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Editor's Choice
  • Bus SR
  • de Haan RJ
  • Vermeulen M
  • van Schaik IN
  • Eftimov F
  • et al.
Cochrane Database Syst Rev. 2024 Feb 14;2(2):CD001797 doi: 10.1002/14651858.CD001797.pub4.
POPULATION:

People with chronic inflammatory demyelinating polyradiculoneuropathy (9 randomised controlled trials, n= 372).

INTERVENTION:

Intravenous immunoglobulin (IVIg).

COMPARISON:

Placebo; plasma exchange; corticosteroids (prednisolone and intravenous methylprednisolone (IVMP)).

OUTCOME:

The primary outcome was significant improvement in disability within six weeks after the start of treatment. There was low statistical heterogeneity between the trial results, and the overall risk of bias was low for all trials that contributed data to the analysis. IVIg compared with placebo increases the probability of significant improvement in disability within six weeks of the start of treatment (risk ratio (RR) 2.40; 95% confidence interval (CI) [1.72, 3.36]; number needed to treat for an additional beneficial outcome (NNTB) 4; 95% CI [3, 5]; 5 trials, 269 participants, high-certainty evidence). The trial comparing IVIg with plasma exchange reported none of our main outcomes. IVIg compared with prednisolone probably has little or no effect on the probability of significant improvement in disability four weeks after the start of treatment (RR 0.91; 95% CI [0.50, 1.68]; 1 trial, 29 participants, moderate-certainty evidence). IVIg compared with IVMP probably increases the likelihood of significant improvement in disability two weeks after starting treatment (RR 1.46; 95% CI [0.40, 5.38]; 1 trial, 45 participants, moderate-certainty evidence).

BACKGROUND:

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, which lasts for at least two months. Uncontrolled studies have suggested that intravenous immunoglobulin (IVIg) could help to reduce symptoms. This is an update of a review first published in 2002 and last updated in 2013.

OBJECTIVES:

To assess the efficacy and safety of intravenous immunoglobulin in people with chronic inflammatory demyelinating polyradiculoneuropathy.

SEARCH METHODS:

We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers on 8 March 2023.

SELECTION CRITERIA:

We selected randomised controlled trials (RCTs) and quasi-RCTs that tested any dose of IVIg versus placebo, plasma exchange, or corticosteroids in people with definite or probable CIDP.

DATA COLLECTION AND ANALYSIS:

We used standard Cochrane methods. Our primary outcome was significant improvement in disability within six weeks after the start of treatment, as determined and defined by the study authors. Our secondary outcomes were change in mean disability score within six weeks, change in muscle strength (Medical Research Council (MRC) sum score) within six weeks, change in mean disability score at 24 weeks or later, frequency of serious adverse events, and frequency of any adverse events. We used GRADE to assess the certainty of evidence for our main outcomes.

MAIN RESULTS:

We included nine RCTs with 372 participants (235 male) from Europe, North America, South America, and Israel. There was low statistical heterogeneity between the trial results, and the overall risk of bias was low for all trials that contributed data to the analysis. Five trials (235 participants) compared IVIg with placebo, one trial (20 participants) compared IVIg with plasma exchange, two trials (72 participants) compared IVIg with prednisolone, and one trial (45 participants) compared IVIg with intravenous methylprednisolone (IVMP). We included one new trial in this update, though it contributed no data to any meta-analyses. IVIg compared with placebo increases the probability of significant improvement in disability within six weeks of the start of treatment (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 5; 5 trials, 269 participants; high-certainty evidence). Since each trial used a different disability scale and definition of significant improvement, we were unable to evaluate the clinical relevance of the pooled effect. IVIg compared with placebo improves disability measured on the Rankin scale (0 to 6, lower is better) two to six weeks after the start of treatment (mean difference (MD) -0.26 points, 95% CI -0.48 to -0.05; 3 trials, 90 participants; high-certainty evidence). IVIg compared with placebo probably improves disability measured on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale (1 to 10, lower is better) after 24 weeks (MD 0.80 points, 95% CI 0.23 to 1.37; 1 trial, 117 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and placebo in the frequency of serious adverse events (RR 0.82, 95% CI 0.36 to 1.87; 3 trials, 315 participants; moderate-certainty evidence). The trial comparing IVIg with plasma exchange reported none of our main outcomes. IVIg compared with prednisolone probably has little or no effect on the probability of significant improvement in disability four weeks after the start of treatment (RR 0.91, 95% CI 0.50 to 1.68; 1 trial, 29 participants; moderate-certainty evidence), and little or no effect on change in mean disability measured on the Rankin scale (MD 0.21 points, 95% CI -0.19 to 0.61; 1 trial, 24 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and prednisolone in the frequency of serious adverse events (RR 0.45, 95% CI 0.04 to 4.69; 1 cross-over trial, 32 participants; moderate-certainty evidence). IVIg compared with IVMP probably increases the likelihood of significant improvement in disability two weeks after starting treatment (RR 1.46, 95% CI 0.40 to 5.38; 1 trial, 45 participants; moderate-certainty evidence). IVIg compared with IVMP probably has little or no effect on change in disability measured on the Rankin scale two weeks after the start of treatment (MD 0.24 points, 95% CI -0.15 to 0.63; 1 trial, 45 participants; moderate-certainty evidence) or on change in mean disability measured with the Overall Neuropathy Limitation Scale (ONLS, 1 to 12, lower is better) 24 weeks after the start of treatment (MD 0.03 points, 95% CI -0.91 to 0.97; 1 trial, 45 participants; moderate-certainty evidence). The frequency of serious adverse events may be higher with IVIg compared with IVMP (RR 4.40, 95% CI 0.22 to 86.78; 1 trial, 45 participants, moderate-certainty evidence).

AUTHORS' CONCLUSIONS:

Evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of 4. During this period, IVIg probably has similar efficacy to oral prednisolone and IVMP. Further placebo-controlled trials are unlikely to change these conclusions. In one large trial, the benefit of IVIg compared with placebo in terms of improved disability score persisted for 24 weeks. Further research is needed to assess the long-term benefits and harms of IVIg relative to other treatments.

Editor's Choice
  • Moulton SG
  • Hartwell MJ
  • Feeley BT
  • Moulton, S. G.
  • Hartwell, M. J.
  • et al.
Am J Sports Med. 2024 Feb 7;3635465231213039 doi: 10.1177/03635465231213039.
POPULATION:

Patients undergoing arthroscopic rotator cuff repair surgery with platelet-rich plasma (PRP) (25 studies).

INTERVENTION:

Systematic review to evaluate the presence of spin bias in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery.

COMPARISON:

OUTCOME:

Each included study was evaluated for the 15 most common forms of spin. Correlations between spin types and study characteristics were evaluated. At least 1 form of spin bias was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio (OR) 1.41 per year increase in publication; 95% CI [1.04, 1.92]) and misleading reporting and publication year (OR 1.41 per year increase in publication; 95% CI [1.02, 1.95]). An association was found between inappropriate extrapolation and journal impact factor (OR 0.21 per unit increase in impact factor; 95% CI [0.044, 0.99]).

BACKGROUND:

The use of platelet-rich plasma (PRP) in orthopaedics continues to increase. One common use of PRP is as an adjunct in rotator cuff repair surgery. Multiple systematic reviews and meta-analyses have summarized the data on PRP use in rotator cuff repair surgery. However, systematic reviews and meta-analyses are subject to spin bias, where authors' interpretations of results influence readers' interpretations.

PURPOSE:

To evaluate spin in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery.

STUDY DESIGN:

Systematic review; Level of evidence, 3.

METHODS:

A PubMed and Embase search was conducted using the terms rotator cuff repair and PRP and systematic review or meta-analysis. After review of 74 initial studies, 25 studies met the inclusion criteria. Study characteristics were documented, and each study was evaluated for the 15 most common forms of spin and using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Version 2) rating system. Correlations between spin types and study characteristics were evaluated using binary logistic regression for continuous independent variables and a chi-square test or Fisher exact test for categorical variables.

RESULTS:

At least 1 form of spin was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio [OR], 1.41 per year increase in publication; 95% CI, 1.04-1.92; P = .029) and misleading reporting and publication year (OR, 1.41 per year increase in publication; 95% CI, 1.02-1.95; P = .037). An association was found between inappropriate extrapolation and journal impact factor (OR, 0.21 per unit increase in impact factor; 95% CI, 0.044-0.99; P = .048).

CONCLUSION:

A significant amount of spin was found in the abstracts of systematic reviews and meta-analyses of PRP use in rotator cuff repair surgery. Given the increasing use of PRP by clinicians and interest among patients, spin found in these studies may have a significant effect on clinical practice.

Editor's Choice
  • Kim D
  • Bashrum BS
  • Kotlier JL
  • Mayfield CK
  • Thompson AA
  • et al.
Arthrosc Sports Med Rehabil. 2024 Jan 16;6(1):100851 doi: 10.1016/j.asmr.2023.100851.
POPULATION:

Patients with hip osteoarthritis (15 systematic reviews).

INTERVENTION:

Systematic review to describe the incidence and types of spin bias in systematic reviews of platelet-rich plasma injections for hip osteoarthritis and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.

COMPARISON:

OUTCOME:

All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration.

PURPOSE:

To describe the incidence and types of spin in systematic reviews of platelet-rich plasma (PRP) injections for hip osteoarthritis (OA) and to determine whether patterns in study characteristics could be identified among studies with identifiable spin.

METHODS:

The PubMed, Scopus, and SPORTDiscus databases were queried. Inclusion criteria were systematic reviews or meta-analyses that included an assessment of intra-articular PRP injections as a stand-alone treatment for hip OA. Two authors independently assessed the presence of spin in the included studies and recorded general study characteristics. The prevalence of the 15 different categories of spin was quantified using descriptive statistics.

RESULTS:

Fifteen studies met inclusion criteria for this study. All studies contained at least two types of spin (range 2-9), with a median of 2. The most common type of spin was type 14 ("Failure to report a wide confidence interval of estimates"), which was observed in 10 studies. The second most common type of spin was type 13 ("Failure to specify the direction of the effect when it favors the control intervention"), found in 6 studies.

CONCLUSIONS:

Spin is highly prevalent in abstracts of systematic reviews of PRP in the treatment of hip OA. Several associations were found between spin types and the study characteristics of AMSTAR 2 rating, Scopus CiteScore, journal impact factor, and PROSPERO preregistration. When present, spin in the abstracts of reviewed studies tended to favor the use of PRP in hip osteoarthritis.

CLINICAL RELEVANCE:

It is important to understand the prevalence of spin in published abstracts, especially in areas of great impact or interest, so authors and readers can have a greater awareness of this potential form of bias.

Editor's Choice
  • Gibbs VN
  • Champaneria R
  • Sandercock J
  • Welton NJ
  • Geneen LJ
  • et al.
Cochrane Database Syst Rev. 2024 Jan 16;1(1):CD013295 doi: 10.1002/14651858.CD013295.pub2.
POPULATION:

People undergoing elective hip or knee surgery (102 randomised controlled trials).

INTERVENTION:

Antifibrinolytics (tranexamic acid, aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.

COMPARISON:

Placebo or one of the active interventions.

OUTCOME:

The primary outcomes were the proportion of participants requiring an allogeneic blood transfusion and all‐cause mortality. Tranexamic acid was the most common drug studied. Mortality was not reported by many trials. Tranexamic acid interventions consistently ranked higher than other treatments such as aprotinin, EACA and topical fibrin sealants compared with placebo. The authors noted that mixed routes of administration (oral and intra‐articular, intravenous and intra‐articular) appear to be more effective than single routes of administration and higher doses of tranexamic acid feature higher up the treatment ranking hierarchy. The authors identified 30 ongoing studies.

BACKGROUND:

Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care.

OBJECTIVES:

To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology.

SEARCH METHODS:

We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP).

SELECTION CRITERIA:

We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants.

DATA COLLECTION AND ANALYSIS:

We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received.

MAIN RESULTS:

We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials).

AUTHORS' CONCLUSIONS:

We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review.