Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort.

BACKGROUND: There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). METHODS: This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. RESULTS: Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47-0.66, p < 0.001). CONCLUSION: In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Technological Aspects of Nanoemulsions for Post-harvest Preservation of Fruits and Vegetables.

Recent times have witnessed a growing demand for sustainable technology for food preservation that can retain its freshness, promises lower contents of additives and preservatives, safe consumption, eco-friendly milder processing technologies and eco-friendlier packaging solutions. Application of Biopolymers has served as the most sustainable and viable option to its synthetic counterparts. These biopolymers have been incorporated to develop biodegradable packaging like edible films and coatings owing to their biological origin. Nanoemulsion technology offers a leap forward to upgrade the features of conventional biodegradable packaging items. The present review discusses various trends and perspectives of nanoemulsion technology in post-harvest preservation for enhancing the shelf life of fresh fruits and vegetables. It investigates the interconnectedness between food preservation techniques, biodegradable packaging materials made from biopolymers, and nanoemulsions. It further addresses the preservation challenges post-harvest and underscores the limitations of conventional preservation methods, advocating for eco-friendly alternatives with a specific focus on the potential of nanoemulsions in enhancing food safety and quality. This review elaborates on the composition, formulation techniques, nanoemulsion products and role of nanoemulsions in the management of foodborne pathogens. Furthermore, it examines the potential health hazards linked to the use of nanoemulsions and stresses the significance of a regulatory framework for food safety. In conclusion, this review offers insights into the promising prospects of using nanoemulsions in food preservation.

Effects of Laser Bandwidth in Direct-Drive High-Performance DT-Layered Implosions on the OMEGA Laser.

In direct-drive inertial confinement fusion, the laser bandwidth reduces the laser imprinting seed of hydrodynamic instabilities. The impact of varying bandwidth on the performance of direct-drive DT-layered implosions was studied in targets with different hydrodynamic stability properties. The stability was controlled by changing the shell adiabat from (α_{F}≃5) (more stable) to (α_{F}≃3.5) (less stable). These experiments show that the performance of lower adiabat implosions improves considerably as the bandwidth is raised indicating that further bandwidth increases, beyond the current capabilities of OMEGA, would be greatly beneficial. These results suggest that the future generation of ultra-broadband lasers could enable achieving high convergence and possibly high gains in direct drive ICF.

The intracortical excitability changes underlying the enhancing effects of rewards and punishments on motor performance.

Monetary rewards and punishments enhance motor performance and are associated with corticospinal excitability (CSE) increases within the motor cortex (M1) during movement preparation. However, such CSE changes have unclear origins. Based on converging evidence, one possibility is that they stem from increased glutamatergic (GLUTergic) facilitation and/or decreased type A gamma-aminobutyric acid (GABAA)-mediated inhibition within M1. To investigate this, paired-pulse transcranial magnetic stimulation was used over the left M1 to evaluate intracortical facilitation (ICF) and short intracortical inhibition (SICI), indirect assays of GLUTergic activity and GABAA-mediated inhibition, in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. Behaviourally, rewards and punishments enhanced both reaction and movement time. During movement preparation, regardless of rewards or punishments, ICF increased when the index finger initiated sequences, whereas SICI decreased when both the index and little fingers initiated sequences. This finding suggests that GLUTergic activity increases in a finger-specific manner whilst GABAA-mediated inhibition decreases in a finger-unspecific manner during preparation. In parallel, both rewards and punishments non-specifically increased ICF, but only rewards non-specifically decreased SICI as compared to neutral. This suggests that to enhance performance rewards both increase GLUTergic activity and decrease GABAA-mediated inhibition, whereas punishments selectively increase GLUTergic activity. A control experiment revealed that such changes were not observed post-movement as participants processed reward and punishment feedback, indicating they were selective to movement preparation. Collectively, these results map the intracortical excitability changes in M1 by which incentives enhance motor performance.

Proteomics profiling and in silico analysis of peptides identified during Fusarium oxysporum infection in castor (Ricinus communis).

Castor is industrially important non-edible oil seeds crop severely affected by soil borne pathogen Fusarium oxysporum f. sp. ricini which causes heavy economic losses among the castor growing states in India and worldwide. The development of Fusarium wilt resistant varieties in castor is also challenging because the genes identified for resistance are recessive in nature. Unlike transcriptomics and genomics, proteomics is always a method of choice for quick identification of novel proteins expressed during biological events. Therefore, comparative proteomic approach was employed for identification of proteins released in resistant genotype during Fusarium infection. Protein was extracted from inoculated 48-1 resistant and JI-35 susceptible genotype and subjected to 2D-gel electrophoresis coupled with RPLC-MS/MS. This analysis resulted in 18 unique peptides in resistant genotype and 8 unique peptides in susceptible genotype were identified through MASCOT search database. The real time expression study showed that 5 genes namely CCR 1, Germin like protein 5-1, RPP8, Laccase 4 and Chitinase like 6 was found highly up-regulated during Fusarium oxysporum infection. Furthermore, end point PCR analysis of c-DNA showed amplification of three genes namely Chitinase 6 like, RPP8 and ß-glucanase exclusively in resistant genotype indicating that these genes may be involved in resistance phenomenon in castor. Up-regulation of CCR-1 and Laccase 4 involved in lignin biosynthesis provides mechanical strength and may help to prevent the entry of fungal mycelia and protein Germin like 5-1 helps to neutralized ROS by SOD activity. The clear role of these genes can be further confirmed through functional genomics for castor improvement and also for development of transgenic in different crops for wilt resistance.

MANAGING ARTHRITIS PAIN: MEDICATIONS AND LIFESTYLE CHANGES.

This study aims to characterize and contrast the triennial rates at which doctors prescribe PT, determine patient, doctor, and practicing characteristics related to every therapy suggestion, and assess pain relievers, lifestyle counseling, and PT as effective treatments for knee osteoarthritis (OA). We analyzed the National Ambulatory Medical Care Survey. Nonsteroidal anti-inflammatory drugs (NSAID), narcotics prescriptions, physical therapy referrals, and primary care physician visits for knee OA have been determined and evaluated. The average yearly rate after three years of therapy was determined. Using multivariable logistic modeling with adjustments for complicated sample design, we analyzed the relationships among patient, physician, and practice characteristics and treatments. Over time the patients were prescribed physical therapy to improve their lifestyle whereas the percentage of patients who were prescribed NSAIDs or drugs. Physical therapy, lifestyle therapy, and drugs were prescribed at similar rates across time for basic care doctor visits. There was an association between nonclinical characteristics and treatment suggestions, such as provider type, practice setting, and geographic proximity. Physical therapy (PT) and lifestyle counseling (LC) seem underused in patients with knee OA, but prescriptions for pain medication rose over the studied period. The treatment decisions varied due to variables outside of medicine. Increased usage of physical therapy and lifestyle changes, as well as decreased treatment variance for knee OA, are important areas for further study.

THE ROLE OF EXERCISE IN PREVENTING CHRONIC DISEASES: CURRENT EVIDENCE AND RECOMMENDATIONS.

Regular exercise helps to enhance health outcomes and lower risk factors, making it a crucial element in the prevention of chronic diseases. By being physically active, people can improve their general health and delay the onset of a number of chronic illnesses. For understanding the relationship between increased physical activity or decreased physical inactivity and favorable health outcomes, observational studies are the main source of information. We will look for systematic analyses of randomized controlled trials with a main emphasis on outcomes linked to diseases in the Cochrane Database of systematic studies. Evaluation will be limited to those in a few key chronic conditions. Preventing chronic illness and achieving better results in the management or treatment of chronic illness are the main outcomes of interest. For each chronic condition (such as the control of glucose in diabetes or any change in hypertension blood pressure), these results will be summarized and displayed. The design and implementation of chronic conditions, physical exercise illness conditions, and adverse physical activity-related events are of secondary interest. Our findings should help decision-makers, guideline organizations, and academics identify the most effective physical activity programs for major chronic disease management and prevention. Exercise and physical activity (PA) offers a non-invasive approach to the management of chronic disorders. More physiological, biochemical, and molecular data on the positive effects of PA and exercise on health should constitute a primary focus of future studies.

Combining ability, heterosis and performance of grain yield and content of Fe, Zn and protein in bread wheat under normal and late sowing conditions.

Wheat (Triticum aestivum L.) is inherently low in protein content, Zn and Fe. Boost yield gains have unwittingly reduced grain Zn and Fe, which has had negative impacts on human health. The aim of this study was to understand the inheritance of grain yield per plant and grain Fe, Zn, and protein concentrations in bread wheat (Triticum aestivum L.) under normal and late sown conditions. Half diallel crosses were performed using 10 parents. The crosses and parents were evaluated in replicated trials for the two conditions, to assess the possibility of exploiting heterosis to improve micronutrient contents. The per se performance, heterosis, combining ability, and genetic components were estimated for different characters in both environments. The results revealed that hybrid GW 451 × GW 173 exhibited better parent heterosis (BPH) and standard heterotic effects (SH) in all environments. In both sowing conditions, the general combining ability (GCA) effects of poor × poor parents also showed high specific combining ability (SCA) effects of hybrids for both the micronutrients and protein contents. However, σ2A/σ2D greater than unity confirmed the preponderance of additive gene action for protein content, and GW 173 was identified as a good general combiner for these characteristics under both environments. SCA had positive significant (P < 0.001) correlations with BPH, SH1, SH2, and the phenotype for yield component traits and grain protein, Fe, and Zn concentrations in both conditions. A supplementary approach for biofortifying wheat grainis required to prevent malnutrition.

Mental health of diplomatic personnel: scoping review.

BACKGROUND: Diplomatic personnel frequently relocate as part of their roles, requiring them to adapt to various cultural and political conditions; many are also at risk of experiencing trauma from being deployed to high-threat postings. With diplomatic personnel having to balance the usual pressures of their work with the uncertainties of COVID-19 in recent years, it is particularly important now to understand how to protect their mental health. AIMS: To synthesize existing literature on the well-being of diplomatic personnel to improve understanding of how to protect their mental health. METHODS: A scoping review was carried out to explore what is already known about the well-being of staff working in diplomatic roles. Four databases were searched and reference lists, as well as one key journal, were hand-searched. RESULTS: Fifteen relevant publications were included. There was little consensus as to how the psychological well-being of diplomatic personnel compares to other populations or which factors predict well-being. Diplomats' psychological responses to traumatic experiences appeared similar to those of other trauma-exposed occupational groups. CONCLUSIONS: Further research is needed to better understand the well-being of diplomatic personnel, particularly those not deployed to high-threat posts.

Effect of bariatric surgery on maternal cardiovascular system.

OBJECTIVE: Bariatric surgery is a successful treatment for sustainable weight loss and has been associated with improvement in cardiovascular function. Pregnancy after bariatric surgery is becoming increasingly common; however, little is known about the maternal cardiovascular system postsurgery. The aim of this study was to investigate maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery, compared with that in women with no history of weight-loss surgery and an early-pregnancy body mass index (BMI) similar to the presurgery BMI of the postbariatric women. METHODS: This was a prospective, observational, longitudinal study conducted from April 2018 to June 2020 including 30 pregnant women who had undergone bariatric surgery and 30 who had not, matched for presurgery BMI. Participants were seen at three timepoints during pregnancy: 12-14, 20-24 and 30-32 weeks' gestation. At all visits, maternal blood pressure (BP) was measured and cardiac geometry and function were assessed using two-dimensional (2D) transthoracic echocardiography. On a subset of patients (15 in each group), 2D speckle tracking was performed to assess global longitudinal and circumferential strain. Offline analysis was performed, and multilevel linear mixed-effects models were used for all comparisons. RESULTS: Compared with the no-surgery group, and across all trimesters, pregnant women with previous bariatric surgery had lower BP, heart rate and cardiac output and higher peripheral vascular resistance (P < 0.01 for all). Similarly, the postbariatric group demonstrated more favorable cardiac geometry and diastolic indices, including lower left ventricular mass, left atrial volume and relative wall thickness, together with higher E-wave/A-wave flow velocity across the mitral valve and higher mitral velocity (E') at the lateral and medial annulus on tissue Doppler imaging (P < 0.01 for all). There was no difference in ejection fraction, although global longitudinal strain was lower in postbariatric women (P < 0.01), indicating better systolic function. CONCLUSION: Our findings indicate better maternal cardiovascular adaptation in women with previous bariatric surgery compared with presurgery BMI-matched pregnant women with no history of weight-loss surgery. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Surgical outcomes of T4b oral cancers: assessment of prognostic factors and a need to re-evaluate the current staging system.

T4b oral cancer is a broad umbrella term for all advanced oral cancers, the prognosis of which varies drastically for disease of the same stage, according to the extent of the masticator space involvement. This was a retrospective observational study including all consecutive T4b oral squamous cell carcinoma patients treated surgically between January 2015 and January 2016 and followed up until January 2020. The disease was classified as upper disease or lower disease based on the anatomical location in relation to an imaginary plane passing through the base of the retromolar trigone. The prime objective was to evaluate overall survival and prognostic factors affecting overall survival. The projected 5-year overall and disease-free survival rates were 40.7% and 35.6%, respectively. The assessment of prognostic factors revealed that lower disease (lower anatomical subsites), bone invasion, and lymph nodal spread significantly affected survival. Patients with disease in an upper anatomical location without bone and nodal involvement can achieve fairly good survival (projected 5-year overall survival of 64.2%) when compared to the other subsets of patients. We propose a re-evaluation of the current staging system based on the prognostic features, so that all patients are not considered under a single stage, since their survival differs significantly.

Predicting hot electron generation in inertial confinement fusion with particle-in-cell simulations.

A series of two-dimensional particle-in-cell simulations with speckled laser drivers was carried out to study hot electron generation in direct-drive inertial confinement fusion on OMEGA. Scaling laws were obtained for hot electron fraction and temperature as functions of laser/plasma conditions in the quarter-critical region. Using these scalings and conditions from hydro simulations, the temporal history of hot electron generation can be predicted. The scalings can be further improved to predict hard x-rays for a collection of OMEGA warm target implosions within experimental error bars. These scalings can be readily implemented into inertial confinement fusion design codes.

Diagnosing low-mode (ℓ < 6) and mid-mode (6 ≤ ℓ ≤ 60) asymmetries in the post-stagnation phase of laser-direct-drive deuterium-tritium cryogenic implosions on OMEGA.

Low- and mid-mode perturbations are possible candidates for performance limitations in cryogenic direct-drive implosions on the OMEGA laser at the Laboratory of Laser Energetics. Simulations with a 3D hydrocode demonstrated that hotspot imagers do not show evidence of the shell breakup in the dense fuel. However, these same simulations revealed that the low- and mid-mode perturbations in the dense fuel could be diagnosed more easily in the post-stagnation phase of the implosion by analyzing the peak in the x-ray emission limb at the coronal-fuel interface than before or at the stagnation phase. In experiments, the asymmetries are inferred from gated images of the x-ray emission of the implosion by using a 16-pinhole array imager filtered to record x-ray energies >800 eV and an x-ray framing camera with 40-ps time integration and 20-µm spatial resolution. A modal analysis is applied to the spatial distribution of the x-ray emission from deuterium and tritium cryogenic implosions on OMEGA recorded after the bang time to diagnose the low- and mid-mode asymmetries, and to study the effect that the beam-to-target ratio (Rb/Rt) has on the shell integrity.

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the "gold-standard" preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.

Effect of a very low negative dietary cation-anion difference (DCAD) diet on plasma and urine metabolomics of prepartum Holstein cows.

The objectives of this cross-sectional, nonintervention, observational study were to compare urine and blood parameters between cows consuming a positive dietary cation-anion difference (DCAD) diet [early dry cows, DCAD + 250 mEq/kg of dry matter (DM), n = 15] with the same cows consuming a negative DCAD diet (-220 mEq/kg of DM) 10 d after moving them from the early dry to the prepartum group. The most remarkable finding was that cows consuming the anionic diet had very low urine pH and very low base excess in blood, suggestive of uncompensated metabolic acidosis. Importantly, the metabolomics data revealed that only urine concentrations of essential and aromatic amino acids were decreased, and that concentrations of total nonessential amino acids and glucogenic amino acids were increased in plasma and reciprocally decreased in urine, suggesting that the cows fed anionic salts were attempting to meet a high glucose demand by mobilizing gluconeogenic amino acid reserves. Notably, the dietary anionic salts exerted marked effects on glycerophospholipids, with a reduction in most phosphatidylcholine containing diacyl (PC aa) and acyl-alkyl (PC ae) moieties in plasma and urine. Further characterization of these metabolomic profiles may lead to the development of novel biomarkers to identify cows susceptible to metabolic acidosis and other metabolic diseases.

Investigation of ion dynamics of laser ablated single and colliding carbon plasmas using Faraday cup.

We report a comparative study of a single plasma and a colliding laser produced plasma, investigated using a Faraday cup. An enhancement in ion emission and stagnation is observed in colliding plasma plume compared to single plasma plume. We observed that fast ion generation in laser ablated plasma can be achieved at large laser intensity on to the target. As laser intensity increases ionic yield increases for both colliding and single plume and at a fixed laser intensity ionic yield decreases with increase in ambient pressure. The double peak structure is observed in the ion signal at large fluence where the peaks correspond to fast and slow species. A Faraday cup composed of nine collectors is used to measure the spatial/angular distribution of ion of expanding plasma plume. Ionic yield is found to be larger in the colliding plasma plume than the single plasma plume at all spatial/angular positions.

Bound on hot-spot mix in high-velocity, high-adiabat direct-drive cryogenic implosions based on comparison of absolute x-ray and neutron yields.

In laser-driven implosions for laboratory fusion, the comparison of hot-spot x-ray yield to neutron production can serve to infer hot-spot mix. For high-performance direct-drive implosions, this ratio depends sensitively on the degree of equilibration between the ion and electron fluids. A scaling for x-ray yield as a function of neutron yield and characteristic ion and electron hot-spot temperatures is developed on the basis of simulations with varying degrees of equilibration. We apply this model to hot-spot x-ray measurements of direct-drive cryogenic implosions typical of the direct-drive designs with best ignition metrics. The comparison of the measured x-ray and neutron yields indicates that hot-spot mix, if present, is below a sensitivity estimated as ∼2% by-atom mix of ablator plastic into the hot spot.

Aetiology and prognosis of community-acquired pneumonia at the Adult University Teaching Hospital in Zambia.

BACKGROUND: Community-acquired pneumonia (CAP) is a frequent cause of death worldwide, and in sub-Saharan Africa particularly. Human immunodeficiency virus infection (HIV) and tuberculosis (TB) influence pathogen distribution in patients with CAP. Previous studies in sub-Saharan Africa have shown different frequencies of respiratory pathogens and antibiotic susceptibility compared to studies outside Africa. This study aimed to investigate the aetiology, presentation, and treatment outcomes of community-acquired pneumonia in adults at the University Teaching Hospital in Lusaka, Zambia. MATERIALS AND METHODS: Three-hundred-and-twenty-seven patients were enrolled at the University Teaching Hospital in Lusaka between March 2018 and December 2018. Clinical characteristics and laboratory data were collected. Sputum samples were tested by microscopy, other TB diagnostics, and bacterial cultures. RESULTS: The commonest presenting complaint was cough (96%), followed by chest pain (60.6%), fever (59.3%), and breathlessness (58.4%). The most common finding on auscultation of the lungs was chest crackles (51.7%). Seventy percent of the study participants had complaints lasting at least a week before enrolment. The prevalence of HIV was 71%. Sputum samples were tested for 286 patients. The diagnostic yield was 59%. The most common isolate was Mycobacterium tuberculosis (20%), followed by Candida species (18%), Klebsiella pneumoniae (12%), and Pseudomonas aeruginosa (7%). Streptococcus pneumoniae was isolated in only four patients. There were no statistically significant differences between the rates of specific pathogens identified in HIV-infected patients compared with the HIV-uninfected. Thirty-day mortality was 30%. Patients with TB had higher 30-day mortality than patients without TB (p = 0.047). CONCLUSION: Mycobacterium tuberculosis was the most common cause of CAP isolated in adults at the University Teaching Hospital in Lusaka, Zambia. Gram-negative organisms were frequently isolated. A high mortality rate was observed, as 30% of the followed-up study population had died after 30 days.

Antibody persistence following administration of a hexavalent DTwP-IPV-HB-PRP∼T vaccine versus separate DTwP-HB-PRP∼T and IPV vaccines at 12-24 months of age and safety and immunogenicity of a booster dose of DTwP-IPV-HB-PRP∼T in healthy infants in India.

Background: The combination of whole-cell pertussis (wP) antigens with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens provides a high-quality DTwP-IPV-HB-PRP∼T vaccine. This study evaluated a DTwP-IPV-HB-PRP∼T booster coadministered with measles, mumps, and rubella (MMR) vaccine. Methods: Phase II, open-label, randomized study. Healthy toddlers who had previously completed a DTwP-IPV-HB-PRP∼T or separate DTwP-HB-PRP∼T and IPV primary vaccination series received a DTwP-IPV-HB-PRP∼T booster vaccine at 12-24 months of age. All participants had also received 1 or 2 doses of measles-containing vaccine between primary vaccination and enrolment (N = 100 and N = 6, respectively). Those who had received 1 prior measles-containing vaccine received an MMR dose either concomitantly (N = 50) or 28 days after (N = 50) the DTwP-IPV-HB-PRP∼T booster. Immunogenicity was evaluated using validated assays and safety by parental reports. Results: Pre-booster vaccination, 100.0% participants showed antibody persistence after DTwP-IPV-HB-PRP∼T or DTwP-HB-PRP∼T and IPV for anti-T (≥0.01 IU/mL), anti-Hib (≥0.15 µg/mL), and anti-polio 3 (≥8 1/dil) and at least 95.8% of participants for anti-D (≥0.01 IU/mL), anti-HB (≥10 mIU/mL), and anti-polio 1 and 2 (≥8 1/dil). For the pertussis antigens, pre-booster antibody persistence (≥2 EU/mL) ranged from 88.6 to 88.7% (anti-PT), 91.4-98.6% (anti-FHA), 69.0-74.3% (anti-PRN), and 97.1-97.2% (anti-FIM). For the booster response, seroprotection based on either the primary series or measles-containing vaccination regimen was 100.0% for anti-D and anti-T (≥0.01 IU/mL and ≥0.10 IU/mL), anti-HB (≥10 mIU/mL and ≥100 mIU/mL), anti-Hib (≥0.15 µg/mL and ≥1 µg/mL) and anti-polio 1, 2, and 3 (≥8 1/dil), and for the pertussis antigens booster response ranged from 88.6 to 91.8% (anti-PT), 91.1-95.9% (anti-FHA), 88.6-93.9% (anti-PRN), and 95.9-98.6% (anti-FIM). There were no safety concerns in any group. Conclusions: This study showed good antibody persistence of the DTwP-IPV-HB-PRP∼T vaccine and good immunogenicity and safety of a booster dose given with MMR in the second year of life.Clinical Trials Registry India Number: CTRI/2018/04/013375.

Safety and immunogenicity of a hexavalent DTwP-IPV-HB-PRP∼T vaccine versus separate DTwP-HB-PRP∼T and IPV vaccines in healthy infants in India.

Background: Multivalent vaccines containing whole-cell pertussis (wP) antigens combined with established diphtheria (D), tetanus (T), hepatitis B (HB), Haemophilus influenzae type b (Hib), and inactivated poliomyelitis (IPV) antigens allow the provision of a high-quality, affordable DTwP-IPV-HB-PRP∼T vaccine. Methods: Phase I/II, randomized, active-controlled, open-label study in healthy toddlers (Cohort I) and infants (Cohort II). Toddlers in Cohort I who had completed primary series D, T, P, HB, Hib, and polio vaccination received a booster dose of DTwP-IPV-HB-PRP∼T (N = 30) or DTwP-HB-PRP∼T + IPV (N = 15) vaccines at 15-18 months of age. After satisfactory review of safety data in Cohort I, infants in Cohort II received DTwP-IPV-HB-PRP∼T (N = 100) or DTwP-HB-PRP∼T + IPV (N = 50) at 6-8, 10-12, and 14-16 weeks of age. All infants in Cohort II had received previous oral polio and HB vaccines per country recommendations. Results: Booster and primary series vaccinations were well tolerated with no clinically significant differences between vaccine groups. Most adverse events were mild and resolved spontaneously; there were no vaccine-related serious adverse events and no deaths. In both vaccine groups, anti-D, anti-T, anti-HB, anti-Hib, and anti-polio 1, 2, and 3 seroprotection was 100% post-booster and post-primary series. For the pertussis antigens, booster response rate was > 86% in both groups. For the primary series, vaccine response rate was slightly higher for DTwP-IPV-HB-PRP∼T than DTwP-HB-PRP∼T + IPV for anti-PT (80.2% and 70.8%) and anti-FHA (81.3% and 68.8%), slightly lower for anti-PRN (72.5% and 81.3%), and similar in each group for anti-FIM (95.6% and 97.9%). Conclusions: This study demonstrated a good safety and immunogenicity profile of the hexavalent DTwP-IPV-HB-PRP∼T vaccine for infant primary series vaccination at 6-8, 10-12, and 14-16 weeks of age and booster vaccination at 15-18 months of age and supported progression to the next development phase.