Abstract Introduction Neurophysin-I (NP-I) is a surrogate marker of oxytocin (OXT), a hypothalamic hormone with putative anti-inflammatory properties. Purpose We investigated whether NP-I measured at diagnosis could predict adverse outcomes in patients hospitalized with community-acquired pneumonia (CAP). Methods This secondary analysis of the prospective STEP Trial (NCT00973154) included adult patients hospitalized with CAP, normal serum sodium at inclusion, and available baseline blood samples for NP-I measurement. Demographic data, laboratory parameters, and Pneumonia Severity Index (PSI) scores were collected. To ensure representation across disease severity, patients were selected to achieve balanced numbers of low/intermediate-risk (PSI I−III) and high-risk (PSI IV−V) cases. Results Sixty-five patients were included (M/F 38/27 [58.5/41.5%], median age 79 [76−83] years). NP-I levels did not differ between low–intermediate and high-risk groups (p=0.441), between patients with and without CAP-related complications (336 [190−607] vs. 225 [147−539] pM, p=0.326), or between survivors and non-survivors (199 [121−429] vs. 304 [174−604] pM, p=0.259). In univariable logistic regression analysis, PSI was associated with in-hospital mortality (OR 1.027, 95% CI 1.008−1.049, p=0.006), whereas adding NP-I did not improve predictive performance (DeLong’s test p=0.509). Patients with impaired renal function (n=28) had higher NP-I levels than those with preserved renal function (446 [278−685] vs. 182 [124−403] pM, p<0.001). NP-I was independently and inversely associated with eGFR after adjustment for age and sex (β = −9.06, p=0.038). Conclusion NP-I levels are strongly influenced by renal function and do not appear to provide prognostic information for adverse outcomes in patients hospitalized with CAP.

BACKGROUND:Our recent Protein Recommendation to Increase Muscle (PRIMe) trial suggested that increasing daily protein intake via nutrition counseling in patients with colorectal cancer positively impacts muscle mass. OBJECTIVES:This post hoc analysis investigated whether baseline systemic inflammation, hormone, and/or amino acid disturbances influenced the effectiveness of nutrition support (focused on high protein) to increase lean soft tissue (LST). Outcomes were analyzed based on actual achieved protein intake, allowing exploration of dose-response effects. METHODS:In patients with stage II-IV colorectal cancer who received nutritional counseling to reach protein intake of 1.0 or 2.0 g/kg/d for 12 wk, LST was assessed by dual-energy X-ray absorptiometry, dietary protein intake by weighted 3-d food records, and cytokine, hormone (Luminex), and amino acid concentrations (liquid chromatography-tandem mass spectroscopy) at baseline and 6 and 12 wk. RESULTS:The mean protein intake of the entire group [50 patients, age 57 y (SD 11 y)] was 88.7 g/d, and baseline cytokines were elevated. Although protein intake (in grams) increased by 22% (9.34%) and 29% (16.42%) at 6 and 12 wk of supplementation, respectively, the LST response varied widely. At 6 wk, 77% of LST response variation was explained by baseline concentrations of interleukin (IL)-6, insulin, and specific amino acids (hydroxyproline, aspartate, taurine) and protein intake changes (P = 0.021). By 12 wk, IL-6 and methionine explained only 32% (P = 0.030). Tumor stage and concurrent chemotherapy type did not play a role. Positive LST change after 6 wk occurred at daily protein increase of 27 g. CONCLUSIONS:Elevated IL-6 blunts the anabolic capacity of protein support in colorectal cancer. At least 27 g/d of supplemental protein is needed to reach anabolism, although higher amounts may be needed in patients with higher IL-6 levels. These findings support the need to consider baseline inflammation to optimize the effectiveness of nutritional support in cancer. This trial was registered at clinicaltrials.gov as NCT02788955. https://clinicaltrials.gov/study/NCT02788955.

RATIONALE:Malnutrition affects 35% to 64% of hospitalised older people, and is associated with adverse health outcomes such as disease complications and hospital readmission. Identifying effective nutritional interventions is essential to improve clinical outcomes and reduce healthcare costs in this population. OBJECTIVES:To evaluate the effects of various nutritional interventions, compared with either a control group (standard care or placebo) or each other, on patient-relevant outcomes in hospitalised older people at risk of or with established malnutrition, and to rank the effects of these different interventions using network meta-analysis (NMA) based on individual participant data (IPD). SEARCH METHODS:We searched CENTRAL, MEDLINE, five other databases, and two trial registries to 2 July 2024, and checked the reference lists of included studies and relevant systematic reviews. ELIGIBILITY CRITERIA:We included older people (≥ 65 years) hospitalised for different acute conditions at risk of or with malnutrition enrolled in randomised controlled trials (RCTs) comparing oral nutritional interventions with control or each other. For RCTs that met our inclusion criteria, either fully or partially, we requested IPD from the study authors. If we did not receive a response or IPD were unavailable, we used published aggregated data. We excluded RCTs that only partially met the eligibility criteria if neither IPD nor sufficient aggregated data were obtainable. OUTCOMES:Critical outcomes were all-cause mortality, serious adverse events (SAEs), and functional status (e.g. activities of daily living). Important outcomes were health-related quality of life (HRQoL), length of hospital stay (LOS), body weight, and fat-free mass. The main outcome assessment time point was at hospital discharge or 30 days after randomisation. RISK OF BIAS:We used the Cochrane risk of bias 2 (RoB 2) tool. SYNTHESIS METHODS:For each outcome, we first analysed IPD within each study. Second, we pooled results in an NMA which also included the aggregated data from RCTs without available IPD. We performed random-effects NMAs based on the frequentist approach and ranked treatments by P-scores. We rated the certainty of evidence using the GRADE approach. INCLUDED STUDIES:We included 21 RCTs (72 reports; 12 RCTs with IPD) with 3309 older participants (mean age ranged from 75 to 85 years; 1863 participants with IPD) with different acute conditions. Interventions included the provision of additional protein (three studies), energy supplements (two studies), oral nutritional supplements (ONS; eight studies), individualised feeding support (two studies), and comprehensive individualised nutritional care (eight studies). In all but two RCTs, interventions were compared to control (standard care with or without a placebo). We judged 16.1% of outcome assessments to be at low risk of bias and 16.8% at high risk. SYNTHESIS OF RESULTS:ONS may reduce all-cause mortality (risk ratio (RR) 0.46, 95% confidence interval (CI) 0.25 to 0.84; absolute risk difference 57 fewer deaths per 1000 people, 95% CI 79 fewer to 17 fewer; low-certainty evidence) compared to control, while comprehensive individualised nutritional care may show little to no effect (RR 0.98, 95% CI 0.55 to 1.73; 1 fewer per 1000 people, 95% CI 26 fewer to 46 more; low-certainty evidence). For all other treatment comparisons, the evidence is very uncertain (NMA with 13 RCTs, 2728 participants; Q between designs: not applicable (NA)). ONS may reduce SAEs compared to control (RR 0.56, 95% CI 0.32 to 0.95; 84 fewer SAEs per 1000 people, 95% CI 131 fewer to 10 fewer; Q between designs: Q 1.95, df 2, P = 0.3772; low-certainty evidence). For all other treatment comparisons, the evidence is very uncertain (NMA with 14 RCTs, 2184 participants). Comprehensive individualised nutritional care may make little to no difference in activities of daily living compared to control (standardised mean difference (SMD) 0.06, 95% CI -0.08 to 0.20; low-certainty evidence) and ONS compared to energy supplements (SMD -0.15, 95% CI -0.53 to 0.23; low-certainty evidence). For all other treatment comparisons, the evidence is very uncertain (NMA with 5 RCTs, 1128 participants; Q between designs: NA). Energy supplements probably make little to no difference in HRQoL compared with ONS (mean difference (MD) 0.01, 95% CI -0.06 to 0.08; Q between designs: NA; moderate-certainty evidence). All other comparisons of different nutritional interventions may make little to no difference to HRQoL (NMA with 3 RCTs, 1513 participants). The provision of additional protein, energy supplements, ONS, and comprehensive individualised nutritional care may make little to no difference in LOS compared to control (18 RCTs, 3013 participants; Q between designs: Q 2.86, df 3, P = 0.4145). Body weight (16 RCTs, 2114 participants; Q between designs: Q 2.03, df 3, P = 0.5655) may increase with ONS when compared to control (MD 0.9 kg, 95% CI 0.37 to 1.42) or comprehensive individualised nutritional care (MD 1.00 kg, 95% CI 0.12 to 1.87), but the evidence is very uncertain. Energy supplements and ONS probably have similar effects on body weight (MD 0.11 kg, 95% CI -0.85 to 0.63; moderate-certainty evidence). For fat-free mass, no meta-analysis was possible. One RCT (102 participants) compared ONS with energy supplements and found little or no difference between groups (MD 0.13 kg, 95% CI -0.63 to 0.90; low-certainty evidence), while evidence regarding the effects of additional protein compared with control was very uncertain (1 RCT, 19 participants). Rankings of treatments by P-scores were not consistent across outcomes. AUTHORS' CONCLUSIONS:In older hospitalised people at risk of or with malnutrition, oral nutritional supplements may reduce mortality and SAEs compared to control 30 days after randomisation. For other outcomes, there may be little or no differences in results. Overall, the evidence was of low to very low certainty, primarily due to a limited number of studies and participants per comparison. The comparison of treatment effects across outcomes was constrained by variations in network structure. When interpreting the results, the heterogeneity of the population in terms of acute and chronic conditions needs to be considered. To improve certainty, adequately powered studies with robust methodologies should compare interventions with controls as well as against each other. FUNDING:The German Federal Ministry of Education and Research funded this work (grant number: 01KG2102). REGISTRATION:Protocol (2022) doi.org/10.1002/14651858.CD015468.

BACKGROUND:Trimethylamine N-oxide (TMAO), a metabolite produced by the gut microbiota, is highly influenced by dietary factors and is linked to negative health outcomes including all-cause mortality and cardiovascular events. We evaluated the prognostic value of TMAO among hospitalized patients at nutritional risk participating in the Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT) regarding clinical outcomes and response to nutritional support. CLINICAL TRIAL REGISTRATION:clinicaltrials.gov as NCT02517476 (registered 7 August 2015) METHODS: This secondary analysis is based on the randomized-controlled EFFORT trial, which compared individualized nutritional therapy with usual care in medical inpatients at nutritional risk. We studied the association of admission TMAO concentrations with all-cause mortality after 180 days (primary endpoint) and major adverse cardiovascular events (MACE) using quartile-based regression analysis. RESULTS:Among 218 patients with available TMAO measurements, those in higher quartiles showed an increased all-cause mortality compared to the lowest quartile after 180 days (adjusted HR 1.92 95% CI 1.03-3.56, p = 0.04) and 5 years (adjusted HR 2.01 95% CI 1.23-3.31, p = 0.006). A similar trend was observed for MACE. We found no significant associations between dietary factors or nutritional history and admission TMAO levels, nor was TMAO predictive regarding the response to nutritional therapy. CONCLUSION:The risk of mortality over six months nearly doubled in patients at risk of malnutrition with elevated baseline TMAO levels. Additional research is needed to determine if dietary interventions can successfully modulate TMAO levels and, in turn, improve clinical outcomes.

In 2019, the global EAT-Lancet Planetary Health Diet (PHD) introduced specific recommendations to promote sustainable, health-focused dietary changes in response to the increasing prevalence of diet-related diseases and escalating environmental challenges. We assessed the alignment of Swiss dietary habits with these recommendations. We analysed data from 2057 adults (18–75 years) from the 2014–2015 national nutrition survey menuCH. We matched different food categories with the PHD classification and calculated mean intakes (g and kcal) per food category, standardised to 2500 kcal, expressed as a percentage of the PHD recommendations (PHD = 100

Indication for visceral surgical procedures should be based on clinical reasoning only and independent of financial incentives. Yet, there is a lack of studies investigating whether insurance type (basic vs. supplementary private) is associated with surgical procedure rates. In this study we assessed whether incidence rates in adults with supplementary private insurance undergoing visceral surgical, non-emergency, in-patient procedures from 2012 to 2020 are higher compared to those with basic insurance only in Switzerland. We assessed incidence rates (IR) for basic only and supplementary private insurance stratified over time and by different age groups, and we fitted negative binomial regression models adjusted by inverse probability weights for specific visceral surgical procedures. We used primary or secondary discharge procedure codes for one of the following procedures: cholecystectomy, fundoplication, sigmoidectomy, rectopexy, haemorrhoidectomy, inguinal, femoral, and umbilical hernia repair. Of 1,954,119 surgical admissions (median age 63, 53.3

BACKGROUND:Chronic hyponatremia is associated with adverse outcomes, including falls, neurocognitive disorders, and mortality, but whether hyponatremia itself increases morbidity and mortality, or is simply an indicator of underlying disease severity, remains unclear. We aimed to evaluate the effects of targeted hyponatremia correction versus routine care on mortality and rehospitalization rates. METHODS:We conducted a randomized, controlled, parallel-group, multicenter trial across nine European centers. Hospitalized participants with plasma sodium lower than 130 mmol/l were assigned to undergo either a multifaceted targeted correction of hyponatremia (intervention) or routine care for hyponatremia (control). The primary outcome was the combined risk of death or rehospitalization within 30 days of trial inclusion. RESULTS:A total of 2173 patients were randomly assigned to intervention (n=1079) or control (n=1094). The median age was 73 years (interquartile range, 63 to 81) and 48% were male. The median baseline sodium levels were 127 mmol/l (interquartile range, 124 to 128) in both groups. The mean (± standard deviation) maximum absolute change in sodium levels during the treatment period was 10.0 mmol/l (±5.6) in the intervention group, compared with 8.7 mmol/l (±5.6) in the control group, resulting in normal sodium levels (defined as 135-145 mmol/l) in 641 (60.4%) and 492 (46.2%) patients in the intervention and control groups, respectively. Within 30 days after inclusion, the primary outcome occurred in 20.5% (218 of 1065 patients) in the intervention group and 21.8% (234 of 1073 patients) in the control group (estimated absolute difference, -1.3 percentage points; 95% confidence interval, -4.9 to 2.2; P=0.45). Death occurred in 86 (8.0%) patients and rehospitalization in 141 (13.2%) patients in the intervention group compared with 88 (8.0%) patients and 151 (14.1%) patients in the control group. Overcorrection occurred in 25 (2.3%) patients in the intervention group and 16 (1.4%) patients in the control group; no cases of osmotic demyelination syndrome were observed. CONCLUSIONS:In hospitalized patients with chronic hyponatremia, a targeted correction intervention resulted in higher normonatremia rates but did not reduce a composite outcome of 30-day mortality and rehospitalization. (Funded by the Swiss National Science Foundation [grant number, 33 IC30_192979]; ClinicalTrials.gov number, NCT03557957.).

Background and objective Patients who cannot meet their nutritional needs orally or enterally require parenteral nutrition (PN) with home parenteral nutrition (HPN) in patients needing long-term PN. While HPN improves quality of life, it carries risks like catheter-related complications, requiring close monitoring and multidisciplinary support. eHealth solutions, particularly videoconferencing, offer a promising approach to enhance patient care by improving accessibility and reducing hospital visits. The purpose of this study is to evaluate the satisfaction and effectiveness of eHealth in the management and quality assurance of therapy in patients receiving HPN. Methods This prospective, multicenter pilot study was conducted in Switzerland in 2023. The study design was a comparative before-and-after study over eight months, four months before (retrospective) and four months after eHealth implementation. The after phase involved eHealth care, which included frequent, shorter interactions between patients and their treating physicians, as well as monitoring through the eSwissHPN App. Patients and physicians completed questionnaires to assess satisfaction (Client-Satisfaction-Questionnaire (CSQ-8) and Telehealth-Usability-Questionnaire (TUQ)) with the App and care at baseline and at the end of the intervention. In addition, physicians documented the occurrence of HPN-related complications. Four different questionnaires were used to assess satisfaction with the service, usability of the application, information technology (IT) skills and general health. Results Out of a total of 15 patients, 11 patients from different clinics across the country were included in the final analysis of the study. Satisfaction with eHealth, measured using the CSQ8, yielded a mean score (SD) of 3.4 ± 0.7 for patients and 3.5 ± 0.6 for physicians, indicating high satisfaction. In the before phase, three manifest complications were reported by the physician, whereas in the after phase, only one complication was reported and arising clinical and device problems were prevented. Conclusion In summary, monthly virtual consultations in HPN have proven to be a patient-centered, flexible, and cost-effective healthcare solution, with high levels of satisfaction reported by both patients and physicians. During the implementation phase, physicians reported fewer complications. In addition, emerging clinical and device issues were handled promptly, avoiding manifest complications. To confirm these promising results, further robust studies are needed.

Malnutrition is a multifactorial and complex condition with significant consequences for recovery, functional outcomes, and healthcare systems. Research in malnutrition is often limited by single-component interventions, heterogeneous study designs, and variable outcome measures. This perspective paper introduces a practical guiding framework for clinical nutrition research, emphasizing interdisciplinary, multifactorial approaches, co-designed interventions, and pragmatic, adaptive study designs. Evidence from several trials demonstrates that individualized nutritional support delivered by multidisciplinary teams improves clinical outcomes, yet challenges remain in recruitment, adherence, and balancing intervention intensity with patient burden. The framework provides a structured approach to intervention development, outcome selection, and implementation, while remaining flexible to accommodate innovation, context-specific adaptation, and emerging outcome measures. By integrating lessons from prior trials, globally, and promoting systematic reporting and feasibility assessment, this framework aims to enhance the design, comparability, and translational impact of future research in clinical nutrition in older and other clinically vulnerable populations. Adoption of such a framework can guide research prioritization, optimize intervention delivery, and ultimately improve patient recovery and quality of life.

BACKGROUND: Initiatives like “Choosing Wisely” promote efficient and high-quality healthcare by reducing overuse. The interdisciplinary copAIN project aims to reduce resource utilisation in medical ward patients by providing specific guidelines to internal medicine residents. METHODS: This study was conducted in the Cantonal Hospital Aarau, a 500-bed tertiary care and academic facility.After implementing the copAIN project for medical inpatients on 1 June 2023, we conducted an interrupted time-series (ITS) cohort study and analysed it using a mixed-effects regression model for comparison. Neurological patients not involved in copAIN served as the control group. The primary outcome was resource utilisation defined by the measurement frequency of five vital signs and laboratory orders. The secondary, safety outcome was in-hospital mortality. RESULTS: Of 51,396 admissions between 1 September 2022 and 31 May 2024, 8344 cases were eligible for analysis. While there were no differences in measurement frequencies in the control group, we found a significant reduction in the intervention group for the frequency of measurements of blood pressure (0.28 measures per day per length of stay [dLOS]), heart rate (0.26 measures per dLOS), oxygen saturation (0.28 measures per dLOS) and temperature (0.27 measures per dLOS). However, this effect was temporary, and adjusted analyses showed no significant difference between pre- and post-intervention periods. There was no change in mortality between study periods in both groups. CONCLUSION: An intervention focusing on the reduction of routine parameters within the hospital settingresulted in a temporary decrease in resource use without increasing in-hospital mortality. This data supports recent initiatives aimed at improving resource efficiency in medicine without compromising quality. The absence of a sustained impact highlights the need for ongoing strategies to maintain and reinforce improvements.

While headache is frequently encountered in patients with prolactinomas, data on its determinants and long-term outcome following upfront medical versus upfront surgical treatment are limited. We aimed to identify clinical and radiological determinants of prolactinoma-associated headache (PAH) and to evaluate long-term headache outcomes according to the primary treatment strategy. We retrospectively analyzed 145 prolactinoma patients treated at a tertiary center. Headache at presentation, endocrine parameters, tumor size, and cavernous sinus involvement were assessed. Independent determinants of PAH at diagnosis were identified using multivariable logistic regression. Long-term headache status and prolactin outcomes were evaluated according to upfront dopamine agonist (DA) therapy or transsphenoidal surgery (TSS). At diagnosis, 42 of 145 patients (28.9

Aims With cardiac myosin inhibitors emerging as a novel pharmacological option instead of septal reduction therapies (SRT) in obstructive hypertrophic cardiomyopathy (HCM), contemporary data on national long-term outcomes after SRT are needed.Methods and results In this nationwide cohort study from 2015 to 2021, patients with obstructive HCM undergoing SRT (surgical myectomy or transcoronary ablation of septal hypertrophy) were 1:8 propensity score-matched with non-obstructive HCM patients or surgical controls undergoing appendectomy without heart disease in recent records. As assessed in time-to-event analyses, the primary outcome was a composite of all-cause mortality after discharge and rehospitalization for heart failure. After matching, 125 patients with obstructive HCM hospitalized for SRT were compared to 743 patients hospitalized with non-obstructive HCM. The incidence rate (IR) of the primary outcome was lower in the SRT group {12.62 vs. 74.86 per 1000 patient-years (py); hazard ratio (HR), 0.17 [95% confidence interval (CI), 0.07-0.42]; median follow-up 31 months}. In the second comparison, 126 patients with obstructive HCM undergoing SRT were matched to 560 surgical controls without heart disease undergoing laparoscopic appendectomy. The IR of the primary outcome after SRT was comparable to that of surgical controls without heart disease [12.61 vs. 8.09 per 1000 py; HR, 1.53 (95% CI, 0.56-4.18); median follow-up 41 months].Conclusion In this nationwide cohort study, SRT was associated with a lower incidence of all-cause mortality after discharge and rehospitalization for heart failure compared to patients hospitalized with non-obstructive HCM, with an incidence comparable to surgical controls without heart disease.

BACKGROUND:Adrenal crises (AC) are life-threatening emergencies for which epidemiological data remain scarce, particularly in older adults. We analyzed nationwide data on AC-related hospitalizations in Switzerland between 2012 and 2022 to determine incidence, clinical outcomes, and predictors of adverse events, emphasizing differences across age groups and etiologies of adrenal insufficiency. METHODS:We conducted a nationwide retrospective cohort study using hospital discharge data linked to the national death registry. The primary outcome was the incidence of AC hospitalizations; secondary outcomes were a composite endpoint of in-hospital mortality, intensive care unit (ICU) admission, and 30-day rehospitalization. We also assessed 1-year mortality and duration of hospital and ICU stay. RESULTS:We identified 2302 AC-related hospitalizations with incidence increasing over time, peaking in patients >80 years, with the steepest rise in those with central adrenal insufficiency. Compared with matched controls, AC was associated with higher odds of the secondary composite outcome (IRR 1.60; 95% confidence interval [CI] 1.48-1.73), primarily driven by ICU admissions (IRR 1.99; 95% CI 1.8-2.21). Patients with unspecified etiology of adrenal insufficiency had the highest odds for in-hospital mortality (IRR 1.8; 95% CI 1.48-2.19) and 1-year all-cause mortality (IRR 1.41; 95% CI 1.23-1.62). Key predictors of adverse outcomes included unspecified etiology of adrenal insufficiency, advanced age, male sex, arginine vasopressin deficiency, sepsis, and cancer. CONCLUSION:In Switzerland, AC-related hospitalizations have increased over the past decade, primarily driven by an increase in central adrenal insufficiency, likely linked to expanding glucocorticoid and immunotherapy use. Older adults remain disproportionately vulnerable to adverse outcomes.

Background:Meningitis and encephalitis are severe infections of the central nervous system (CNS) causing substantial morbidity and mortality. Contemporary nationwide data on epidemiological trends and outcomes are limited. Methods:We conducted a nationwide, retrospective cohort study using hospital discharge data from the Swiss National Health Registry. All hospitalizations for infectious meningitis and encephalitis between January 2012 and December 2021 were included. We assessed temporal and age-specific trends, pathogen distributions, and in-hospital outcomes using descriptive statistics and multivariable regression analysis. Results:Among 23 426 identified hospitalizations (10 160 for meningitis; 13 266 for encephalitis), the overall incidence of CNS infections increased from 22 to 34 per 100 000 inhabitants between 2012 and 2019, followed by a marked decline in 2020-2021. For meningitis, this decline was driven by reductions in pneumococcal (∼65%) and enteroviral (∼90%) infections. Enteroviral and streptococcal meningitis rates were highest in children younger than 10 years, whereas Streptococcus pneumoniae, Listeria monocytogenes, tick-borne encephalitis virus, and varicella-zoster virus infections were more frequent in adults older than 50 years. Compared with viral meningitis, bacterial meningitis was associated with higher odds of intensive care unit admissions (odds ratio [OR], 8.40; 95% confidence interval [CI], 7.29 to 9.67) and in-hospital mortality (OR 4.23; 95% CI, 2.95 to 6.05). Similar risk patterns were observed for bacterial encephalitis. Conclusions:Nationwide hospitalization rates for CNS infections showed distinct temporal and age-specific patterns. Bacterial infections, particularly among older adults, were associated with substantially worse outcomes, underscoring the importance of early diagnosis, optimized treatment, and preventive strategies, including vaccination.

Purpose:Hyponatremia remains one of the most prevalent electrolyte disorders among geriatric inpatients but is frequently under-recognized in clinical coding. This cost-of-illness (COI) study aimed to (1) estimate the corrected prevalence of uncoded hyponatremia (ucHn) by integrating laboratory and administrative data, and (2) quantify its incremental social and economic burden on elderly patients. Patients and Methods:A retrospective COI analysis covered 72,730 inpatient cases ≥70 years (2016-2024) in a Swiss hospital network. Hyponatremia was classified as coded (cHn; ICD-10 E87.1) or uncoded (ucHn; Na <135 mmol/L). Incremental costs were estimated via generalized linear models and probabilistic sensitivity analysis. Results:Among 13,657 patients with hyponatremia (18.7%), only 2,070 (2.8%) were coded. Prevalences were as follows: coded 2.8%, hidden15.9%, true prevalence 18.7%. ucHn was more prevalent in men (p<0.0001), presented with more mild cases (83.1/34.9%, p<0.0001), more incident cases (14.3/4.7%, p<0.0001), lower chronic hyponatremia (20.8/39.6% p<0.0001), significantly more frequent heart failure and lung cancer (p<0.0001), had higher asset cost (2,463 vs 1,654, p<0.0001), lower contribution margin 1 and 2 (p<0.0001) and a markedly higher 30-day mortality (46% vs 7%, p<0.0001). Mean length of stay (LOS) was 9.9 days vs 7.4 days (p<0.0001). ucHn generated incremental costs of CHF per case with a total systemic burden (2016-2024) amounted to ≈ 355 to 473 MCHF. Losses of autonomy, mobility, cognitive control and life years underline the impressive social impact for nearly every ucHn case. Conclusion:For the first time, the detected ucHn is evaluated. It presents a substantial social and economic burden with a previously unquantified excess mortality associated with uncoded hyponatremia. ucHn is widely underestimated in administrative hospital data. This COI study supports policy measures to improve documentation and awareness of hyponatremia in elderly patients with the aim of reducing its social impact.

Introduction Malnutrition is a highly prevalent chronic condition that contributes to higher morbidity and mortality in patients with multiple comorbidities. While positive effects of nutritional therapy in the in-hospital setting have recently been demonstrated, the benefits of long-term nutritional therapy after hospital discharge remain uncertain. Herein, we outline the design and rationale of the EFFORTII trial, the largest nutritional trial to date to assess the effects of continued nutritional support after hospital discharge in medical patients, with particular attention to key design decisions regarding nutritional strategy, patient selection criteria and study endpoints.Methods and analysis The Effect of Continued Nutritional Support at Hospital Discharge on Mortality, Frailty, Functional Outcomes and Recovery (EFFORTII) is an investigator-initiated, non-commercial randomised controlled trial designed to evaluate whether ongoing, individualised nutritional therapy after hospital discharge—targeted to meet specific energy and protein requirements—offers a cost-effective approach to lowering mortality, minimising complications and maintaining functional status compared with standard care. Eligible participants are adult, chronically ill medical inpatients at risk of malnutrition. Patients in the intervention group receive individualised nutritional therapy delivered by an experienced dietitian through a combination of telemedicine and in-person consultations. The intervention aims to meet personalised nutritional targets, supported by a trained dietitian. Control group patients receive nutritional counselling at discharge, but no structured nutritional management during follow-up. We designed the trial as an event-driven trial with a target of 247 mortality events (primary endpoint), which will be assessed over approximately 5 years until event-driven endpoint is met. The minimum total sample size is at least 802 participants, based on the assumed treatment HR of 0.70. The main trial is enrolling patients across multiple sites in Switzerland. During the trial, additional sites in Spain joined the study, and their data will be analysed using a patient-level pooled approach.Ethics and dissemination This study involves human participants and was first granted ethical approval by the Ethics Committee Northwest- and Central Switzerland and then by all participating local ethics committees. Written informed consent will be obtained from all participants. Findings will be disseminated in peer-reviewed journals and academic conferences.Trial registration number NCT04926597.

Code status discussions are often inadequate, omitting key information on prognosis and resuscitation risks. In the randomized controlled CLEAR trial, use of a checklist to guide shared decision-making for code status discussions improved the quality of care by reducing patients’ uncertainty and increasing their satisfaction with discussions and knowledge of this topic. Moreover, a higher rate of “do-not-resuscitate” (DNR) code status preference was observed during the index hospital stay. The present analysis evaluates whether these effects were sustained over time. To evaluate the documented code status (primary outcome) and exploratory secondary outcomes, including patients’ general knowledge about resuscitation measures after a mean follow-up time of 3.2 years, assessed by telephone interview. Long-term follow-up of a prospective, randomized controlled study. Of the 1954 medical inpatients in the previous CLEAR trial, 604 had died and 10 were excluded due to missing information, leaving 1340 patients for analysis (mean age 65.0 (SD ± 16.3) years, 44.1

Protein is a central component of artificial nutrition, yet its optimal dose and timing remain controversial. Provision of both insufficient and excessive protein is associated with adverse outcomes. Inadequate intake promotes negative nitrogen balance, muscle wasting, impaired tissue healing and repair, and increased risk of infection, whereas excessive protein may exceed metabolic capacity, causing azotemia, hepatic or renal strain, and reduced metabolic flexibility — particularly in patients with renal dysfunction. Emerging evidence indicates that the optimal protein dose is strongly influenced by patient-specific characteristics and evolves throughout the course of illness, supporting an individualized, phase-adapted strategy for protein provision rather than a fixed universal target. During early critical illness, catabolism predominates and high protein doses may not be effectively utilized. In contrast, during recovery and stabilization, higher protein targets appear beneficial for restoring lean body mass and functional capacity. This dynamic trajectory underscores the need to abandon universal recommendations in favor of personalized prescriptions. Although instruments such as nitrogen balance, body composition analysis, and indirect calorimetry can provide information about protein dosage, their routine use in clinical practice is limited and interpretation in acute illnesses remains difficult. Pragmatic, bedside strategies and the phenotyping of patients using biomarkers are, therefore, needed to tailor protein provision according to disease stage, organ function, and anabolic capacity.This opinion paper explores mechanistic insights, evidence from clinical trials, and guidelines on protein supplementation, explores biomarker-driven personalization, and highlights ongoing challenges and future research priorities in nutritional therapy.

Code status discussions represent a fundamental aspect of advanced care planning and impose major challenges for clinicians in patients for whom cardiopulmonary resuscitation (CPR) is considered futile. To investigate the effect of a structured communication approach in code status discussions on decisions regarding code status and various quality-of-care measures for patients in whom resuscitation is considered futile. The GUIDE trial is a multicenter randomized clinical trial, which included patients deemed futile regarding CPR measures. The study was conducted between June 1, 2019, and April 30, 2023, in medical inpatients wards across 6 Swiss teaching hospitals. Medical inpatients for whom CPR measures were considered futile based on a prearrest Good Outcome Following Attempted Resuscitation score of 14 or higher or a Clinical Frailty Scale score of 7 or higher were eligible. Patients with cognitive or physical condition hindering meaningful conversation were excluded. Main outcomes included patients’ code status decisions as well as preference for mechanical ventilatory assistance and intensive care unit admission. Additional outcomes assessed patients’ psychological burden after the discussion measured by the State-Trait Anxiety Inventory and Hospital Anxiety and Depression scale and physicians’ perception regarding the discussions. A total of 177 patients (mean [SD] age, 76.3 [12.0] years; 90 [51%] female) were studied. Overall, the rate of do-not-resuscitate orders was 85%. No significant difference was observed between groups (checklist vs usual care group, 79 of 89 [89%] vs 72 of 88 [82%]; odds ratio, 1.76; 95% CI, 0.75-4.12; P = .20). However, patients in the checklist group were less likely to prefer intensive care unit admission compared with usual care (31 of 89 [36%] vs 44 of 88 [52%]; odds ratio, 0.53; 95% CI, 0.29-0.99; P = .046). Physicians perceived code status discussions using the checklist less challenging (mean [SD], 3.5 [2.8] vs 4.7 [2.8]; difference, −1.23; 95% CI, −2.1 to −0.35; P = .006). There was no significant difference in patients’ psychological reaction to code status discussions measured by State-Trait Anxiety Inventory and Hospital Anxiety and Depression scale. This analysis of a randomized clinical trial found that checklist-guided code status discussions in patients for whom CPR was considered futile reduced their preference for intensive care unit admission while alleviating physicians’ challenges during code status discussions without adversely affecting patients’ psychosocial burden. ClinicalTrials.gov Identifier: NCT03872154