Efficacy of ablative fractional carbon dioxide laser combined with autologous platelet-rich plasma versus ablative fractional carbon dioxide laser and placebo in the treatment of striae gravidarum: A randomized clinical trial
Journal of cosmetic dermatology. 2022
BACKGROUND Striae gravidarum (SG) is a connective tissue disorder seen commonly in primigravidas. It is associated with impairment in the quality of life. OBJECTIVE To determine the efficacy of ablative fractional carbon dioxide (CO2) laser combined with autologous platelet-rich plasma (PRP) versus ablative fractional CO2 laser and placebo in the treatment of SG. STUDY DESIGN Randomized, double-blinded, placebo-controlled trial METHODOLOGY The study was conducted in 16 patients with SG. The assigned treatment area (abdomen) was divided into two sides and was randomly assigned to the PRP side and the control side. All patients received ablative fractional CO2 laser. Immediately after each laser procedure, the PRP side received autologous PRP, while the control side received plain normal saline solution (pNSS) as a placebo. The study was done for three sessions, at intervals of 4 weeks. An independent assessor used the photographs taken at weeks 6, 10, 14 and 16 to assess the clinical improvement. The patient satisfaction was reported at the same intervals. A quartile grading scale was used to measure both the clinical improvement and patient satisfaction. Data were analyzed using the Jonckheere-Terpstra test. Histopathology was done before treatment, and at the end of the study period. RESULTS The combination of ablative fractional CO2 laser and autologous PRP had better clinical improvement and patients' satisfaction compared to ablative fractional CO2 laser and placebo. However, both outcome measures were not statistically significant. CONCLUSION Ablative fractional CO2 laser combined with autologous PRP appears to be an effective treatment in SG.
The Effect of Topical Tranexamic Acid in Endoscopic Sinus Surgery: A Triple Blind Randomized Clinical Trial
The Annals of otology, rhinology, and laryngology. 2022;:34894221086086
OBJECTIVE Our aim is to evaluate the effect of topical tranexamic acid (TA) on bleeding and surgical quality field in the functional endoscopic sinus surgery (FESS). METHODS A total of 74 patients who underwent FESS due to chronic rhinosinusitis were included. The patients were randomized into 2 groups. TA group (n = 37) received a topical cotton pledget soaked with TA and placebo (PL) group (n = 37) received a pledget soaked with saline solution. RESULTS A significant effect was noted for the TA group versus the PL group in the grade 1 of the Boezaart scale at 35 minutes (4 for TA group and no case for PL group). This effect was absent for higher grades. We did not notice a significant effect between the 2 groups at 5 minutes. Blood loss was 359 ml in the TA group versus 441 ml in the PL group. No significant change was observed between the 2 groups concerning the blood parameters. No side effects were reported. CONCLUSION Despite its safety when administrated locally and its low cost, TA provides limited effect on quality of surgical field after 35 minutes of the start of FESS in the patients with chronic rhinosinusitis. This effect was absent at the start of the intervention and when analyzing the blood loss and hematologic parameters.
Comparisons of Ultrasound-Guided Platelet-Rich Plasma Intra-Articular Injection and Extracorporeal Shock Wave Therapy in Treating ARCO I-III Symptomatic Non-Traumatic Femoral Head Necrosis: A Randomized Controlled Clinical Trial
Journal of pain research. 2022;15:341-354
BACKGROUND AND OBJECTIVE Osteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients. METHODS A total of 60 patients aged 40-79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the "group by time" interaction effects. RESULTS There were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P<0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = -0.82, 95% CI [-1.39, -0.25], P=0.005), WOMAC (mean difference = -4.19, 95% CI [-7.00, -1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported. CONCLUSION This study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.
High-titre methylene blue-treated convalescent plasma as an early treatment for outpatients with COVID-19: a randomised, placebo-controlled trial
The Lancet. Respiratory medicine. 2022
BACKGROUND Convalescent plasma has been proposed as an early treatment to interrupt the progression of early COVID-19 to severe disease, but there is little definitive evidence. We aimed to assess whether early treatment with convalescent plasma reduces the risk of hospitalisation and reduces SARS-CoV-2 viral load among outpatients with COVID-19. METHODS We did a multicentre, double-blind, randomised, placebo-controlled trial in four health-care centres in Catalonia, Spain. Adult outpatients aged 50 years or older with the onset of mild COVID-19 symptoms 7 days or less before randomisation were eligible for enrolment. Participants were randomly assigned (1:1) to receive one intravenous infusion of either 250-300 mL of ABO-compatible high anti-SARS-CoV-2 IgG titres (EUROIMMUN ratio ≥6) methylene blue-treated convalescent plasma (experimental group) or 250 mL of sterile 0·9% saline solution (control). Randomisation was done with the use of a central web-based system with concealment of the trial group assignment and no stratification. To preserve masking, we used opaque tubular bags that covered the investigational product and the infusion catheter. The coprimary endpoints were the incidence of hospitalisation within 28 days from baseline and the mean change in viral load (in log(10) copies per mL) in nasopharyngeal swabs from baseline to day 7. The trial was stopped early following a data safety monitoring board recommendation because more than 85% of the target population had received a COVID-19 vaccine. Primary efficacy analyses were done in the intention-to-treat population, safety was assessed in all patients who received the investigational product. This study is registered with ClinicalTrials.gov, NCT04621123. FINDINGS Between Nov 10, 2020, and July 28, 2021, we assessed 909 patients with confirmed COVID-19 for inclusion in the trial, 376 of whom were eligible and were randomly assigned to treatment (convalescent plasma n=188 [serum antibody-negative n=160]; placebo n=188 [serum antibody-negative n=166]). Median age was 56 years (IQR 52-62) and the mean symptom duration was 4·4 days (SD 1·4) before random assignment. In the intention-to-treat population, hospitalisation within 28 days from baseline occurred in 22 (12%) participants who received convalescent plasma versus 21 (11%) who received placebo (relative risk 1·05 [95% CI 0·78 to 1·41]). The mean change in viral load from baseline to day 7 was -2·41 log(10) copies per mL (SD 1·32) with convalescent plasma and -2·32 log(10) copies per mL (1·43) with placebo (crude difference -0·10 log(10) copies per mL [95% CI -0·35 to 0·15]). One participant with mild COVID-19 developed a thromboembolic event 7 days after convalescent plasma infusion, which was reported as a serious adverse event possibly related to COVID-19 or to the experimental intervention. INTERPRETATION Methylene blue-treated convalescent plasma did not prevent progression from mild to severe illness and did not reduce viral load in outpatients with COVID-19. Therefore, formal recommendations to support the use of convalescent plasma in outpatients with COVID-19 cannot be concluded. FUNDING Grifols, Crowdfunding campaign YoMeCorono.
Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis knee: A single-blind, randomized clinical trial
BACKGROUND Subchondral bony structure damage plays an essential role in the pathogenesis of osteoarthritis (OA) knee. An intra-articular injection cannot reach the damaged subchondral bony structure and treat its pathologies effectively. The objective of the study was to compare the clinical effects of single intra-articular injection with or without intra-osseous injections of PRP in the treatment of osteoarthritis (OA) knee. METHODS This was a single-blind, parallel-group, randomized clinical trial. Fifty patients, with OA knee (K&L grade III), with ages between 50 and 65 years, were randomly allocated into 'intra-osseous, intra-articular PRP' ('IO+IA-PRP') (n = 25) or 'intra-articular PRP' group ('IA-PRP') (n = 25). Patients in the 'IO+IA-PRP' group received 18 ml PRP injection, and the 'IA-PRP' group received 8 ml PRP injection. Intra-osseous injections were given at the tibial plateau (5 ml) and femoral condyle (5 ml), along with intra-articular knee injection (8 ml), under fluoroscopic guidance. Outcomes were measured using VAS-pain, the knee injury and osteoarthritis outcome score (KOOS), and the treatment satisfaction scale. All patients (n = 50) were followed up till six months. RESULTS The mean age was 57.12(4.27) years and 57.00(4.96) years in the 'IO+IA-PRP' and 'IA-PRP' groups. Both groups showed significant improvement in pain relief (VAS pain) and KOOS parameters: pain, symptoms, ADL function, sport and recreation function, and quality of life. Compared to the 'IA-PRP' group, the 'IO+IA-PRP' group showed a greater reduction of VAS pain at six months. However, no significant difference was obtained in VAS pain-relief between these two groups (p = 0.422) at six months. Similarly, at 6 months, in inter-group comparison, except 'sport and recreation function' (p < 0.05), no significant differences were obtained in mean-scores of KOOS parameters: pain (p = 0.514); symptom (p = 0.148), ADL-function (p = 0.991), QoL-(p = 0.376). Patients in the 'IO+IA-PRP' group complained of significant 'injection-associated' adverse events and consumed a greater number of Acetaphenomen. CONCLUSIONS Both groups showed significant improvement following the intervention. Intra-osseous PRP injections did not provide any additional benefit over intra-articular PRP injection until six months regarding pain relief and functional improvement.
Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial
Lancet (London, England). 2022;399(10324):530-40
BACKGROUND Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77-1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66-1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14-4·29); for patients who were antibody negative, the OR was 0·51 (0·29-0·90; p(interaction)=0·001). INTERPRETATION When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING US National Institutes of Health.
Hospitalised patients with COVID-19 enrolled in the ITAC trial in 11 countries (n= 593).
Hyperimmune intravenous immunoglobulin (hIVIG), (n= 301).
Placebo (n= 292).
The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extra-pulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7. Infusion reactions were more common in the hIVIG group (18.6%) than placebo (9.5%). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%).
Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial
Pediatric nephrology (Berlin, Germany). 2022
BACKGROUND The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. METHODS We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. RESULTS Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. CONCLUSION In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.
Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Lancet (London, England). 2022;399(10325):665-676
BACKGROUND Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. METHODS RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab. INTERPRETATION In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline. FUNDING UK Research and Innovation (Medical Research Council) and National Institute of Health Research.
Patients from 12 years old admitted to hospital with COVID-19; enrolled in the RECOVERY trial which took part in 127 UK hospitals (n= 9,785).
Casirivimab and imdevimab plus usual care (n= 4,839).
Usual care alone (n= 4,946).
In the primary efficacy population of seronegative patients, 396 (24%) of 1,633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1,520 patients allocated to usual care died within 28 days. In an analysis of all patients (regardless of baseline antibody status), 943 (19%) of 4,839 patients allocated to casirivimab and imdevimab versus 1,029 (21%) of 4,946 patients allocated to usual care died within 28 days. The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients. There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions were reported in 7 (<1%) patients.
Atorvastatin versus placebo in patients with covid-19 in intensive care: randomized controlled trial
BMJ (Clinical research ed.). 2022;376:e068407
OBJECTIVE To assess the effect of statin treatment versus placebo on clinical outcomes in patients with covid-19 admitted to the intensive care unit (ICU). DESIGN INSPIRATION/INSPIRATION-S was a multicenter, randomized controlled trial with a 2×2 factorial design. Results for the anticoagulation randomization have been reported previously. Results for the double blind randomization to atorvastatin versus placebo are reported here. SETTING 11 hospitals in Iran. PARTICIPANTS Adults aged ≥18 years with covid-19 admitted to the ICU. INTERVENTION Atorvastatin 20 mg orally once daily versus placebo, to be continued for 30 days from randomization irrespective of hospital discharge status. MAIN OUTCOME MEASURES The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality within 30 days from randomization. Prespecified safety outcomes included increase in liver enzyme levels more than three times the upper limit of normal and clinically diagnosed myopathy. A clinical events committee blinded to treatment assignment adjudicated the efficacy and safety outcomes. RESULTS Of 605 patients randomized between 29 July 2020 and 4 April 2021 for statin randomization in the INSPIRATION-S trial, 343 were co-randomized to intermediate dose versus standard dose prophylactic anticoagulation with heparin based regimens, whereas 262 were randomized after completion of the anticoagulation study. 587 of the 605 participants were included in the primary analysis of INSPIRATION-S, reported here: 290 were assigned to atorvastatin and 297 to placebo (median age 57 years (interquartile range 45-68 years); 256 (44%) women). The primary outcome occurred in 95 (33%) patients assigned to atorvastatin and 108 (36%) assigned to placebo (odds ratio 0.84, 95% confidence interval 0.58 to 1.21). Death occurred in 90 (31%) patients in the atorvastatin group and 103 (35%) in the placebo group (odds ratio 0.84, 95% confidence interval 0.58 to 1.22). Rates for venous thromboembolism were 2% (n=6) in the atorvastatin group and 3% (n=9) in the placebo group (odds ratio 0.71, 95% confidence interval 0.24 to 2.06). Myopathy was not clinically diagnosed in either group. Liver enzyme levels were increased in five (2%) patients assigned to atorvastatin and six (2%) assigned to placebo (odds ratio 0.85, 95% confidence interval 0.25 to 2.81). CONCLUSIONS In adults with covid-19 admitted to the ICU, atorvastatin was not associated with a significant reduction in the composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or all cause mortality compared with placebo. Treatment was, however, found to be safe. As the overall event rates were lower than expected, a clinically important treatment effect cannot be excluded. TRIAL REGISTRATION ClinicalTrials.gov NCT04486508.
Tranexamic acid combined with compression dressing reduces blood loss in gluteal muscle contracture surgery
BMC surgery. 2022;22(1):46
BACKGROUND Blood loss and incision-related complications caused by the surgical procedure to release gluteal muscle contracture (GMC) put negative effects on the surgical outcomes. Current procedures to prevent blood loss and complications are not satisfactory. The current study aimed to determine whether tranexamic acid (TXA) in combination with pressure dressing reduce the amount of blood loss, the rate of incision-related complications, and the rate of readmission for patients undergoing surgeries to release GMC. METHODS 49 GMC patients were finally included in the study and were randomly divided into two groups: study group and control group. Patients in both groups received minimally invasive surgery to release GMC except that in the study group, patients were administered a dosage of 20 mg/kg of intravenous TXA preoperatively, and 2 subsequent dosages of TXA at 10 mg/kg at two time points: 3 and 6 h after the first dose. Gauze soaked with TXA was used to pack the wound for 10 min before the incision closure. Then the wound was pressure-wrapped with a hip-spica bandage for 24 h after the surgery in the study group. RESULTS The level of UBL in the study group was significantly lower compared to that in the control group. Similar results were also found for UMHD and UMAD. The incision-related postoperative complications were greatly decreased in the study group compared to those of the control group as well. So was the 30-day readmission rate. All patients in both groups reached "excellent" or "good" level with respect to the postoperative function evaluation. CONCLUSIONS Intravenous and topical application of TXA combined with 24 h pressure hip-spica bandage reduces perioperative blood loss, rate of incision-related complications, and the rate of readmission for GMC patients undergoing minimally invasive surgical releasing procedure. Trial Registration Chinese Clinical and Trial Registry ChiCTR2000039216, registration date 2020/10/22, retrospectively registered.