High-Dose Quadrivalent Influenza Vaccine for Prevention of Cardiovascular and Respiratory Hospitalizations in Older Adults.

BACKGROUND: We assessed the relative vaccine effectiveness (rVE) of high-dose quadrivalent influenza vaccine (QIV-HD) versus standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing respiratory or cardiovascular hospitalizations in older adults. METHODS: FinFluHD was a phase 3b/4 modified double-blind, randomized pragmatic trial. Enrolment of 121,000 adults ≥65 years was planned over three influenza seasons (October to December 2019-2021). Participants received a single injection of QIV-HD or QIV-SD. The primary endpoint was first occurrence of an unscheduled acute respiratory or cardiovascular hospitalization (ICD-10 primary discharge J/I codes), from ≥14 days post-vaccination until May 31. The study was terminated after one season due to COVID-19; follow-up data for 2019-2020 are presented. RESULTS: 33,093 participants were vaccinated (QIV-HD, n = 16,549; QIV-SD, n = 16,544); 529 respiratory or cardiovascular hospitalizations (QIV-HD, n = 257; QIV-SD, n = 272) were recorded. The rVE of QIV-HD versus QIV-SD to prevent respiratory/cardiovascular hospitalizations was 5.5% (95% CI, -12.4 to 20.7). When prevention of respiratory and cardiovascular hospitalizations were considered separately, rVE estimates of QIV-HD versus QIV-SD were 5.4% (95% CI, -28.0 to 30.1) and 7.1% (95% CI, -15.0 to 25.0), respectively. Serious adverse reactions were <0.01% in both groups. CONCLUSIONS: Despite insufficient statistical power due to the impact of COVID-19, rVE point estimates demonstrated a trend toward a benefit of QIV-HD over QIV-SD. QIV-HD was associated with lower respiratory or cardiovascular hospitalization rates than QIV-SD, with a comparable safety profile. Adequately powered studies conducted over multiple influenza seasons are needed to determine statistical significance of QIV-HD compared with QIV-SD against preventing respiratory and cardiovascular hospitalizations. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT04137887.

Nirsevimab for Prevention of Hospitalizations Due to RSV in Infants.

BACKGROUND: The safety of the monoclonal antibody nirsevimab and the effect of nirsevimab on hospitalizations for respiratory syncytial virus (RSV)-associated lower respiratory tract infection when administered in healthy infants are unclear. METHODS: In a pragmatic trial, we randomly assigned, in a 1:1 ratio, infants who were 12 months of age or younger, had been born at a gestational age of at least 29 weeks, and were entering their first RSV season in France, Germany, or the United Kingdom to receive either a single intramuscular injection of nirsevimab or standard care (no intervention) before or during the RSV season. The primary end point was hospitalization for RSV-associated lower respiratory tract infection, defined as hospital admission and an RSV-positive test result. A key secondary end point was very severe RSV-associated lower respiratory tract infection, defined as hospitalization for RSV-associated lower respiratory tract infection with an oxygen saturation of less than 90% and the need for supplemental oxygen. RESULTS: A total of 8058 infants were randomly assigned to receive nirsevimab (4037 infants) or standard care (4021 infants). Eleven infants (0.3%) in the nirsevimab group and 60 (1.5%) in the standard-care group were hospitalized for RSV-associated lower respiratory tract infection, which corresponded to a nirsevimab efficacy of 83.2% (95% confidence interval [CI], 67.8 to 92.0; P<0.001). Very severe RSV-associated lower respiratory tract infection occurred in 5 infants (0.1%) in the nirsevimab group and in 19 (0.5%) in the standard-care group, which represented a nirsevimab efficacy of 75.7% (95% CI, 32.8 to 92.9; P = 0.004). The efficacy of nirsevimab against hospitalization for RSV-associated lower respiratory tract infection was 89.6% (adjusted 95% CI, 58.8 to 98.7; multiplicity-adjusted P<0.001) in France, 74.2% (adjusted 95% CI, 27.9 to 92.5; multiplicity-adjusted P = 0.006) in Germany, and 83.4% (adjusted 95% CI, 34.3 to 97.6; multiplicity-adjusted P = 0.003) in the United Kingdom. Treatment-related adverse events occurred in 86 infants (2.1%) in the nirsevimab group. CONCLUSIONS: Nirsevimab protected infants against hospitalization for RSV-associated lower respiratory tract infection and against very severe RSV-associated lower respiratory tract infection in conditions that approximated real-world settings. (Funded by Sanofi and AstraZeneca; HARMONIE ClinicalTrials.gov number, NCT05437510).

Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial.

TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: -1.44% and G3: -1.48% vs. G1: -0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.

A Randomized Controlled Study Evaluating the Clinical Benefits of a Cellulose Acetate Mesh Coated with a Soft Silicone in the Management of Acute Wounds.

INTRODUCTION: Dressings are a mainstay for wound management; however, dressing adherence to the wound or periwound area can cause pain and trauma at removal. Dressing-related trauma includes skin reactions, adherence to the wound, and skin stripping. The development of atraumatic wound contact layer dressings has been a major advancement in reducing trauma. OBJECTIVE: This study compares the benefits of a cellulose acetate mesh (CAM) coated with soft silicone versus a flexible polyamide net (FPN) coated with soft silicone. MATERIALS AND METHODS: A multicenter, randomized controlled study was conducted in 70 patients (35 in CAM group [1 patient exclused due to not receiving treatment], 35 in the FPN group) with traumatic, postsurgical, and burn wounds. Wounds were assessed once per week for 4 weeks to measure dressing adherence to the wound bed, percent reepithelialization, and patient tolerance. All wounds were prepared according to standard of care wound management protocol at the time of assessment. RESULTS: In this study, 97.06% (n = 33) of patients in the CAM group and 91.43% (n = 32) in the FPN group did not report dressing adherence during any of the assessments. Average time to complete reepithelialization was 16 days in the CAM group versus 15 days in the FPN group (P = .4958), and both products had excellent tolerance. CONCLUSIONS: This study demonstrated that CAM coated with a soft silicone performed as well as the FPN contact layer in minimizing dressing adherence, time to complete reepithelialization, and patient tolerance.

Technology Applications: Use of Digital Health Technology to Enable Drug Development.

PURPOSE: This pilot study developed and evaluated the feasibility, usability, and perceived satisfaction with an end-user mobile medical application and provider web portal. The two interfaces allowed for remote monitoring, provided daily guidance in the management of hypertension and diarrhea, and allowed for rapid management of adverse events during a clinical trial of olaparib and cediranib. PATIENTS AND METHODS: eCO (eCediranib/Olaparib) was designed for patient self-reported, real-time management of hypertension and diarrhea using remote monitoring. eCO links to a Bluetooth-enabled blood pressure (BP) monitor and transmits data to a secure provider web portal. eCO use was assessed for suitability, usability, and satisfaction after 4 weeks using a 17-item questionnaire. Metrics regarding patient-reported BP and diarrhea events were analyzed. RESULTS: Sixteen patients enrolled in the pilot. A total of 98.2% of expected BP values were reported: 94.2% via Bluetooth and 5.8% entered manually. Twelve patients experienced 21 BP events (systolic BP > 140 and/or diastolic BP > 90 mmHg on two consecutive readings); data from cycle 1 were comparable to the study database. Thirteen patients reported diarrhea (more than one stool per 24 hours over baseline) categorized as grade 1 or 2, which was comparable to the study database. Survey analysis showed that patients had statistically significant, positive responses to the use of the eCO application. Patients indicated eCO use made them feel more involved in their care and better connected to their health care team. The only aspect of the application that did not show a statistically significant positive response was the process of reporting diarrhea. CONCLUSION: The eCO application was designed to assist in managing acute treatment-related events most often associated with treatment discontinuation, need for drug holidays, or dose interruption. Hypertension and diarrhea events reported via eCO allowed rapid provider response and a positive overall patient experience.

A bivalent pneumococcal histidine triad protein D-choline-binding protein A vaccine elicits functional antibodies that passively protect mice from Streptococcus pneumoniae challenge.

Vaccines based on conserved pneumococcal proteins are being investigated because serotype coverage by pneumococcal polysaccharide and polysaccharide conjugate vaccines is incomplete and may eventually decrease due to serotype replacement. Here, we examined the functionality of human antibodies induced by a candidate bivalent choline-binding protein A- pneumococcal histidine triad protein D (PcpA-PhtD) vaccine. Pre- and post-immune sera from subjects who had been vaccinated with the PcpA-PhtD candidate vaccine were tested in an established passive protection model in which mice were challenged by intravenous injection with Streptococcus pneumoniae serotype 3 strain A66.1. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial surface binding by serum antibodies was determined by a flow cytometry-based assay. Sera from 20 subjects were selected based on low activity of pre-immune samples in the passive protection model. Bacterial surface binding correlated more strongly with anti-PcpA (0.87; p < 0.0001) than with anti-PhtD (0.71; p < 0.0001). The odds ratio for predicting survival in the passive protection assay was higher for the anti-PcpA concentration (470 [95% confidence interval (CI), 46.8 to >999.9]) than for the anti-PhtD concentration (3.4 [95% CI, 1.9 to 5.6]) or bacterial surface binding (9.4 [95% CI, 3.6 to 24.3]). Pooled post-immune serum also protected mice against a challenge with S. pneumoniae serotype 3 strain WU2. Both anti-PcpA and anti-PhtD antibodies induced by the bivalent candidate vaccine mediate protection against S. pneumoniae. The results also showed that the ELISA titer might be useful as a surrogate for estimating the functional activity of antibodies induced by pneumococcal protein vaccines.

Predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis.

OBJECTIVE: To evaluate the predictive value of tender joints compared to synovitis for structural damage in rheumatoid arthritis (RA). METHODS: A post hoc analysis was performed on a prospective 2-year study of 59 patients with active RA starting on antitumour necrosis factor (TNF). Tenderness and synovitis was assessed clinically at baseline, followed by blinded ultrasound assessment (B-mode and power Doppler ultrasound (PDUS)) on the hands and feet (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal and 10 metatarsophalangeal (MTP) joints). Radiographs of these joints were performed at baseline and at 2 years. The risk of radiographic progression with respect to the presence of baseline tenderness or synovitis, as well as its persistence (after 4 months of anti-TNF), was estimated by OR (95% CI). RESULTS: Baseline tender joints were the least predictive for radiographic progression (OR=1.53 (95% CI 1.02 to 2.29) p<0.04), when compared to synovitis (clinical OR=2.08 (95% CI 1.39 to 3.11) p<0.001 or PDUS OR=1.80 (95% CI 1.20 to 2.71) p=0.005, respectively). Tender joints with the presence of synovitis were predictive of radiographic progression (OR=1.89 (95% CI 1.25 to 2.85) p=0.002), especially seen in the MTP joints. Non-tender joints with no synovitis were negatively predictive (OR=0.57 (95% CI 0.39 to 0.82) p=0.003). Persistence of tender joints was negatively predictive (OR=0.38 (95% CI 0.18 to 0.78) p=0.009) while persistence of synovitis was predictive (OR=2.41 (95% CI 1.24 to 4.67) p=0.01) of radiographic progression. CONCLUSIONS: Synovitis is better than tenderness to predict for subsequent structural progression. However, coexistence of tenderness and synovitis at the level of an individual joint is predictive of structural damage, particularly in the MTP joints. TRIAL REGISTRATION NUMBER: NCT00444691.

Therapeutic effects of recombinant feline interferon-omega on feline leukemia virus (FeLV)-infected and FeLV/feline immunodeficiency virus (FIV)-coinfected symptomatic cats.

The clinical efficacy of a recombinant feline interferon, rFeIFN-omega, was evaluated for the treatment of cats presented with clinical signs associated with feline leukemia virus (FeLV) infection and FeLV/feline immunodeficiency virus (FIV) coinfection in the field. In this multicentric, double-blind, placebo-controlled trial, 81 cats meeting the inclusion criteria were randomly placed into 2 groups and treated subcutaneously with rFelFN-omega (1 million [M]U/kg per day) or placebo once daily for 5 consecutive days in 3 series (day 0, 14, 60). The cats were monitored for up to 1 year for clinical signs and mortality. During the initial 4-month period, interferon (IFN)-treated cats (n = 39) had significantly reduced clinical scores compared with placebo (n = 42), with all cats having received concomitant supportive therapies. Compared with the control, the IFN-treated group showed significantly lower rates of mortality: 39% versus 59% (1.7-fold higher risk of death for controls) at the 9-month time point and 47% versus 59% (1.4-fold higher risk of death for controls) at the 12-month time point. The IFN treatment was associated with minor but consistent improvement in abnormal hematologic parameters (red blood cell count, packed cell volume, and white blood cell count), apparently underlying the positive effects of IFN on clinical parameters. These data demonstrate that rFeIFN-omega initially has statistically significant therapeutic effects on clinical signs and later on survival of cats with clinical signs associated with FeLV infection and FeLV/FIV coinfection.