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Health and Quality of Life Outcomes Jun 2020End-stage renal disease (ESRD) leads to renal replacement therapy and certainly has an impact on patients' health-related quality of life (HRQoL). This study aimed to... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
End-stage renal disease (ESRD) leads to renal replacement therapy and certainly has an impact on patients' health-related quality of life (HRQoL). This study aimed to review and compare the HRQoL between peritoneal dialysis (PD) and hemodialysis (HD) patients using the 36-Item Short Form Health Survey (SF-36), EuroQoL-5-dimension (EQ-5D) and the Kidney Disease Quality of Life Instrument (KDQOL).
METHODOLOGY
Systematic review was conducted by identify relevant studies through MEDLINE and SCOPUS up to April 2017. Studies were eligible with following criteria: studied in ESRD patients, compare any pair of renal replacement modalities, and reported HRQoL. The unstandardized mean differences (USMD) of HRQoL among modalities were calculated and pooled using a random-effect models if heterogeneity was present, otherwise a fixed-effect model was applied.
RESULTS
A total of twenty-one studies were included with 29,000 participants. Of them, mean age and percent male were 48.1 years and 45.1, respectively. The pooled USMD (95% CI) of SF-36 between PD and HD (base) were 1.86 (0.47, 3.24) and 0.42 (- 1.99, 2.82) for mental component and physical component summary scores, respectively. For EQ-5D, the pooled USMD of utility and visual analogue scale (VAS) score were 0.02 (- 0.06, 0.10) and 3.56 (1.73, 5.39), respectively. The pooled USMD of KDQOL were 9.67 (5.67, 13.68), 6.71 (- 5.92, 19.32) 6.30 (- 0.41, 12.18), 2.35 (- 4.35, 9.04), 2.10 (0.07, 4.13), and 1.21 (- 2.98, 5.40) for burden of kidney disease, work status, effects of kidney disease, quality of social interaction, symptoms, and cognitive function.
CONCLUSION
Patients with chronic kidney disease (CKD) stage 5 or ESRD treated with PD had better generic HRQoL measured by SF-36 and EQ-5D than HD patients. In addition, PD had higher specific HRQoL by KDQOL than HD patients in subdomain of physical functioning, role limitations due to emotional problems, effects and burden of kidney disease.
Topics: Adult; Aged; Disease Progression; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Quality of Life; Renal Dialysis; Surveys and Questionnaires
PubMed: 32552800
DOI: 10.1186/s12955-020-01449-2 -
Kidney & Blood Pressure Research 2017The increase in the survival rate of patients with chronic renal failure due to substitution treatment prompts an investigation of their quality of life (QoL), a key... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND/AIMS
The increase in the survival rate of patients with chronic renal failure due to substitution treatment prompts an investigation of their quality of life (QoL), a key measure to evaluate the outcomes of chronic disease treatment. To determine whether hemodialysis or peritoneal dialysis provide a better QoL, a systematic meta-analysis was performed.
METHODS
We searched through the database Cinahl, Medline, PubMed, Scopus and Proquest, including articles published from 2011 until June 2016. We selected articles that compared, through KDQOL-SF 1.3 or 36 questionnaires, QoL among patients undergoing hemodialysis and peritoneal dialysis. The data was collected using Excel Office, and t-test has been performed on independent samples to identify significant differences.
RESULTS
Only some of the seven articles found significant differences between the two treatments. One of the studies showed a better QoL for peritoneal dialysis patients, while, on the contrary, two other studies support that the best QoL is in patients receiving hemodialysis. Another article displayed significant difference only for satisfaction in relation to care, better in patients on peritoneal dialysis, and for physical health, better in hemodialysis.
CONCLUSIONS
The analysis has not led to a unanimous conclusion. Quantitative analysis showed that the only statistically significant difference between the QoL of patients on hemodialysis and peritoneal dialysis regards the effect of kidney disease, which happens to be better in patients undergoing peritoneal dialysis.
Topics: Humans; Kidney Diseases; Peritoneal Dialysis; Quality of Life; Renal Dialysis; Surveys and Questionnaires
PubMed: 29049991
DOI: 10.1159/000484115 -
American Journal of Physiology. Renal... May 2019Patients with end-stage kidney disease on dialysis have increased mortality and reduced physical activity, contributing to impaired physical function. Although exercise... (Meta-Analysis)
Meta-Analysis
Patients with end-stage kidney disease on dialysis have increased mortality and reduced physical activity, contributing to impaired physical function. Although exercise programs have demonstrated a positive effect on physiological outcomes such as cardiovascular function and strength, there is a reduced focus on physical function. The aim of this review was to determine whether exercise programs improve objective measures of physical function indicative of activities of daily living for patients with end-stage kidney disease on dialysis. A systematic search of Medline, Embase, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature identified 27 randomized control trials. Only randomized control trials using an exercise intervention or significant muscular activation in the intervention, a usual care, nonexercising control group, and at least one objective measure of physical function were included. Participants were ≥18 yr of age, with end-stage kidney disease, undergoing hemo- or peritoneal dialysis. Systematic review of the literature and quality assessment of the included studies used the Cochrane Collaboration's tool for assessing risk bias. A meta-analysis was completed for the 6-min walk test. Data from 27 studies with 1,156 participants showed that exercise, regardless of modality, generally increased 6-min walk test distance, sit-to-stand time or repetitions, and grip strength as well as step and stair climb times or repetitions, dynamic mobility, and short physical performance battery scores. From the evidence available, exercise, regardless of modality, improved objective measures of physical function for end-stage kidney disease patients undergoing dialysis. It is acknowledged that further well-designed randomized control trials are required.
Topics: Activities of Daily Living; Adult; Aged; Aged, 80 and over; Exercise Therapy; Exercise Tolerance; Female; Health Status; Humans; Kidney Failure, Chronic; Male; Middle Aged; Muscle Strength; Peritoneal Dialysis; Quality of Life; Recovery of Function; Renal Dialysis; Treatment Outcome
PubMed: 30759022
DOI: 10.1152/ajprenal.00317.2018 -
Journal of Critical Care Oct 2017To compare clinical outcomes among critically ill adults with acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT), intermittent... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To compare clinical outcomes among critically ill adults with acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT), intermittent hemodialysis (IHD) or sustained low efficiency dialysis (SLED).
MATERIALS AND METHODS
We completed a systematic review and meta-analysis of studies published in 2015 or earlier using MEDLINE®, EMBASE®, Cochrane databases and grey literature. Eligible studies included randomized clinical trials (RCTs) or prospective cohort studies comparing outcomes of mortality, dialysis dependence or length of stay among critically ill adults receiving CRRT, IHD or SLED to treat AKI. Mortality and dialysis dependence from RCTs were pooled using meta-analytic techniques. Length of stay from RCTs and results from prospective cohort studies were described qualitatively.
RESULTS
Twenty-one studies were eligible. RRT modality was not associated with in-hospital mortality (CRRT vs IHD: RR 1.00 [95% CI, 0.92-1.09], CRRT vs SLED: RR 1.23 [95% CI, 1.00-1.51]) or dialysis dependence (CRRT vs IHD: RR 0.90 [95% CI, 0.59-1.38], CRRT vs SLED: RR 1.15 [95% CI, 0.67-1.99]).
CONCLUSIONS
We did not find a definitive advantage for any RRT modality on short-term patient or kidney survival. Well-designed, adequately-powered trials are needed to better define the role of RRT modalities for treatment of critically ill patients with AKI.
Topics: Acute Kidney Injury; Critical Illness; Hospital Mortality; Humans; Intensive Care Units; Prospective Studies; Renal Dialysis; Renal Replacement Therapy
PubMed: 28525779
DOI: 10.1016/j.jcrc.2017.05.002 -
JAMA Network Open Oct 2022The benefits and disadvantages of different pretransplant dialysis modalities and their posttransplant outcomes remain unclear in contemporary kidney transplant care. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The benefits and disadvantages of different pretransplant dialysis modalities and their posttransplant outcomes remain unclear in contemporary kidney transplant care.
OBJECTIVE
To summarize the available evidence of the association of different pretransplant dialysis modalities, including hemodialysis and peritoneal dialysis (PD), with posttransplant outcomes.
DATA SOURCES
MEDLINE, Embase, PubMed, Cochrane Library, Scopus, CINAHL, and gray literature were searched from inception to March 18, 2022 (updated to April 1, 2022), for relevant studies and with no language restrictions.
STUDY SELECTION
Randomized clinical trials and nonrandomized observational (case-control and cohort) studies that investigated the association between pretransplant dialysis modality and posttransplant outcomes regardless of age or donor sources (living or deceased) were abstracted independently by 2 reviewers.
DATA EXTRACTION AND SYNTHESIS
Following Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology reporting guidelines, 2 reviewers independently extracted relevant information using a standardized approach. Random-effects meta-analysis was used to estimate pooled adjusted hazard ratio (HR) or odds ratio and 95% CI.
MAIN OUTCOMES AND MEASURES
Primary outcomes included all-cause mortality, overall graft failure, death-censored graft failure, and delayed graft function. Secondary outcomes included acute rejection, graft vessel thrombosis, oliguria, de novo heart failure, and new-onset diabetes after transplant.
RESULTS
The study analyzed 26 nonrandomized studies (1 case-control and 25 cohort), including 269 715 patients (mean recipient age range, 14.5-67.0 years; reported proportions of female individuals, 29.4%-66.9%) whose outcomes associated with pretransplant hemodialysis vs pretransplant PD were compared. No significant difference, with very low certainty of evidence, was observed between pretransplant PD and all-cause mortality (13 studies; n = 221 815; HR, 0.92 [95% CI, 0.84-1.01]; P = .08) as well as death-censored graft failure (5 studies; n = 96 439; HR, 0.98 [95% CI, 0.85-1.14]; P = .81). However, pretransplant PD was associated with a lower risk for overall graft failure (10 studies; n = 209 287; HR, 0.96 [95% CI, 0.92-0.99]; P = .02; very low certainty of evidence) and delayed graft function (6 studies; n = 47 118; odds ratio, 0.73 [95% CI, 0.70-0.76]; P < .001; low certainty of evidence). Secondary outcomes were inconclusive due to few studies with available data.
CONCLUSIONS AND RELEVANCE
Results of the study suggest that pretransplant PD is a preferred dialysis modality option during the transition to kidney transplant. Future studies are warranted to address shared decision-making between health care professionals, patients, and caregivers as well as patient preferences.
Topics: Humans; Female; Adolescent; Young Adult; Adult; Middle Aged; Aged; Kidney Transplantation; Renal Dialysis; Delayed Graft Function; Peritoneal Dialysis; Odds Ratio
PubMed: 36264575
DOI: 10.1001/jamanetworkopen.2022.37580 -
Clinical Journal of the American... Apr 2021Hemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for individuals receiving hemodialysis. Aerobic exercise may be an effective, nonpharmacologic treatment for specific hemodialysis-related symptoms. This systematic review investigated the effect of aerobic exercise on hemodialysis-related symptoms in adults with kidney failure undergoing maintenance hemodialysis.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We searched MEDLINE, PubMed, Cochrane CENTRAL, CINAHL, PsycINFO, SPORTDiscus, EMBASE, PEDro, and Scopus databases from 1960 or inception until April 15, 2020 for randomized controlled trials investigating the effect of aerobic exercise on hemodialysis-related symptoms, identified as prespecified primary or secondary outcomes, as compared with controls in adults on maintenance hemodialysis. We identified restless legs syndrome as the primary outcome.
RESULTS
Of 3048 studies identified, 15 randomized controlled trials met the eligibility criteria. These studies investigated the effect of aerobic exercise on restless legs syndrome (two studies), sleep disturbance (four studies), anxiety (four studies), depression (nine studies), muscle cramping (one study), and fatigue (one study). Exercise interventions were intradialytic in ten studies and outside of hemodialysis in five studies. Heterogenous interventions and outcomes and moderate to high risk of bias precluded meta-analysis for most symptoms. Aerobic exercise demonstrated improvement in symptoms of restless legs syndrome, muscle cramping, and fatigue, as compared with nonexercise controls. Meta-analysis of depressive symptoms in studies using the Beck Depression Inventory demonstrated a greater reduction in Beck Depression Inventory score with exercise as compared with control (mean difference -7.57; 95% confidence interval, -8.25 to -6.89).
CONCLUSIONS
Our review suggests that in adults on maintenance hemodialysis, aerobic exercise improves several hemodialysis-related symptoms, including restless legs syndrome, symptoms of depression, muscle cramping, and fatigue. However, the use of validated outcome measures with demonstrated reliability and responsiveness in more diverse hemodialysis populations is required to fully characterize the effect of this intervention.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
PROSPERO #CRD42017056658.
Topics: Exercise; Exercise Therapy; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 33766925
DOI: 10.2215/CJN.15080920 -
PloS One 2019In patients with end stage kidney disease (ESKD) on dialysis, treatment non-adherence is common and results in poor health outcomes. However, the clinical benefits of... (Meta-Analysis)
Meta-Analysis
Strategies to improve dietary, fluid, dialysis or medication adherence in patients with end stage kidney disease on dialysis: A systematic review and meta-analysis of randomized intervention trials.
BACKGROUND
In patients with end stage kidney disease (ESKD) on dialysis, treatment non-adherence is common and results in poor health outcomes. However, the clinical benefits of interventions to improve adherence in dialysis patients are difficult to evaluate since trialled interventions and reported outcomes are highly diverse/ heterogeneous. This review summarizes existing literature on randomized controlled trials (RCTs) evaluating adherence interventions in ESKD patients focusing on the intervention category, outcome efficacy and persistence of benefit beyond the intervention.
METHODS
We performed electronic database searches in Medline, Embase & Cochrane CENTRAL upto 1st July 2018 for RCTs evaluating interventions to improve diet, fluid, medication or dialysis adherence in ESKD patients. Study characteristics including category of interventions, outcomes, efficacy and follow-up were assessed. Meta-analysis was used to compute pooled estimates of the effects on the commonest reported outcome measures.
RESULTS
From 1311 citations, we included 36 RCTs (13 cluster-randomized trials), recruiting a total of 3510 dialysis patients (mean age 55.1 ± 5.8 years, males 58.1%). Overall risk of bias was 'high' for 24 and of 'some concern' for 12 studies. Most interventions (33 trials, 92%) addressed patient related factors, and included educational/cognitive (N = 11), behavioural / counselling (N = 4), psychological/affective (N = 4) interventions or a combination (N = 14) of the above. A majority of (28/36) RCTs showed improvement in some reported outcomes. Surrogate measures like changes in phosphate (N = 19) and inter-dialytic weight gain (N = 15) were the most common reported outcomes and both showed significant improvement in the meta-analysis. Sixteen trials reported follow-up (1-12 months) beyond intervention and the benefits waned or were absent in nine trials within 12 months post-intervention.
CONCLUSIONS
Interventions to improve treatment adherence result in modest short-term benefits in surrogate outcome measures in dialysis patients, but significant improvements in trial design and outcome reporting are warranted to identify strategies that would achieve meaningful and sustainable clinical benefits.
LIMITATIONS
Poor methodological quality of trials. Frequent use of surrogate outcomes measures. Low certainly of evidence.
Topics: Diet; Health Behavior; Health Knowledge, Attitudes, Practice; Humans; Kidney Failure, Chronic; Male; Medication Adherence; Middle Aged; Patient Education as Topic; Phosphates; Renal Dialysis; Self Care
PubMed: 30695068
DOI: 10.1371/journal.pone.0211479 -
Journal of Gastroenterology and... May 2021Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF)...
Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF) and acute-on-chronic liver failure. There are five artificial systems currently in use: molecular adsorbent recirculating system (MARS), single-pass albumin dialysis (SPAD), Prometheus, selective plasma filtration therapy, and hemodiafiltration. The aim is to compare existing data on the efficiency of these devices. A literature search was conducted using online libraries. Inclusion criteria included randomized control trials or comparative human studies published after the year 2000. A systematic review was conducted for the five individual devices with a more detailed comparison of the biochemistry for the SPAD and MARS systems. Eighty-nine patients were involved in the review comparing SPAD and MARS. Results showed that there was an average reduction in bilirubin (-53 μmol/L in MARS and -50 μmol/L in SPAD), creatinine (-19.5 μmol/L in MARS and -7.5 μmol/L in SPAD), urea (-0.9 mmol/L in MARS and -0.75 mmol/L in SPAD), and gamma-glutamyl transferase (-0.215 μmol/L·s in MARS and -0.295 μmol/L·s in SPAD) in both SPAD and MARS. However, there was no significant difference between the changes in the two systems. This review demonstrated that both MARS and SPAD aid recovery of ALF. There is no difference between the efficiency of MARS and SPAD. Because of the limited data, there is a need for more randomized control trials. Evaluating cost and patient preference would aid in differentiating the systems.
Topics: Acute-On-Chronic Liver Failure; Bilirubin; Creatinine; Dialysis; Female; Hemodiafiltration; Humans; Liver Failure, Acute; Liver, Artificial; Male; Sorption Detoxification; Treatment Outcome; Urea; gamma-Glutamyltransferase
PubMed: 32918840
DOI: 10.1111/jgh.15255 -
Nephron 2017Dialysis in older adults with chronic kidney disease (CKD) and comorbidities may not be associated with improved life expectancy compared to conservative management. To... (Review)
Review
BACKGROUND
Dialysis in older adults with chronic kidney disease (CKD) and comorbidities may not be associated with improved life expectancy compared to conservative management. To inform clinical practice, we performed a systematic review of all available studies examining this hypothesis.
METHODS
We performed a systematic review of retrospective and prospective cohort studies of older adults with stage-5 CKD who chose dialysis (hemodialysis or peritoneal dialysis) or opted for conservative management (including management of complications of CKD and palliative care). Outcomes of interest included hospitalizations and mortality.
RESULTS
Twelve cohort studies (11,515 patients) were identified with most of them focusing on older adults. Patients choosing dialysis were younger compared to those opting for conservative management and were less functionally impaired. Patients opting for conservative management received care in a multidisciplinary setting focusing on palliative care and management of complications of CKD. Patients choosing dialysis and conservative management had a median survival time of 8-67 and 6-30 months, respectively. In a subset of studies of patients 65 years and older with an estimated glomerular filtration rate <15 mL/min/1.73 m2, and where the multivariable analyses included age and comorbidities, by meta-analysis, patients choosing dialysis had a pooled adjusted hazard ratio for mortality of 0.53 (95% CI 0.30-0.91, p = 0.02) relative to those opting for conservative management; however, significant heterogeneity precluded definitive conclusions.
CONCLUSIONS
When caring for older adults with advanced CKD who are contemplating dialysis therapy vs. conservative management, efforts must focus on promoting patient values and preferences, shared decision-making, and symptom burden alleviation.
Topics: Aged; Aged, 80 and over; Choice Behavior; Conservative Treatment; Female; Glomerular Filtration Rate; Humans; Kidney Failure, Chronic; Male; Patient Participation; Peritoneal Dialysis; Renal Dialysis
PubMed: 28538218
DOI: 10.1159/000477361 -
The Cochrane Database of Systematic... Apr 2022Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous... (Review)
Review
BACKGROUND
Patients with kidney failure require vascular access to receive maintenance haemodialysis (HD), which can be achieved by an arteriovenous fistula or a central venous catheter (CVC). CVC use is related to frequent complications such as venous stenosis and infection. Venous stenosis occurs mainly due to trauma caused by the entrance of the catheter into the venous lumen and repeated contact with the vein wall. A biofilm, a colony of irreversible adherent and self-sufficient micro-organisms embedded in a self-produced matrix of exopolysaccharides, is associated with the development of infections in patients with indwelling catheters. Despite its clinical relevance, the treatment of catheter-related bloodstream infections (CRBSIs) in patients receiving maintenance HD remains controversial, especially regarding catheter management. Antibiotic lock solutions may sterilise the catheter, treat the infection and prevent unnecessary catheter procedures. However, such treatment may also lead to antibiotic resistance or even clinical worsening in certain more virulent pathogens. Catheter removal and delayed replacement may remove the source of infection, improving infectious outcomes, but this approach may also increase vascular access stenosis, thrombosis or both, or even central vein access failure. Catheter guidewire exchange attempts to remove the source of infection while maintaining access to the same vein and, therefore, may improve clinical outcomes and preserve central veins for future access.
OBJECTIVES
To assess the benefits and harms of different interventions for CRBSI treatment in patients receiving maintenance HD through a permanent CVC, such as systemic antibiotics alone or systemic antibiotics combined with either lock solutions or catheter guidewire exchange or catheter replacement.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 21 December 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register were 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) and quasi-RCTs evaluating the management of CRBSI in permanent CVCs in people receiving maintenance HD.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion, assessed their risk of bias, and performed data extraction. Results were expressed as risk ratios (RR) or hazard ratios (HR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, with their 95% confidence intervals (CI). The certainty of the evidence was assessed using GRADE.
MAIN RESULTS
We identified two RCTs and one quasi-RCT that enrolled 760 participants addressing the treatment of CRBSIs in people (children and adults) receiving maintenance HD through CVC. No two studies compared the same interventions. The quasi-RCT compared two different lock solutions (tissue plasminogen activator (TPA) and heparin) with concurrent systemic antibiotics. One RCT compared systemic antibiotics alone and in association with an ethanol lock solution, and the other compared systemic antibiotics with different catheter management strategies (guidewire exchange versus removal and replacement). The overall certainty of the evidence was downgraded due to the small number of participants, high risk of bias in many domains, especially randomisation, allocation, and other sources of bias, and missing outcome data. It is uncertain whether an ethanol lock solution used with concurrent systemic antibiotics improved CRBSI eradication compared to systemic antibiotics alone (RR 1.61, 95% CI 1.16 to 2.23) because the certainty of this evidence is very low. There were no reported differences between the effects of TPA and heparin lock solutions on cure rates (RR 0.92, 95% CI 0.74 to 1.15) or between catheter guidewire exchange versus catheter removal with delayed replacement, expressed as catheter infection-free survival (HR 0.88, 95% CI 0.43 to 1.79). To date, no results are available comparing other interventions. Outcomes such as venous stenosis and/or thrombosis, antibiotic resistance, death, and adverse events were not reported.
AUTHORS' CONCLUSIONS
Currently, there is no available high certainty evidence to support one treatment over another for CRBSIs. The benefit of using ethanol lock treatment in combination with systemic antibiotics compared to systemic antibiotics alone for CRBSIs in patients receiving maintenance HD remains uncertain due to the very low certainty of the evidence. Hence, further RCTs to identify the benefits and harms of CRBSI treatment options are needed. Future studies should unify CRBSI and cure definitions and improve methodological design.
Topics: Adult; Catheter-Related Infections; Central Venous Catheters; Child; Heparin; Humans; Renal Dialysis; Sepsis
PubMed: 35363884
DOI: 10.1002/14651858.CD013554.pub2