From ICU Syndromes to ICU Subphenotypes: Consensus Report and Recommendations for Developing Precision Medicine in the ICU.

Critical care uses syndromic definitions to describe patient groups for clinical practice and research. There is growing recognition that a "precision medicine" approach is required and that integrated biologic and physiologic data identify reproducible subpopulations that may respond differently to treatment. This article reviews the current state of the field and considers how to successfully transition to a precision medicine approach. To impact clinical care, identification of subpopulations must do more than differentiate prognosis. It must differentiate response to treatment, ideally by defining subgroups with distinct functional or pathobiological mechanisms (endotypes). There are now multiple examples of reproducible subpopulations of sepsis, acute respiratory distress syndrome, and acute kidney or brain injury described using clinical, physiological, and/or biological data. Many of these subpopulations have demonstrated the potential to define differential treatment response, largely in retrospective studies, and that the same treatment-responsive subpopulations may cross multiple clinical syndromes (treatable traits). To bring about a change in clinical practice, a precision medicine approach must be evaluated in prospective clinical studies requiring novel adaptive trial designs. Several such studies are underway, but there are multiple challenges to be tackled. Such subpopulations must be readily identifiable and be applicable to all critically ill populations around the world. Subdividing clinical syndromes into subpopulations will require large patient numbers. Global collaboration of investigators, clinicians, industry, and patients over many years will therefore be required to transition to a precision medicine approach and ultimately realize treatment advances seen in other medical fields.

Preferences for albumin use in adult intensive care unit patients with shock: An international survey.

INTRODUCTION: Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians. METHODS: We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the use versus no use of albumin. RESULTS: A total of 1248 respondents participated, with a mean response rate of 37%, ranging from 18% to 75% across 21 countries. Respondents mainly worked in mixed ICUs and 92% were specialists in intensive care medicine. The reported use of albumin in general shock varied as 18% reported 'almost never', 22% 'rarely', 34% 'occasionally', 22% 'frequently' and 4% 'almost always' using albumin. In septic shock, 19% reported 'almost never', 22% 'rarely', 29% 'occasionally', 22% 'frequently' and 7% 'almost always' using albumin. Physicians' preferences were more consistent for haemorrhagic- and cardiogenic shock, with more than 45% reporting 'almost never' using albumin. While the reported use of albumin for other purposes than resuscitation was infrequent (40%-85% reported 'almost never' for five other indications), the most frequent other indications were low serum albumin levels and improvement of the efficacy of diuretics. Most respondents (93%) would randomise adult ICU patients with shock to a trial of albumin versus no albumin. CONCLUSIONS: In this international survey, the reported preferences for the use of albumin in adult ICU patients with shock varied considerably among surveyed ICU physicians. The support for a future randomised trial was high.

The Effects of Early-Phase, Low- or Standard-Intensity Continuous Renal Replacement Therapy on Acid-Base Control and Clinical Outcomes: An Observational Study.

INTRODUCTION: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline recommends administering an effluent volume of 20-25 mL/kg/h during continuous renal replacement therapy (CRRT) for acute kidney injury. Recent evidence on CRRT initiation showed that less intervention might be beneficial for renal recovery. This study aimed to explore the association between early-phase low CRRT intensity and acid-base balance corrections and clinical outcomes. METHODS: This was a single-centre, retrospective, observational study at a tertiary intensive care unit (ICU) in Japan. All adult patients requiring CRRT in the ICU were included. Eligible patients were classified into the Low group (dialysate flow rate [QD] 10.0-19.9 mL/kg/h) and the Standard group (QD ≥20 mL/kg/h) by the intensity of CRRT at the beginning. The primary outcomes were acid-base parameters 6 h after CRRT initiation. We used an inverse probability of treatment weighting analysis to estimate the association between the intensity group and the outcomes. RESULTS: Overall, 194 patients were classified into the Low group (n = 144) and the Standard group (n = 50). The Standard group presented with more severe acid-base disturbances, including lower pH and base excess (BE) at baseline. At 6 h after CRRT initiation, pH, BE, and strong ion difference values were comparable, even after adjusting for baseline severity. Despite the efficient correction, no evident differences were observed in clinical outcomes between the two groups. CONCLUSIONS: The initial standard intensity appeared to be efficient in correcting acid-base imbalance at the early phase of CRRT; however, further studies are needed to assess the impact on clinical outcomes.

Dose of nafamostat mesylate during continuous kidney replacement therapy in critically ill patients: a two-centre observational study.

BACKGROUND: Nafamostat mesylate is an anticoagulant used for critically ill patients during continuous kidney replacement therapy (CKRT), characterised by its short half-life. However, its optimal dosage remains unclear. This study aimed to explore the optimal dosage of nafamostat mesylate during CKRT. METHODS: We conducted a two-centre observational study. We screened all critically ill adult patients who required CKRT in the intensive care unit (ICU) from September 2013 to August 2021; we included patients aged ≥ 18 years who received nafamostat mesylate during CKRT. The primary outcome was filter life, defined as the time from CKRT initiation to the end of the first filter use due to filter clotting. The secondary outcomes included safety and other clinical outcomes. The survival analysis of filter patency by the nafamostat mesylate dosage adjusted for bleeding risk and haemofiltration was performed using a Cox proportional hazards model. RESULTS: We included 269 patients. The mean dose of nafamostat mesylate was 15.8 mg/hr (Standard deviation (SD), 8.8; range, 5.0 to 30.0), and the median filter life was 18.3 h (Interquartile range (IQR), 9.28 to 36.7). The filter survival analysis showed no significant association between the filter life and nafamostat mesylate dosage (hazard ratio 1.12; 95 CI 0.74-1.69, p = 0.60) after adjustment for bleeding risk and addition of haemofiltration to haemodialysis. CONCLUSIONS: We observed no dose-response relationship between the dose of nafamostat mesylate (range: 5 to 30 mg/h) and the filter life during CKRT in critically ill patients. The optimal dose to prevent filter clotting safely needs further study in randomised controlled trials. TRIAL REGISTRATION: Not applicable.

Sodium Bicarbonate for Metabolic Acidosis in the ICU: Results of a Pilot Randomized Double-Blind Clinical Trial.

OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] < -4 mEq/L, and Pa co2 < 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-to-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference, -45.86 [95% CI, -63.11 to -28.61] hr; p < 0.001) and pH correction (median difference, -10.69 [95% CI, -19.16 to -2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI, -9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.

Update on the management of acute respiratory failure using non-invasive ventilation and pulse oximetry.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

The Sequential Organ Failure Assessment (SOFA) Score: has the time come for an update?

The Sequential Organ Failure Assessment (SOFA) score was developed more than 25 years ago to provide a simple method of assessing and monitoring organ dysfunction in critically ill patients. Changes in clinical practice over the last few decades, with new interventions and a greater focus on non-invasive monitoring systems, mean it is time to update the SOFA score. As a first step in this process, we propose some possible new variables that could be included in a SOFA 2.0. By so doing, we hope to stimulate debate and discussion to move toward a new, properly validated score that will be fit for modern practice.

Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline.

BACKGROUND: This Rapid Practice Guideline provides an evidence-based recommendation to address the question: in adults with sepsis or septic shock, should we recommend using or not using intravenous vitamin C therapy? METHODS: The panel included 21 experts from 16 countries and used a strict policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation approach, we evaluated the certainty of evidence and developed recommendations using the evidence-to-decision framework. We conducted an electronic vote, requiring >80% agreement among the panel for a recommendation to be adopted. RESULTS: At longest follow-up, 90 days, intravenous vitamin C probably does not substantially impact (relative risk 1.05, 95% confidence interval [CI] 0.94 to 1.17; absolute risk difference 1.8%, 95% CI -2.2 to 6.2; 6 trials, n = 2148, moderate certainty). Effects of vitamin C on mortality at earlier timepoints was of low or very low certainty due to risk of bias of the included studies and significant heterogeneity between study results. Few adverse events were reported with the use of vitamin C. The panel did not identify any major differences in other outcomes, including duration of mechanical ventilation, ventilator free days, hospital or intensive care unit length of stay, acute kidney injury, need for renal replacement therapy. Vitamin C may result in a slight reduction in duration of vasopressor support (MD -18.9 h, 95% CI -26.5 to -11.4; 21 trials, n = 2661, low certainty); but may not reduce sequential organ failure assessment scores (MD -0.69, 95% CI -1.55 to 0.71; 24 trials, n = 4002, low certainty). The panel judged the undesirable consequences of using IV vitamin C to probably outweigh the desirable consequences, and therefore issued a conditional recommendation against using IV vitamin C therapy in sepsis. CONCLUSIONS: The panel suggests against use of intravenous vitamin C in adult patients with sepsis, beyond that of standard nutritional supplementation. Small and single center trials on this topic should be discouraged.

Unfractionated heparin versus nafamostat mesylate for anticoagulation during continuous kidney replacement therapy: an observational study.

BACKGROUND: Unfractionated heparin sodium and nafamostat mesylate have long been used as anticoagulants in continuous kidney replacement therapy (CKRT) where citrate is unavailable. This study aimed to determine whether heparin or nafamostat mesylate used during CKRT was associated with a longer filter life. METHODS: In this single-centre observational study, we included adult patients who required CKRT and used heparin or nafamostat mesylate for their first CKRT in the intensive care unit from September 1, 2013, to December 31, 2020. The primary outcome was filter life (from the start to the end of using the first filter). We used propensity score matching to adjust for the imbalance in patients' characteristics and laboratory data at the start of CKRT and compared the outcomes between the two groups. We also performed restricted mean survival time analysis to compare the filter survival times. RESULTS: We included 286 patients, 157 patients on heparin and 129 patients on nafamostat mesylate. After propensity score matching, the mean filter life with heparin was 1.58 days (N = 91, Standard deviation [SD], 1.52) and with nafamostat mesylate was 1.06 days (N = 91, SD, 0.94, p = 0.006). Multivariable regression analysis adjusted for confounding factors supported that heparin was associated with a longer filter life compared with nafamostat mesylate (regression coefficient, days, 0.52 [95% CI, 0.15, 0.89]). The between group difference of the restricted mean filter survival time in the matched cohort was 0.29 (95% CI, 0.07-0.50, p = 0.008). CONCLUSION: Compared to nafamostat mesylate, heparin was associated with one-third to one-half a day longer filter life. TRIAL REGISTRATION: Not applicable.

Update on vitamin C administration in critical illness.

PURPOSE OF REVIEW: Several studies have recently explored the effects of intravenous vitamin C in sepsis. We aimed to summarize their findings to provide perspectives for future research. RECENT FINDINGS: Sepsis trials examined 6 g/day of intravenous vitamin C with or without the thiamine and/or hydrocortisone compared with placebo or hydrocortisone. Network meta-analysis reported that intravenous vitamin C, thiamine, hydrocortisone, or combinations of these drugs was not proven to reduce long-term mortality. However, the component network meta-analysis suggested an association of high-dose (>6 g/day) and very-high dose vitamin C (>12 g/day) and decreased mortality but with low certainty. The preclinical investigations have, however, advanced to much higher doses of intravenous vitamin C therapy since a scoping review on harm reported that mega-doses of intravenous vitamin C (50-100 g/day) had been administered without any conclusive adverse effects. In a Gram-negative sheep model, renal tissue hypoperfusion was reversed, followed by improvements in kidney function when a mega-dose of vitamin C (150 g/day equivalent) was administered. SUMMARY: The effect of intravenous vitamin C in critically ill patients has yet to be determined and might be dose-dependent. Clinical studies of very high or mega doses of vitamin C are justified by preclinical data.

How to Prolong Filter Life During Continuous Renal Replacement Therapy?

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Prevalence and municipal variation in chronic musculoskeletal pain among independent older people: data from the Japan Gerontological Evaluation Study (JAGES).

BACKGROUND: Urbanization and population aging may affect prevalence of chronic pain from various causes. This cross-sectional study aimed to investigate the prevalence of chronic musculoskeletal pain, including some subtypes, in independent Japanese older people, and whether population density and population aging rate explained prevalence and differences in pain levels between municipalities. METHODS: We analyzed data from 12,883 independent older people living in 58 municipalities who completed mailed questionnaires and did not need support for daily living. We identified three types of pain: "chronic musculoskeletal pain" lasting ≥ 3 months (overall and in each part of the body), "chronic widespread-type pain" in the spinal and peripheral area, and "chronic multisite pain" in at least three sites. The latter two were measured using new definitions. These types of pain are correlated with depressive symptoms and we therefore examined the construct validity of the definitions by comparing the Geriatric Depression Scale score. We also used analysis of covariance to compare the prevalence of these three types of pain between municipalities. Odds ratios, median odds ratios, and the municipal variance in prevalence of chronic musculoskeletal pain were estimated by Bayesian multilevel logistic regression analysis using the Markov Chain Monte Carlo method. RESULTS: The construct validity of the definitions of chronic widespread-type pain and chronic multisite pain was confirmed. The prevalence of the three types of pain (chronic musculoskeletal, widespread, and multisite pain) was 39.0%, 13.9%, and 10.3%, respectively. Chronic musculoskeletal pain showed a higher prevalence among older people and women. Individuals in underpopulated, suburban, or metropolitan areas tended to have more pain than those in urban areas, but this was not statistically significant (odds ratio [95% credible interval] 1.15 [0.86-1.51], 1.17 [0.93-1.43], 1.17 [0.94-1.46]). Population density and population aging rate did not explain the differences between municipalities. CONCLUSIONS: The prevalence of chronic musculoskeletal pain was consistent with previous global reports. Areas with overpopulation and depopulation tended to have higher pain prevalence, but population density and population aging rate did not explain municipal variance. Further research is needed to identify other factors that contribute to regional variance.

Negative effect of anger on chronic pain intensity is modified by multiple mood states other than anger: A large population-based cross-sectional study in Japan.

OBJECTIVES: To investigate whether mood states other than anger can modify the association between anger and pain intensity in individuals with chronic pain. METHODS: We analysed 22,059 participants with chronic pain, including 214 participants with rheumatoid arthritis (RA), who completed a questionnaire. The Profile of Mood States short form (POMS-SF) was used to assess six dimensions of mood states (anger-hostility, tension-anxiety, depression-dejection, confusion, fatigue, and vigour). A numerical rating scale (NRS) assessed pain intensity. We examined the association between anger-hostility and the NRS and the relationship between POMS-SF components. Moderation analyses were used to investigate whether the five mood states other than anger-hostility modified the effect of anger-hostility on the NRS. RESULTS: Anger-hostility contributed to pain intensity. Although increased mood states other than vigour were associated with increased pain intensity, these increased mood states appeared to suppress the effect of anger-hostility on pain intensity. Increased vigour was associated with decreased pain intensity and increased the effect of anger-hostility on pain intensity. CONCLUSIONS: Mood states other than anger may influence the association between anger and pain intensity in individuals with chronic pain. It is important to focus on complicated mood states and anger in individuals with chronic pain, including RA.

Management of acute metabolic acidosis in the ICU: sodium bicarbonate and renal replacement therapy.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Translation and validation of the Japanese version of the measure of moral distress for healthcare professionals.

OBJECTIVES: Moral distress occurs when professionals cannot carry out what they believe to be ethically appropriate actions because of constraints or barriers. We aimed to assess the validity and reliability of the Japanese translation of the Measure of Moral Distress for Healthcare Professionals (MMD-HP). METHODS: We translated the questionnaire into Japanese according to the instructions of EORTC Quality of Life group translation manual. All physicians and nurses who were directly involved in patient care at nine departments of four tertiary hospitals in Japan were invited to a survey to assess the construct validity, reliability and factor structure. Construct validity was assessed with the relation to the intention to leave the clinical position, and internal consistency was assessed with Cronbach's alpha. Confirmatory factor analysis was conducted. RESULTS: 308 responses were eligible for the analysis. The mean total score of MMD-HP (range, 0-432) was 98.2 (SD, 59.9). The score was higher in those who have or had the intention to leave their clinical role due to moral distress than in those who do not or did not have the intention of leaving (mean 113.7 [SD, 61.3] vs. 86.1 [56.6], t-test p < 0.001). The confirmatory factor analysis and Cronbach's alpha confirmed the validity (chi-square, 661.9; CMIN/df, 2.14; GFI, 0.86; CFI, 0.88; CFI/TLI, 1.02; RMSEA, 0.061 [90%CI, 0.055-0.067]) and reliability (0.91 [95%CI, 0.89-0.92]) of the instrument. CONCLUSIONS: The translated Japanese version of the MMD-HP is a reliable and valid instrument to assess moral distress among physicians and nurses.

Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy.

BACKGROUND: Acute kidney injury (AKI) is a common complication amongst people who are critically ill, and it is associated with an increased risk of death. For people with severe AKI, continuous kidney replacement therapy (CKRT), which is delivered over 24 hours, is needed when they become haemodynamically unstable. When CKRT is interrupted due to clotting of the extracorporeal circuit, the delivered dose is decreased and thus leading to undertreatment. OBJECTIVES: This review assessed the efficacy of non-pharmacological measures to maintain circuit patency in CKRT. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 which includes records identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) (parallel-group and cross-over studies), cluster RCTs and quasi-RCTs that examined non-pharmacological interventions to prevent clotting of extracorporeal circuits during CKRT.  DATA COLLECTION AND ANALYSIS: Three pairs of review authors independently extracted information including participants, interventions/comparators, outcomes, study methods, and risk of bias. The primary outcomes were circuit lifespan and death due to any cause at day 28. We used a random-effects model to perform quantitative synthesis (meta-analysis). We assessed risk of bias in included studies using the Cochrane Collaboration's tool for assessing risk of bias. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: A total of 20 studies involving 1143 randomised participants were included in the review. The methodological quality of the included studies was low, mainly due to the unclear randomisation process and blinding of the intervention. We found evidence on the following 11 comparisons: (i) continuous venovenous haemodialysis (CVVHD) versus continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF); (ii) CVVHDF versus CVVH; (iii) higher blood flow (≥ 250 mL/minute) versus standard blood flow (< 250 mL/minute); (iv) AN69 membrane (AN69ST) versus other membranes; (v) pre-dilution versus post-dilution; (vi) a longer catheter (> 20 cm) placing the tip targeting the right atrium versus a shorter catheter (≤ 20 cm) placing the tip in the superior vena cava; (vii) surface-modified double-lumen catheter versus standard double-lumen catheter with identical geometry and flow design; (viii) single-site infusion anticoagulation versus double-site infusion anticoagulation; (ix) flat plate filter versus hollow fibre filter of the same membrane type; (x) a filter with a larger membrane surface area versus a smaller one; and (xi) a filter with more and shorter hollow fibre versus a standard filter of the same membrane type. Circuit lifespan was reported in 9 comparisons. Low certainty evidence indicated that CVVHDF (versus CVVH: MD 10.15 hours, 95% CI 5.15 to 15.15; 1 study, 62 circuits), pre-dilution haemofiltration (versus post-dilution haemofiltration: MD 9.34 hours, 95% CI -2.60 to 21.29; 2 studies, 47 circuits; I² = 13%), placing the tip of a longer catheter targeting the right atrium (versus placing a shorter catheter targeting the tip in the superior vena cava: MD 6.50 hours, 95% CI 1.48 to 11.52; 1 study, 420 circuits), and surface-modified double-lumen catheter (versus standard double-lumen catheter: MD 16.00 hours, 95% CI 13.49 to 18.51; 1 study, 262 circuits) may prolong circuit lifespan. However, higher blood flow may not increase circuit lifespan (versus standard blood flow: MD 0.64, 95% CI -3.37 to 4.64; 2 studies, 499 circuits; I² = 70%). More and shorter hollow fibre filters (versus standard filters: MD -5.87 hours, 95% CI -10.18 to -1.56; 1 study, 6 circuits) may reduce circuit lifespan. Death from any cause was reported in four comparisons We are uncertain whether CVVHDF versus CVVH, CVVHD versus CVVH or CVVHDF, longer versus a shorter catheter, or surface-modified double-lumen catheters versus standard double-lumen catheters reduced death due to any cause, in very low certainty evidence. Recovery of kidney function was reported in three comparisons. We are uncertain whether CVVHDF versus CVVH, CVVHDF versus CVVH, or surface-modified double-lumen catheters versus standard double-lumen catheters increased recovery of kidney function. Vascular access complications were reported in two comparisons. Low certainty evidence indicated using a longer catheter (versus a shorter catheter: RR 0.40, 95% CI 0.22 to 0.74) may reduce vascular access complications, however the use of surface-modified double lumen catheters versus standard double-lumen catheters may make little or no difference to vascular access complications. AUTHORS' CONCLUSIONS: The use of CVVHDF as compared with CVVH, pre-dilution haemofiltration, a longer catheter, and surface-modified double-lumen catheter may be useful in prolonging the circuit lifespan, while higher blood flow and more and shorter hollow fibre filter may reduce circuit life. The Overall, the certainty of evidence was assessed to be low to very low due to the small sample size of the included studies. Data from future rigorous and transparent research are much needed in order to fully understand the effects of non-pharmacological interventions in preventing circuit coagulation amongst people with AKI receiving CKRT.

Validity of the Japanese core outcome measures index (COMI)-neck for cervical spine surgery: a prospective cohort study.

PURPOSE: To investigate the psychometric properties of the Japanese version of the Core Outcome Measures Index-Neck (COMI-Neck) in patients undergoing cervical spine surgery. METHODS: A total of 177 patients undergoing cervical spine surgery for spinal disorders from April to December 2017 were enrolled. Patient-reported outcomes (PROs) included EuroQOL, Neck Disability Index, and treatment satisfaction. To address whether the questionnaire's scores relate to other outcomes based on a predefined hypothesis, the correlations between the COMI-Neck and the other PROs were measured (Spearman's rank correlation coefficients). The minimum clinically important difference (MCID) of the COMI summary score was calculated using the receiver operating characteristic (ROC) curve with a 7-point Likert scale of satisfaction with the treatment results. To assess reproducibility, another group of 59 volunteers with chronic neck pain were asked to reply to the COMI-Neck twice with an interval of 7-14 days. RESULTS: The COMI summary score showed no floor or ceiling effects preoperatively or postoperatively. Each of the COMI domains and the COMI summary score correlated to the hypothesized extent with the scores of the reference questionnaires (ρ = 0.40-0.79). According to the ROC curve with satisfaction (including "very satisfied" and "satisfied"), the area under the curve and MCID of the COMI summary score were 0.78 and 2.1. The intraclass correlation coefficient and the minimum detectable change (MDC 95%) of the COMI summary score were 0.97 and 0.77. CONCLUSION: The Japanese version of the COMI-Neck is valid and reliable for Japanese-speaking patients with cervical spinal disorders.

Joint Initiative Between Infectious Diseases and Podiatry in Outpatient Settings Improves Outcomes and Adherence to Treatment.

BACKGROUND: A joint infectious disease-podiatry clinic (JIDPC) in which an infectious diseases physician and a podiatrist see patients with diabetic foot infections together once a week was initiated in January 2017. This study was designed to investigate if the JIDPC can improve patient adherence and reduce recurrent infections. METHODS: A retrospective analysis of patients with diabetic foot infection admitted to Wheeling Hospital from March 2013 to December 2018 was performed. Initially, the patients were followed by infectious diseases and podiatry in their clinics separately (preintervention group). Beginning January 2017, they were followed together at the JIDPC (postintervention group). Recurrent infection, mortality, and loss to follow-up were compared using logistic regression models. RESULTS: Surgeries were performed in 52.5% of preintervention group participants (n = 99) and 81.9% of postintervention group participants (n = 55; P < .001). The preintervention group was more likely to be lost to follow-up (30.3% vs 9.1%; odds ratio [OR], 4.35 [confidence interval (CI), 1.58-11.99]), but the association was attenuated with further adjustment for surgery (OR 3.35 [CI, 1.17-9.62]). The risk of infection recurrence in 6 months was significantly higher in the preintervention group (36.1% vs 20.8%; OR, 2.16 [CI, 0.99-4.71]), but with further adjustment for surgery, this was not significant (P = .067; OR, 2.17 [CI, 0.95-4.94]). Mortality and 90-day readmission were not significantly different. CONCLUSIONS: Implementation of JIDPCs may decrease the incidence of recurrent infections among patients with diabetic foot infections.

Harm of IV High-Dose Vitamin C Therapy in Adult Patients: A Scoping Review.

OBJECTIVES: The potential harm associated with the use of IV vitamin C has not been systematically assessed. We aimed to review the available evidence on harm related to such treatment. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane Library, National Institute of Health Clinical Trials Register, and World Health Organization International Clinical Trials Registry Platform. STUDY SELECTION: We included studies in adult population that reported harm related to IV high-dose vitamin C which we defined as greater than or equal to 6 g/d, greater than or equal to 75 mg/kg/d, or greater than or equal to 3 g/m/d. DATA EXTRACTION: Two independent investigators screened records and extracted data. DATA SYNTHESIS: We identified 8,149 reports, of which 650 full text were assessed for eligibility, leaving 74 eligible studies. In these studies, 2,801 participants received high-dose vitamin C at a median (interquartile range) dose of 22.5 g/d (8.25-63.75 g/d), 455 mg/kg/d (260-925 mg/kg/d), or 70 g/m/d (50-90 g/m/d); and 932 or more adverse events were reported. Among nine double-blind randomized controlled trials (2,310 patients), adverse events were reported in three studies with an event rate per patient for high-dose vitamin C identical to placebo group in one study (0.1 [1/10] vs 0.1 [1/10]), numerically lower in one study (0.80 [672/839] vs 0.82 [709/869]), and numerically higher in one study (0.33 [24/73] vs 0.23 [17/74]). Six double-blind randomized controlled trials reported no adverse event in either group. Five cases of oxalate nephropathy, five cases of hypernatremia, three cases of hemolysis in glucose-6-phosphate dehydrogenase deficiency patients, two cases of glucometer error, and one case of kidney stones were also reported overall. CONCLUSIONS: There is no consistent evidence that IV high-dose vitamin C therapy is more harmful than placebo in double-blind randomized controlled trials. However, reports of oxalate nephropathy, hypernatremia, glucometer error, and hemolysis in glucose-6-phosphate dehydrogenase deficiency patients warrant specific monitoring.