease—CKD-REIN Cohort

Abstract Background and Aims Iron deficiency (ID) is common in patients with chronic kidney disease (CKD) but remains under-diagnosed and its prognosis poorly documented in the absence of anemia. Data from CKDopps showed low TSAT levels were associated with increased risk of all-cause mortality and incidence of major cardiovascular events in patients with moderate to advanced CKD, an effect that was not modified by the presence of anemia [1]. Additionally, patients with both low TSAT and high ferritin levels displayed the highest risk of all-cause mortality. The aim of the study was to assess the relationship between ID and the risk of major adverse outcomes in patients with CKD in France. Method Using data from the French CKD-REIN cohort which included and followed over 5 years, 3,033 nephrology outpatients with CKD stage 2 to 5 CKD [2], we estimated the prevalence of ID, defined by a ferritin level &amp;lt; 100 mg/L and/or a transferrin saturation (TSAT) &amp;lt; 20%, and associated hazard ratios (HR) of kidney failure with replacement therapy, kidney failure defined by an eGFR &amp;lt; 15 ml/min per 1.73 m2 or initiation of kidney replacement therapy, all-cause mortality, all-cause hospitalization and death or hospitalization for heart failure. The analysis was conducted using a Cox model in which ID was included as a time-dependent variable and adjusted for identified confounders (socio-demographic characteristics, comorbidities, and biological measures) and hemoglobin level. Results A total of 2 914 patients with at least one ferritin or TSAT measurement at baseline or during follow-up were included in the analysis. The majority were men (66%), with a mean age of 67 ± 13 years; 49.6%, 41.2%, and 9.2%, had CKD stage 2/3, 4, and 5, respectively. Baseline prevalence of ID in the cohort was 50% [48-52]. Mean hemoglobin was 13 ± 1.7 g/dL, and only 31% of patients with ID also had a hemoglobin &amp;lt; 12 g/dL. Of the 2 914 patients included in the analysis, 627 (22%) required dialysis or transplantation, and 382 (13%) died before kidney replacement therapy. The incidence rate of kidney failure with replacement therapy was 6.76 versus 3.53 per 100 person-years in patients with and without ID. ID was associated with significant increased risk of kidney failure with replacement therapy, with adjusted HRs for confounders and hemoglobin level of 1.51 [1.24-1.82] (Fig. 1). A total of 836 patients (29%) progressed to kidney failure during the study period, and 341 (12%) died before this stage. The incidence rate of kidney failure was 8.66 versus 6.43 per 100 person-years in patients with and without ID. ID was associated with significant increased risk of kidney failure, with adjusted HRs for confounders and hemoglobin level of 1.19 [1.02-1.38] (Fig. 1). Adjusted HRs for all-cause mortality, for all-cause hospitalization, and for hospitalization or death for heart failure, were 1.31 [1.04-1.66], 1.04 [0.93-1.15], and 1.38 [1.07-1.80], respectively (Fig. 2). Conclusion This study confirms that ID is common in patients with CKD and shows that ID is significantly associated with the risk for kidney failure, all-cause mortality, and heart failure, independent of the presence of anemia. An intervention trial would be needed to assess whether correction of this ID in CKD patients is associated with a reduction in associated risks.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140–159/90–104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72–0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71–0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82–1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Emicizumab as a Promising Form of Therapy for Type A Hemophilia - A Review of Current Knowledge from Clinical Trials.

Hemophilia is a plasma bleeding disorder characterized by a deficiency of certain blood clotting factors. The most common forms of this disease, i.e., type A and type B, affect approximately 400,000 people worldwide. Without appropriate treatment ensuring the proper coagulation cascade, this disease may lead to serious disability. Minimizing patient discomfort is possible via replacement therapy, consisting of the substitution of a missing coagulation factor via intravenous administration. Frequent medication and the risk related to factor inhibitors are significant disadvantages, necessitating the improvement of current therapies or the development of novel ones. This review examines the humanized bispecific antibody Emicizumab which ensures hemostasis by mimicking the action of the coagulation factor VIII, a deficiency of which causes type A hemophilia. The paper outlines the topic and then summarizes available clinical trials on Emicizumab in type A hemophilia. Several interventional clinical trials have found Emicizumab to be effective in decreasing bleeding episodes and raising patient satisfaction among various hemophilia A populations. Current Emicizumab-related trials are forecast to be completed between 2024 and 2030, and in addition to congenital hemophilia A, the trials cover acquired hemophilia A and patients playing sports. Providing a more comprehensive understanding of Emicizumab may revolutionize the management of hemophilia type A and improve quality of life. Conclusively, Emicizumab is a gentler therapy owing to subcutaneous delivery and fewer injections, which reduces injection-site reactions and makes therapy less burdensome, ultimately decreasing hospital visits and indirect costs.

#2320 The impact of interventions for people with chronic kidney disease on health-related quality of life: a systematic review

Abstract Background and Aims Health-related quality of life (HRQoL) is poorer for those with chronic kidney disease (CKD) than the general population and worsens as CKD progresses. Evidence is mixed as to which interventions improve HRQoL for those with CKD, and HRQoL is often under-reported in randomised controlled trials where it is most commonly a secondary outcome. Reviews including HRQoL as an outcome have thus far focused on the impact per intervention, therefore we aimed to ascertain which interventions, of any type, have an impact on HRQoL outcomes for those with non-dialysis dependent CKD (NDD-CKD). Method The protocol was prospectively registered on PROSPERO (CRD42022364474) and PRISMA guidelines were followed. Inclusion criteria were randomised controlled trials in an NDD-CKD population (excluding transplant recipients), any intervention type, usual care/placebo comparators, using validated and reported HRQoL outcomes measures. Databases searched were Embase, Medline, PsychINFO, CINAHL plus, Web of Science, PubMed, and Google Scholar, with reference searching of included studies. Reports were independently screened by two researchers who also performed data extraction and quality assessment (using the Cochrane Risk of Bias 2.0 tool). Synthesis was undertaken using Synthesis without Meta-analysis (SWiM) methods. Conversion to one-sided p-values, synthesising outcomes in albatross plots and combining p-values via Fisher's method was performed using the metap package in R. HRQoL measures were broken down into physical, mental, kidney disease symptoms, adverse effects of kidney disease, burden of kidney disease, overall kidney disease, and overall HRQoL domains for analysis. Results Searches yielded 8983 records, and 39 studies met inclusion criteria, with a total of 11,940 participants. Nine groups were formed based on type of intervention, with data synthesis possible in the eight groups with more than one study (Fig. 1). 26 (66%) studies were rated as having high risk of bias, largely due to frequent lack of blinding and HRQoL being a patient reported outcome. 37 studies had sufficient data for presentation in albatross plots (Fig. 2). Using combined p-values for all HRQoL outcomes in each group of studies, benefit to HRQoL in at least one study was shown for education interventions (p &amp;lt; 0.001, seven studies, none with low risk of bias), exercise interventions (p &amp;lt; 0.001, eight studies, all with high risk of bias), medications to treat CKD-related anaemia (p &amp;lt; 0.001, eight studies, four with low risk of bias), nutritional interventions (p &amp;lt; 0.001, four studies, all with high risk of bias) and weight loss interventions (p &amp;lt; 0.001, two studies, one with low risk of bias). No benefit to HRQoL was shown for medications aimed at slowing CKD progression (p = 0.492, five studies), medications for depression (p = 0.266, two studies) and medications to treat acidosis (p = 0.99, two studies). Conclusion This review identified several interventions with evidence of benefit to HRQoL for people with NDD-CKD, including medications to treat anaemia and weight loss interventions. Studies of education, exercise and nutritional interventions showed potential benefit, but with high risk of bias. Further high-quality randomised controlled trials of interventions for people with NDD-CKD should include and report HRQoL outcomes, in addition to targeting potentially modifiable determinants of HRQoL in these groups.

Critical outcomes to be included in the Core Outcome Set for nutritional intervention studies in older adults with malnutrition or at risk of malnutrition: a modified Delphi Study.

As part of the development of an agreed minimum set of outcomes or Core Outcome Set (COS) for future nutritional intervention trials in older adults with malnutrition or at risk of malnutrition, this work reports on the Delphi surveys and final consensus. Outcomes from a scoping review were incorporated into a two-round Delphi survey. Researchers and healthcare professionals experienced in malnutrition in older adults were invited to take part in an online survey to rate 38 selected outcomes on a nine-point Likert scale ranging from 'not important' to 'critical' for their setting (community, hospital, or long-term care). Consensus for inclusion was reached when ≥75% (or ≥60% if a patient-reported outcome) of the participants scored the outcome as 'critical' and <15% as 'not important'. Resulting outcomes were voted for inclusion or exclusion in the COS in a final online consensus meeting. Ninety-three and 72 participants from diverse professional backgrounds and countries participated in the 1st and 2nd Delphi round, respectively. After both rounds eleven outcomes met the inclusion criteria, largely irrespective of setting. Fifteen participants, representing academia, health care, health policy, industry, and PPI, voted in a final online consensus meeting resulting in ten outcomes: malnutrition status, dietary intake, appetite, body weight or BMI, muscle strength, muscle mass, functional performance, functional limitations, quality of life, and acceptability of the intervention. Ten outcomes will form the COS which is intended to be used by the scientific community in all future nutritional intervention studies for older adults with malnutrition or at risk of malnutrition. The subsequent phase will establish the appropriate methods to measure these outcomes.

#2539 Effects of relative blood volume and ultrafiltration volume on pulse wave characteristics during hemodialysis

Abstract Background and Aims Measures of non-invasive pulse wave (PW) analysis can help to assess the status of the central cardiovascular system and to predict clinical outcomes, including morbidity and mortality. During hemodialysis (HD), fluid is extracted from blood. The resulting reduction in relative blood volume (RBV) and collected ultrafiltration volume (UFV) were hypothesized to substantially influence PW characteristics during HD. Volume overload (VO) is common in HD patients and may affect the chance of improving the cardiovascular status of patients during HD. The present study aimed to explore associations between RBV, UFV, VO and a wide range of PW parameters. Method In a single center in Vienna, Austria, 24 patients on maintenance HD underwent four HD sessions each, with whole-body bioimpedance spectroscopy (BIS) before, and automated, cuff-based PW measurements every 15 minutes, RBV- and UFV-monitoring throughout each session. Associations between RBV or UFV as independent variable and 26 different PW characteristics as dependent variables (52 separate models) were tested using confounder-adjusted generalized estimating equations with sandwich estimator and multilevel nested working covariance structure, reporting standardized effect estimates and drop-in-R² to assess variable importance. Sensitivity models including both RBV and UFV as predictors (26 models) were used to assess effects adjusted for confounding and mediation, respectively. The intra-patient correlation between BIS-derived VO and PW parameters at the start of sessions and PW parameter change by end of sessions was assessed using repeated measures correlation analysis. Results Data from 990 PW measurements were available for analysis from an 88% male cohort with median age of 66 years. In half of the PW parameters analyzed, each percent RBV was significantly associated with in summary about 4.3 to 5.7% (95% confidence intervals [CI] 0.9 to 10.46) of the PW parameter's respective standard deviation (SD), negatively so only in heart rate and R-Peak. UFV was negatively associated with a third of PW parameters (effects ranging from −2.5 to −5.47% SD [95% CIs −0.9 to −10.0]), mostly in classical peripheral and central pressures and peripheral resistance. In models including both predictors, RBV overall exhibited greater effect size and variance capture than UFV, except for peripheral resistance. On within-patient level, VO was positively correlated with initial medians of pressure excess (r=0.34, p=0.034), augmentation-index (0.34, p=0.031) and augmentation-pressure (0.32, p=0.042), increase in heart rate (0.32, p=0.04) and decreases in peripheral resistance (0.31, p=0.05), peripheral (systolic: 0.34, p=0.032; diastolic: 0.45, p=0.004; mean: 0.41, p=0.008) and central (diastolic: 0.46, p=0.003) blood pressures during HD. Conclusion The observed PW characteristics were associated with RBV and UFV during HD and may represent modifiable targets for intervention studies. Pressure excess, S-Peak, R-Peak, cardiac and preload parameters were more closely associated with RBV, while classic (especially diastolic) blood pressure parameters, ejection duration and S/D-Ratio were more associated with UFV, in models using both predictors. On average, blood pressure and peripheral resistance tended to decrease less when a patient began HD in a volume-expanded state, which may affect day-to-day feasibility of more classical pressure targets, but perhaps not of other PW parameters. Multiple PW characteristics have previously been shown to be associated with mortality and morbidity and are potential target parameters for future intervention trials. Utilizing RBV modification as an intervention may offer superior precision compared to UFV goals, requiring further studies. PW technology could also be adopted by HD-machine manufacturers at low cost, enabling more precise and individualized treatment options.