Pharmacological Treatment Research Articles

The long-term adherence following the end of Community Treatment Order: A systematic review.

The community treatment order (CTO) is designed to deliver mental healthcare in the community and has been introduced in around 75 jurisdictions worldwide. It constitutes a legal obligation in which individuals with severe mental illness must adhere to out-of-hospital treatment plans. Despite intense criticism and the debated nature of published evidence, it has emerged as a clinical and policy response to frequent hospital readmissions and to enhance adherence in cases where there is refusal of pharmacological treatments. This systematic review outlines findings on CTO long-term adherence, after mandatory outpatient treatment has ended, in studies that include people with psychiatric disorders. Following PRISMA guidelines, we performed a review of published articles from PubMed, PsycINFO, EMBASE, and CINAHL up to January 15, 2023. We included studies that assessed adherence after CTO ends. The study is registered with PROSPERO number CRD42022360879. Six independent studies analyzing the main indicators of long adherence: engagement with services and medication adherence, were included. The average methodological quality of the studies included is fair. Long-term adherence was assessed over a period ranging from 11 to 28 months. Only two studies reported a statistically significant improvement. Regarding the remaining studies, no positive correlation was observed, except for certain subgroup samples, while in one study, medication adherence decreased. Scientific evidence supporting the hypothesis that CTO has a positive role on long-term adherence post-obligation is currently not sufficient. Given the importance of modern recovery-oriented approaches and the coercive nature of compulsory outpatient treatment, it is necessary that future studies ensure the role of CTO in effectively promoting adherence.

Modulation of neuroinflammation and oxidative stress by targeting GPR55 - new approaches in the treatment of psychiatric disorders.

Pharmacological treatment of psychiatric disorders remains challenging in clinical, pharmacological, and scientific practice. Even if many different substances are established for treating different psychiatric conditions, subgroups of patients show only small or no response to the treatment. The neuroinflammatory hypothesis of the genesis of psychiatric disorders might explain underlying mechanisms in these non-responders. For that reason, recent research focus on neuroinflammatory processes and oxidative stress as possible causes of psychiatric disorders. G-protein coupled receptors (GPCRs) form the biggest superfamily of membrane-bound receptors and are already well known as pharmacological targets in various diseases. The G-protein coupled receptor 55 (GPR55), a receptor considered part of the endocannabinoid system, reveals promising modulation of neuroinflammatory and oxidative processes. Different agonists and antagonists reduce pro-inflammatory cytokine release, enhance the synthesis of anti-inflammatory mediators, and protect cells from oxidative damage. For this reason, GPR55 ligands might be promising compounds in treating subgroups of patients suffering from psychiatric disorders related to neuroinflammation or oxidative stress. New approaches in drug design might lead to new compounds targeting different pathomechanisms of those disorders in just one molecule.

Comparative Analysis of Pharmacological and Non-Pharmacological Interventions in Hypertensive Patients at Cumilla Medical College Hospital

Background: Hypertension is a prevalent cardiovascular condition requiring effective management to reduce associated morbidity and mortality. Both pharmacological and non-pharmacological interventions play crucial roles in its treatment. This study aims to compare the effectiveness of these interventions in hypertensive patients at Cumilla Medical College Hospital, Bangladesh. Objective: To conduct a comparative analysis of pharmacological and non-pharmacological interventions in hypertension management. Method: A prospective study was conducted using data from the Department of Medicine at Cumilla Medical College Hospital, Bangladesh, from January 2023 to December 2023. A total of 184 patients were included in the study. Data on pharmacological and non-pharmacological interventions were collected, and blood pressure measurements were recorded. Result: Among the 184 patients, 65% received pharmacological interventions, while 35% received non-pharmacological interventions. Of those receiving pharmacological interventions, 82% achieved blood pressure control, compared to 73% in the non-pharmacological group. The mean reduction in systolic blood pressure was 20 mmHg in the pharmacological group and 15 mmHg in the non-pharmacological group. Regarding lifestyle modifications, 45% of patients in the non-pharmacological group reported improved dietary habits, and 55% reported increased physical activity. Conclusion: Both pharmacological and non-pharmacological interventions effectively manage hypertension, with pharmacological interventions showing slightly higher blood pressure control rates. However, non-pharmacological interventions are valuable for improving lifestyle factors. A combination of both approaches may be optimal for hypertension management.

Targeting inflammation in glioblastoma: An updated review from pathophysiology to novel therapeutic approaches.

Glioblastoma (GBM) is a highly aggressive primary malignant brain tumor with a dismal prognosis despite current treatment strategies. Inflammation plays an essential role in GBM pathophysiology, contributing to tumor growth, invasion, immunosuppression, and angiogenesis. As a result, pharmacological intervention with anti-inflammatory drugs has been used as a potential approach for the management of GBM. To provide an overview of the current understanding of GBM pathophysiology, potential therapeutic applications of anti-inflammatory drugs in GBM, conventional treatments of glioblastoma and emerging therapeutic approaches currently under investigation. A narrative review was carried out, scanning publications from 2000 to 2023 on PubMed and Google Scholar. The search was not guided by a set research question or a specific search method but rather focused on the area of interest. Conventional treatments such as surgery, radiotherapy, and chemotherapy have shown some benefits, but their effectiveness is limited by various factors such as tumor heterogeneity and resistance.

Drug Development for Alzheimer’s and Parkinson’s Disease: Where Do We Go Now?

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop new, disease-modifying drugs to treat AD and PD, describing as representative examples some advances in the development of drug candidates targeting oxidative stress and adenosine A2A receptors.

First-line pharmacological treatment of vasovagal syncope based on syndrome phenotype

Abstract Background/Introduction The pharmacological treatment of recurrent vasovagal syncope (VVS) remains suboptimal. A significant proportion of patients exhibit a specific, stress-related personality trait, defined as anxiety sensitivity; fluoxetine treatment seems more effective than placebo in initial studies, underpinning the importance of central mechanisms in VVS pathophysiology. In addition, midodrine is a proposed treatment for the hypotensive VVS phenotype (class IIb ESC indication), implying that peripheral mechanisms may be more important in the hypotensive VVS phenotype. Purpose The purpose of this study was 2-fold: a) to classify recurrent VVS episodes based on history, initial examination (including anxiety sensitivity questionnaire results) and head-up tilt testing into i) central type, ii) peripheral type, and b) to study the effect of fluoxetine in patients with recurrent central-type syncope as well as the effect of midodrine in patients with peripheral-type syncope. Methods Sixty-eight consecutive patients with at least 2 VVS episodes during the preceding 6 months and a positive head-up tilt test were studied, in a 2:1 randomized, single-blind, placebo-controlled way. They were initially classified into i) patients with central-type VVS, and ii) those with peripheral-type VVS based on history, clinical examination, tilt test characteristics, as well as a positive or negative 16-item anxiety sensitivity screening questionnaire. The first group (n=33) was randomized to fluoxetine vs placebo, while the second group (n=31) to midodrine vs placebo. During 2 years of follow-up, and after a 1-month blanking period, we assessed i) syncope/presyncope-free time in patients receiving fluoxetine (or midodrine) vs similar-type patients assigned to placebo treatment, ii) total number of patients who experienced syncope or presyncope between the respective groups. Results Fluoxetine vs placebo. In the intention-to-treat analysis the fluoxetine group exhibited more syncope-free time (14% vs 48%, p <0.05) and similar results were observed regarding presyncope (22% vs 57%, p <0.05). A significant difference was also observed between the two groups regarding the total number of patients who experienced syncope or presyncope during follow-up. Midodrine vs placebo. Midodrine was more effective than placebo regarding presyncope (presyncope-free time 19% vs 45%, p<0.05), while a non-significant difference was observed regarding syncope. However, a significant difference was observed between the two groups regarding the total number of patients who experienced syncope or presyncope during follow-up (p<0.05). Conclusions Fluoxetine or midodrine seem superior to placebo as a first-line pharmacological treatment for recurrent VVS and a central or peripheral phenotype, respectively. Each substance may be an effective first-line pharmacological treatment for patients specifically selected by a simple, initial clinical assessment of VVS phenotype.

Tango and physiotherapy interventions in Parkinson’s disease: a pilot study on efficacy outcomes on motor and cognitive skills

Pharmacological treatments in Parkinson’s disease (PD), albeit effective in alleviating many motor symptoms, have limited effects in non-motor signatures as cognitive impairment, as well as in other aspects included postural instability. Consequently, complementary interventions are nowadays a prerogative of clinical practice managing PD symptomatology. In this pilot longitudinal study, we recruited twenty-four PD patients participating in one of two interventions: adapted Argentine Tango or group-based physiotherapy. Participants underwent a motor and neuropsychological evaluation before and after four months of activities, carried out twice a week. We found a general stabilization of motor and cognitive abilities, with significant improvements in several motor skills, mainly pertaining to static and dynamic balance, similarly in both groups. At cognitive level, we measured a significant improvement in both groups in the Action Naming task. Interestingly, only PD patients in the Tango group improved their performance in the test measuring facial emotion recognition. These findings highlight the crucial role that physical activities have in the stabilization and slowdown of disease’s progression in PD. They further highlight the beneficial effects of a group-based physical intervention, which, especially in the case of Tango, could lead to behavioral ameliorations in domains other than the motor, such as emotion recognition.

Useful aid or futile hassle - continuous rhythm monitoring following acute myocardial infarction

Abstract Background Patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) face an increased risk of cardiac events, including arrhythmias. Current guidelines therefore recommend ECG monitoring for at least 24 hours after AMI in patients with ST segment elevation myocardial infarction (STEMI) and high-risk non-ST segment elevation myocardial infarction (NSTEMI). However, in the last decades medical treatment of AMI has been substantially improved, limiting the risk of arrhythmias post-PCI. Furthermore, continuous ECG monitoring puts additional strain on healthcare personnel during an international healthcare crisis. Purpose To evaluate the contemporary burden of ventricular arrhythmias (VA) in AMI patients post-PCI. Methods This is a retrospective analysis of consecutive patients undergoing PCI for AMI between 2016 and 2020 at a secondary care centre. We defined the primary endpoint as any VA requiring intervention (electric cardioversion or pharmacologic treatment) after PCI. Baseline characteristics and outcome were compared in patients with NSTEMI vs. STEMI. Results A total of 931 patients were included in the analysis, with a mean age of 65 years and 28.6% were female. Patients with NSTEMI (47.3%) were older (median 66 vs. 63 years) and had significantly more comorbidities: hypertension (67.5% vs. 52.1 %), diabetes mellitus (25.4% vs. 15.8%), chronic obstructive pulmonary disease (11.5% vs. 6.7%), and peripheral arterial disease (11.4% vs. 5.3%, p<0.05 for all). VAs requiring intervention occurred in 3.6% vs. 7.1% (p = 0.017) before PCI and in 0% vs. 2.2% (p < 0.001) during PCI in NSTEMI vs. STEMI patients. After PCI the primary endpoint occurred in no NSTEMI patient and in 1.6% of patients with STEMI (p = 0.004). Discussion In a cohort of contemporary AMI patients, ventricular arrhythmias occurred rarely and significantly less often in NSTEMI patients compared to STEMI patients. Due to the low risk of VAs in patients with NSTEMI after PCI, the need for post-procedural rhythm monitoring in NSTEMI patients may be questioned. The identification of predictors for VA after AMI should be subject for future trials.

Management of Arrhythmias and Conduction Disorders in Amyloid Cardiomyopathy

Cardiac amyloidosis, a condition characterized by abnormal protein deposition in the heart, leads to restrictive cardiomyopathy and is notably associated with an increased risk of arrhythmias and conduction disorders. This article reviews the current understanding and management strategies for these cardiac complications, with a focus on recent advancements and clinical challenges. The prevalence and impact of atrial arrhythmias, particularly atrial fibrillation, are examined, along with considerations for stroke risk and anticoagulation therapy. The article also addresses the complexities of managing rate and rhythm control, outlining the utility and limitations of pharmacological agents and interventions such as catheter ablation. Furthermore, it reviews the challenges in the treatment of ventricular arrhythmias, including the contentious use of implantable cardioverter-defibrillators for primary and secondary prevention. Individualized approaches, considering the unique characteristics of cardiac amyloidosis, are paramount. Continuous research and clinical exploration are essential to refine treatment strategies and improve outcomes in this challenging patient population.

AV nodal ablation in atrial fibrillation: long term outcomes

Abstract Background Ablation of the atrioventricular (AV) node, following the insertion of a permanent pacemaker, is a treatment option for symptomatic atrial fibrillation (AF) where rate control is poor, despite maximally tolerated pharmacological intervention or percutaneous AF ablation [1], and yet there is limited data on long-term outcomes. Purpose The purpose of this study is to investigate post AV node ablation follow up outcomes, including the incidence and timeframe of conversion of paroxysmal to persistent AF; incidence and timeframe of upgrade to biventricular pacemakers; and mortality. Methods This observational descriptive study looked at the post-procedure follow-up outcomes of patients who underwent AV node ablation at our centre between March 2015 and June 2019. Retrospective analysis of prospectively collected data was analysed. The demographics of the patients, including their age, gender, co-morbidities, pre-ablation left ventricular ejection fraction (LVEF) and medications were recorded. The follow up outcomes investigated included the change in LVEF, the proportion of patients whose AF converted from paroxysmal to persistent, the proportion of patients requiring upgrade to biventricular devices, and deaths within 6 months of ablation. Outcomes were compared between those who had a biventricular pacemaker pre-ablation and those who had single/dual chamber pacemakers. Results 296 patients with a mean age of 72.7± 8.5 years and a female to male ratio of 54.1% : 45.9% were included. 94 patients (31.8%) had paroxysmal AF pre- ablation. 51.6% of those who had paroxysmal AF pre-ablation converted to persistent AF over a median period of 3 years (interquartile range, 3 years). Among those who had a biventricular pacemaker pre-ablation, 56.5% of those with paroxysmal AF converted to persistent, compared to 47.4% of those with a dual pacemaker pre-ablation p=ns Among patients with dual chamber pacemakers, those who remained in paroxysmal AF post-ablation had a mean CHADVASC score of 3.2 (range of 1-6) compared to 3.7 (range of 2-6) in those whose AF converted to persistent (p=0.19). 9 patients (3%) died within less than 6 months of the procedure, with 1 patient dying within 6 days. 13% of the patients originally having a single or dual chamber pacemaker required an upgrade to a biventricular pacemaker over a median period of 1.25 years (interquartile range 1.1 years). All the patients who required an upgrade to a biventricular pacemaker had normal LVEF pre-ablation except for one patient who had mild LV impairment. Conclusions A significant proportion of patients with paroxysmal AF converted to persistent AF following AV node ablation and having a biventricular pacemaker did not offer benefit in keeping people in paroxysmal AF.A considerable number of people required an upgrade to biventricular pacemaker over a short time frame even though they had normal LVEF pre AV nodal ablation.

Acute safety and efficacy of ablation for atrial fibrillation in elderly patients by means of pulsed field ablation

Abstract Background It is well known that age affects the efficacy of pharmacological treatment for atrial fibrillation (AF). Thermal ablation (radiofrequency or cryoballoon) is an established strategy for AF. However, there is no evidence evaluating efficiency, effectiveness, and safety outcomes in elderly patients in the context of the novel pulsed-field ablation (PFA) technology. Purpose We aimed to analyze the efficacy and safety of PFA in elderly (age≥75 years) patients with AF compared to non-elderly (age<75 years) patients with AF. Methods All consecutive patients undergoing AF ablation with the Farapulse system at 10 centers were included. Protocol-directed PVI was delivered using 2000 V with eight applications per vein, that is, four applications each in the basket and flower poses. Additional lesions were performed at the operator’s discretion. Results A total of 851 consecutive patients were included: 83 (9.8%) had ≥75 years (median of 77[75-78] years) whereas 768 (90.2%) had <75 years (median of 62[56-68] years, p<0.0001). Older patients had more comorbidities compared to younger patients (kidney disease: 9.6% vs 1.2%, p<0.0001; chronic obstructive pulmonary disease: 8.4% vs 3%, p=0.021; cancer history: 18.1% vs 6.1%, p=0.0004; hypertension: 61.4% vs 43.8%, p=0.002), whereas they exhibited a higher LVEF (60±6% vs 57±8%, p=0.0243). No differences between older and younger patients were found in terms of underlying AF type (paroxysmal AF: 66.3% vs 68.9%, p=0.62), procedure type (repeat ablation: 8.4% vs 13.4%, p=0.29), more extensive lesion set than PVI only (28.9% vs 22.5%, p=0.22) and the use of 3D mapping system (22.9% vs 21.1%, p=0.67). By looking at procedural metrics, no differences were also found between groups: 73±28 min vs 72±32 min for skin-to-skin time, p=0.41; 93±41 min vs 88±43 min for preparation plus skin-to-skin time, p=0.11; 18±9 min vs 17±9 min for fluoroscopy time, p=0.61 and 32[32-40] vs 32[32-38] PFA spots to achieve PVI, p=0.29. PVI was achieved in all patients. No major procedure-related adverse events were reported. Conclusion In our experience, the use of Farapulse PFA system for AF ablation in elderly patients was rapid, safe and effective, with no differences compared to the younger population.

Reduced Pharmacological Intervention of Prehospital Services for Acute Alcohol Intoxication during the COVID-19 Pandemic in A Large District of Southern Italy

Background Stress during a pandemic increases the risk of alcohol consumption, which may require pharmacological management. Methods An observational single-center retrospective study was conducted from 1 January 2018 to 31 December 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the emergency departments (EDs) of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ESs) who were either admitted or not admitted, due to their refusal. Results A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, an inverse association was found between pharmacological treatment and number of calls coded green (non-critical) and yellow (fairly critical) in patients admitted to EDs. An inverse association was also found for calls coded green in patients not admitted to EDs and pharmacological treatment. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. Conclusions ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

Treatment of harmful gambling: a scoping review of United Kingdom-based intervention research

BackgroundUnderstanding and treating the harm caused by gambling is a growing international psychiatric and public health challenge. Treatment of gambling harm may involve psychological and pharmacological intervention, in conjunction with peer support. This scoping review was conducted to identify, for the first time, the characteristics and extent of United Kingdom (UK) based gambling treatment research. We reviewed studies conducted among people seeking treatment for disordered or harmful gambling in the UK, the settings, research designs, and outcome measures used, and to identify any treatment research gaps.MethodsSystematic searches of PsycInfo, PsycArticles, Scopus, PubMed, and Web of Science databases were carried out for gambling treatment research or evaluation studies conducted in the UK. Studies were included if they evaluated the effectiveness of an intervention or treatment designed to improve symptoms of harmful or problematic gambling, reported outcomes of interventions on treatment adherence, gambling symptoms, or behaviours using standardised measures, were conducted in the UK, and were published since 2000.ResultsEight studies met the inclusion criteria. Four were retrospective chart reviews, two were single-participant case reports, one described a retrospective case series, and one employed a cross-sectional design. None used an experimental design.ConclusionThe limited number of studies included in this review highlights a relative paucity of gambling treatment research conducted in UK settings. Further work should seek to identify potential barriers and obstacles to conducting gambling treatment research in the UK.

#1400 Acidosis-induced inflammatory response in tubule cells and fibroblasts is amplified by tubule-fibroblast crosstalk and mediated via p38 signaling

Abstract Background and Aims Tubulointerstitial kidney disease, associated with micromilieu changes such as acidification and inflammation, impacts tubule cells and fibroblasts. Micromilieu homeostasis influences intracellular signaling and intercellular crosstalk. Furthermore, cell-cell communication modulates the interstitial microenvironment. In the early stages of kidney failure, fibroblasts undergo a transition to an inflammatory phenotype driven by rapid and long-lasting p38 or CREB (cAMP response element-binding protein) signaling. This phenotypic shift involves an increased secretion of cytokines such as IL-6, TNF, or COX-2 metabolites, thereby changing the microenvironment. Additionally, the phenotype switch is characterized by remodelling of the cytoskeleton and alterations in cell-cell contacts. The objective of our study was to evaluate the impact of acidosis on inflammatory responses in proximal tubule cells and fibroblasts in the context of cellular crosstalk. Furthermore, we aimed to investigate the involvement of p38 and CREB signaling. Method HK-2 (human proximal tubule) and CCD-1092Sk (human fibroblasts), in mono and coculture, were exposed to acidic or control media for 3 or 48 h. Protein expression levels of inflammation markers (IL-6, TNF, TGF-ß, and COX-2), dedifferentiation markers (N-cadherin, vinculin, ß-catenin, and vimentin), as well as phospho- and total p38 and CREB, were determined through western blot analysis. The impact of p38 activation was assessed using pharmacological interventions. Furthermore, the influence of IL-6 incubation on the expression of phospho-p38 was investigated Results In tubule cells acidosis led, independent of culture conditions, to an increase of IL-6 after 3h and a decrease of vimentin and COX-2 after 48h. Moreover, acidosis caused an increase of TNF solely in coculture after 3h. Only in monoculture, ß-Catenin expression decreased in tubule cells during acidosis. In fibroblasts acidosis led to an increase of TNF, COX-2, vimentin, vinculin, N-cadherin and a decrease of TGF-ß expression exclusively in co-culture after 48 h. Independent of incubation or culture conditions acidosis induced a strong increase of IL-6 protein expression in fibroblasts. In co-culture, acidosis enhanced phosphorylation of p38 phosphorylation only after 3 h and that of CREB appeared after 3h and was persistent after 48h. In fibroblasts, acidosis enhanced phosphorylation of p38 in a sustained and very strong manner. Moreover, acidosis caused an increased phosphorylation of CREB independent of culture conditions and incubation time. Inhibition of p38 under co-culture conditions reduced acidosis-induced changes in fibroblasts significantly. In monoculture, incubation with IL-6 under acidic conditions caused an increase in p38 phosphorylation after 3 hours in tubule cells and after 48 hours in fibroblasts. Conclusion Our data indicate that acidosis-induced pathophysiological changes are significantly amplified by tubule-fibroblast crosstalk. The synergy between cellular crosstalk and acidosis triggers the activation of the p38, CREB, and IL-6 signaling pathways, leading to a phenotype switch in fibroblasts that promotes inflammation and fibrosis. If these findings hold true in vivo, the synergistic interplay between tubule-fibroblast crosstalk and acidosis emerges as a crucial factor in the development of kidney failure.

Biomarker endpoints in cancer cachexia clinical trials: Systematic Review 5 of the cachexia endpoint series.

Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkersfeatures frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2023) was completed. Eligible trials met the following criteria: adults (≥18years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants=6522) included biomarkers as endpoints. Most studies (n=29, 55.7%) included a variety of cancer types. Pharmacological interventions (n=27, 51.9%) were most evaluated, followed by nutritional interventions (n=20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n=29, 55.8%) was assessed most often, followed by C-reactive protein (n=22, 42.3%), interleukin-6 (n=16, 30.8%) and tumour necrosis factor-α (n=14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.

#2020 The use of the target trial approach in kidney failure: a systematic methodological review

Abstract Background and Aims The concept of target trial emulation has recently been introduced and implemented in nephrology as a complement to when randomized trials may not be feasible. Thereby critical questions in the comparative effectiveness and safety of interventions during kidney failure can be addressed. This methodological systematic review aims to evaluate the scope, validity and robustness of the target trial approach for studying outcomes in patients with kidney disease. Method MEDLINE, Embase, and reference lists were searched up until 1st June 2023 to identify studies on kidney disease patients that use target trial emulation. Dual study selection (AA, PK) was undertaken, with a third reviewer settling disagreements (JP). Interventional observational studies were eligible that used target trial emulation to mimic a hypothetical trial where the conduct of a randomized trial was unfeasible, unethical, or untimely. We included studies across the range of chronic kidney diseases, i.e., predialysis, dialysis and transplantation; studies assessing acute disease states (including acute kidney injury) were excluded as well as non-primary research (i.e., case series/editorials/reports/narrative reviews). The quality of reporting and risk of bias was assessed independently by three reviewers and differences resolved through consensus with a fourth reviewer. The critical appraisal was piloted using a previously published reporting checklist and refined throughout the process. Results The systematic search yielded 2883 studies, of which 649 duplicates were removed. From 2232 studies, 367 full-text studies were assessed for eligibility according to target trial emulation criteria and 74 studies were included. A large number of studies (47) focused on patients with kidney failure undergoing renal replacement therapy, mainly haemodialysis. 30 studies were reported before 2019. Of the 74 studies, 46 focused on pharmacological interventions, six on surgical interventions, four on transplantation and 18 on other interventions. Studies used either registries (41), health administration data (4), insurance data (5), electronic health records (15), study databases (8) or other (1). It should be noted that in multiple instances more than one data source was used. The majority (66) of studies did not explicitly mention target trial emulation in the title or abstract. Only a minority (8) of studies explicitly prespecified a target trial protocol. To mitigate confounding, studies mainly focused on exact matching of the groups by using inverse probability weighting and propensity score matching. Conclusion In the past decade the use of the target trial emulation framework in nephrology has substantially increased. However, reporting and quality of study conduct is variable and shows the clear need for a reporting framework to increase clarity and reliability, and to understand to what extent study findings are generalisable into clinical practice to improve health outcomes

Chronic Intestinal Failure and Short Bowel Syndrome in Adults: The State of the Art

<b><i>Background:</i></b> Short bowel syndrome (SBS) is a devastating malabsorptive condition and the most common cause of chronic intestinal failure (CIF). During the intestinal rehabilitation process, patients may need parenteral support for months or years, parenteral nutrition (PN), or hydration/electrolyte supplementation, as a bridge for the desired enteral autonomy. <b><i>Summary:</i></b> Several classification criteria have been highlighted to reflect different perspectives in CIF. The management of CIF-SBS in adults is a multidisciplinary process that aims to reduce gastrointestinal secretions, slow transit, correct/prevent malnutrition, dehydration, and specific nutrient deficiencies, and prevent refeeding syndrome. The nutritional support team should have the expertise to take care of these complex patients: fluid support; oral, enteral, and PN; disease/PN-related complications; pharmacologic treatment; and surgical prevention/treatment. <b><i>Key Messages:</i></b> CIF-SBS is a complex disease with undesired consequences, if not adequately identified and managed. A comprehensive approach performed by a multidisciplinary team is essential to reduce PN dependence, promote enteral independence, and improve quality of life.

#2277 Artificial Intelligence for predicting heart failure in chronic kidney disease: analysis of a 5000-patient cohort

Abstract Background and Aims Chronic kidney disease (CKD) and heart failure share a complex, bidirectional interaction, and are therefore an area of crucial interest in nephrology due to their prevalence and effect on mortality. It is basic to identify the risk of heart failure in patients with CKD as soon as possible to improve treatment outcomes and complications. It is important to note that while there is wide experience in prediction of heart failure, the use of models based on artificial intelligence is practically non-existent with this objective in mind. Based on the experience of our group in the prediction of mortality in patients with CKD and in CKD progression with machine learning algorithms, this study aims to predict the onset of heart failure in CKD patients. This study addresses this issue using machine learning techniques to offer new opportunities for accurate prediction of cardiac disease. This approach facilitates the individualization of risk assessment and allows the implementation of early and personalized interventions that can significantly influence the management of both diseases. Method Design: Retrospective observational study of a historical cohort from the Registry of Renal Patients of Catalonia (RMRC) and the Catalan Agency for Health Quality and Evaluation. Sample: 5000 patients with CKD, selected for having the minimum number of missing data. Follow-up: 10 years, from January 2010 to December 2020. Inclusion criteria: patients older than 18 years with CKD. Variables: 333 variables: a) Age, gender, weight, height (4); b) Status on the transplant waiting list (2); c) Renal replacement therapy (3); d) Diagnoses (ICD-10) excluding group I50 diagnoses, used as the outcome (146); e) Laboratory variables (78); f) Pharmacological treatments (100). Label and models: The algorithm used was the Light Gradient Boosting Machine (LGBM), with which four models were trained to perform a binary classification to predict whether a patient would develop heart failure in a period of 3, 4, 5 or 6 years. Label 0 was used to represent the absence of heart failure, while label 1 was used to represent the presence of heart failure. The methodology used to train the models was as follows: 1. Pre-processing of the data to manage missing data and data errors. 2. Creating different datasets, one for each prediction horizon. 3. Training and evaluating the LGBM models (with 5-fold CV). Results Age: 63 ± 13 years, Gender: 66% male and 34% were female. Different prediction horizons were tested, and the best results were obtained for 6 years where was achieved an area under the curve of 0.86 and an accuracy of 0.76. The 5 variables with major relevance according to SHAP values (SHapley Additive exPlanations) and in this order are: age, CKD diagnosis, hypertension, haemoglobin, and lymphocytes. The results presented in Fig. 1 and Table 1 correspond to the mean obtained for the 5-folds of the Group Cross-Validation. Conclusion –Advanced artificial intelligence algorithms present promising results for the prediction of heart failure in CKD patients. –This enables early, personalized, and more effective treatments for CKD patients.

Interventions for insomnia in cancer patients and survivors-a comprehensive systematic review and meta-analysis.

Considering the persistent nature and higher prevalence of insomnia in cancer patients and survivors compared to the general population, there is a need for effective management strategies. This systematic review and meta-analysis aimed to comprehensively evaluate the available evidence for the efficacy of pharmacological and non-pharmacological interventions for insomnia in adult cancer patients and survivors. Following the PRISMA guidelines, we analyzed data from 61 randomized controlled trials involving 6528 participants. Interventions included pharmacological, physical, and psychological treatments, with a focus on insomnia severity and secondary sleep and non-sleep outcomes. Frequentist and Bayesian analytical strategies were employed for data synthesis and interpretation. Cognitive-Behavioral Therapy for Insomnia (CBT-I) emerged as the most efficacious intervention for reducing insomnia severity in cancer survivors, and further demonstrated significant improvements in fatigue, depressive symptoms, and anxiety. CBT-I showed a large post-intervention effect (g = 0.86; 95%CI : 0.57-1.15) and a medium effect at follow-up (g = 0.55; 0.18-0.92). Other interventions like BWL therapy, sleep medication, melatonin, exercise, mind-body therapies, and mindfulness-based therapies showed benefits, but the evidence for their efficacy was less convincing compared to CBT-I. Brief Behavioral Therapy for Insomnia showed promise as a less burdensome alternative for patients in active cancer treatment. CBT-I is supported as first-line treatment for insomnia in cancer survivors, with significant benefits observed across sleep and non-sleep outcomes. The findings also highlight the potential of less intensive alternatives. The research contributes valuable insights for clinical practice and underscores the need for further exploration into the complexities of sleep disturbances in cancer patients and survivors.

Bronchiectasis management in adults: state of the art and future directions.

Formerly regarded as a rare disease, bronchiectasis is increasingly recognised. A renewed interest in this disease has led to significant progress in bronchiectasis research. Randomised clinical trials have demonstrated the benefits of airway clearance techniques, inhaled antibiotics and long-term macrolide therapy in bronchiectasis patients. However, the heterogeneity of bronchiectasis remains one of the most challenging aspects of management. Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity. The goals of therapy for bronchiectasis are to reduce the symptom burden, improve quality of life, reduce exacerbations and prevent disease progression. We review the pharmacological and non-pharmacological treatments that can improve mucociliary clearance, reduce airway inflammation and tackle airway infection, the key pathophysiological features of bronchiectasis. There are also promising treatments in development for the management of bronchiectasis, including novel anti-inflammatory therapies. This review provides a critical update on the management of bronchiectasis focusing on treatable traits and recent randomised clinical trials.