A randomized, placebo-controlled trial of long-acting dexamethasone viscous gel delivered by transforaminal injection for lumbosacral radicular pain.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03372161.

Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.

BACKGROUND: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days. METHODS: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both. Participants were randomly assigned in a 2:1 ratio to receive a single dose (two consecutive intramuscular injections, one containing tixagevimab and the other containing cilgavimab) of either 300 mg of AZD7442 or saline placebo, and they were followed for up to 183 days in the primary analysis. The primary safety end point was the incidence of adverse events after a single dose of AZD7442. The primary efficacy end point was symptomatic Covid-19 (SARS-CoV-2 infection confirmed by means of reverse-transcriptase-polymerase-chain-reaction assay) occurring after administration of AZD7442 or placebo and on or before day 183. RESULTS: A total of 5197 participants underwent randomization and received one dose of AZD7442 or placebo (3460 in the AZD7442 group and 1737 in the placebo group). The primary analysis was conducted after 30% of the participants had become aware of their randomized assignment. In total, 1221 of 3461 participants (35.3%) in the AZD7442 group and 593 of 1736 participants (34.2%) in the placebo group reported having at least one adverse event, most of which were mild or moderate in severity. Symptomatic Covid-19 occurred in 8 of 3441 participants (0.2%) in the AZD7442 group and in 17 of 1731 participants (1.0%) in the placebo group (relative risk reduction, 76.7%; 95% confidence interval [CI], 46.0 to 90.0; P<0.001); extended follow-up at a median of 6 months showed a relative risk reduction of 82.8% (95% CI, 65.8 to 91.4). Five cases of severe or critical Covid-19 and two Covid-19-related deaths occurred, all in the placebo group. CONCLUSIONS: A single dose of AZD7442 had efficacy for the prevention of Covid-19, without evident safety concerns. (Funded by AstraZeneca and the U.S. government; PROVENT ClinicalTrials.gov number, NCT04625725.).

Coronary artery disease (CAD) risk factor analysis in an age-stratified hospital population with systemic lupus erythematosus (SLE).

OBJECTIVES: Patients with systemic lupus erythematosus (SLE) are at higher risk for coronary artery disease (CAD) particularly at a younger age. We sought to determine the effect of risk factors on the prevalence of CAD in age stratified hospitalized patients with SLE. METHODS: The National Inpatient Sample (NIS) was queried for hospitalized patients with SLE during the years 2010-2015, and a control group without SLE. The study sample was stratified by age, 18-35 years, 36-55 years, and adults >55 years. The effect of SLE and traditional Framingham risk factors on the prevalence of CAD were assessed. Dominance analysis allowed for ranking of CAD risk factors in each age group. RESULTS: A total 167,466 patients were matched to an equal number of controls. 88.8% were women, 48.5% Caucasian and 29% African-American. In lupus patients 18-35 years prevalent risk factors included hyperlipidemia, hypertension, hypercoagulability and CKD. Diabetes and depression ranked least important. In middle and older patients, traditional risk factors were dominant. In adults >55 years the prevalence of CAD appears higher in Caucasians whereas in young patients 18-35 years, African Americans are dominant. CONCLUSION: CAD in the young adult patient with SLE is represented predominately by an African-American population and it is dominated by a hypercoagulable state and a less significant role for diabetes. In the lupus cohort over 55 years, which is predominantly Caucasian, SLE specific factors are less significant.

Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee: A Randomized Clinical Trial.

Importance: Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments. Objective: To assess 2 subcutaneous tanezumab dosing regimens for OA. Design, Setting, and Participants: A randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit). Patients enrolled were 18 years or older with hip or knee OA, inadequate response to OA analgesics, and no radiographic evidence of prespecified joint safety conditions. Interventions: Patients received by subcutaneous administration either tanezumab, 2.5 mg, at day 1 and week 8 (n = 231); tanezumab, 2.5 mg at day 1 and 5 mg at week 8 (ie, tanezumab, 2.5/5 mg; n = 233); or placebo at day 1 and week 8 (n = 232). Main Outcomes and Measures: Co-primary end points were change from baseline to week 16 in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10, no to extreme pain), WOMAC Physical Function (0-10, no to extreme difficulty), and patient global assessment of osteoarthritis (PGA-OA) (1-5, very good to very poor) scores. Results: Among 698 patients randomized, 696 received 1 or more treatment doses (mean [SD] age, 60.8 [9.6] years; 65.1% women), and 582 (83.6%) completed the trial. From baseline to 16 weeks, mean WOMAC Pain scores decreased from 7.1 to 3.6 in the tanezumab, 2.5 mg, group; 7.3 to 3.6 in the tanezumab, 2.5/5 mg, group; and 7.3 to 4.4 in the placebo group (least squares mean differences [95% CI] vs placebo were -0.60 [-1.07 to -0.13; P = .01] for tanezumab, 2.5 mg, and -0.73 [-1.20 to -0.26; P = .002] for tanezumab, 2.5/5 mg). Mean WOMAC Physical Function scores decreased from 7.2 to 3.7 in the 2.5-mg group, 7.4 to 3.6 in the 2.5/5-mg group, and 7.4 to 4.5 with placebo (differences vs placebo, -0.66 [-1.14 to -0.19; P = .007] for tanezumab, 2.5 mg, and -0.89 [-1.37 to -0.42; P < .001] for tanezumab, 2.5/5 mg). Mean PGA-OA scores decreased from 3.4 to 2.4 in the 2.5-mg group, 3.5 to 2.4 in the 2.5/5-mg group, and 3.5 to 2.7 with placebo (differences vs placebo, -0.22 [-0.39 to -0.05; P = .01] for tanezumab, 2.5 mg, and -0.25 [-0.41 to -0.08; P = .004] for tanezumab, 2.5/5 mg). Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%). The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively. Conclusions and Relevance: Among patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and adverse event findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02697773.

Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease.

Allogeneic hematopoietic stem cell transplantation (HSCT) is rarely performed in adult patients with sickle cell disease (SCD). We utilized the chemotherapy-free, alemtuzumab/total body irradiation 300 cGy regimen with sirolimus as post-transplantation immunosuppression in 13 high-risk SCD adult patients between November 2011 and June 2014. Patients received matched related donor (MRD) granulocyte colony-stimulating factor-mobilized peripheral blood stem cells, including 2 cases that were ABO incompatible. Quality-of-life (QoL) measurements were performed at different time points after HSCT. All 13 patients initially engrafted. A stable mixed donor/recipient chimerism was maintained in 12 patients (92%), whereas 1 patient not compliant with sirolimus experienced secondary graft failure. With a median follow-up of 22 months (range, 12 to 44 months) there was no mortality, no acute or chronic graft-versus-host disease (GVHD), and no grades 3 or 4 extramedullary toxicities. At 1 year after transplantation, patients with stable donor chimerism have normalized hemoglobin concentrations and improved cardiopulmonary and QoL parameters including bodily pain, general health, and vitality. In 4 patients, sirolimus was stopped without rejection or SCD-related complications. These results underscore the successful use of a chemotherapy-free regimen in MRD HSCT for high-risk adult SCD patients and demonstrates a high cure rate, absence of GVHD or mortality, and improvement in QoL including the applicability of this regimen in ABO mismatched cases (NCT number 01499888).

A parallel open-label trial to evaluate microbial cellulose wound dressing in the treatment of diabetic foot ulcers.

The purpose of this study was to compare the rate of wound healing in diabetic foot ulcers (DFU) using either a microbial cellulose (MC) wound dressing or Xeroform™ Petrolatum gauze. In a parallel, open-label trial in which the primary outcome was the rate of wound healing and the time to wound closure, 15 ulcers in type II diabetic patients received an MC dressing. Wounds in 19 control patients with type II diabetes were treated with a Xeroform gauze dressing. All wounds were non infected, Wagner stage II or III and received standard care including debridement, non weight bearing limb support and weekly wound evaluation. The mean time to heal in the MC (±SE) treated group was 32 days ± 2.5 and for controls it was 48 days ± 4.7 (P < 0.01). The rate of weekly wound closure (mean ± SE) was 1.7 times faster in the MC-treated group (cellulose treated, -5.04% per week ± 0.38 versus control, -2.93% per week ± 0.19), (P < 0.001). Among covariants tested by univariate regression, only the original wound area correlated with the time to wound closure (P < 0.001). In conclusion, with the provision of current standards of care, the application of an MC dressing to a diabetic ulcer may enhance the rate of wound healing and shorten the time course of epithelisation.

Microbial cellulose wound dressing in the treatment of skin tears in the frail elderly.

  In a randomized trial of predominantly category II and III skin tears in a population of frail elderly nursing home residents, standard wound care (24 residents) with Xeroform™ and a secondary dressing (Tegaderm™) was compared with a single application of a microbial cellulose membrane Dermafill (27 residents). Outcomes included the time to wound closure, pain reduction, and ease of use. While wound area was slightly larger in the microbial cellulose treated group, the healing time was equivalent to controls. However, pain control, ease of use, and patient and nursing staff satisfaction were superior to control with the use of the microbial cellulose wound dressing.

Microbial cellulose wound dressing in the treatment of nonhealing lower extremity ulcers.

Following standard care, nonhealing lower extremity (LE) ulcers were managed with a bacterial cellulose (BC) wound dressing, Dermafill™, (AMD/Ritmed, Tonawanda, NY), derived from Acetobacter xylinum. The time to 75% reduction in wound size was compared in 11 chronic wounds before and after the application of BC. The mean period of observation before the application of BC was 315 days; (95% CI: 239-392 days). With the application of BC to these chronic wounds, the mean time to 75% epithelization was reduced to 81 days (95% CI: 50-111 days) with a median of 79 days. The rate of wound closure with BC was significantly faster than with standard care (P < 0.001). When applied to nonhealing LE ulcers, a BC wound dressing shortens the time to wound closure over standard care.

Asymptomatic hyperuricemia: to treat or not to treat.

Treatment of asymptomatic hyperuricemia is not necessary in most patients, unless perhaps they have very high levels of uric acid or are otherwise at risk of complications, such as those with a personal or strong family history of gout, urolithiasis, or uric acid nephropathy.