Major mistakes or errors in the use of trial sequential analysis in systematic reviews or meta-analyses - the METSA systematic review.

BACKGROUND: Systematic reviews and data synthesis of randomised clinical trials play a crucial role in clinical practice, research, and health policy. Trial sequential analysis can be used in systematic reviews to control type I and type II errors, but methodological errors including lack of protocols and transparency are cause for concern. We assessed the reporting of trial sequential analysis. METHODS: We searched Medline and the Cochrane Database of Systematic Reviews from 1 January 2018 to 31 December 2021 for systematic reviews and meta-analysis reports that include a trial sequential analysis. Only studies with at least two randomised clinical trials analysed in a forest plot and a trial sequential analysis were included. Two independent investigators assessed the studies. We evaluated protocolisation, reporting, and interpretation of the analyses, including their effect on any GRADE evaluation of imprecision. RESULTS: We included 270 systematic reviews and 274 meta-analysis reports and extracted data from 624 trial sequential analyses. Only 134/270 (50%) systematic reviews planned the trial sequential analysis in the protocol. For analyses on dichotomous outcomes, the proportion of events in the control group was missing in 181/439 (41%), relative risk reduction in 105/439 (24%), alpha in 30/439 (7%), beta in 128/439 (29%), and heterogeneity in 232/439 (53%). For analyses on continuous outcomes, the minimally relevant difference was missing in 125/185 (68%), variance (or standard deviation) in 144/185 (78%), alpha in 23/185 (12%), beta in 63/185 (34%), and heterogeneity in 105/185 (57%). Graphical illustration of the trial sequential analysis was present in 93% of the analyses, however, the Z-curve was wrongly displayed in 135/624 (22%) and 227/624 (36%) did not include futility boundaries. The overall transparency of all 624 analyses was very poor in 236 (38%) and poor in 173 (28%). CONCLUSIONS: The majority of trial sequential analyses are not transparent when preparing or presenting the required parameters, partly due to missing or poorly conducted protocols. This hampers interpretation, reproducibility, and validity. STUDY REGISTRATION: PROSPERO CRD42021273811.

New randomized controlled trials on micronutrients in critical care nutrition: A narrative review.

There has been increasing interest in the role of micronutrient supplementation in critical care. This narrative review summarizes the recent studies on micronutrients in critically ill patients. We searched two databases for primary randomized controlled trials that investigated the effects of micronutrient supplementation in patients with critical illness published from January 2021 to August 2023. Personal files, reference lists of included studies, and previous reviews were also screened. Twelve studies reported on vitamin C, four studies on vitamin D, three studies on thiamin, two studies on multivitamins, and one study on cobalamin. The therapeutic effects of vitamin C appear mixed, although vitamin C monotherapy appears more promising than vitamin C combination therapy. Intramuscular administration of vitamin D appeared to lower mortality, mechanical ventilation duration, and intensive care unit stay, whereas enteral administration showed limited clinical benefits. Intravenous thiamin was not associated with improved outcomes in patients with septic shock or hypophosphatemia. Preliminary evidence suggests reduced vasopressor dose with cobalamin. Decreased disease severity and hospital stay in patients with COVID-19 with vitamins A-E requires further investigation, whereas providing solely B-group vitamins did not demonstrate therapeutic effects. It is currently premature to endorse the provision of high-dose micronutrients in critical illness to improve clinical outcomes. This review may help to inform the design of future trials that will help better elucidate the optimal dosage and form of micronutrients, methods of administration, and subgroups of patients with critical illness who may most benefit.

Early protein delivery in critically ill patients with acute kidney injury: post hoc analysis of a multicenter cluster-randomized controlled trial.

Background: There is controversy over the optimal early protein delivery in critically ill patients with acute kidney injury (AKI). This study aims to evaluate whether the association between early protein delivery and 28-day mortality was impacted by the presence of AKI in critically ill patients. Methods: This is a post hoc analysis of data from a multicenter cluster-randomised controlled trial enrolling newly admitted critically ill patients (n = 2772). Participants without chronic kidney disease and with complete data concerning baseline renal function were included in this study. The primary outcome was 28-day mortality. Cox proportional hazards models were used to analyze the association between early protein delivery, reflected by mean protein delivery from day 3-5 after enrollment, 28-day mortality and whether baseline AKI stages interacted with this association. Results: Overall, 2552 patients were included, among whom 567 (22.2%) had AKI at enrollment (111 stage I, 87 stage II, 369 stage III). Mean early protein delivery was 0.60 ± 0.38 g/kg/day among the study patients. In the overall study cohort, each 0.1 g/kg/day increase in protein delivery was associated with a 5% reduction in 28-day mortality[hazard ratio (HR) = 0.95; 95% confidence interval (CI) 0.92-0.98, p < 0.001]. The association between early protein delivery and 28-day mortality significantly interacted with baseline AKI stages (adjusted interaction p = 0.028). Each 0.1 g/kg/day increase in early protein delivery was associated with a 4% reduction in 28-day mortality (HR = 0.96; 95%CI 0.92-0.99, p = 0.011) among patients without AKI and 9% (HR = 0.91; 95%CI 0.84-0.99, p = 0.021) among those with AKI stage III. However, such associations cannot be observed among patients with AKI stages I and II. Conclusions: Increased early protein delivery (up to close to the guideline recommendation) was associated with reduced 28-day mortality in critically ill patients without AKI and with AKI stage III, but not in those with AKI stage I or II.

The Association Between Malnutrition and High Protein Treatment on Outcomes in Critically Ill Patients: A Post Hoc Analysis of the EFFORT Protein Randomized Trial.

BACKGROUND: Preexisting malnutrition in critically ill patients is associated with adverse clinical outcomes. Malnutrition can be diagnosed with the Global Leadership Initiative on Malnutrition using parameters such as weight loss, muscle wasting, and BMI. International critical care nutrition guidelines recommend high protein treatment to improve clinical outcomes in critically ill patients diagnosed with preexisting malnutrition. However, this recommendation is based on expert opinion. RESEARCH QUESTION: In critically ill patients, what is the association between preexisting malnutrition and time to discharge alive (TTDA), and does high protein treatment modify this association? STUDY DESIGN AND METHODS: This multicenter randomized controlled trial involving 16 countries was designed to investigate the effects of high vs usual protein treatment in 1,301 critically ill patients. The primary outcome was TTDA. Multivariable regression was used to identify if preexisting malnutrition was associated with TTDA and if protein delivery modified their association. RESULTS: The prevalence of preexisting malnutrition was 43.8%, and the cumulative incidence of live hospital discharge by day 60 was 41.2% vs 52.9% in the groups with and without preexisting malnutrition, respectively. The average protein delivery in the high vs usual treatment groups was 1.6 g/kg per day vs 0.9 g/kg per day. Preexisting malnutrition was independently associated with slower TTDA (adjusted hazard ratio, 0.81; 95% CI, 0.67-0.98). However, high protein treatment in patients with and without preexisting malnutrition was not associated with TTDA (adjusted hazard ratios of 0.84 [95% CI, 0.63-1.11] and 0.97 [95% CI, 0.77-1.21]). Furthermore, no effect modification was observed (ratio of adjusted hazard ratio, 0.84; 95% CI, 0.58-1.20). INTERPRETATION: Malnutrition was associated with slower TTDA, but high protein treatment did not modify the association. These findings challenge current international critical care nutrition guidelines. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03160547; URL: www. CLINICALTRIALS: gov.

The effects of higher versus lower protein delivery in critically ill patients: an updated systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent large multicentre trial found no difference in clinical outcomes but identified a possibility of increased mortality rates in patients with acute kidney injury (AKI) receiving higher protein. These alarming findings highlighted the urgent need to conduct an updated systematic review and meta-analysis to inform clinical practice. METHODS: From personal files, citation searching, and three databases searched up to 29-5-2023, we included randomized controlled trials (RCTs) of adult critically ill patients that compared higher vs lower protein delivery with similar energy delivery between groups and reported clinical and/or patient-centred outcomes. We conducted random-effect meta-analyses and subsequently trial sequential analyses (TSA) to control for type-1 and type-2 errors. The main subgroup analysis investigated studies with and without combined early physical rehabilitation intervention. A subgroup analysis of AKI vs no/not known AKI was also conducted. RESULTS: Twenty-three RCTs (n = 3303) with protein delivery of 1.49 ± 0.48 vs 0.92 ± 0.30 g/kg/d were included. Higher protein delivery was not associated with overall mortality (risk ratio [RR]: 0.99, 95% confidence interval [CI] 0.88-1.11; I2 = 0%; 21 studies; low certainty) and other clinical outcomes. In 2 small studies, higher protein combined with early physical rehabilitation showed a trend towards improved self-reported quality-of-life physical function measurements at day-90 (standardized mean difference 0.40, 95% CI - 0.04 to 0.84; I2 = 30%). In the AKI subgroup, higher protein delivery significantly increased mortality (RR 1.42, 95% CI 1.11-1.82; I2 = 0%; 3 studies; confirmed by TSA with high certainty, and the number needed to harm is 7). Higher protein delivery also significantly increased serum urea (mean difference 2.31 mmol/L, 95% CI 1.64-2.97; I2 = 0%; 7 studies). CONCLUSION: Higher, compared with lower protein delivery, does not appear to affect clinical outcomes in general critically ill patients but may increase mortality rates in patients with AKI. Further investigation of the combined early physical rehabilitation intervention in non-AKI patients is warranted. PROSPERO ID: CRD42023441059.

Macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2: A narrative review.

BACKGROUND: COVID-19 can lead to critical illness and induce hypermetabolism, protein catabolism, and inflammation. These pathological processes may alter energy and protein requirements, and certain micronutrients may attenuate the associated detriments. This narrative review summarizes the macronutrient and micronutrient requirements and therapeutic effects in critically ill patients with SARS-CoV-2. METHODS: We searched four databases for randomized controlled trials (RCTs) and studies that measured macronutrient and micronutrient requirements, published from February 2020 to September 2022. RESULTS: Ten articles reported on energy and protein requirements, and five articles reported the therapeutic effects of ω-3 (n = 1), group B vitamins (n = 1), and vitamin C (n = 3). Patients' resting energy expenditure gradually increased with time, measuring approximately 20 kcal/kg body weight (BW), 25 kcal/kg BW, and 30 kcal/kg BW for the first, second, and third week onwards, respectively. Patients remained in negative nitrogen balances in the first week, and a protein intake of ≥1.5 g/kg BW may be necessary to achieve nitrogen equilibrium. Preliminary evidence suggests that ω-3 fatty acids may protect against renal and respiratory impairments. The therapeutic effects of group B vitamins and vitamin C cannot be ascertained, although intravenous vitamin C appears promising in reducing mortality and inflammation. CONCLUSION: There are no RCTs to guide the optimal dose of energy and protein in critically ill patients with SARS-CoV-2. Additional larger-scale, well-designed RCTs are needed to elucidate the therapeutic effects of ω-3, group B vitamins, and vitamin C.

Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: A recent landmark randomized controlled trial (RCT) in septic patients demonstrated an increased risk of death and persistent organ dysfunction with intravenous Vitamin C (IVVC) monotherapy, which represents a disparate result from previous systematic reviews and meta-analyses (SRMA). We performed an updated SRMA of IVVC monotherapy to summarize and explore heterogeneity across current trials and conduct trial sequential analysis (TSA) to guard against type-I or type-II statistical errors. METHODS: RCTs evaluating IVVC in adult critically ill patients were included. Four databases were searched from inception to 22 June 2022 without language restrictions. The primary outcome was overall mortality. Random effect meta-analysis was performed to estimate the pooled risk ratio. TSA for mortality was performed using the DerSimonian-Laird random effect model, alpha 5%, beta 10%, and relative risk reduction (RRR) of 30%, 25%, and 20%. RESULTS: We included 16 RCTs (n = 2130). IVVC monotherapy is associated with significant reduction in overall mortality [risk ratio (RR) 0.73, 95% confidence interval (CI) 0.60-0.89; p = 0.002; I2 = 42%]. This finding is supported by TSA using RRR of 30% and 25%, and sensitivity analysis using fixed-effect meta-analysis. However, the certainty of our mortality finding was rated low using GRADE due to the serious risk of bias and inconsistency. In a priori subgroup analyses, we found no differences between single vs multicenter, higher (≥ 10,000 mg/day) vs lower dose and sepsis vs non-sepsis trials. Post-hoc, we found no differences in subgroup analysis of earlier (< 24 h) vs delayed treatment, longer (> 4 days) vs shorter treatment duration, and low vs other risk of bias studies. IVVC may have the greatest benefit in trials that enrolled patients above (i.e., > 37.5%; RR 0.65, 95% CI 0.54-0.79) vs below (i.e., ≤ 37.5%; RR 0.89, 95% CI 0.68-1.16) median control group mortality (test for subgroup differences: p = 0.06), and TSA supported this. CONCLUSIONS: IVVC monotherapy may be associated with mortality benefits in critically ill patients, particularly in patients with a high risk of dying. Given the low certainty of evidence, this potentially life-saving therapy warrants further studies to identify the optimal timing, dosage, treatment duration, and patient population that will benefit most from IVVC monotherapy. PROSPERO Registration ID: CRD42022323880. Registered 7th May 2022.

Benefits and harm of probiotics and synbiotics in adult critically ill patients. A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND & AIMS: Several systematic reviews and meta-analyses of randomized controlled trials concluded that probiotics administration in critically ill patients was safe and associated with reduced rates of ventilator-associated pneumonia and diarrhea. However, a recent large multicenter trial found probiotics administration, compared to placebo, was not efficacious and increased adverse events. An updated meta-analysis that controls for type-1 and -2 errors using trial sequential analysis, with a detailed account of adverse events associated with probiotic administration, is warranted to confirm the safety and efficacy of probiotic use in critically ill patients. METHODS: RCTs that compared probiotics or synbiotics to usual care or placebo and reported clinical and diarrheal outcomes were searched in 4 electronic databases from inception to March 8, 2022 without language restriction. Four reviewers independently extracted data and assessed the study qualities using the Critical Care Nutrition (CCN) Methodological Quality Scoring System. Random-effect meta-analysis and trial sequential analysis (TSA) were used to synthesize the results. The primary outcome was ventilator-associated pneumonia (VAP). The main subgroup analysis compared the effects of higher versus lower quality studies (based on median CCN score). RESULTS: Seventy-five studies with 71 unique trials (n = 8551) were included. In the overall analysis, probiotics significantly reduced VAP incidence (risk ratio [RR] 0.70, 95% confidence interval [CI] 0.56-0.88; I2 = 65%; 16 studies). However, such benefits were demonstrated only in lower (RR 0.47, 95% CI 0.32, 0.69; I2 = 44%; 7 studies) but not higher quality studies (RR 0.89, 95% CI 0.73, 1.08; I2 = 43%; 9 studies), with significant test for subgroup differences (p = 0.004). Additionally, TSA showed that the VAP benefits of probiotics in the overall and subgroup analyses were type-1 errors. In higher quality trials, TSA found that future trials are unlikely to demonstrate any benefits of probiotics on infectious complications and diarrhea. Probiotics had higher adverse events than control (pooled risk difference: 0.01, 95% CI 0.01, 0.02; I2 = 0%; 22 studies). CONCLUSION: High-quality RCTs did not support a beneficial effect of probiotics on clinical or diarrheal outcomes in critically ill patients. Given the lack of benefits and the increased incidence of adverse events, probiotics should not be routinely administered to critically ill patients. PROSPERO REGISTRATION: CRD42022302278.

Nutrition therapy in the older critically ill patients: A scoping review.

INTRODUCTION: There is a lack of guidelines or formal systematic synthesis of evidence for nutrition therapy in older critically ill patients. This study is a scoping review to explore the state of evidence in this population. METHOD: MEDLINE and Embase were searched from inception until 9 February 2022 for studies that enrolled critically ill patients aged ≥60 years and investigated any area of nutrition therapy. No language or study design restrictions were applied. RESULTS: Thirty-two studies (5 randomised controlled trials) with 6 topics were identified: (1) nutrition screening and assessments, (2) muscle mass assessment, (3) route or timing of nutrition therapy, (4) determination of energy and protein requirements, (5) energy and protein intake, and (6) pharmaconutrition. Topics (1), (3) and (6) had similar findings among general adult intensive care unit (ICU) patients. Skeletal muscle mass at ICU admission was significantly lower in older versus young patients. Among older ICU patients, low muscularity at ICU admission increased the risk of adverse outcomes. Predicted energy requirements using weight-based equations significantly deviated from indirect calorimetry measurements in older vs younger patients. Older ICU patients required higher protein intake (>1.5g/kg/day) than younger patients to achieve nitrogen balance. However, at similar protein intake, older patients had a higher risk of azotaemia. CONCLUSION: Based on limited evidence, assessment of muscle mass, indirect calorimetry and careful monitoring of urea level may be important to guide nutrition therapy in older ICU patients. Other nutrition recommendations for general ICU patients may be used for older patients with sound clinical discretion.

Nutrition support practices for critically ill patients with severe acute respiratory syndrome coronavirus-2: A multicentre observational study in Singapore.

INTRODUCTION: To improve the nutritional care and resource allocation of critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), we described their characteristics, treatment modalities and clinical outcomes, and compared their nutrition interventions against the American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations. METHODS: This was a retrospective observational study conducted in 5 tertiary hospitals in Singapore. Characteristics, treatment modalities, clinical outcomes and nutrition interventions of critically ill patients with SARS-CoV-2 who received enteral and parenteral nutrition were collected between January and May 2020. RESULTS: Among the 83 critically ill patients with SARS-CoV-2, 22 (28%) were obese, 45 (54%) had hypertension, and 21 (25%) had diabetes. Neuromuscular blockade, prone therapy and dialysis were applied in 70% (58), 47% (39) and 35% (29) of the patients, respectively. Refeeding hypophosphataemia and hospital mortality occurred respectively in 6% (5) and 18% (15) of the critically ill patients with SARS-CoV-2. Late enteral nutrition and cardiovascular comorbidities were associated with higher hospital mortality (adjusted relative risk 9.00, 95% confidence interval [CI] 2.25-35.99; 6.30, 95% CI 1.15-34.40, respectively). Prone therapy was not associated with a higher incidence of high gastric residual volume (≥250mL). The minimum caloric (15kcal/kg) and protein (1.2g/kg) recommendations of ASPEN were achieved in 54% (39) and 0% of the patients, respectively. CONCLUSION: The high obesity prevalence and frequent usage of neuromuscular blockade, prone therapy, and dialysis had considerable implications for the nutritional care of critically ill patients with SARS-CoV-2. They also did not receive adequate calories and protein. More audits should be conducted to refine nutritional interventions and guidelines for this ever-evolving disease.

Correlation between gastric residual volumes and markers of gastric emptying: A post hoc analysis of a randomized clinical trial.

BACKGROUND: The correlation between gastric residual volumes (GRVs) and markers of gastric emptying (GE) in critically ill patients is unclear. This particularly applies to critically ill surgical patients, as they are underrepresented in previous studies. METHODS: We conducted a post hoc analysis of a multicenter trial that investigated the effectiveness of a promotility drug. Pharmacokinetic markers of GE (3-O-methylglucose [3-OMG] and acetaminophen) were correlated with GRV measurements. High GRV was defined as one episode of >400 ml or two consecutive episodes of >250 ml, and delayed GE was defined as <20th percentile of the pharmacokinetic GE marker that had the strongest correlation with GE. RESULTS: Of 77 patients, 8 (10.4%) had high GRV, and 15 (19.5%) had delayed GE. The 3-OMG concentration at 60 min had the strongest correlation with GRV (ρ = -0.631), and high GRV had low sensitivity (46.7%) but high specificity (98.4%) in discriminating delayed GE. The positive (87.5%) and negative (88.4%) predictive values were similar. Compared with medical patients, surgical patients (n = 14, 18.2%), had a significantly higher incidence of high GRV (29% vs 6%, P = .032) and a trend toward delayed GE (36% vs 16%, P = .132). CONCLUSION: GRV reflects GE, and high GRV is an acceptable surrogate marker of delayed GE. From our preliminary observation, surgical patients may have a higher risk of high GRV and delayed GE. In summary, GRV should be monitored to determine whether complex investigations or therapeutic interventions are warranted.

Bone mineral density following liver transplantation: a 10-year trend analysis.

We evaluated the prevalence of osteoporosis and annual changes in bone mineral density (BMD) over 10 years post-liver transplantation. BMD in the lumbar spine improved significantly post-transplantation, reaching a 12% increase at year 10. In contrast, BMD in the femoral neck and hip deteriorated and did not return to baseline levels. INTRODUCTION: This study (1) evaluated the prevalence of osteoporosis, and the annual changes in bone mineral density (BMD) over 10 years, and (2) identified the risk factors for worsened BMD in stable liver transplant recipients (LTRs). METHODS: LTRs who underwent liver transplantation (LT) at Singapore General Hospital between February 2006 and Mar 2019 were included. Demographic, clinical data, and BMD in the lumbar spine (LS), femoral neck (FN), and total hip (TH) were collected retrospectively from the medical records. RESULTS: Eighty-three patients (mean age: 55 ± 8 years) with a median follow-up of 80 months were included. The prevalence of osteoporosis increased significantly from 18.1% pre-LT to 34.3% post-LT (p = 0.021), and the incidence of osteoporosis was 18.2%. Worsened BMD (normal to osteopenia/osteopenia to osteoporosis) was found in 27.2% of LTRs. No significant risk factors were associated with worsened BMD, but females had a trend towards a higher odd (adjusted odds ratio: 3.54, 95%CI (0.61-20.5), p = 0.159). The LS BMD increased within 6-month post-LT and continued to improve throughout the entire follow-up period. In contrast, BMD in the FN and TH deteriorated and did not return to baseline levels post-LT. CONCLUSION: Prevalence of osteoporosis increased significantly post-LT. Over a 10-year follow-up, 27.2% of LTRs had worsened BMD status, and a possible risk factor may be female gender. While the LS BMD improved with time, the BMD in the FN and TH persisted below baseline throughout the follow-up period. Future studies should explore long-term therapies to improve BMD in the FN and TH post-LT.

A systematic review of the malnutrition prevalence in hospitalized hip fracture patients and its associated outcomes.

BACKGROUND: Malnutrition is associated with poorer outcomes in hospitalized patients. However, in hip fracture patients, the associations between malnutrition and poorer outcomes are unclear because of the use of nonestablished nutrition assessment tools in previous studies that may have some degree of misclassification bias. Therefore, this review aims to determine (1) the prevalence of malnutrition diagnosed in hospitalized hip fracture patients using established nutrition assessment tools and (2) the outcomes associated with malnutrition given some of the nonestablished nutrition assessment tools used in previous studies. METHODS: Four electronic databases were used. Studies that used established nutrition assessment tools to diagnose malnutrition in hip fracture patients within 48 h of hospital admission were included. RESULTS: Nine studies were included (n = 1665). Patients' mean age ranged from 79.9 to 86.1 years. Eight studies reported the frequencies of each sex, and for females, it ranged from 70% to 81.8%. The prevalence of malnutrition was 4.0% to 39.4%. Malnutrition was independently associated with (1) increased mortality and (2) functional dependence. There was also a trend towards more supported living arrangements and impaired mobility in the longer term. Malnutrition was not associated with (1) hospital length of stay, (2) hospital readmissions, and (3) incidence of complications. CONCLUSION: The prevalence of malnutrition in hip fracture patients is highly variable and is associated with poorer outcomes. Therefore, identifying malnourished hip fracture patients using established nutrition assessment tools is important, and adequate resources can be allocated to prevent malnutrition through early screening and intervention.

Singapore multidisciplinary consensus recommendations on muscle health in older adults: assessment and multimodal targeted intervention across the continuum of care.

BACKGROUND: The rapidly aging societies worldwide and in Singapore present a unique challenge, requiring an integrated multidisciplinary approach to address high-value targets such as muscle health. We propose pragmatic evidence-based multidisciplinary consensus recommendations for the assessment and multi-modal management of muscle health in older adults (≥65 years) across the continuum of care. METHODS: The recommendations are derived from an in-depth review of published literature by a multidisciplinary working group with clinical experience in the care of the older population in both acute and community settings. RESULTS: The panel recommends screening for muscle impairment using the SARC-F questionnaire, followed by assessment for low muscle strength (handgrip strength or 5-times chair stand test ≥10 s as a surrogate for lower limb strength) to diagnose possible/probable sarcopenia. For uncomplicated cases, lifestyle modifications in exercise and diet can be initiated in the community setting without further assessment. Where indicated, individuals diagnosed with possible/probable sarcopenia should undergo further assessment. Diagnosis of sarcopenia should be based on low muscle strength and low muscle mass (bioimpedance analysis, dual-energy X-ray absorptiometry or calf circumference as a surrogate). The severity of sarcopenia should be determined by assessment of physical performance (gait speed or 5-times chair stand test ≥12 s as a surrogate for gait speed). To treat sarcopenia, we recommend a combination of progressive resistance-based exercise training and optimization of nutritional intake (energy, protein and functional ingredients). High quality protein in sufficient quantity, to overcome anabolic resistance in older adults, and distributed throughout the day to enable maximum muscle protein synthesis, is essential. The addition of resistance-based exercise training is synergistic in improving the sensitivity of muscle protein synthesis response to the provision of amino acids and reducing anabolic resistance. An expected dose-response relationship between the intensity of resistance-based training, lean mass and muscle strength is described. CONCLUSIONS: Reviewed and endorsed by the Society of Rehabilitation Medicine Singapore and the Singapore Nutrition and Dietetics Association, these multidisciplinary consensus recommendations can provide guidance in the formulation of comprehensive and pragmatic management plans to improve muscle health in older adults in Singapore and Asia.

Refeeding Hypophosphatemia in Patients Receiving Parenteral Nutrition: Prevalence, Risk Factors, and Predicting Its Occurrence.

BACKGROUND: Patients receiving parenteral nutrition (PN) support may develop refeeding hypophosphatemia (RH), and its prevalence is highly variable in the literature. Identifying at-risk patients is crucial to minimize clinical complications. The National Institute for Health and Clinical Excellence (NICE) guidelines are used widely to assess the risk of RH, but they lack validation. We aim to (1) identify the prevalence of RH by multiple diagnostic criteria; (2) assess the predictive ability of the NICE guidelines for RH; and (3) identify important risk factors for RH and evaluate their predictive abilities for RH in a new model. METHODS: This is a single-center retrospective study on adult patients with PN ≥48 hours. Prevalence of RH was determined by 4 established diagnostic criteria. Prognostic accuracy of the NICE guidelines were assessed by the area under the receiver operating characteristic (ROC) curve. Multivariable logistic regressions were performed to develop a new risk-assessment model. RESULTS: Of 149 enrolled patients, 23%-48% (35 to 72 of 149 patients) developed RH (depending on the diagnostic criteria used). The NICE guidelines demonstrated poor discrimination across all diagnostic criteria (ROC, 0.43-0.53). Critical illness, the use of diuretics, and hypomagnesemia prior to PN were independently associated with RH. These risk factors formed the new model for predicting RH and had good discrimination (ROC 0.74; 95% confidence interval, 0.66-0.82). CONCLUSION: Prevalence of RH varied according to established diagnostic criteria. The current NICE guidelines poorly predict the occurrence of RH, and modification is likely beneficial. A new risk-assessment model was developed; nevertheless, further validation is required.