Pharmacotherapy for Reducing RBC Transfusion for Patients in the ICU: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To determine optional therapeutic strategies by comparing monotherapies and combination therapies to reduce RBC transfusion requirement for patients in the ICU. DATA SOURCES: MEDLINE, CENTRAL, and Embase were searched for studies published from database inception until July 2023. DATA EXTRACTION: We included randomized controlled trials comparing erythropoiesis-stimulating agents (Epo), iron, combination therapy with iron and Epo, hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), vitamin D 3 (VD3), and placebo/no treatment. A frequentist network meta-analysis (NMA) was performed using a random effects model, and the confidence in NMA was rated. DATA SYNTHESIS: Of 117 eligible studies, 75 studies (15,091 patients) were included in the quantitative analysis. Compared with placebo/no treatment, the combination therapy reduces the requirement for RBC transfusion (risk ratio [RR]: 0.60; 95% CI, 0.49-0.74; confidence rating: moderate). The Epo or iron monotherapy may reduce the requirement for RBC transfusion (RR: 0.81; 95% CI, 0.63-1.04; confidence rating: low; RR: 0.83; 95% CI, 0.70-0.98; confidence rating: low, respectively). Combination therapy may not increase the prevalence of both venous thromboembolism (VTE) (RR: 0.73; 95% CI, 0.25-2.08; confidence rating: low) and infection. Epo monotherapy may not increase the prevalence of VTE but may increase that of infections (RR: 1.27; 95% CI, 0.94-1.73; confidence rating: low). Iron monotherapy may not increase the prevalence of both VTE and infection. Evidence for VD3 and HIF-PHI remains uncertain. CONCLUSIONS: Combination therapy with iron and Epo likely reduces the requirement for RBC transfusion and may be less harmful than other therapies.

Long-term, patient-centered, frailty-based outcomes of older critical illness survivors from the emergency department: a post hoc analysis of the LIFE Study.

BACKGROUND: Evidence indicates frailty before intensive care unit (ICU) admission leads to poor outcomes. However, it is unclear whether quality of life (QOL) and activities of daily living (ADL) for survivors of critical illness admitted to the ICU via the emergency department remain consistent or deteriorate in the long-term compared to baseline. This study aimed to evaluate long-term QOL/ADL outcomes in these patients, categorized by the presence or absence of frailty according to Clinical Frailty Scale (CFS) score, as well as explore factors that influence these outcomes. METHODS: This was a post-hoc analysis of a prospective, multicenter, observational study conducted across Japan. It included survivors aged 65 years or older who were admitted to the ICU through the emergency department. Based on CFS scores, participants were categorized into either the not frail group or the frail group, using a threshold CFS score of < 4. Our primary outcome was patient-centered outcomes (QOL/ADL) measured by the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and the Barthel Index six months post-ICU admission, comparing results from baseline. Secondary outcomes included exploration of factors associated with QOL/ADL six months post-ICU admission using multiple linear regression analyses. RESULTS: Of 514 candidates, 390 participants responded to the EQ-5D-5L questionnaire, while 237 responded to the Barthel Index. At six months post-admission, mean EQ-5D-5L values declined in both the not frail and frail groups (0.80 to 0.73, p = 0.003 and 0.58 to 0.50, p = 0.002, respectively); Barthel Index scores also declined in both groups (98 to 83, p < 0.001 and 79 to 61, p < 0.001, respectively). Multiple linear regression analysis revealed that baseline frailty (ß coefficient, -0.15; 95% CI, - 0.23 to - 0.07; p < 0.001) and pre-admission EQ-5D-5L scores (ß coefficient, 0.14; 95% CI, 0.02 to 0.26; p = 0.016) affected EQ-5D-5L scores at six months. Similarly, baseline frailty (ß coefficient, -12.3; 95% CI, - 23.9 to - 0.80; p = 0.036) and Barthel Index scores (ß coefficient, 0.54; 95% CI, 0.30 to 0.79; p < 0.001) influenced the Barthel Index score at six months. CONCLUSIONS: Regardless of frailty, older ICU survivors from the emergency department were more likely to experience reduced QOL and ADL six months after ICU admission compared to baseline.

Association between changes in disease severity and physical function after surviving a critical illness: A multicentre retrospective observational study.

BACKGROUND: Whilst disease severity can significantly impact functional outcomes, the ability to predict the scale of this impact has not been consistent. AIM: We aimed to investigate whether changes in disease severity within the first 48 h of ICU admission are more strongly associated with physical dysfunction than a single-time assessment of disease severity at ICU admission. METHODS: A multicentre retrospective study in seven tertiary ICUs in Japan, including all consecutive adult ICU patients (>48 h ICU stay) between September 2019 and February 2020. The primary outcome was physical function defined as the Barthel Index, which is an ordinal scale (0-100: larger indicates better function) to measure physical independence and performance. The association between Barthel Index score at hospital discharge and the Sequential Organ Failure Assessment (SOFA) scores, measured at ICU admission, the highest recorded score within 48 h of ICU admission, and the level of change between these two timepoints were investigated in multivariable analysis. RESULTS: A total of 199 patients were included. Median SOFA score at ICU admission and the highest recorded score within the first 48 h were 6 (interquartile range: 5-10) and 8 (interquartile range: 6-11), respectively. A quarter of patients had a Barthel Index score of 60 or less at hospital discharge. The highest SOFA score within 48 h of ICU admission and the level of change in SOFA scores between ICU admission and the highest recorded score within 48 h were significantly associated with lower Barthel Index scores at hospital discharge. No significant association was identified with regard to Barthel Index scores and SOFA score at ICU admission. An increase in SOFA score of 1 or more within the first 48 h of ICU admission was the threshold to predict a Barthel Index score of 60 or less at hospital discharge. Larger changes in SOFA scores over the first 48 h of ICU admission were also significantly associated with smaller changes in Barthel Index scores from ICU discharge to hospital discharge. CONCLUSIONS: The level of change in SOFA score between ICU admission and the highest recorded score within the first 48 h of ICU stay can more accurately predict the presence of physical dysfunction at hospital discharge than a single-time assessment of disease severity at ICU admission. The larger worsening in SOFA potentially indicates lower recovery after a critical illness.

Effect of Neuromuscular Electrical Stimulation in Patients With Critical Illness: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Neuromuscular electrical stimulation (NMES) is used in the rehabilitation of patients with critical illness. However, it is unclear whether NMES prevents ICU-acquired weakness (ICU-AW). For this purpose, we conducted an updated systematic review and meta-analysis. DATA SOURCES: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases from April 2019 to November 2022 to identify new randomized controlled trials to the previous meta-analysis. STUDY SELECTION: We systematically searched the literature for all randomized controlled trials on the effect of NMES in patients with critical illness. DATA EXTRACTION: Two authors independently selected the studies and extracted data. They calculated the pooled effect estimates associated with the occurrence of ICU-AW and adverse events as primary outcomes and muscle mass change, muscle strength, length of ICU stay, mortality, and quality of life as secondary outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Overall, eight studies were added to the previous 10 studies. Evidence suggests that the use of NMES reduces the occurrence of ICU-AW (six trials; risk ratio [RR], 0.48; 95% CI, 0.32-0.72); however, NMES may have little to no effect on pricking sensation in patients (eight trials; RR, 6.87; 95% CI, 0.84-56.50). NMES is likely to reduce the change in muscle mass (four trials; mean difference, -10.01; 95% CI, -15.54 to -4.48) and may increase muscle strength (six trials; standardized mean difference, 0.43; 95% CI, 0.19-0.68). Further, NMES may result in little to no difference in the length of ICU stay, and the evidence is uncertain about the effect on mortality and quality of life. CONCLUSIONS: This updated meta-analysis revealed that the use of NMES may result in a lower occurrence of ICU-AW in patients with critical illness, but its use may have little to no effect on pricking sensation in patients.

Beta-lactam allergy and drug challenge test in children: a systematic review and meta-analysis.

BACKGROUND: Most cases of beta-lactam allergy in children are likely to be mislabeled. This study aimed to assess the prevalence of true positives, as determined by drug challenge tests, and the rate of false negatives in children with suspected allergies and confirm the safety of the drug challenge test. METHODS: We conducted a systematic review and meta-analysis according to established procedures. Study participants were children with suspected beta-lactam allergy who underwent a drug challenge. PubMed MEDLINE, Dialog EMBASE, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and clinicaltrials.gov were searched from inception until March 5, 2021. RESULTS: The pooled prevalence of (a) positive results in the first challenge was 0.049 (95% CI, 0.041-0.057; I2 = 71%) from 78 studies; (b) serious adverse events was 0.00 (95% CI, 0.00-0.00; I2 = 0.0%) from 62 studies; and (c) positive results in the second challenge after the first negative result was 0.028 (95% CI, 0.016-0.043; I2 = 38%) from 18 studies. CONCLUSIONS: The prevalence of children with suspected beta-lactam allergy with true-positive results and false-negative results from the drug challenge test was very low. Serious adverse events resulting from drug challenge tests were also very rare. IMPACT: Most children with suspected beta-lactam allergy were likely to be mislabeled. Serious adverse events caused by the drug challenge test were rare. Few false-negative results were obtained from the drug challenge test.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Repetitive peripheral magnetic stimulation for impairment and disability in people after stroke.

BACKGROUND: Repetitive peripheral magnetic stimulation (rPMS) is a non-invasive treatment method that can penetrate to deeper structures with painless stimulation to improve motor function in people with physical impairment due to brain or nerve disorders. rPMS for people after stroke has proved to be a feasible approach to improving activities of daily living and functional ability. However, the effectiveness and safety of this intervention for people after stroke remain uncertain. This is an update of the review published in 2019. OBJECTIVES: To assess the effects of rPMS for improving activities of daily living and functional ability in people after stroke. SEARCH METHODS: We searched the Cochrane Stroke Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); PsycINFO; the Allied and Complementary Medicine Database (AMED); OTseeker: Occupational Therapy Systematic Evaluation of Evidence; the Physiotherapy Evidence Database (PEDro); Ichushi-Web; and six ongoing trial registries on 5 October 2021. We screened reference lists and contacted experts in the field. We placed no restrictions on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs) conducted to assess the therapeutic effect of rPMS for people after stroke. The following comparisons were eligible for inclusion: 1) active rPMS only compared with 'sham' rPMS (a very weak form of stimulation or a sound only); 2) active rPMS only compared with no intervention; 3) active rPMS plus rehabilitation compared with sham rPMS plus rehabilitation; and 4) active rPMS plus rehabilitation compared with rehabilitation only. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion in the review. The same review authors assessed methods and risk of bias, undertook data extraction, and evaluated the certainty of the evidence using the GRADE approach. We contacted trial authors to request unpublished information if necessary. Any disagreements were resolved through discussion. MAIN RESULTS: We included four trials (three parallel-group RCTs and one cross-over trial) involving a total of 139 participants. This result was unchanged from the review published in 2019. Blinding of participants and physicians was well reported in three trials, with no information on whether personnel were blinded in one trial. We judged the overall risk of bias across trials as low. Only two trials (with 63 and 18 participants, respectively) provided sufficient information to be included in the meta-analysis. We found no clear effect of rPMS on activities of daily living at the end of treatment (mean difference (MD) -3.00, 95% confidence interval (CI) -16.35 to 10.35; P = 0.66; 1 trial; 63 participants; low-certainty evidence) and at the end of follow-up (MD -2.00, 95% CI -14.86 to 10.86; P = 0.76; 1 trial; 63 participants; low-certainty evidence) when comparing rPMS plus rehabilitation versus sham rPMS plus rehabilitation. We found no statistical difference in improvement of upper limb function at the end of treatment (MD 2.00, 95% CI -4.91 to 8.91; P = 0.57; 1 trial; 63 participants; low-certainty evidence) and at the end of follow-up (MD 4.00, 95% CI -2.92 to 10.92; P = 0.26; 1 trial; 63 participants; low-certainty evidence) when comparing rPMS plus rehabilitation versus sham rPMS plus rehabilitation. We observed a decrease in spasticity of the elbow at the end of follow-up (MD -0.41, 95% CI -0.89 to 0.07; 1 trial; 63 participants; low-certainty evidence) when comparing rPMS plus rehabilitation versus sham rPMS plus rehabilitation. In terms of muscle strength, rPMS treatment was not associated with improved muscle strength of the ankle dorsiflexors at the end of treatment (MD 3.00, 95% CI -2.44 to 8.44; P = 0.28; 1 trial; 18 participants; low-certainty evidence) when compared with sham rPMS. No studies provided information on lower limb function or adverse events, including death. Based on the GRADE approach, we judged the certainty of evidence related to the primary outcome as low, owing to the small sample size of the studies. AUTHORS' CONCLUSIONS: There is insufficient evidence to permit the drawing of any conclusions about routine use of rPMS for people after stroke. Additional trials with large sample sizes are needed to provide robust evidence for rPMS after stroke.

Steroid treatment in patients with acute respiratory distress syndrome: a systematic review and network meta-analysis.

PURPOSE: Although the most recent systematic review and meta-analyses on acute respiratory distress syndrome (ARDS) have shown that the use of steroids decreases mortality in adult patients, its benefits and risks may differ depending on the type and dosage of the steroid. Therefore, we conducted a network meta-analysis (NMA) to compare the differences in the efficacy among different doses and types of steroids. METHODS: We searched MEDLINE, CENTRAL, ICHUSHI, ClinicalTrials.gov, and WHO ICTRP databases from the earliest records to March 2021 for randomized control trials, which compared steroids with placebo or conventional therapy for ARDS. Using the random-effects model, we compared various categories of steroids (high-dose methylprednisolone, low-dose methylprednisolone, hydrocortisone, dexamethasone, and no steroid) concerning hospital mortality, incidence of infection, and ventilator-free days (VFD). RESULTS: We analyzed nine studies involving adult patients (n = 1212). Although there were no significant differences between the groups in terms of the mortality and incidence of infection, the number of VFD were greater when using low-dose methylprednisolone than when not using any steroids (Mean difference: 6.06; 95% confidence intervals: [2.5, 10.5]). Moreover, the rank probability showed that low-dose methylprednisolone might be the optimal treatment, whereas using no steroid or high-dose methylprednisolone may be inferior to other treatments in terms of mortality, infection, and VFD. CONCLUSION: This NMA suggested that the effect of steroids on the outcome in patients with ARDS might depend on the type of the steroid drug administered. Moreover, further studies are needed to identify the optimal type and dosage.

Neonatal jaundice, phototherapy and childhood allergic diseases: An updated systematic review and meta-analysis.

BACKGROUND: Neonatal jaundice and phototherapy have been associated with the development of allergic diseases. It has been suggested, however, that effect estimates of the associations might be smaller than expected. We sought to update the evidence of their associations including recently published large longitudinal studies. METHODS: We sought published and unpublished observational studies through the major databases. We used a random-effect meta-analysis model weighted by the inverse variance estimate, the Quality in Prognosis Studies tool to assess the methodological quality for each study, and the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the certainty of evidence (COE). RESULTS: Nineteen studies were enrolled in the qualitative syntheses, and fourteen studies were synthesized in the meta-analyses. Neonatal jaundice was associated with a higher risk of childhood-onset asthma (odds ratio [OR], 1.46; 95% confidence interval [95% CI], 1.39-1.53; COE, moderate), atopic dermatitis (AD; OR, 1.30; 95% CI, 1.07-1.57; COE, moderate), and allergic rhinitis (AR; OR, 3.01; 95% CI, 0.8810.30; COE, low). Neonatal phototherapy was also associated with a higher risk of childhood-onset asthma (OR, 1.24; 95% CI, 1.11-1.38; COE, moderate), AD (OR, 1.31; 95% CI, 1.24-1.39; COE, moderate), and AR (OR, 1.38; 95% CI, 0.93-2.04; COE, very low). There were no studies that reported effect estimates of the associations between childhood-onset food allergies and neonatal jaundice and phototherapy. CONCLUSION: Neonatal jaundice and phototherapy were probably a prognostic factor of childhood-onset allergic diseases; however, the associations were likely to be smaller than previously estimated.

Does methotrexate have no beneficial effect in reducing flares in the treatment of polymyalgia rheumatica patients?

We read the article by Marsman et al. regarding the efficacy of methotrexate (MTX) in the treatment of polymyalgia rheumatica (PMR) with great interest. This study added new insights regarding the use of MTX in a real-world clinical setting and its effect on the incidence rates of flares. However, we would like to voice our concerns regarding the definition of the participants and interventions that were performed in the study, as well as the comparability of the intervention and control groups. Our concerns include the possibility of the inadvertent enrollment of patients with rheumatoid arthritis in a study on PMR, a lack of a clear definition of glucocorticoid ineffectiveness, a lack of adjustment of glucocorticoid dosages, and a reliance on the judgement of individual medical providers rather than clearly defined investigative guidelines in the study procedures. To summarize, we would like to voice concerns about how and to whom MTX was prescribed, as well as the definition of the control group. These revisions and modifications would clarify the importance of the results regarding the efficacy of MTX administration in the treatment of PMR.

Correction to: Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.

In the original publication of the article, the reference 14 was published incorrectly. The correct reference is given below.

Voice rehabilitation for laryngeal cancer after radiotherapy: a systematic review and meta-analysis.

PURPOSE: We aimed to determine whether voice rehabilitation after radiotherapy improves the quality of life (QOL), voice function, and self-rated voice function in patients with laryngeal cancer. METHODS: We searched CENTRAL, MEDLINE, EMBASE, PEDro, and World Health Organization International Clinical Trials Registry Platform for randomized controlled trials published between inception and October 2018. The primary outcome was QOL, adverse events and mortality. Secondary outcomes included voice function and self-rated voice function. The quality of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Three trials (enrolling 122 patients) compared voice rehabilitation to usual care or no intervention after radiotherapy. Voice rehabilitation did not significantly improve any QOL scores. Data on adverse events and mortality were not available in any of the trials. Voice rehabilitation did not improve any voice function scores, such as jitter (mean difference: - 0.48 [- 1.27 to 0.32]), shimmer (mean difference: - 0.04 [- 0.27 to 0.19]), maximum phonation time (mean difference: 1.54 [- 1.13 to 4.22]), and the grade, roughness, breathiness, asthenia, and strain scale (mean difference: - 0.39 [- 2.59 to 1.80]). Voice rehabilitation also did not improve the voice handicap index, which was used as a self-rated voice function score (mean difference: 5.54 [- 2.07 to 13.16]). The certainty of the evidence was graded as low for primary and secondary outcomes. CONCLUSION: Voice rehabilitation for patients with laryngeal cancer after radiotherapy might not improve QOL, voice function, and self-rated voice function. Pre-specified voice rehabilitation programs may not be necessary for all patients with laryngeal cancer after radiotherapy.