Local Adverse Reactions Research Articles

Rho-Kinase Inhibitors as Emerging Targets for Glaucoma Therapy.

Glaucoma, the leading cause of irreversible blindness worldwide, is a chronic and progressive optic neuropathy characterized by damage to the optic and retinal nerve fiber layers, which can lead to permanent loss of peripheral or central vision. Reduction of intraocular pressure (IOP) is the only known modifiable risk factor for preventing and treating glaucoma. Rho kinase (ROCK) inhibitors are a new class of glaucoma drugs with a novel mechanism of action and good safety profile. They exert neuroprotective effects, act on the trabecular tissue, increase the outflow of aqueous humor, and reduce intraocular pressure. However, they also cause local adverse reactions, including common conjunctival congestion and subconjunctival bleeding; however, most are self-limiting and temporary. Netarsudil (0.02%), a ROCK inhibitor, relaxes the trabecular meshwork, increases the outflow of aqueous humor, reduces scleral venous pressure, anddirectly decreases IOP. Conjunctival congestion can be reduced if netarsudil is administered at night. The combination of these medications is always more effective than the single drug. Ripasudil (0.4%), another ROCK inhibitor, also lowers IOP; however, conjunctival hyperemia is the most common adverse drug reaction. The purpose of this review is to summarize the effects and adverse reactions of ROCK inhibitors in the experimental trial stage and in clinical treatment in recent years, providing suggestions for future clinical drug use, and research and development to reduce the side effects of these drugs, maximize the potential for reducing IOP, and improve the therapeutic effect.

Efficacy of hemoporfin-PDT on port-wine stains: A retrospective analysis of 2952 cases

ObjectiveTo conduct a retrospective analysis of Hemoporfin photodynamic therapy (HMME-PDT) in the treatment of port-wine stains (PWS). MethodA retrospective analysis was conducted based on the clinical data from March 2017 to December 2022, so as to summarize the demographic characteristics, clinical efficacy and adverse reactions. The effectiveness of HMME-PDT was examined with respect to treatment times, age, gender, subtype, and location of PWS lesions. ResultThe age of the 2952 cases ranged from 8 months to 56 years old (median, 2.8 years), with 1419 males (48.07 %), and 1533 females (51.93 %). There were 669 cases of pink type (22.66 %), 2184 cases of purplish red type (73.98 %), and 99 cases of nodular thickening type (3.35 %). The prevalence location was face (88.04 %), neck (14.94 %), limbs and trunk. 1602 cases (54.27 %) had never received treatment, 661 cases (22.39 %) had been treated by pulse dye laser (PDL), 229 cases (7.76 %) had previously been treated by PDT, 296 cases (10.03 %) had received both the modalities.The 2952 cases completed totally 7996 HMME-PDT times. Cure rate and effective rate increased continuously with the number of treatments. The pink type has the highest cure rate and effective rate, followed by the purplish red type and the last was the nodular thickening type. The therapeutic effects are considerably influenced by age, subtype, and treatment site (P < 0.05). However, there was no significant difference in the effectiveness of HMME-PDT between both genders.The local adverse reactions after the first treatment included edema (97.73 %), itching (82.62 %), purpura-like change (79.51 %), crusts (24.59 %), infection (4.07 %), scars (1.08 %), hyperpigmentation (0.61 %), and depigmentation (0.41 %). Nausea and vomiting occurred in 2 juveniles and 1 young adult (5, 6 and 22 years old respectively) immediately after treatment, and did not interfere with the administration of the treatment. Patients aged 21–30 were found to have a 3.4-fold higher likelihood of undergoing HMME-PDT under general anesthesia compared to those aged 15 or younger. There was no distinct systemic adverse reaction, such as allergic responses, cardiovascular effects, neurological symptoms, hematological abnormalities, respiratory symptoms, or musculoskeletal issues. ConclusionHMME-PDT is preferred in treating PWS, with relatively high effective rate and cure rate, mild local reactions and no distinct systemic adverse reaction.

Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China

ObjectivesDuring the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. MethodsThis study was a follow-up trial of the “Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial.” Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. ResultsThe geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. ConclusionCo-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

Phase II, Safety and Immunogenicity of RAZI Cov Pars (RCP) SARS Cov-2 Vaccine in Adults Aged 18–70 Years; A Randomized, Double-Blind Clinical Trial

BackgroundThis study explores the safety and immunogenicity of the Razi-Cov-Pars (RCP) SARS Cov-2 recombinant spike protein vaccine. MethodIn a randomized, double-blind, placebo-controlled trial, adults aged 18–70 were randomly allocated to receive selected 10 µg/200 µl vaccine strengths or placebo (adjuvant). It included two intramuscular injections at days 0 and 21, followed by an intranasal dose at day 51. Immediate and delayed solicited local and systemic adverse reactions after each dose up to a week, and specific IgG antibodies against SARS Cov-2 spike antigens two weeks after the 2nd dose were assessed as primary outcomes. Secondary safety outcomes were abnormal laboratory findings and medically attended adverse events (MAAE) over six months follow up. Secondary immunogenicity outcomes were neutralizing antibody activity and cell-mediated immune response. ResultBetween May 27th and July 15th, 2021, 500 participants were enrolled. Participants' mean (SD) age was 37.8 (9.0), and 67.0 % were male. No immediate adverse reaction was observed following the intervention. All solicited local and systemic adverse events were moderate (Grade I-II). Specific IgG antibody response against S antigen in the vaccine group was 5.28 times (95 %CI: 4.02–6.94) the placebo group with a 75 % seroconversion rate. During six months of follow-up, 8 SAEs were reported, unrelated to the study intervention. The participants sustained their acquired humoral responses at the end of the sixth month. The vaccine predominantly resulted in T-helper 1 cell-mediated immunity, CD8+ cytotoxic T-cell increase, and no increase in inflammatory IL-6 cytokine. ConclusionRCP vaccine is safe and creates strong and durable humoral and cellular immunity. Trial registration(IRCT20201214049709N2).

Efficacy and safety assessment of netakimab in scalp psoriasis

Introduction. Scalp psoriasis is a common disease that has a long, recurrent course with severe desquamation, dryness and itching of the skin. The location of the pathological process in an aesthetically significant area, constant therapy leads to low satisfaction and adherence to treatment and, as a result, to a pronounced decrease in the quality of life.Aim. To study the efficacy and safety of netakimab in psoriasis of the scalp.Materials and methods. 52 adult patients (n = 52) with psoriasis of the face and scalp were under observation. The severity of the psoriatic lesion of the scalp was determined using the PSSI index (Psoriasis Severity Scalp Index). The assessment was carried out before the start of treatment, in the first week, and then every 4 weeks up to and including 52 weeks. The Dermatological Quality of Life Index (DLQI) – were determined by questionnaires before the start of treatment, at the 12th and 52nd weeks. All patients on an outpatient basis received netakimab monotherapy at a dose of 120 mg in the form of two subcutaneous injections of 1 ml (60 mg) of the drug, each administered once a week at weeks 0, 1 and 2, then 1 time every 4 weeks. The total duration of treatment for each patient was 1 year (52 weeks). The safety of netakimab was evaluated based on the development of adverse events and local reactions to the administration of the drug.Results. The results of the study (n = 52) for 52 weeks showed high efficacy of netakimab. 48% of patients achieved PSSI 90 by the week 12 of treatment and 77% of patients achieved PSSI 90 by the week 52, itching of the scalp significantly decreased and the quality of life improved. During the 52 weeks of the study, there were no cases of early withdrawal due to adverse events and cases of serious adverse events.Conclusion. Based on the study results we recommend netakimab for medical use among patients with moderate and severe scalp psoriasis.

The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

Short-term efficacy and safety observation of standardized mite allergen extract rush subcutaneous immunotherapy for allergic rhinitis: a prospective study

Objective: To conduct a comparative analysis of the efficacy, safety, and cytokine changes associated with three distinct dose escalation regimens of allergen-specific immunotherapy (AIT), and to provide valuable insights into the implementation of safer and more effective accelerated immunotherapy in clinical practice. Methods: A prospective study of subcutaneous immunotherapy (SCIT) was conducted at Renmin Hospital of Wuhan University, involving patients with allergic rhinitis visited from 2019 to 2022. Participants were allocated to one of three treatment groups based on their preferences: conventional immunotherapy (CIT, 23 cases), cluster immunotherapy (CLIT, 25 cases), or rush immunotherapy (RIT, 18 cases). The RIT group received a single subcutaneous injection of 150 mg of omalizumab one week before commencing treatment. Subjective evaluation indices, including the Combined Symptom and Medication Score (CSMS), Visual Analogue Scale (VAS), and single symptom score, were recorded alongside objective evaluation indices (e.g., sIgE, tIgE, Th1/2 and Th17 cytokines) and adverse reactions. Assessments were conducted at baseline, and at 1, 7, and 15 weeks after treatment. SPSS 22.0 software was used for data processing and analysis. Results: The study included a total of 66 patients, comprising 37 males and 29 females, who completed the treatment regimen. In all three groups, CSMS and VAS scores showed significant reductions at 1, 7, and 15 weeks post-treatment (all P<0.05). Notably, the RIT group demonstrated a significantly lower VAS score (4.33±0.94) compared to the CIT (9.48±1.37) and CLIT (9.44±1.33) groups at 1 week post-treatment (P<0.05). Additionally, the RIT group (0.62±0.23) exhibited a lower CSMS score than the CIT (1.54±0.21) and CLIT (1.06±0.22) groups at 15 weeks post-treatment (P<0.05). Furthermore, at the point of reaching the maintenance dose, the RIT group (0.61±0.20) demonstrated superior improvement in nasal itching symptoms compared to the CIT (1.78±0.38) and CLIT groups (1.56±0.32), with P<0.05. The incidence of local adverse reactions in the RIT group (36/11.76%) was lower than that in the CIT (69/20.00%) and CLIT groups (62/16.53%), with P<0.05. Notably, none of the three groups reported grade 3/4 systemic adverse reactions, and there was no statistically significant difference in systemic adverse reactions among the three groups. Following treatment, IL-4, IL-5, IL-6, IL-17, sIgE, sIgE/tIgE, and Eos% exhibited varying degrees of decrease in all three groups, whereas IL-10, TNF, and IFN-γ did not show significant changes. Conclusions: All three distinct dose escalation regimens of SCIT demonstrated substantial clinical efficacy. Of note, the approach of combining a single injection of omalizumab with RIT significantly improved early-stage efficacy and exhibited the advantages of safety, effectiveness, and convenience, establishing it as a reliable immunotherapy method.

Safety evaluation of simultaneous administration of quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and older

Objective: To evaluate the safety of simultaneous administration of quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine in adults aged 60 years and older. Methods: From November 2021 to May 2022, eligible participants aged 60 years and older were recruited in Taizhou City, Jiangsu Province, China, and a total of 2 461 participants were ultimately enrolled in this study. Each participant simultaneously received one dose of quadrivalent influenza split virion vaccine and one dose of 23-valent pneumococcal polysaccharide vaccine. The safety was observed within 28 days after vaccination. Safety information was collected through voluntary reporting and regular follow-ups. Results: All 2 461 participants completed the simultaneous administration of both vaccines and the safety follow-ups for 28 days after vaccination. The mean age of the participants was (70.66±6.18) years, with 54.61% (1 344) being male, and all participants were Han Chinese residents. About 22.51% (554) of the participants had underlying medical conditions. The overall incidence of adverse reactions within 0-28 days after simultaneous vaccination was 2.07% (51/2 461), mainly consisting of Grade 1 adverse reactions [1.83% (45/2 461)], with no reports of Grade 4 or higher adverse reactions or vaccine-related serious adverse events. The incidence of local adverse reactions was 0.98% (24/2 461), primarily presenting as pain at the injection site [0.93% (23/2 461)]. The incidence of systemic adverse reactions was 1.42% (35/2 461), with fever [0.85% (21/2 461)] being the main symptom. In the group with underlying medical conditions and the healthy group, their overall incidence of adverse reactions was 2.53% (14/554) and 1.94% (37/1 907), respectively. The incidence of local adverse reactions in the two groups was 1.62% (9/554) and 0.79% (15/1 907), respectively, and the incidence of systemic adverse reactions was 1.44% (8/554) and 1.42% (27/1 907), respectively, with no statistically significant differences between them (all P>0.05). Conclusion: It is safe for adults aged 60 years and older to receive quadrivalent influenza split virion vaccine and 23-valent pneumococcal polysaccharide vaccine at the same time.

The biointegration profile of fiber-reinforced plates following tibial implantation in sheep.

Biointegrative, mineral fiber-reinforced bone fixation implants recently introduced in orthopedic surgery have expanded available treatment options for fractures and bone deformities. This new technology aims to address the disadvantages of permanent metallic implants while overcoming inherent concerns of adverse inflammatory reactions when using polymer-based orthopedic implants. The purpose of this double-arm preclinical study was to evaluate the safety, biocompatibility, and biointegration of fiber-reinforced plates, following implantation on the tibias of eight sheep. Left tibias underwent periosteal elevation, allowing for implant attachment directly onto the cortical surface; right tibia plates were implanted over intact periosteum. Microcomputed tomography and histopathology were performed at 13, 26, 52, 78, 104, and 134 weeks postimplantation. All animals were evaluated clinically at each time point, with no evidence of local adverse reactions. Histopathology demonstrated anti-inflammatory M2-like macrophages and multinucleated giant cells corresponding to implant bioabsorption, similar for both groups at each time point, and indicating expected implant biocompatibility. Inflammatory cells (i.e., eosinophils, lymphophyctes, plasma cells, and M1-like macrophages) were absent throughout the study. The bioabsorption process had started at 13 W, with the highest rate at 52-78 W. At 104 W, only residual polymer material was left (∼5% of implant area). Low amounts of mineral fibers were evident at 78 W and were absent (fully remodeled) by 104 W. At 134 W, implants at both sites were fully bioabsorbed. In conclusion, these new fiber-reinforced implants demonstrated bone remodeling and complete biointegration, with no adverse tissue response. Clinical significance: In this double-arm, 2.5-year study, a biointegrative, fiber-reinforced plate implanted on the tibias of sheep was fully absorbed within 134 weeks, with no adverse tissue reaction. Bioabsorption was similar, with or without periosteal elevation, mimicking conditions like those observed in traumatic injuries disrupting the periosteum, open reduction and internal fixation, or minimally invasive surgeries. These results demonstrate the feasibility, versatility, and safety of this new class of biointegrative bone implants. This newly developed technology avoids the complications of the removal of metal implants.

Revealing the composite fretting-corrosion mechanisms of Ti6Al4V alloy against zirconia-toughened alumina ceramic in simulated body fluid

The composite fretting-corrosion damage due to combinations of radial, tangential, rotational, and other fretting causes local adverse tissue reactions and failure of artificial joints. Previous studies have mainly focused on the single fretting mode, while ignoring the coupled effects of multimode fretting. The fretting-corrosion mechanisms between the components are not yet fully understood. In this study, the tangential-radial composite fretting was realized by applying a normal alternating load to the tangential fretting. The composite fretting corrosion behavior of zirconia toughened alumina ceramic/Ti6Al4V alloy used for the head-neck interface of an artificial hip joint under simulated body fluid was investigated. The effects of displacement and alternating load amplitude were considered. The alternating load amplitude was given by the maximum normal load and minimum normal load ratio R. The results showed that the composite fretting damage mechanisms of this pair were mainly abrasion and tribocorrosion. Cracking also existed under large displacement. The effect of alternating load on fretting corrosion was found to be mainly caused by changes in the contact area and instantaneous contact state. In addition, the alternating load during the composite fretting promoted the formation of the three-body layer in the contact area. A decrease in load ratio caused fretting to change from gross to partial slip. In the case of small displacement, the load ratio had little effect on the friction work or wear scar profile. The corrosion rate of materials and the concentration of metal ions released into the solution increased as load ratio decreased. In cases of large and medium displacement, load ratio reduction increased the friction work and expanded the wear scar. The reduction in load ratio also caused the corrosion rate of the material to increase and then decrease, and the metal ion concentration decreased.

EXTRA-ARTICULAR KNEE LIGAMENT RECONSTRUCTIONS USING LARS (LIGAMENT AUGMENTATION AND RECONSTRUCTION SYSTEM) SYNTHETIC GRAFTS IN ELITE ATHLETES

AbstractIntroductionThe aim of this study was to determine if elite athletes could return to professional sport after MCL or PLC reconstruction using LARS ligaments and to demonstrate the safety and efficacy of LARS by reporting sport longevity, subsequent surgeries and complications.MethodsA retrospective review of all extra-articular knee ligament reconstructions in elite athletes utilising LARS ligaments by 3 knee surgeons between January 2013 and October 2020 was undertaken. Return to play (RTP) was defined as competing at professional level or national/ international level in amateur sport.ResultsSixty-four (84.2%) MCL and 12 (15.8%) PLC reconstructions utilising LARS in elite athletes were included. 52 (68.4%) underwent concomitant cruciate(s) reconstruction. The mean age was 25.1 years (SD +/− 4.50. Most were football (35, 46.1%) or rugby players (35, 46.1%).Sixty-seven athletes (88.2%) RTP with 65 (97.0%) of these playing at the same or higher Tegner level. 56 (83.6%) and 20 (57.1%) were still playing at 2 and 5 years post-surgery.Six (7.9%) players (5 of whom RTP) required further surgery relating to the LARS / metalwork and there was one case of adverse local inflammatory reaction to the synthetic material. There was one MCL re-rupture, sustained 4 years after RTP.ConclusionUtilising LARS in extra-articular knee ligament reconstructions allows 88.2% of athletes, with a variety of knee ligament injuries, to return to elite sport. The low morbidity rates coupled with 57% of athletes still playing 5 years post-surgery suggests the LARS is safe and effective in these cases.

Safety and efficacy of the FAKHRAVAC compared with BBIBP-Corv2 against SARS-CoV-2 in adults: a non-inferiority multi-center trial

BackgroundWe compared Fakhravac and BBIBP-Corv2 vaccines in a phase III trial.MethodWe conducted a multicenter, parallel-group, active-control, non-inferiority clinical trial with pragmatic considerations assessing the safety and efficacy of Fakhravac and BBIBP-Corv2 vaccines. We started with two randomized double-blind arms and added two non-randomized open-label arms (based on participant preference) because of slow recruitment. The adult population received 0.5 ml (10 µg per dose) intramuscular injections of Fakhravac or BBIBP-Corv-2 vaccines 21 days apart. The primary outcome was the occurrence of PCR-positive symptomatic Covid-19 disease 14 days or more after the second injection. A 10% non-inferiority margin to the reported 72.8% efficacy of BBIBP-Corv2 was assumed. Cox proportional hazard modeling was used to estimate hazard ratios and their 95% confidence intervals.ResultWe enrolled 24,056 adults in four groups (randomized-Fakhravac: 824, randomized-BBIBP-Corv2: 832; Non-randomized-Fakhravac: 19,429, Non-randomized-BBIBP-Corv2: 2971). All observed local and systemic adverse reactions were generally self-limited and resolved completely. We observed similar Serious Adverse Event (SAE) rates in the BBIBP-Corv2 (2.57, 95% CI 1.33–4.49) and Fakhravac (2.25, 95% CI 1.72–2.89) groups; none of which were related to the vaccines received. We recorded 9815 Medically Attendant Adverse Events (MAAE), 736 of which were categorized as somehow related. The rate of related MAAE in the Fakhravac was similar to the BBIBP-Corv2 groups (0.31 and 0.26 per 1000 person-day) in the randomized and considerably higher (0.24 and 0.07 per 1000 person-day) in the non-randomized arms. We observed 129 (35% of the 365 required by target sample size) events of PCR + symptomatic Covid-19 during four months of active follow-up in the randomized arm, demonstrating that those receiving the Fakhravac vaccine were significantly less likely (HR = 0.69; 95% CI 0.49–0.98) to be diagnosed with PCR + symptomatic Covid-19 compared with those receiving BBIBP-Corv2 vaccine. After adjusting for type I error using the O’Brien Fleming method, the Fakhravac vaccine was non-inferior to the BBIBP-Corv2 (assuming a 10% non-inferiority margin to the reported 72.8% BBIBP-Corv2 vaccine efficacy; HR < 1.35) (One-way test: HR = 0.66; 99.8% CI 0.38–1.15). In the non-randomized arm, the results were inconclusive (HR = 1.23; 95% CI 0.96–1.61). We observed 5 cases of hospitalized Covid-19 in the randomized arm, none of which occurred in the Fakhravac vaccine group. Those receiving the Fakhravac vaccine were four times less likely to go to the hospital because of a Covid-19 diagnosis (HR = 0.24; 95% CI 0.10–0.60). The vaccine efficacy of the Fakhravac vaccine is estimated to be 81.5% (95% CI 81–82.4%).ConclusionFakhravac inactivated SARS-CoV-2 vaccine has comparable safety and efficacy to the BBIBP-Corv2 vaccine.Trial registration This study was registered with the Iranian Registry of Clinical Trials (www.irct.ir: IRCT20210206050259N3).

Immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine in people aged 60 years and above

Objective: To evaluate the immunogenicity and safety of revaccination of 23-valent pneumococcal polysaccharide vaccine (PPV23) in elderly people aged ≥60 years. Methods: The elderly aged ≥60 years with 1 dose of PPV23 vaccination were selected as revaccination group and those without history of pneumococcal vaccine immunization were selected as the first vaccination group. One dose of PPV23 was administered to both groups, and the first blood samples were collected before vaccination while the second blood samples were collected on day 28-40 after vaccination. ELISA was used to detect the concentrations of anti-specific serotype Streptococcus pneumoniae podocyte polysaccharide immunoglobulin G, and the safety of the vaccination was evaluated after 30 days. Results: The geometric mean concentration (GMC) of antibody to 23 serotypes before the vaccination (0.73-13.73 μg/ml) was higher in revaccination group than in the first vaccination group (0.39-7.53 μg/ml), the GMC after the vaccination (1.42-31.65 μg/ml) was higher than that before the vaccination (0.73-13.73 μg/ml) in the revaccination group, and the GMC after the vaccination (1.62-43.76 μg/ml) was higher than that before the vaccination (0.39-7.53 μg/ml) in the first vaccination group; the geometric mean growth multiple in revaccination group (2.16-3.60) was lower than that in the first vaccination group (3.86-16.13); The mean 2-fold antibody growth rate was lower in revaccination group (53.68%, 95%CI: 52.30%-55.06%) than in the first vaccination group (93.16%, 95%CI: 92.18%- 94.15%), all differences were significant (P<0.001). After the vaccination, 13 serotypes of GMC were higher in the first vaccination group than in revaccination group (P<0.001), the differences were not significant for 10 serotypes of GMC (P>0.05). The incidence of local adverse reaction was 19.20% and 13.27% in revaccination group and the first vaccination group, respectively (P=0.174). Conclusions: The antibody level in ≥60 years people who received one dose of PPV23 after a 5-year interval was still higher than that in unvaccinated people. The antibody level decreased after 5 years of the first vaccination, and the antibody level could be rapidly increased by one more dose vaccination, but the overall immune response was lower than that of the first vaccination; revaccination with PPV23 has a good safety.

Infant vaccination against pertussis in Argentina: Parent-reported outcomes on reactogenicity, impact on daily routine and satisfaction after pentavalent whole-cell or hexavalent acellular pertussis vaccines

IntroductionIn Argentina, a pentavalent whole-cell pertussis vaccine (wP) is used in the National Immunization Program, however hexavalent acellular pertussis (aP) vaccines are available in the private market. ObjectiveTo describe parent or guardianś perceptions on reactogenicity, daily routine and satisfaction after a first or third dose of a wP-pentavalent plus IPV (wP-group) or the fully-liquid aP-hexavalent vaccine (aP-group) in infants. Material and methodsThis was a prospective observational and analytical study. Parents or guardians of infants born at term attending a public or private vaccination center in Buenos Aires City were invited to participate. All parents or guardians had completed 12-year schooling and were asked to fill out an online 7-day post vaccination questionnaire. The questionnaire was validated as the first phase of the study. Descriptive analysis of study variables was carried out, REDCap was used for the online survey, and STATA 14 for data analysis. Results1071 parents or guardians answered the questionnaire (response rate 82%), 530 for wP-group and 541 for aP-group.Local and systemic adverse reactions, in groups wP and aP respectively, were: pain 83%, 28%; swelling 63%, 16%; redness 52%, 22%; irritability 72%, 52%; fever 37%, 8%; loss of appetite 36%, 19%; drowsiness 38%, 27%; and vomiting 15%, 11%.Impact on daily life: social activities 36%, 20%; routine 48%, 24%; mood 39%, 23%; vitality 47%, 24%; sleep 50%, 30%; and appetite 22%, 7%.Parents were satisfied with the vaccination process in 96% and 98% for wP-group and aP-group respectively. Parents reported willingness to bring infant for future vaccine doses in 97% and 99% for wP-group and aP-group respectively. ConclusionsReported reactogenicity and impact on family daily routine was higher in infants receiving wP-pentavalent than aP-hexavalent vaccines. Parents in both groups conveyed vaccine acceptance and positive intentions for future immunizations.

Adverse Events and Vaccination: Extensive Local Reaction after Anatoxin Vaccine—A Case Report

Post-vaccine adverse reactions are unwanted medical events that concern both the public and healthcare professionals. The objective of this paper is to present a detailed analysis of the case of an extensive local adverse reaction after the administration of a vaccine dose containing diphtheria–tetanus anatoxins. A good knowledge of post-vaccine side effects allows for complete and correct diagnosis, as well as appropriate individualized recommendations. Such an approach contributes to restoring public confidence in vaccines and vaccinations. The patient was a 6-year-old boy, with a history of asthma under chronic treatment with corticosteroids. He developed extensive local inflammatory lesions accompanied by functional disorders of the left arm, which began six hours after the administration of the fifth dose of the diphtheria–tetanus–pertussis–poliomyelitis vaccine. The lesions, which extended to the forearm, were locally treated with antiseptics and systemically treated with hydrocortisone hemisuccinate. They completely remitted within 14 days. Laboratory investigations revealed neutrophilia (6,870 neutrophils/µL), which could be related to the long-term treatment with steroids. The investigation needed the plasma concentration of diphtheria and tetanus anatoxins antibodies and the pro-inflammatory cytokines to be complete.

#6501 MULTICENTER STUDY ESTIMATING THE INCIDENCE OF ADVERSE EVENTS FROM SARS-CoV-2 VACCINATION AND ITS POTENTIAL EFFECT ON THE OUTCOME OF LUPUS NEPHRITIS

Abstract Background and Aims The present study aimed to investigate the incidence of adverse events associated with SARS-CoV-2 vaccination in patients with a history of lupus nephritis (LN). Method Patients with biopsy-proven LN, who were vaccinated against SARS-CoV-2, were retrospectively studied. Patients who had reached end-stage kidney disease prior to vaccination were excluded. We recorded the histopathological diagnosis of LN, immunosuppressive regimens which were given for LN, the outcome of LN as a result of treatment, the tome interval form the diagnostic biopsy to vaccination, the number of doses each patient received, all reported adverse effects associated with the vaccine against SARS-CoV-2, including systemic and local adverse events. We also estimated the potential effect of the vaccination on the clinical course of LN among patients who were in remission. Results Ninety patients with systemic lupus erythematosus and renal involvement were included with a mean age of 31 (±18) years, of whom 80% were women. Proliferative LN was present in the diagnostic kidney biopsy in 68 (77.2%) cases and 91.8% of the included patients had achieved remission with treatment prior to vaccination. 86.7% of patients were vaccinated with 3 (2.75, 3) doses. The median time from diagnosis to vaccination was 59 (32-137) months and 70.5% of patients were receiving immunosuppression at the time of vaccination. 30.5% of patients reported systemic adverse reactions and 36.1% local adverse reactions at the site of administration. Among patients in remission who were vaccinated, only 1 (1.2%) patient experienced a relapse of LN within 3 weeks of the 1st dose. Three (3.4%) patients who had treatment-resistant disease experienced a worsening of SLE activity after vaccine administration. Conclusion In this cohort of patients with a history of LN, the SARS-CoV-2 vaccine appears safe, with no effect on the likelihood of disease recurrence among patients who have achieved remission.

Comparing recombinant human rabies monoclonal antibody (ormutivimab) with human rabies immunoglobulin (HRIG) for postexposure prophylaxis: A phase III, randomized, double-blind, non-inferiority trial

ObjectivesTo evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). MethodsThis phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. ResultsA total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. Conclusionormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. Clinical trials registrationChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

Immune response after vaccination using inactivated vaccine for coronavirus disease 2019.

Immune response after vaccination using inactivated vaccine for coronavirus disease 2019.

Pharmacokinetics comparison of vardenafil as administered by an intranasal spray formulation vs a 10-mg oral tablet.

Oral vardenafil (VDF) tablet is an effective treatment for erectile dysfunction (ED), but intranasal administration with a suitable formulation can lead to a faster onset of action and offer more convenient planning for ED treatment. The primary purpose of the present pilot clinical study was to determine whether intranasal VDF with an alcohol-based formulation can result in more "user-friendly pharmacokinetics" as compared with oral tablet administration. This single-dose randomized crossover study was conducted in 12 healthy young volunteers receiving VDF as a 10-mg oral tablet or 3.38-mg intranasal spray. Multiple blood concentrations were obtained, and VDF concentrations were determined with a liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters following each treatment were compared and adverse events assessed. Pharmacokinetic parameters were obtained: apparent elimination rate constant, elimination half-life, peak concentration, peak time, total area under the curve, and relative bioavailability. Although mean apparent elimination rate constant, elimination half-life, peak concentration, and total area under the curve were similar between intranasal and oral administration, the median peak time from intranasal was much shorter (10vs 58minutes, P < .001, Mann-Whitney U test). The variability of the pharmacokinetic parameters was also less with intranasal than oral administration. The relative bioavailability of intranasal to oral was 1.67. Intranasal VDF caused transient but tolerable local nasal reactions in 50% of subjects. Other adverse events (eg, headache) were similar between the treatments. The incidence of adverse events was, however, significantly less in the second treatment after initial exposure to VDF. No serious adverse events were noted. Intranasal VDF potentially offers a more timely and lower dose for the treatment of ED in patients who can tolerate the transient local adverse reactions. The strength of this study is its randomized crossover design. Because the study was conducted in 12 healthy young subjects, the results may not reflect those observed in elderly patients who may be likely taking VDF for ED. Nevertheless, the changes of pharmacokinetic parameters in the present study are likely a reflection of the differences between intranasal and oral administration of the formulations. Our study indicated that the present VDF formulation, when administered intranasally, can achieve a more rapid but similar plasma concentration with only about one-third dose when compared with the oral administration.

Safety and immunogenicity of heterologous ChAdOx1-nCoV19 and BNT162b2 vaccination: A meta-analysis of the heterologous COVID-19 vaccination outcomes.

Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.