Abstract

BACKGROUND Higher rates of thrombotic events have been reported in myocardial infarction (MI) patients requiring blood transfusion. The impact of blood transfusion strategy on thrombosis and inflammation is still unknown. OBJECTIVE To compare the impact of a liberal vs. a restrictive transfusion strategy on P2Y12 platelet reactivity and biomarkers in the multicentric randomized REALITY trial. METHODS Patients randomized to a liberal (hemoglobin ≤10 g/dL) or a restrictive (hemoglobin ≤8 g/dL) transfusion strategy had VASP-PRI platelet reactivity measured centrally in a blinded fashion and platelet reactivity unit (PRU) measured locally using encrypted VerifyNow; at baseline and after randomization. Biomarkers of thrombosis (P-selectin, PAI-1, vWF) and inflammation (TNF-α) were also measured. The primary endpoint was the change in the VASP-PRI (difference from baseline and post randomization) between the randomized groups. RESULTS A total of 100 patients randomized were included in this study (n = 50 in each group). Transfused patients received on average 2.4 ± 1.6 units of blood. We found no differences in change of the VASP PRI (difference 1.2% 95% CI (-10.3-12.7%)) or by the PRU (difference 13.0 95% CI (-21.8-47.8)) before and after randomization in both randomized groups. Similar results were found in transfused patients (n = 71) regardless of the randomized group, VASP PRI (difference 1.7%; 95% CI (-9.5-1.7%)) or PRU (difference 27.0; 95% CI (-45.0-0.0)). We did not find an impact of transfusion strategy or transfusion itself in the levels of P-selectin, PAI-1, vWF, and TNF-α. CONCLUSION In this study, we found no impact of a liberal vs. a restrictive transfusion strategy on platelet reactivity and biomarkers in MI patients with anemia. A conclusion that should be tempered due to missing patients with exploitable biological data that has affected our power to show a difference.

Abstract

PURPOSE Temporomandibular joint (TMJ) sub-luxation can have a significant psycho-social impact on a patients' well-being. Several treatment modalities have been described in the literature for the same. The present study was undertaken to investigate the efficacy of heavy bupivacaine-dextrose prolotherapy (HDP) for the peri-articular tissues, superior joint space and the retro-discal area in the patients with symptomatic chronic sub-luxation. MATERIALS AND METHODS A preliminary clinical study was conducted among 60 patients diagnosed with chronic painful sub-luxation of the TMJ. Patients were divided into control group (CG), n = 30, where autologous blood was injected in the superior joint space, peri-capsular tissues and retro-discal area bilaterally as per the predetermined protocol; and the study group (SG), n = 30 patients were administered heavy bupivacaine-dextrose injection bilaterally in the peri-articular tissues, superior joint space and retro-discal area. The efficacy of the treatment was evaluated by assessing pain, maximum inter-incisal opening (MIO), changes in computed tomography scan, magnetic resonance imaging study, number and need for subsequent injections in both the groups. RESULT Among the 60 patients, majority of the patients exhibited successful outcome after both the interventions, ABI and HDP. There was statistically significant reduction in recorded pain score with reduced MIO post-treatment. No morphological changes were noted in the condyle in both the groups. No complications were recorded among the study population. CONCLUSION HDP is a safe and simple modality for treating symptomatic sub-luxation with predictable clinical outcome. Heavy bupivacaine-dextrose can be considered as a prolotherapeutic agent for symptomatic chronic temporomandibular joint sub-luxation with the pharmacological benefit of local anaesthesia and proliferent delivery through the same injection.

Abstract

BACKGROUND Recent work has shown that cluster-randomised trials can estimate two distinct estimands: the participant-average and cluster-average treatment effects. These can differ when participant outcomes or the treatment effect depends on the cluster size (termed informative cluster size). In this case, estimators that target one estimand (such as the analysis of unweighted cluster-level summaries, which targets the cluster-average effect) may be biased for the other. Furthermore, commonly used estimators such as mixed-effects models or generalised estimating equations with an exchangeable correlation structure can be biased for both estimands. However, there has been little empirical research into whether informative cluster size is likely to occur in practice. METHOD We re-analysed a cluster-randomised trial comparing two different thresholds for red blood cell transfusion in patients with acute upper gastrointestinal bleeding to explore whether estimates for the participant- and cluster-average effects differed, to provide empirical evidence for whether informative cluster size may be present. For each outcome, we first estimated a participant-average effect using independence estimating equations, which are unbiased under informative cluster size. We then compared this to two further methods: (1) a cluster-average effect estimated using either weighted independence estimating equations or unweighted cluster-level summaries, and (2) estimates from a mixed-effects model or generalised estimating equations with an exchangeable correlation structure. We then performed a small simulation study to evaluate whether observed differences between cluster- and participant-average estimates were likely to occur even if no informative cluster size was present. RESULTS For most outcomes, treatment effect estimates from different methods were similar. However, differences of >10% occurred between participant- and cluster-average estimates for 5 of 17 outcomes (29%). We also observed several notable differences between estimates from mixed-effects models or generalised estimating equations with an exchangeable correlation structure and those based on independence estimating equations. For example, for the EQ-5D VAS score, the independence estimating equation estimate of the participant-average difference was 4.15 (95% confidence interval: -3.37 to 11.66), compared with 2.84 (95% confidence interval: -7.37 to 13.04) for the cluster-average independence estimating equation estimate, and 3.23 (95% confidence interval: -6.70 to 13.16) from a mixed-effects model. Similarly, for thromboembolic/ischaemic events, the independence estimating equation estimate for the participant-average odds ratio was 0.43 (95% confidence interval: 0.07 to 2.48), compared with 0.33 (95% confidence interval: 0.06 to 1.77) from the cluster-average estimator. CONCLUSION In this re-analysis, we found that estimates from the various approaches could differ, which may be due to the presence of informative cluster size. Careful consideration of the estimand and the plausibility of assumptions underpinning each estimator can help ensure an appropriate analysis methods are used. Independence estimating equations and the analysis of cluster-level summaries (with appropriate weighting for each to correspond to either the participant-average or cluster-average treatment effect) are a desirable choice when informative cluster size is deemed possible, due to their unbiasedness in this setting.

Abstract

BACKGROUND Anemia is a known risk factor for ischemic heart disease and serves as an independent predictor of major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). This meta-analysis pools data from randomized controlled trials (RCTs) to better define hemoglobin (Hb) thresholds for transfusion in this setting. RESULTS MEDLINE, EMBASE, and Cochrane databases were searched using the terms "Acute Coronary Syndrome" AND "Blood Transfusion" including their synonyms. A total of three randomized controlled trials were included. Restrictive transfusion strategy (RTS) was defined as transfusing for Hb ≤ 8 g/dl with a post-transfusion goal of 8 to 10 g/dl. Liberal transfusion strategy (LTS) was defined as Hb ≤ 10 g/dl and post-transfusion goal of at least 11 g/dl. The primary end point was 30-day mortality. Secondary outcomes included recurrent ACS events, new or worsening CHF within 30 days, and major adverse cardiac events (MACE). The primary analytic method used was random effects model. Out of 821 patients, 400 were randomized to LTS, and 421 to RTS. Mean age was 70.3 years in RTS versus 76.4 in LTS. There was no statistically significant difference for 30-day mortality in LTS compared to RTS [odds ratio (OR) 1.69; 95% CI 0.35 to 8.05]. Similarly, there was no difference in MACE (OR 0.74; 95% CI 0.21 to 2.63), CHF (OR 0.82; 95% CI 0.18 to 3.76), or the incidence of recurrent ACS (OR 1.21; 95% CI 0.49 to 2.95). CONCLUSIONS In the setting of ACS, there is no difference between LTS and RTS for the outcomes of mortality, MACE, recurrent ACS, or CHF at 30 days. Further evidence in the form of high-quality RCTs are needed to compare RTS and LTS.

Abstract

PURPOSE To investigate the quantitative and qualitative efficacy of finger-prick autologous blood (FAB) eye drops versus conventional medical therapy for the treatment of severe dry eye disease (DED). METHODS Two centre, single masked, randomised controlled trial. Sixty patients in total were recruited with thirty patients (sixty eyes) treated with FAB eye drops four times per day in addition to their conventional DED treatment, and thirty patients (fifty-eight eyes) served as control subjects on conventional treatment alone. Ocular surface disease index (OSDI), Schirmer's test, fluorescein ocular staining grade (OCSG) Oxford schema and fluorescein tear film break-up time (TBUT), were performed at baseline, at 4 and 8 weeks. RESULTS OSDI scores significantly decreased in the FAB arm by greater than -17.68 (-37.67 to -2.96, p=0.02) compared to the control arm. There were greater improvements in OCSG and TBUT in the FAB arm but these were non-significant (p>0.05). CONCLUSION This feasibility study demonstrates adding FAB eye drops to conventional medical therapy for DED improves mean OSDI symptom score compared to conventional medical therapy alone. It may have particular use in settings where serum is unobtainable. An adequately powered and well-designed randomised trial is needed to further evaluate the long-term clinical benefit of FAB.

Abstract

IMPORTANCE Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date. OBJECTIVE To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH. DESIGN, SETTING, AND PARTICIPANTS Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022. INTERVENTIONS Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life. MAIN OUTCOMES AND MEASURES Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023). RESULTS Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores. CONCLUSIONS AND RELEVANCE This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02076373.

Abstract

BACKGROUND AND OBJECTIVES There is an ongoing controversy regarding the risks of restrictive and liberal red blood cell (RBC) transfusion strategies. This meta-analysis assessed whether transfusion at a lower threshold was superior to transfusion at a higher threshold, with regard to thrombosis-related events, that is, whether these outcomes can benefit from a restrictive transfusion strategy is debated. MATERIALS AND METHODS We searched PubMed, Cochrane Central Register of Controlled Trials and Scopus from inception up to 31 July 2021. We included randomized controlled trials (RCTs) in any clinical setting that evaluated the effects of restrictive versus liberal RBC transfusion in adults. We used random-effects models to calculate the risk ratios (RRs) and 95% confidence intervals (CIs) based on pooled data. RESULTS Thirty RCTs involving 17,334 participants were included. The pooled RR for thromboembolic events was 0.65 (95% CI 0.44-0.94; p = 0.020; I(2) = 0.0%, very low-quality evidence), favouring the restrictive strategy. There were no significant differences in cerebrovascular accidents (RR = 0.83; 95% CI 0.64-1.09; p = 0.180; I(2) = 0.0%, very low-quality evidence) or myocardial infarction (RR = 1.05; 95% CI 0.87-1.26; p = 0.620; I(2) = 0.0%, low-quality evidence). Subgroup analyses showed that a restrictive (relative to liberal) strategy reduced (1) thromboembolic events in RCTs conducted in North America and (2) myocardial infarctions in the subgroup of RCTs where the restrictive transfusion threshold was 7 g/dl but not in the 8 g/dl subgroup (with a liberal transfusion threshold of 10 g/dl in both subgroups). CONCLUSIONS A restrictive (relative to liberal) transfusion strategy may be effective in reducing venous thrombosis but not arterial thrombosis.

Abstract

OBJECTIVE Surgical management of aneurysmal subarachnoid hemorrhage (SAH) often involves red blood cell (RBC) transfusion, which increases the risk of postoperative complications. RBC transfusion guidelines report on chronically critically ill patients and may not apply to patients with SAH. Our study aims to synthesize the evidence to recommend RBC transfusion thresholds among adult patients with SAH undergoing surgery. METHODS A systematic review was conducted using PubMed, Google Scholar, and Web of Science electronic databases according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to critically assess primary articles discussing RBC transfusion thresholds and describe complications secondary to RBC transfusion in adult patients with SAH in the perioperative period. RESULTS Sixteen articles meeting our search strategy were reviewed. Patients with SAH who received blood transfusion were older, female, had World Federation of Neurosurgical Societies grade IV-V and modified Fisher grade 3-4 scores, and presented with more comorbidities such as hypertension, diabetes, and cardiovascular and pulmonary diseases. In addition, transfusion was associated with multiple postoperative complications, including higher rates of vasospasms, surgical site infections, cardiovascular and respiratory complications, increased postoperative length of stay, and 30-day mortality. Analysis of transfused patients showed that a higher hemoglobin (>10 g/dL) goal after SAH was safe and that patients may benefit from a higher whole hospital stay hemoglobin nadir, as shown by a reduction in risk of cerebral vasospasm and improvement in clinical outcomes (level B class II). CONCLUSIONS Among patients with SAH, the benefits of reducing cerebral ischemia and anemia are shown to outweigh the risks of transfusion-related complications.

Abstract

BACKGROUND Autologous blood injection (ABI) for patients with chronic plantar fasciitis has been promoted as an approach to improve outcomes over standard dry-needling approaches. The purpose of this trial was to investigate if there are improved outcomes following an ultrasonography-guided ABI compared to dry needling alone for patients with chronic plantar fasciitis. METHODS A double-blinded (participant-blinded and observer-blinded) RCT within a single clinic enrolled 90 patients with symptoms of plantar fasciitis that had failed to improve with a minimum of 3 months of rehabilitation. The mean age was 49.5±8.9 years, 67% were female, and the mean symptom duration was 40.0±28.2 months (range: 8 months-10 years). Participants were randomized to receive ABI or an identical dry-needle fenestration-procedure without coadministration of autologous blood. All participants received identical structured rehabilitation and were followed up at 2, 6, 12, and 26 weeks. Outcome measures included local foot pain, validated foot patient-reported outcome measures (Foot Function Index-revised, Manchester-Oxford Foot Questionnaire, Foot and Ankle Ability Measure), measures of general function and "ability" (EuroQol [EQ]-5D-5L, Oswestry Disability Index), specific measures of activity (International Physical Activity Questionnaire), sleep (Pittsburgh Sleep Quality Index), and mood (Hospital Anxiety and Depression Scale). RESULTS There were no significant between-group differences seen at any time-point studied. There were a number of statistically significant within-group improvements for local foot pain and function in both groups comparing baseline/follow-up data. Overall, levels of pain improved by 25% by 6 weeks and by 50% at 6 months. There were improvements in some generalized function markers. Activity rates did not change, demonstrating that improvements in pain did not necessarily influence physical activity. CONCLUSION Coadministration of 3 mL of autologous blood had no additional effect compared to a dry-needling procedure alone for patients with chronic plantar fasciitis. LEVEL OF EVIDENCE Level I, double-blinded randomized controlled trial.

Abstract

BACKGROUND Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.