-
Journal of Clinical Nursing Dec 2019Venepuncture involves the introduction of a needle into a vein to collect a representative blood sample for laboratory testing. In the pre-analytical phase, haemolysis...
BACKGROUND
Venepuncture involves the introduction of a needle into a vein to collect a representative blood sample for laboratory testing. In the pre-analytical phase, haemolysis (the rupturing of erythrocytes and release of their contents into the extracellular compartment) has safety, quality and cost implications. Training in correct venepuncture practice has the potential to reduce in vitro haemolysis rates, but the evidence for this notion has yet to be synthesised.
DESIGN
Systematic review (PRISMA Checklist).
METHODS
Published studies on the effectiveness of venepuncture training on haemolysis rates were searched in relevant databases. The McMaster critical appraisal tool was used to assess methodological quality. The GRADE tool was used to evaluate the body of evidence in relation to the research questions. Implementation fidelity was also scrutinised in each study.
RESULTS
Eight out of 437 retrieved studies met the inclusion criteria. None were randomised controlled trials (RCT). Between-study heterogeneity in design, intervention characteristics and the biochemical threshold for haemolysis precluded a meta-analysis. Post-training reductions in haemolysis rates of between 0.4%-19.8% were reported in four of the studies, which developed their intervention according to a clear evidence base and included mentoring in the intervention. Rises in haemolysis rates of between 1.3%-1.9% were reported in two studies, while the intervention effect was inconsistent within two other studies.
CONCLUSION
There are no RCTS on the effectiveness of venepuncture training for reducing haemolysis rates, and findings from the existing uncontrolled studies are unclear. For a more robust evidence base, we recommend more RCTs with standardisation of haemolysis thresholds and training-related factors.
RELEVANCE TO CLINICAL PRACTICE
While venepuncture training is an important factor influencing quality of blood sample in clinical practice, more robust evidence is needed to make specific recommendations about training content for reduction of haemolysis rates. Standardisation of haemolysis thresholds would also enable future meta-analyses.
Topics: Clinical Competence; Health Personnel; Hemolysis; Humans; Phlebotomy
PubMed: 31294491
DOI: 10.1111/jocn.14997 -
BioMed Research International 2019Many trials have reported that bloodletting therapy is effective when treating chronic urticaria. There are currently no systematic reviews of bloodletting therapy for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many trials have reported that bloodletting therapy is effective when treating chronic urticaria. There are currently no systematic reviews of bloodletting therapy for chronic urticaria.
OBJECTIVE
The aim of this review is to assess the effectiveness and safety of bloodletting therapy for chronic urticaria.
METHODS
A systematic review and meta-analysis of randomized controlled trials were performed. Disease activity control was assessed as the primary outcome. Response rate, recurrence rate, and adverse events were assessed as secondary outcomes.
RESULTS
Seven studies with 512 participants were included. One trial showed a significant difference between bloodletting therapy plus medicine and medicine alone in disease activity control (MD 0.67; 95% CI 0.03 to 1.31; p=0.04). Six trials (372 participants) showed a significant difference between bloodletting therapy and pharmacological medication in response rate (RR 1.10; 95% CI 0.97-1.26; P =0.15). Two studies (170 participants) showed a significant difference between bloodletting therapy plus pharmacological medication and pharmacological medication in response rate (RR 1.34; 95% CI 1.10-1.63; p=0.003). Two studies (126 participants) reported a statistically significant difference between bloodletting therapy and pharmacological medication in recurrence rate. No serious adverse events related to bloodletting therapy were reported.
CONCLUSIONS
Bloodletting therapy might be an effective and safe treatment for chronic urticaria, but the evidence is scarce. More high quality trials are needed in the future.
Topics: Adolescent; Adult; Aged; Bloodletting; Child; Chronic Disease; Humans; Middle Aged; Publication Bias; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Urticaria; Young Adult
PubMed: 31139656
DOI: 10.1155/2019/8650398 -
The Cochrane Database of Systematic... Oct 2018This is the second update of a Cochrane Review (Issue 4, 2006). Pain and distress from needle-related procedures are common during childhood and can be reduced through... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the second update of a Cochrane Review (Issue 4, 2006). Pain and distress from needle-related procedures are common during childhood and can be reduced through use of psychological interventions (cognitive or behavioral strategies, or both). Our first review update (Issue 10, 2013) showed efficacy of distraction and hypnosis for needle-related pain and distress in children and adolescents.
OBJECTIVES
To assess the efficacy of psychological interventions for needle-related procedural pain and distress in children and adolescents.
SEARCH METHODS
We searched six electronic databases for relevant trials: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; PsycINFO; Embase; Web of Science (ISI Web of Knowledge); and Cumulative Index to Nursing and Allied Health Literature (CINAHL). We sent requests for additional studies to pediatric pain and child health electronic listservs. We also searched registries for relevant completed trials: clinicaltrials.gov; and World Health Organization International Clinical Trials Registry Platform (www.who.int.trialsearch). We conducted searches up to September 2017 to identify records published since the last review update in 2013.
SELECTION CRITERIA
We included peer-reviewed published randomized controlled trials (RCTs) with at least five participants per study arm, comparing a psychological intervention with a control or comparison group. Trials involved children aged two to 19 years undergoing any needle-related medical procedure.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data and assessed risks of bias using the Cochrane 'Risk of bias' tool. We examined pain and distress assessed by child self-report, observer global report, and behavioral measurement (primary outcomes). We also examined any reported physiological outcomes and adverse events (secondary outcomes). We used meta-analysis to assess the efficacy of identified psychological interventions relative to a comparator (i.e. no treatment, other active treatment, treatment as usual, or waitlist) for each outcome separately. We used Review Manager 5 software to compute standardized mean differences (SMDs) with 95% confidence intervals (CIs), and GRADE to assess the quality of the evidence.
MAIN RESULTS
We included 59 trials (20 new for this update) with 5550 participants. Needle procedures primarily included venipuncture, intravenous insertion, and vaccine injections. Studies included children aged two to 19 years, with few trials focused on adolescents. The most common psychological interventions were distraction (n = 32), combined cognitive behavioral therapy (CBT; n = 18), and hypnosis (n = 8). Preparation/information (n = 4), breathing (n = 4), suggestion (n = 3), and memory alteration (n = 1) were also included. Control groups were often 'standard care', which varied across studies. Across all studies, 'Risk of bias' scores indicated several domains at high or unclear risk, most notably allocation concealment, blinding of participants and outcome assessment, and selective reporting. We downgraded the quality of evidence largely due to serious study limitations, inconsistency, and imprecision.Very low- to low-quality evidence supported the efficacy of distraction for self-reported pain (n = 30, 2802 participants; SMD -0.56, 95% CI -0.78 to -0.33) and distress (n = 4, 426 participants; SMD -0.82, 95% CI -1.45 to -0.18), observer-reported pain (n = 11, 1512 participants; SMD -0.62, 95% CI -1.00 to -0.23) and distress (n = 5, 1067 participants; SMD -0.72, 95% CI -1.41 to -0.03), and behavioral distress (n = 7, 500 participants; SMD -0.44, 95% CI -0.84 to -0.04). Distraction was not efficacious for behavioral pain (n = 4, 309 participants; SMD -0.33, 95% CI -0.69 to 0.03). Very low-quality evidence indicated hypnosis was efficacious for reducing self-reported pain (n = 5, 176 participants; SMD -1.40, 95% CI -2.32 to -0.48) and distress (n = 5, 176 participants; SMD -2.53, 95% CI -3.93 to -1.12), and behavioral distress (n = 6, 193 participants; SMD -1.15, 95% CI -1.76 to -0.53), but not behavioral pain (n = 2, 69 participants; SMD -0.38, 95% CI -1.57 to 0.81). No studies assessed hypnosis for observer-reported pain and only one study assessed observer-reported distress. Very low- to low-quality evidence supported the efficacy of combined CBT for observer-reported pain (n = 4, 385 participants; SMD -0.52, 95% CI -0.73 to -0.30) and behavioral distress (n = 11, 1105 participants; SMD -0.40, 95% CI -0.67 to -0.14), but not self-reported pain (n = 14, 1359 participants; SMD -0.27, 95% CI -0.58 to 0.03), self-reported distress (n = 6, 234 participants; SMD -0.26, 95% CI -0.56 to 0.04), observer-reported distress (n = 6, 765 participants; SMD 0.08, 95% CI -0.34 to 0.50), or behavioral pain (n = 2, 95 participants; SMD -0.65, 95% CI -2.36 to 1.06). Very low-quality evidence showed efficacy of breathing interventions for self-reported pain (n = 4, 298 participants; SMD -1.04, 95% CI -1.86 to -0.22), but there were too few studies for meta-analysis of other outcomes. Very low-quality evidence revealed no effect for preparation/information (n = 4, 313 participants) or suggestion (n = 3, 218 participants) for any pain or distress outcome. Given only a single trial, we could draw no conclusions about memory alteration. Adverse events of respiratory difficulties were only reported in one breathing intervention.
AUTHORS' CONCLUSIONS
We identified evidence supporting the efficacy of distraction, hypnosis, combined CBT, and breathing interventions for reducing children's needle-related pain or distress, or both. Support for the efficacy of combined CBT and breathing interventions is new from our last review update due to the availability of new evidence. The quality of trials and overall evidence remains low to very low, underscoring the need for improved methodological rigor and trial reporting. Despite low-quality evidence, the potential benefits of reduced pain or distress or both support the evidence in favor of using these interventions in clinical practice.
Topics: Adolescent; Adult; Anxiety; Central Venous Catheters; Child; Child, Preschool; Cognitive Behavioral Therapy; Humans; Hypnosis; Immunization; Needles; Pain, Procedural; Phlebotomy; Punctures; Randomized Controlled Trials as Topic; Self Report
PubMed: 30284240
DOI: 10.1002/14651858.CD005179.pub4 -
The Cochrane Database of Systematic... Aug 2018Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Red blood cell (RBC) transfusions are used to treat complications of SCD, e.g. acute chest syndrome (ACS) (this often involves a single transfusion episode), or they can be part of a regular long-term transfusion programme to prevent SCD complications.
OBJECTIVES
To summarize the evidence in Cochrane Reviews of the effectiveness and safety of RBC transfusions versus no transfusion, or restrictive (to increase the total haemoglobin) versus liberal (to decrease the haemoglobin S level below a specified percentage) transfusion, for treating or preventing complications experienced by people with SCD.
METHODS
We included Cochrane Reviews of randomised or quasi-randomised controlled trials published in the Cochrane Database of Systematic Reviews, that addressed various SCD complications and had RBC transfusion as an intervention or comparator. We assessed the methodological quality of included reviews according to the AMSTAR quality assessment.
MAIN RESULTS
We included 15 Cochrane Reviews, 10 of which had no included studies with an RBC transfusion intervention (five reported RCTs with other interventions; and five contained no studies). Five of the 15 reviews included participants randomised to RBC transfusion, but in one of these reviews only 10 participants were randomised with no usable data. Four reviews (nine trials with 1502 participants) reported data comparing short- or long-term RBC transfusions versus standard care, disease-modifying agents, a restrictive versus a liberal transfusion strategy and long-term RBC transfusions versus transfusions to treat complications. All reviews were of high quality according to AMSTAR quality assessment, however, the quality of the included trials was highly variable across outcomes. Trials were downgraded according to GRADE methodology for risk of bias, indirectness (most trials were conducted in children with HbSS), and imprecision (outcomes had wide confidence intervals).In all four reviews and all comparisons there was little or no difference in the risk of death (very low-quality evidence). There were either no deaths or death was a rare event.Short-term RBC transfusion versus standard care (one review: two trials, 434 participants, GRADE very low- to low-quality evidence)In people undergoing low- to medium-risk surgery, RBC transfusions may decrease the risk of acute chest syndrome (ACS) in people with African haplotypes compared to standard care (low-quality evidence), but there was little or no difference in people with the Arabic haplotype (very-low quality evidence). There was also little or no difference in the risk of other SCD-related or transfusion-related complications (very-low quality evidence).Long-term RBC transfusion versus standard care (two reviews: three trials, 405 participants, very low- to moderate-quality evidence)In children and adolescents at high risk of stroke (abnormal transcranial doppler (TCD) velocities or silent cerebral infarct (SCI)), long-term RBC transfusions probably decrease the risk of stroke (moderate-quality evidence) and may decrease the risk of ACS and painful crisis compared to standard care (low-quality evidence). Long-term RBC transfusions may also decrease the risk of SCI in children with abnormal TCD velocities (low-quality evidence), but there may be little or no difference in the risk of SCI in children with normal TCD velocities and previous SCI (low-quality evidence).In children and adolescents already receiving long-term RBC transfusions for preventing stroke, in comparison to standard care, continuing long-term RBC transfusions may reduce the risk of SCI (low-quality evidence) but we do not know whether there is a difference in the risk of stroke (very-low quality evidence). In children with normal TCD velocities and SCI there was little or no difference in the risk of alloimmunisation or transfusion reactions, but RBC transfusions may increase the risk of iron overload (low-quality evidence).Long-term RBC transfusion versus RBC transfusion to treat complications (one review: one trial, 72 participants, very low- to low-quality evidence)In pregnant women, long-term RBC transfusions may decrease the risk of painful crisis compared to transfusion for complications (low-quality evidence); but there may be little or no difference in the risk of other SCD-related complications or transfusion reactions (very-low quality evidence).RBC transfusion versus disease-modifying agents (hydroxyurea) (two reviews: two trials; 254 participants, very low- to low-quality evidence)For primary prevention of stroke in children, with abnormal TCD and no severe vasculopathy on magnetic resonance imaging/magnetic resonance angiography (MRI/MRA), who have received at least one year of RBC transfusions, we do not know whether there is a difference between RBC transfusion and disease-modifying agents in the risk of stroke; SCI; ACS; or painful crisis (very-low quality evidence). There may be little or no difference in the risk of iron overload (low-quality evidence).Similarly, for secondary prevention of stroke in children and adolescents, we do not know whether there is a difference between these interventions in the risk of stroke; SCI; or ACS (very-low quality evidence); but hydroxyurea with phlebotomy may increase the risk of painful crisis and global SCD serious adverse events compared to RBC transfusion (low-quality evidence). There may be little or no difference in the risk of iron overload (low-quality evidence).Restrictive versus liberal RBC transfusion strategy (one review: one trial; 230 participants, very low-quality evidence)In people undergoing cholecystectomy, there was little or no difference between strategies in the risk of SCD-related or transfusion-related complications (very-low quality evidence).
AUTHORS' CONCLUSIONS
This overview provides support from two high-quality Cochrane Reviews for the use of RBC transfusions in preventing stroke in children and adolescents at high risk of stroke (abnormal TCDs or SCI) and evidence that it may decrease the risk of SCI in children with abnormal TCD velocities. In addition RBC transfusions may reduce the risk of ACS and painful crisis in this population.This overview highlights the lack of high-quality evidence in adults with SCD and the number of reviews that have no evidence for the use of RBC transfusions across a spectrum of SCD complications. Also of concern is the variable and often incomplete reporting of patient-relevant outcomes in the included trials such as SCD-related serious adverse events and quality of life.
Topics: Adolescent; Anemia, Sickle Cell; Antisickling Agents; Child; Erythrocyte Transfusion; Humans; Hydroxyurea; Randomized Controlled Trials as Topic; Stroke; Systematic Reviews as Topic
PubMed: 30067867
DOI: 10.1002/14651858.CD012082.pub2 -
Revista Gaucha de Enfermagem Jun 2018To describe the scientific evidence published in literature regarding the risk factors for the development of phlebitis.
OBJECTIVE
To describe the scientific evidence published in literature regarding the risk factors for the development of phlebitis.
METHOD
Integrative literature review with the inclusion of 14 original articles found in the LILACS, Scielo and Pubmed bases from January 2004 to April 2015, analyzed by levels of evidence and frequency, associated factors, degree and treatment of phlebitis.
RESULTS
The frequency / incidence / minimum rate of phlebitis was 3% and the maximum was 59.1%. Most articles (57.14%) reported an association of phlebitis with risk factors, including the dwell time, puncture site and / or anatomical region, hospitalization period, number of accesses, reason for removal, sex, antibiotics, intermittent maintenance and emergency insertion.
CONCLUSIONS
The need for standardizing the quantification of this event and a weak connection between the risk factors associated with phlebitis were identified. Further studies need to be developed in order to grant a real understanding of this disease in the daily routines of a hospital.
Topics: Anti-Bacterial Agents; Bibliometrics; Catheterization, Peripheral; Disease Susceptibility; Epidemiologic Studies; Evidence-Based Medicine; Female; Hospitalization; Humans; Male; Observational Studies as Topic; Phlebitis; Phlebotomy; Randomized Controlled Trials as Topic; Risk Factors; Veins
PubMed: 29933415
DOI: 10.1590/1983-1447.2017.04.57489 -
The British Journal of Dermatology Dec 2018Porphyria cutanea tarda (PCT) is the most common human porphyria. It is caused by hepatic deficiency of uroporphyrinogen decarboxylase activity, which is acquired in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Porphyria cutanea tarda (PCT) is the most common human porphyria. It is caused by hepatic deficiency of uroporphyrinogen decarboxylase activity, which is acquired in the presence of multiple susceptibility factors. PCT presents clinically with cutaneous blistering photosensitivity and is readily treatable with either repeated phlebotomy or 4-aminoquinoline antimalarials.
OBJECTIVES
To perform a systematic review and meta-analysis to compare the effectiveness of these quite different treatment approaches, especially on relapse rates (RRs) after achieving remission.
METHODS
Published studies that included follow-up for at least 1 year after treatment of PCT were included. The primary study outcome was PCT relapse. Pooled data are reported as the RRs per person-year of follow-up with 95% confidence intervals (CIs).
RESULTS
Of 375 articles identified as pertaining to PCT treatment, 12 were eligible for analysis. Of these, five used high-dose 4-aminoquinoline regimens (two combined with phlebotomy and three without phlebotomy), five used low-dose 4-aminoquinoline regimens and three used phlebotomy. RRs during the year after treatment were similar for the high- and low-dose 4-aminoquinoline groups (35-36%) and lower in the phlebotomy group (20%). The pooled RRs with their 95% CIs were 8·6 (3·9-13·3) per 100 person-years in the high-dose 4-aminoquinoline group, 17·1 (8·9-25·3) per 100 person-years in the low-dose 4-aminoquinoline group and 5·1 (0·5-10·6) per 100 person-years in the phlebotomy group. Subgroup and sensitivity analyses showed similar results.
CONCLUSIONS
Clinical or biochemical RRs ranged from 5 to 17 per 100 person-years after remission of PCT. Relapses were somewhat more frequent after remission with 4-aminoquinoline regimens than after remission following phlebotomy. Prospective studies are needed to define better how often relapses occur with these treatments after documenting both clinical and biochemical remission of PCT.
Topics: Aminoquinolines; Antimalarials; Dose-Response Relationship, Drug; Humans; Phlebotomy; Porphyria Cutanea Tarda; Recurrence; Treatment Outcome
PubMed: 29750336
DOI: 10.1111/bjd.16741 -
The Journal of Applied Laboratory... Sep 2017Specimen labeling errors have long plagued the laboratory industry putting patients at risk of transfusion-related death, medication errors, misdiagnosis, and patient...
Effectiveness of Laboratory Practices to Reducing Patient Misidentification Due to Specimen Labeling Errors at the Time of Specimen Collection in Healthcare Settings: LMBP™ Systematic Review.
BACKGROUND
Specimen labeling errors have long plagued the laboratory industry putting patients at risk of transfusion-related death, medication errors, misdiagnosis, and patient mismanagement. Many interventions have been implemented and deemed to be effective in reducing sample error rates. The objective of this review was to identify and evaluate the effectiveness of laboratory practices/ interventions to develop evidence based recommendations for the best laboratory practices to reduce labeling errors.
CONTENT
The standardized LMBP™ A-6 methods were used to conduct this systematic review. Total evidence included 12 studies published during the time periods of 1980 to September 2015. Combined data from seven studies found that the interventions developed as a result of improved communication and collaboration between the laboratory and clinical staff resulted in substantial decrease in specimen labeling errors (Median relative percent change in labeling errors: -75.86; IQI: -84.77, -58.00). Further data from subset of four studies showed a significant decrease in specimen labeling errors after the institution of the standardized specimen labeling protocols (Median relative percent decrease in specimen labeling errors: -72.45; IQI: -83.25, -46.50).
SUMMARY
Based on the evidence included in this review, the interventions that enhance the communication and collaboration between laboratory and healthcare professionals can decrease the specimen identification errors in healthcare settings. However, more research is needed to make the conclusion on the effectiveness of other evaluated practices in this review including training and education of the specimen collection staff, audit and feedback of labeling errors, and implementation of new technology (other than barcoding).
PubMed: 29181454
DOI: 10.1373/jalm.2017.023762 -
The Cochrane Database of Systematic... May 2017Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Silent cerebral infarcts are the commonest neurological complication in children and probably adults with SCD. Silent cerebral infarcts also affect academic performance, increase cognitive deficits and may lower intelligence quotient.
OBJECTIVES
To assess the effectiveness of interventions to reduce or prevent silent cerebral infarcts in people with SCD.
SEARCH METHODS
We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 19 September 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 06 October 2016.
SELECTION CRITERIA
Randomised controlled trials comparing interventions to prevent silent cerebral infarcts in people with SCD. There were no restrictions by outcomes examined, language or publication status.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures.
MAIN RESULTS
We included five trials (660 children or adolescents) published between 1998 and 2016. Four of the five trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of SCD. One trial focused on preventing silent cerebral infarcts or stroke; three trials were for primary stroke prevention and one trial dealt with secondary stroke prevention.Three trials compared the use of regular long-term red blood cell transfusions to standard care. Two of these trials included children with no previous long-term transfusions: one in children with normal transcranial doppler (TCD) velocities; and one in children with abnormal TCD velocities. The third trial included children and adolescents on long-term transfusion.Two trials compared the drug hydroxyurea and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children), and one in secondary prevention (children and adolescents).The quality of the evidence was moderate to very low across different outcomes according to GRADE methodology. This was due to trials being at high risk of bias because they were unblinded; indirectness (available evidence was only for children with HbSS); and imprecise outcome estimates. Long-term red blood cell transfusions versus standard care Children with no previous long-term transfusions and higher risk of stroke (abnormal TCD velocities or previous history of silent cerebral infarcts) Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, risk ratio (RR) 0.11 (95% confidence interval (CI) 0.02 to 0.86) (one trial, 124 participants, low-quality evidence); but make little or no difference to the incidence of silent cerebral infarcts in children with previous silent cerebral infarcts on magnetic resonance imaging and normal or conditional TCDs, RR 0.70 (95% CI 0.23 to 2.13) (one trial, 196 participants, low-quality evidence).No deaths were reported in either trial.Long-term red blood cell transfusions may reduce the incidence of: acute chest syndrome, RR 0.24 (95% CI 0.12 to 0.49) (two trials, 326 participants, low-quality evidence); and painful crisis, RR 0.63 (95% CI 0.42 to 0.95) (two trials, 326 participants, low-quality evidence); and probably reduces the incidence of clinical stroke, RR 0.12 (95% CI 0.03 to 0.49) (two trials, 326 participants, moderate-quality evidence).Long-term red blood cell transfusions may improve quality of life in children with previous silent cerebral infarcts (difference estimate -0.54; 95% confidence interval -0.92 to -0.17; one trial; 166 participants), but may have no effect on cognitive function (least squares means: 1.7, 95% CI -1.1 to 4.4) (one trial, 166 participants, low-quality evidence). Transfusions continued versus transfusions halted: children and adolescents with normalised TCD velocities (79 participants; one trial)Continuing red blood cell transfusions may reduce the incidence of silent cerebral infarcts, RR 0.29 (95% CI 0.09 to 0.97 (low-quality evidence).We are very uncertain whether continuing red blood cell transfusions has any effect on all-cause mortality, Peto odds ratio (OR) 8.00 (95% CI 0.16 to 404.12); or clinical stroke, RR 0.22 (95% CI 0.01 to 4.35) (very low-quality evidence).The trial did not report: comparative numbers for SCD-related adverse events; quality of life; or cognitive function. Hydroxyurea and phlebotomy versus transfusions and chelation Primary prevention, children (121 participants; one trial)We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts (no infarcts); all-cause mortality (no deaths); risk of stroke (no strokes); or SCD-related complications, RR 1.52 (95% CI 0.58 to 4.02) (very low-quality evidence). Secondary prevention, children and adolescents with a history of stroke (133 participants; one trial)We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: silent cerebral infarcts, Peto OR 7.28 (95% CI 0.14 to 366.91); all-cause mortality, Peto OR 1.02 (95%CI 0.06 to 16.41); or clinical stroke, RR 14.78 (95% CI 0.86 to 253.66) (very low-quality evidence).Switching to hydroxyurea and phlebotomy may increase the risk of SCD-related complications, RR 3.10 (95% CI 1.42 to 6.75) (low-quality evidence).Neither trial reported on quality of life or cognitive function.
AUTHORS' CONCLUSIONS
We identified no trials for preventing silent cerebral infarcts in adults, or in children who do not have HbSS SCD.Long-term red blood cell transfusions may reduce the incidence of silent cerebral infarcts in children with abnormal TCD velocities, but may have little or no effect on children with normal TCD velocities. In children who are at higher risk of stroke and have not had previous long-term transfusions, long-term red blood cell transfusions probably reduce the risk of stroke, and other SCD-related complications (acute chest syndrome and painful crises).In children and adolescents at high risk of stroke whose TCD velocities have normalised, continuing red blood cell transfusions may reduce the risk of silent cerebral infarcts. No treatment duration threshold has been established for stopping transfusions.Switching to hydroxyurea with phlebotomy may increase the risk of silent cerebral infarcts and SCD-related serious adverse events in secondary stroke prevention.All other evidence in this review is of very low-quality.
Topics: Adolescent; Anemia, Sickle Cell; Antisickling Agents; Brain Infarction; Cause of Death; Child; Cognition; Erythrocyte Transfusion; Humans; Hydroxyurea; Phlebotomy; Primary Prevention; Quality of Life; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke
PubMed: 28500860
DOI: 10.1002/14651858.CD012389.pub2 -
The Cochrane Database of Systematic... Apr 2017Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. It is associated with lifelong morbidity and a reduced life expectancy. Hydroxyurea (hydroxycarbamide), an oral chemotherapeutic drug, ameliorates some of the clinical problems of SCD, in particular that of pain, by raising fetal haemoglobin. This is an update of a previously published Cochrane Review.
OBJECTIVES
To assess the effects of hydroxyurea therapy in people with SCD (all genotypes), of any age, regardless of setting.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Register, comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries.Date of the most recent search: 16 January 2017.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials, of one month or longer, comparing hydroxyurea with placebo, standard therapy or other interventions for people with SCD.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias.
MAIN RESULTS
Seventeen studies were identified in the searches; eight randomised controlled trials were included, recruiting 899 adults and children with SCD (haemoglobin SS (HbSS), haemoglobin SC (HbSC) or haemoglobin Sβºthalassaemia (HbSβºthal) genotypes). Studies lasted from six to 30 months.Four studies (577 adults and children with HbSS or HbSβºthal) compared hydroxyurea to placebo; three recruited individuals with only severe disease and one recruited individuals with all disease severities. There were statistically significant improvements in terms of pain alteration (using measures such as pain crisis frequency, duration, intensity, hospital admissions and opoid use), measures of fetal haemoglobin and neutrophil counts and fewer occurrences of acute chest syndrome and blood transfusions in the hydroxyurea groups. There were no consistent statistically significant differences in terms of quality of life and adverse events (including serious or life-threatening events). Seven deaths occurred during the studies, but the rates by treatment group were not statistically significantly different.Two studies (254 children with HbSS or HbSβºthal also with risk of primary or secondary stroke) compared hydroxyurea and phlebotomy to transfusion and chelation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts, but more occurrences of acute chest syndrome and infections in the hydroxyurea and phlebotomy group. There were no consistent statistically significant differences in terms of pain alteration and adverse events (including serious or life-threatening events). Two deaths occurred during the studies (one in a the hydroxyurea treatment arm and one in the control arm), but the rates by treatment group were not statistically significantly different. In the primary prevention study, no strokes occurred in either treatment group but in the secondary prevention study, seven strokes occurred in the hydroxyurea and phlebotomy group (none in the transfusion and chelation group) and the study was terminated early.The quality of the evidence for the above two comparisons was judged as moderate to low as the studies contributing to these comparisons were mostly large and well designed (and at low risk of bias); however evidence was limited and imprecise for some outcomes such as quality of life, deaths during the studies and adverse events and results are applicable only to individuals with HbSS and HbSβºthal genotypes.Of the remaining two studies, one (22 children with HbSS or HbSβºthal also at risk of stoke) compared hydroxyurea to observation; there were statistically significant improvements in terms of measures of fetal haemoglobin and neutrophil counts but no statistically significant differences in terms of adverse events (including serious or life-threatening events).The final study (44 adults and children with HbSC) compared treatment regimens with and without hydroxyurea - there was statistically significant improvement in terms of measures of fetal haemoglobin, but no statistically significant differences in terms of adverse events (including serious or life-threatening events). No participants died in either of these studies and other outcomes relevant to the review were not reported.The quality of the evidence for the above two comparisons was judged to be very low due to the limited number of participants, the lack of statistical power (as both studies were terminated early with approximately only 20% of their target sample size recruited) and the lack of applicability to all age groups and genotypes.
AUTHORS' CONCLUSIONS
There is evidence to suggest that hydroxyurea is effective in decreasing the frequency of pain episodes and other acute complications in adults and children with sickle cell anaemia of HbSS or HbSβºthal genotypes and in preventing life-threatening neurological events in those with sickle cell anaemia at risk of primary stroke by maintaining transcranial doppler velocities. However, there is still insufficient evidence on the long-term benefits of hydroxyurea, particularly in preventing chronic complications of SCD, recommending a standard dose or dose escalation to maximum tolerated dose. There is also insufficient evidence about the long-term risks of hydroxyurea, including its effects on fertility and reproduction. Evidence is also limited on the effects of hydroxyurea on individuals with HbSC genotype. Future studies should be designed to address such uncertainties.
Topics: Adult; Anemia, Sickle Cell; Antisickling Agents; Chelation Therapy; Child; Erythrocyte Transfusion; Genotype; Hemoglobin SC Disease; Humans; Hydroxyurea; Phlebotomy; Randomized Controlled Trials as Topic; Watchful Waiting
PubMed: 28426137
DOI: 10.1002/14651858.CD002202.pub2 -
The Cochrane Database of Systematic... Mar 2017Hereditary haemochromatosis is a genetic disorder related to proteins involved in iron transport, resulting in iron load and deposition of iron in various tissues of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hereditary haemochromatosis is a genetic disorder related to proteins involved in iron transport, resulting in iron load and deposition of iron in various tissues of the body. This iron overload leads to complications including liver cirrhosis (and related complications such as liver failure and hepatocellular carcinoma), cardiac failure, cardiac arrhythmias, impotence, diabetes, arthritis, and skin pigmentation. Phlebotomy (venesection or 'blood letting') is the currently recommended treatment for hereditary haemochromatosis. The optimal treatment of hereditary haemochromatosis remains controversial.
OBJECTIVES
To assess the comparative benefits and harms of different interventions in the treatment of hereditary haemochromatosis through a network meta-analysis and to generate rankings of the available treatments according to their safety and efficacy. However, we found only one comparison. Therefore, we did not perform the network meta-analysis and we assessed the comparative benefits and harms of different interventions using standard Cochrane methodology.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised clinical trials registers to March 2016 to identify randomised clinical trials on treatments for hereditary haemochromatosis.
SELECTION CRITERIA
We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with hereditary haemochromatosis. We excluded trials which included participants who had previously undergone liver transplantation. We considered any of the various interventions compared with each other or with inactive treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models with RevMan 5 based on available-participant analysis. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE.
MAIN RESULTS
Three trials with 146 participants met the inclusion criteria of this review. Two parallel group trials with 100 participants provided information on one or more outcomes. The remaining trial was a cross-over trial, with no usable data for analysis. All the trials were at high risk of bias. Overall, all the evidence was of very low quality. All three trials compared erythrocytapheresis (removal of red cells only, instead of whole blood) versus phlebotomy. Two of the trials shared the same first author. The mean or median age in the three trials ranged from 42 to 55 years. None of the trials reported whether the included participants were symptomatic or asymptomatic or a mixture of both. Two trials were conducted in people who were haemochromatosis treatment-naive. The trial that provided most data for this review excluded people with malignancy, heart failure, and serious cardiac arrhythmias. We found no trials assessing iron-chelating agents.Only one of the trials with 38 participants reported no short-term mortality and no serious adverse events at the end of the short-term follow-up (eight months). Two trials reported the proportion of people with adverse events: 10/49 (20.4%) in the erythrocytapheresis group versus 11/51 (21.6%) in the phlebotomy group. One of these two trials provided data on adverse event rates (42.1 events per 100 participants with erythrocytapheresis versus 52.6 events per 100 participants with phlebotomy). There was no evidence of differences in the proportion of people with adverse events and the number of adverse events (serious and non-serious) between the groups (proportion of people with adverse events: OR 0.93, 95% CI 0.36 to 2.43; participants = 100; trials = 2; number of adverse events: rate ratio 0.80, 95% CI 0.32 to 2.03; participants = 38; trial = 1). There was no difference between the groups regarding short-term health-related quality of life (mean difference (MD) 1.00, 95% CI -10.80 to 12.80; participants = 38; trials = 1). This outcome was measured using EQ-VAS (range: 0 to 100 where a higher score indicates better health-related quality of life). None of the trials reported mortality beyond one year, health-related quality of life beyond one year, liver transplantation, decompensated liver disease, cirrhosis, hepatocellular carcinoma, diabetes, or cardiovascular complications during the long-term follow-up.The two trials that provided data for this review were funded by parties with no vested interest in the results; the source of funding of the third trial was not reported.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence to determine whether erythrocytapheresis is beneficial or harmful compared with phlebotomy. Phlebotomy has less equipment requirements and remains the treatment of choice in people with hereditary haemochromatosis who require blood letting in some form. However, it should be noted that there is no evidence from randomised clinical trials that blood letting in any form is beneficial in people with hereditary haemochromatosis. Having said this, a trial including no treatment is unlikely to be conducted. Future trials should compare different frequencies of phlebotomy and erythrocytapheresis versus phlebotomy with and without different iron-chelating agents compared with each other, and with placebo. Such trials should include long-term follow-up of participants (e.g. using national record linkage databases) to determine whether treatments are beneficial or harmful in terms of clinical outcomes such as deaths, health-related quality of life, liver damage and its consequences, heart damage and its consequences, and other outcomes that are of importance to people with hereditary haemochromatosis.
Topics: Adult; Cytapheresis; Erythrocytes; Hemochromatosis; Humans; Middle Aged; Phlebotomy; Quality of Life; Randomized Controlled Trials as Topic; Time Factors
PubMed: 28273330
DOI: 10.1002/14651858.CD011647.pub2