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1.
Front Pediatr ; 12: 1419515, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39363970

RESUMEN

Introduction: Impaired future fertility potential secondary to gonadotoxic therapies for childhood cancer is a shattering aftermath faced by childhood cancer survivors. Fertility preservation (FP) has emerged as a key to mitigate this unwelcomed sequelae. FP services catering to the needs of children and adolescents (C&A) population in developing countries are limited. Malaysia recently launched its pioneering pediatrics FP services. Aims of study: To evaluate healthcare providers' (HCPs) FP knowledge, practice behaviors, attitudes, perceptions, and barriers towards FP counseling/services (C/S) for the C&A cohort. Methods: A questionnaire-based study was conducted utilizing a questionnaire consisting of 51 items which was adapted from G.Quinn et al. The questionnaire was distributed both online and physically amongst HCPs in a tertiary center. Ethical committee approval was granted by the Research Ethical Committee, Universiti Kebangsaan Malaysia. Results: A total of 102 HCPs completed the questionnaires. The majority of respondents were Malays (74.5%), females (80.4%), gynecology/pediatrics specialty (76.5%), and had children (88.2%). Nearly 72% of HCPs demonstrated good knowledge of FP. Almost 73% of HCPs consulted reproductive specialists (RES) on potential fertility issues and over 80% of HCPs referred patients who enquired on fertility issues to RES. Only 17% of HCPs practiced FP discussion, 12% reported no available person to discuss FP, and 10% of HCPs were unaware of who to discuss FP with. Patients' inability to afford FP (30.4%) tops the list of barriers to FP C/S, followed by limited available information on FP for patients (17.6%) and patients too ill to delay treatment (12.7%). Most HCPs (88.2%) demonstrated unfavorable attitudes towards FP C/S. Discussions: In general, the majority of our HCP respondents demonstrated good current FP knowledge and practice behaviors. Mitigating several controversial issues in FP would improve HCPs' attitude towards FP. Main barriers to the uptake of FP C/S for C&A were patient and resource barriers. Addressing these issues by funding aid for FP procedures, increasing FP knowledge dispersion, as well as developing age-appropriate FP-related educational materials would improve FP service provision for C&A in the future. Conclusions: In conclusion, successful corrective action combined with strategic planning points to a promising future for Malaysia's FP services provision for C&A.

2.
Front Public Health ; 12: 1383060, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376998

RESUMEN

Introduction: Evidence suggests that advice from health care professionals (HCP) increases the likelihood of quit attempts and successful quitting of tobacco use. However, previous studies primarily focussed on cigarette smoking and did not include all forms of tobacco products. This study aimed to investigate the prevalence and disparities in receiving HCP's advice to quit tobacco use (combustible or noncombustible) in the US adult population. Methods: Using the 2022 National Health Information Survey (NHIS) data, we examined 4,424 adults who reported (i) any tobacco product use within the past 12 months and (ii) having seen an HCP within the past 12 months. The outcome variable included the receipt of advice to quit tobacco use from an HCP, and predictors included sociodemographic variables. Weighted prevalence estimates were calculated, and multivariable regression analyses were conducted. Results: Over 38% of tobacco users who visited an HCP were advised to quit. The odds of receiving such advice were lower among Hispanics (AOR: 0.625; 95% confidence interval (CI) [0.464-0.843];p = 0.002), males (AOR: 0.767; 95% CI [0.659-0.893], p = 0.001), those above the poverty level (AOR: 0.795; 95% CI [0.641-0.987];p = 0.037), foreign-born (AOR: 0.664; 95% CI [0.496-0.888]; p = 0.006), those with a bachelor's degree or higher educational level (AOR: 0.477; 95% CI [0.349-0.653]; p < 0.001) and those aged less than 45 years (AOR: 0.404; 95% CI: [0.344-0.473]; p < 0.001). Conclusion: The prevalence of receiving HCP's advice to quit tobacco use remains suboptimal and disparate among sociodemographic groups. Our findings call for strategic implementation of the USPHS's recommendation on treating tobacco use and taking further actions to equip HCPs with the training and resources needed to provide appropriate advice to quit tobacco.


Asunto(s)
Cese del Hábito de Fumar , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Prevalencia , Cese del Hábito de Fumar/estadística & datos numéricos , Adolescente , Adulto Joven , Uso de Tabaco/epidemiología , Anciano , Disparidades en Atención de Salud/estadística & datos numéricos , Cese del Uso de Tabaco/estadística & datos numéricos , Encuestas Epidemiológicas
3.
mBio ; : e0160024, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258903

RESUMEN

Hantaviruses are rodent-borne viruses that cause severe disease in infected humans. In the New World, major hantaviruses include Andes virus (ANDV) and Sin Nombre virus (SNV) causing hantavirus pulmonary syndrome. In the Old World, major hantaviruses include Hantaan virus (HTNV) and Puumala virus (PUUV) causing hemorrhagic fever with renal syndrome. Here, we produced a pan-hantavirus therapeutic (SAB-163) comprised of fully human immunoglobulin purified from the plasma of transchromosomic bovines (TcB) vaccinated with hantavirus DNA plasmids coding for the major glycoproteins of ANDV, SNV, HTNV, and PUUV. SAB-163 has potent neutralizing antibodies (PRNT50 > 200,000) against the four targeted hantavirus and cross-neutralization against several other heterotypic hantaviruses. At a dosage of 10 mg/kg, SAB-163 is bioavailable in Syrian hamsters out to 70 days post-treatment with a half-life of 10-15 days. At this same dosage, SAB-163 administered 1 day before, or 5 days after exposure, protected all hamsters from lethal disease caused by ANDV. At a higher dose, partial but significant protection was achieved as late as day 6. SAB-163 also protected hamsters in the HTNV, PUUV, and SNV infection models when administered 1 day before or up to 3 days after challenge. This pan-hantavirus therapeutic is attractive because it is fully human, multi-targeted, safe, stable at 4°C, and effective in animal models. SAB-163 was evaluated for safety in GLP human tissue binding studies and a GLP rabbit toxicity study at 365 and 730 mg/kg and is investigational new drug enabled for phase 1 clinical trial(s). IMPORTANCE: This candidate polyclonal human IgG product was produced using synthetic gene-based vaccines and transgenic cows. Having now gone through cGMP production, GLP safety testing, and efficacy testing in animals, SAB-163 is the world's most advanced anti-hantavirus antibody-based medical countermeasure, aside from convalescent human plasma. Importantly, SAB-163 targets the most prevalent hantaviruses on four continents.

4.
Biotechnol Bioeng ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267334

RESUMEN

Purification of recombinantly produced biopharmaceuticals involves removal of host cell material, such as host cell proteins (HCPs). For lysates of the common expression host Escherichia coli (E. coli) over 1500 unique proteins can be identified. Currently, understanding the behavior of individual HCPs for purification operations, such as preparative chromatography, is limited. Therefore, we aim to elucidate the elution behavior of individual HCPs from E. coli strain BLR(DE3) during chromatography. Understanding this complex mixture and knowing the chromatographic behavior of each individual HCP improves the ability for rational purification process design. Specifically, linear gradient experiments were performed using ion exchange (IEX) and hydrophobic interaction chromatography, coupled with mass spectrometry-based proteomics to map the retention of individual HCPs. We combined knowledge of protein location, function, and interaction available in literature to identify trends in elution behavior. Additionally, quantitative structure-property relationship models were trained relating the protein 3D structure to elution behavior during IEX. For the complete data set a model with a cross-validated R2 of 0.55 was constructed, that could be improved to a R2 of 0.70 by considering only monomeric proteins. Ultimately this study is a significant step toward greater process understanding.

5.
Lancet Reg Health Am ; 37: 100836, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39100240

RESUMEN

Background: In the United States (U.S.), hantavirus pulmonary syndrome (HPS) and non-HPS hantavirus infection are nationally notifiable diseases. Criteria for identifying human cases are based on clinical symptoms (HPS or non-HPS) and acute diagnostic results (IgM+, rising IgG+ titers, RT-PCR+, or immunohistochemistry (IHC)+). Here we provide an overview of diagnostic testing and summarize human Hantavirus disease occurrence and genotype distribution in the U.S. from 2008 to 2020. Methods: Epidemiological data from the national hantavirus registry was merged with laboratory diagnostic testing results performed at the CDC. Residual hantavirus-positive specimens were sequenced, and the available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the U.S. Findings: From 1993 to 2020, 833 human hantavirus cases have been identified, and from 2008 to 2020, 335 human cases have occurred. Among New World (NW) hantavirus cases detected at the CDC diagnostic laboratory (representing 29.2% of total cases), most (85.0%) were detected during acute disease, however, some convalescent cases were detected in states not traditionally associated with hantavirus infections (Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont). From 1993 to 2020, 94.9% (745/785) of U.S. hantaviruses cases were detected west of the Mississippi with 45.7% (359/785) in the Four Corners region of the U.S. From 2008 to 2020, 67.7% of NW hantavirus cases were detected between the months of March and August. Sequencing of RT-PCR-positive cases demonstrates a geographic separation of Orthohantavirus sinnombreense species [Sin Nombre virus (SNV), New York virus, and Monongahela virus]; however, there is a large gap in viral sequence data from the Northwestern and Central U.S. Finally, these data indicate that commercial IgM assays are not concordant with CDC-developed assays, and that "concordant positive" (i.e., commercial IgM+ and CDC IgM+ results) specimens exhibit clinical characteristics of hantavirus disease. Interpretation: Hantaviral disease is broadly distributed in the contiguous U.S, viral variants are localised to specific geographic regions, and hantaviral disease infrequently detected in most Southeastern states. Discordant results between two diagnostic detection methods highlight the need for an improved standardised testing plan in the U.S. Hantavirus surveillance and detection will continue to improve with clearly defined, systematic reporting methods, as well as explicit guidelines for clinical characterization and diagnostic criteria. Funding: This work was funded by core funds provided to the Viral Special Pathogens Branch at CDC.

6.
J Family Med Prim Care ; 13(5): 1683-1687, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38948543

RESUMEN

Objective: Delay in the diagnosis of tuberculosis (TB) is a significant problem at both individual and community levels. Delayed diagnosis of TB contributes to more severe disease manifestations, higher risk of death, and higher disease transmission in the community. We conducted this study to assess the extent and associated reasons for delay in diagnosis of pulmonary TB. Methods: This study was conducted in the Department of TB and Respiratory Diseases, J. N. Medical College, Aligarh, from June 2020 to May 2022. A total of 2053 new pulmonary TB patients, who first consulted any private healthcare provider (HCP) for treatment, were enrolled in the study. The required information was collected by interview technique using a predesigned questionnaire. Results: A total of 2053 patients were enrolled in the study. There was a significant delay of more than 2 weeks in the diagnosis of pulmonary TB after the onset of symptoms in 94% of patients. The extent of delay ranged from 8 days to 240 days with a mean of 36.33 days. The delay in visiting the HCPs by the patient was not significant. Only 5.85% of patients had a significant delay of more than 2 weeks in seeking any health care after the appearance of symptoms. A delay by HCP contributed to a greater portion of the total delay, with a mean of 31.77 days. The main reason for the delay by HCPs was not investigating TB. The hospital delay was not significant. The mean hospital delay was 5.82 days. Conclusion: The delay in the diagnosis of TB in India is very high. A delay by HCPs contributes to a greater portion of the total delay. Information, Education and Communication (IEC) activities will play an important role in reducing the delay. All HCPs should be actively involved in subjecting the suspects to TB diagnosis at the earliest possible as per National Tuberculosis Elimination Programme (NTEP) guidelines.

7.
J Family Med Prim Care ; 13(5): 1734-1738, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38948578

RESUMEN

Background: Healthcare professionals (HCPs) worldwide suffer from stress and poor sleep and the COVID-19 pandemic has further raised these issues. This study sought to determine whether HCPs had reduced stress and increased sleep quality while participating in a heartfulness meditation program. Subjects and Methods: For a 2-month (8 weeks) heartfulness meditation program, we included 41 individuals in a prospective one-group pretest post-test intervention design from February 2023 to April 2023. Scores on the Perceived Stress Scale and Pittsburgh Sleep Quality Index were gathered at baseline and 8 weeks. Forty-one (76%) of the 54 participants completed this study for 8 weeks. Results: Results showed a substantial decline in stress (preintervention mean ± standard deviation [SD] = 20.54 ± 4.46; postintervention mean ± SD = 18.42 ± 6.14; t-value = -1.947 [0.05*]) and improvement in sleep quality (preintervention mean ± SD = 6.63 ± 3.82; postintervention mean ± SD = 5.29 ± 2.44) among HCPs after following this 8-week heartfulness meditation program. In the end, a substantial decrease in perceived stress score and an improvement in the sleep quality index was found. Conclusion: Additionally, practicing heartfulness meditation may aid in developing the traits of empathy, acceptance, and inner serenity. We draw the conclusion that more extensive research is required to fully understand the impact of heartfulness meditation practice.

8.
J Chromatogr A ; 1732: 465202, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39079362

RESUMEN

Despite advancements in therapeutic monoclonal antibodies (mAbs) and cell line engineering, separating host cell proteins (HCPs) from mAbs during downstream purification remains challenging. Therefore, in this study, we developed a novel multimodal chromatography (MMC) resin to enhance HCP removal during mAb polishing processes. We evaluated the impact of both ligand structure and pore size of the MMC resin by purifying a post-protein A chromatography solution in flow-through mode. We observed that the efficiency of HCP clearance depended on the hydrophobic moiety structure of the ligand and predicted the mAb purification capability of MMC through linear salt-gradient elution experiments involving a mixture of transferrin, bovine serum albumin (BSA), and pepsin. Our findings revealed that the prototype immobilized 1,12-dodecanediamine via the formyl group exhibited the best performance attributed to its long alkyl chain. Furthermore, an investigation of effects of base bead pore size on HCP capacity using cellulose base beads of five different pore sizes showed that larger pore resin base beads had the highest HCP removal capacity. Specifically, MMC resins with a pore diameter exceeding 440 nm reduced the HCP level by three orders of magnitude under high mAb loading conditions (> 1000 mg/mL-resin). The MMC resin developed in this study, along with the insights gained into ligand structure and pore size, not only enhances mAb polishing efficiency but also contributes to improving downstream processes in mAb biopharmaceutical production.


Asunto(s)
Anticuerpos Monoclonales , Cricetulus , Albúmina Sérica Bovina , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/aislamiento & purificación , Animales , Células CHO , Ligandos , Albúmina Sérica Bovina/química , Porosidad , Cromatografía de Afinidad/métodos , Proteína Estafilocócica A/química , Transferrina/química , Transferrina/aislamiento & purificación , Pepsina A/química , Pepsina A/metabolismo , Proteínas/aislamiento & purificación , Proteínas/química , Resinas Sintéticas/química , Interacciones Hidrofóbicas e Hidrofílicas
9.
Front Med (Lausanne) ; 11: 1399947, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38898937

RESUMEN

The article shows that the input given by healthcare professionals (HCPs) adds value to the regulatory processes surrounding the development, authorisation, and monitoring of a medicine, but is also an instrument for accountability, trust, mutual exchange as well as an insight into the public health issues that matter most to one of the key stakeholder groups the Agency works with. We highlight the role of HCPs in the EU regulatory process and take stock of the first 10 years of the Framework for Interaction with HCPs to describe how practises have evolved over this time to meet the goals of informing, consulting and improving trust in the EU regulatory system. We will analyse what led European Medicines Agency (EMA) to develop this framework through to the next steps and where the interaction might lead in the future.

10.
Sensors (Basel) ; 24(3)2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38339656

RESUMEN

This article presents a novel hardware-assisted distributed ledger-based solution for simultaneous device and data security in smart healthcare. This article presents a novel architecture that integrates PUF, blockchain, and Tangle for Security-by-Design (SbD) of healthcare cyber-physical systems (H-CPSs). Healthcare systems around the world have undergone massive technological transformation and have seen growing adoption with the advancement of Internet-of-Medical Things (IoMT). The technological transformation of healthcare systems to telemedicine, e-health, connected health, and remote health is being made possible with the sophisticated integration of IoMT with machine learning, big data, artificial intelligence (AI), and other technologies. As healthcare systems are becoming more accessible and advanced, security and privacy have become pivotal for the smooth integration and functioning of various systems in H-CPSs. In this work, we present a novel approach that integrates PUF with IOTA Tangle and blockchain and works by storing the PUF keys of a patient's Body Area Network (BAN) inside blockchain to access, store, and share globally. Each patient has a network of smart wearables and a gateway to obtain the physiological sensor data securely. To facilitate communication among various stakeholders in healthcare systems, IOTA Tangle's Masked Authentication Messaging (MAM) communication protocol has been used, which securely enables patients to communicate, share, and store data on Tangle. The MAM channel works in the restricted mode in the proposed architecture, which can be accessed using the patient's gateway PUF key. Furthermore, the successful verification of PUF enables patients to securely send and share physiological sensor data from various wearable and implantable medical devices embedded with PUF. Finally, healthcare system entities like physicians, hospital admin networks, and remote monitoring systems can securely establish communication with patients using MAM and retrieve the patient's BAN PUF keys from the blockchain securely. Our experimental analysis shows that the proposed approach successfully integrates three security primitives, PUF, blockchain, and Tangle, providing decentralized access control and security in H-CPS with minimal energy requirements, data storage, and response time.


Asunto(s)
Inteligencia Artificial , Cadena de Bloques , Humanos , Seguridad Computacional , Computadores , Atención a la Salud/métodos
11.
Eur J Pharm Sci ; 192: 106656, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38029932

RESUMEN

A key aspect that must be supervised during the development of recombinant therapeutic products is the potential presence of impurities. Residual host cell proteins (HCPs) are a major class of process-related impurities derived from the host organism that even in trace amount have the potential to affect product quality, safety, and efficacy. Therefore, the product purification processes must be optimized to consistently remove as many HCPs as feasible, with the goal of making the product as pure as possible. The workhorse of HCP monitoring and quantitation during bioprocessing manufacturing is sandwich ELISA (enzyme-linked immunosorbent assay), which employs polyclonal anti-HCP antibodies for both capture and detection. Commercial ELISA kits developed from Chinese Hamster Ovary (CHO) cell lines are widely applied in early drug development stages (preclinical, phase I, and phase II), but are not specifically designed for a given manufacturer's proprietary cell line, and users do not have control over reagent availability and lot-to-lot consistency. For later development stages, the upstream process-specific method is preferred to guarantee an improved sensitivity and coverage. In agreement with the USP General Chapter 〈1132〉, a platform assay can be used in place of the commercial one through all stages of product development, if already available when product development starts. This proof-of-concept study was carried out to demonstrate the feasibility and the advantages of the development of a proprietary CHO HCPs platform ELISA. Different proprietary mock materials have been characterized and compared by orthogonal bidimensional electrophoresis techniques (SDS-PAGE coupled to SS/WB and 2D DIGE) with the scope of selecting the best antigen-antibody couple for setting up the in-house ELISA. A preliminary evaluation of the in-house method performance has been done in comparison with the commercial assay, demonstrating that the platform method is promising for an accurate and precise CHO HCPs quantification during the early phase product and process development.


Asunto(s)
Desarrollo de Medicamentos , Proteínas , Cricetinae , Animales , Cricetulus , Células CHO , Ensayo de Inmunoadsorción Enzimática/métodos
12.
Eur J Cancer ; 197: 113496, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38134481

RESUMEN

PURPOSE: To describe the attitudes of healthcare professionals and drug regulators about progression-free survival (PFS) as efficacy endpoint in clinical trials with patients with advanced cancer and to explore to what extent these attitudes influence the willingness to trade between PFS and toxicity. METHODS: Cross-sectional survey with regulators from the European Medicines Agency (EMA), and healthcare professionals (HCP) from the "Stichting Hemato-Oncologie voor Volwassenen Nederland" (HOVON) collaborative group and the European Organisation for Research and Treatment of Cancer (EORTC). Attitudes towards PFS were elicited using 5-point Likert items. The respondents' willingness to trade between PFS and grade 3 or 4 (G34) toxicity was assessed using the threshold technique and quantified in terms of their maximum acceptable risk (MAR). RESULTS: Responses were collected from 287 HCPs and 64 regulators with mainly clinical expertise. Attitudes towards PFS were often spread out in both groups and related to beliefs about PFS being a likely surrogate for clinical benefit, being an intrinsic benefit to be distinguished from OS, or on the importance given to OS. Being a regulator or holding stronger beliefs about PFS being a likely surrogate or an intrinsic benefit were associated with a higher MAR. Presence of a supportive trend in OS was stated as important but was not associated with MAR. There was agreement on the need to address bias in the adjudication of PFS and the need for improving communication to patients about meaning, strengths, and limitations of improvements in PFS. CONCLUSION: Attitudes towards PFS were spread out and were associated with individual differences in the willingness to trade between toxicity and PFS. There was agreement on the need to address bias in the adjudication of PFS and improving communication to patients.


Asunto(s)
Neoplasias , Humanos , Supervivencia sin Progresión , Estudios Transversales , Neoplasias/tratamiento farmacológico , Personal de Salud , Atención a la Salud , Supervivencia sin Enfermedad
13.
Biology (Basel) ; 12(11)2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37998012

RESUMEN

Sin Nombre virus (SNV) is an emerging virus that was first discovered in the Four Corners region of the United States in 1993. The virus causes a disease known as Hantavirus Pulmonary Syndrome (HPS), sometimes called Hantavirus Cardiopulmonary Syndrome (HCPS), a life-threatening illness named for the predominance of infection of pulmonary endothelial cells. SNV is one of several rodent-borne hantaviruses found in the western hemisphere with the capability of causing this disease. The primary reservoir of SNV is the deer mouse (Peromyscus maniculatus), and the virus is transmitted primarily through aerosolized rodent excreta and secreta. Here, we review the history of SNV emergence and its virus biology and relationship to other New World hantaviruses, disease, treatment, and prevention options.

14.
Healthcare (Basel) ; 11(20)2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37893856

RESUMEN

INTRODUCTION: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders that are routinely screened for. Referenced publications insist on the importance of adequate screening, but the proper course of action has yet to be defined. AIM OF STUDY: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. MATERIAL AND METHODS: We led a semi structured interview with professionals, which included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient's initial demand or lack thereof and the baby's importance within, while identifying mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. CONCLUSIONS: HCPs need to enable patients' trust on a personal and an institutional level, as well as empowering the patient in the moment and respecting their values and choices. HCPs also convey the stability of the institution that has become a reference of refuge and assistance for patients from their pregnancy onwards.

15.
Eur J Pharm Sci ; 191: 106597, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37770006

RESUMEN

Polysorbates (PS) are esters of ethoxylated sorbitol anhydrides of different composition and are widely used surfactants in biologics. PSs are applied to increase protein stability and concomitant shelf-life via shielding against e.g., interfacial stresses. Due to the presence of specific lipolytic host cell protein (HCP) contaminations in the drug substance, PSs can be degraded via enzymatic hydrolysis. Surfactant hydrolysis leads to the formation of degradants, such as free fatty acids that might form fatty acid particles. In addition, PS degradation may reduce surfactant functionality and thus reduce the protection of the active pharmaceutical ingredient (API). Although enzymatic degradation was observed and reported in the last years, less is known about the relationship between certain polysorbate degradation patterns and the increase of mechanical and interfacial stress towards the API. In this study, the impact of specifically hydrolyzed polysorbate 20 (PS20) towards the stabilization of two monoclonal antibodies (mAbs) during accelerated shaking stress conditions was investigated. The results show that a specific enzymatic degradation pattern of PS20 can influence the colloidal stability of biopharmaceutical formulations. Furthermore, the kinetics of the appearance of visual phenomena, opalescence, and particle formation depended on the polysorbate degradation fingerprint as induced via the presence of surrogate enzymes. The current case study shows the importance of focusing on specific polysorbate ester fractions to understand the overall colloidal protein stabilizing effect. The performed study gives first insight into the functional properties of PS and helps to evaluate the impact of PS degradation in the formulation development of biopharmaceuticals in general.


Asunto(s)
Productos Biológicos , Polisorbatos , Hidrólisis , Tensoactivos , Anticuerpos Monoclonales , Estabilidad Proteica , Estabilidad de Medicamentos
16.
Cureus ; 15(8): e42978, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37671230

RESUMEN

Background and objective Developing and implementing nursing interventions to educate nurses on infection control procedures in hemodialysis units is of utmost importance and offers significant benefits in enhancing the quality of care. This study aimed to assess the impact of training on nursing professionals' practices of hospital infection control measures in hemodialysis services. The research also intended to explore the potential association between these practices and various sociodemographic variables. Materials and methods This was a single-group, pre- and post-interventional study carried out in Haryana State, India. A pretested questionnaire consisting of 29 statements, the responses of which were measured on a 5-point Likert scale, was used as the study tool. Descriptive and statistical tests like paired-t-test were used to analyze the data. Results The practices section of the questionnaire comprised 29 statements, the responses to which were measured on a five-point Likert scale. The scoring ranged from 5 ("strongly agree", i.e., positive practice) to 1 ("strongly disagree", i.e., negative practice). The maximum achievable score was 145 and the minimum achievable score was 9. The pre-test group (i.e., before training intervention) had a mean practice score of 115.0945 [standard deviation (SD)=9.34, standard error of the mean (SE)=0.66]. However, the post-test group (i.e. after training intervention) had a mean score of 135.26 (SD=8.34, SE=0.59). The study found that structured training significantly increased the mean practice score (t=-33.70, p=0.001). In addition, the study also highlighted the significant association of mean practice scores with various demographic variables among the pre-test and post-test groups. The improvement in mean practice scores among the post-test group after the structured training program reveals that such interventions will ultimately lead to a decrease in central line-associated bloodstream infections (CLABSIs) among hemodialysis patients. Conclusions Our findings showed that the educational intervention led to significant improvements in the practices of the participants.

17.
Hum Vaccin Immunother ; 19(2): 2256442, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37724556

RESUMEN

Mandatory vaccinations are widely debated since they restrict individuals' autonomy in their health decisions. As healthcare professionals (HCPs) are a common target group of vaccine mandates, and also form a link between vaccination policies and the public, understanding their attitudes toward vaccine mandates is important. The present study investigated physicians' attitudes to COVID-19 vaccine mandates in four European countries: Finland, France, Germany, and Portugal. An electronic survey assessing attitudes to COVID-19 vaccine mandates and general vaccination attitudes (e.g. perceived vaccine safety, trust in health authorities, and openness to patients) was sent to physicians in the spring of 2022. A total of 2796 physicians responded. Across all countries, 78% of the physicians were in favor of COVID-19 vaccine mandates for HCPs, 49% favored COVID-19 vaccine mandates for the public, and 67% endorsed COVID-19 health passes. Notable differences were observed between countries, with attitudes to mandates found to be more positive in countries where the mandate, or similar mandates, were in effect. The associations between attitudes to mandates and general vaccination attitudes were mostly small to neglectable and differed between countries. Nevertheless, physicians with more positive mandate attitudes perceived vaccines as more beneficial (in Finland and France) and had greater trust in medical authorities (in France and Germany). The present study contributes to the body of research within social and behavioral sciences that support evidence-based vaccination policymaking.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , Estudios Transversales , COVID-19/prevención & control , Actitud del Personal de Salud , Vacunación
18.
Indian J Occup Environ Med ; 27(2): 126-131, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37600639

RESUMEN

Background: Pregnant Health Care Professionals (HCPs), who serve as front-line warriors of COVID-19 will invariably experience a stressful pregnancy period. Ensuring their well-being during this COVID-19 pandemic period is a big challenge and guidelines or standard operating procedures (SOP) for the same are non-existent or are scarce. Objectives: To explore the challenges and experiences of pregnant HCPs during the COVID-19 pandemic. Methods: A qualitative study was conducted among 19 pregnant HCPs (14 Doctors and 5 staff nurses) working in Pondicherry, who were selected using purposive sampling for in-depth interviews. After obtaining informed written consent, face-to-face interviews were conducted until the attainment of the point of saturation. Audio recordings of the interviews were transcribed in English. Transcripts were proofread and manually analyzed for content. Codes obtained from the analysis of transcripts were merged to form broad categories. Results: The majority 15 (78.9%) of HCPs belonged to the clinical department and had work experience from 2-4 years. The mean age of the respondents was 29.4 ± 3.6 years. Four broad categories (of challenges), namely, Personnel level (Fear of infection in workplace, Inadequate antenatal care), Family level (Family pressure to quit job, Guilt of spreading the infection to family members), society level (Criticism by neighbor for working, Stigma), and work level challenges (Fear of losing the job, Uncomfortable work environment) emerged from the study. Conclusion and Recommendations: Challenges faced by the pregnant HCPs due to their nature of work remain by and large not addressed. Hence, specific guidelines or SOPs addressing these issues of pregnant health care workers and their swift and strict implementation are the need of the hour.

19.
bioRxiv ; 2023 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-37577539

RESUMEN

Background: Hantaviruses - dichotomized into New World (i.e. Andes virus, ANDV; Sin Nombre virus, SNV) and Old-World viruses (i.e. Hantaan virus, HTNV) - are zoonotic viruses transmitted from rodents to humans. Currently, no FDA-approved vaccines against hantaviruses exist. Given the recent breakthrough to human-human transmission by the ANDV, an essential step is to establish an effective pandemic preparedness infrastructure to rapidly identify cell tropism, infective potential, and effective therapeutic agents through systematic investigation. Methods: We established human cell model systems in lung (airway and distal lung epithelial cells), heart (pluripotent stem cell-derived (PSC-) cardiomyocytes), and brain (PSC-astrocytes) cell types and subsequently evaluated ANDV, HTNV and SNV tropisms. Transcriptomic, lipidomic and bioinformatic data analyses were performed to identify the molecular pathogenic mechanisms of viruses in different cell types. This cell-based infection system was utilized to establish a drug testing platform and pharmacogenomic comparisons. Results: ANDV showed broad tropism for all cell types assessed. HTNV replication was predominantly observed in heart and brain cells. ANDV efficiently replicated in human and mouse 3D distal lung organoids. Transcriptomic analysis showed that ANDV infection resulted in pronounced inflammatory response and downregulation of cholesterol biosynthesis pathway in lung cells. Lipidomic profiling revealed that ANDV-infected cells showed reduced level of cholesterol esters and triglycerides. Further analysis of pathway-based molecular signatures showed that, compared to SNV and HTNV, ANDV infection caused drastic lung cell injury responses. A selective drug screening identified STING agonists, nucleoside analogues and plant-derived compounds that inhibited ANDV viral infection and rescued cellular metabolism. In line with experimental results, transcriptome data shows that the least number of total and unique differentially expressed genes were identified in urolithin B- and favipiravir-treated cells, confirming the higher efficiency of these two drugs in inhibiting ANDV, resulting in host cell ability to balance gene expression to establish proper cell functioning. Conclusions: Overall, our study describes advanced human PSC-derived model systems and systems-level transcriptomics and lipidomic data to better understand Old and New World hantaviral tropism, as well as drug candidates that can be further assessed for potential rapid deployment in the event of a pandemic.

20.
Cureus ; 15(6): e41073, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37519624

RESUMEN

INTRODUCTION: The first wave of the coronavirus disease 2019 (COVID-19) pandemic created havoc and confusion in choosing appropriate treatment, as well as prophylaxis, due to its rapid surge, disease novelty, and lack of evidence-based literature. It was even more concerning among the healthcare workers (HCWs), who had to take care of patients, themselves, and their own families. OBJECTIVE: This online survey-based study targeted finding the various options for COVID-19 precautionary or prophylactic measures opted for by HCWs. METHODOLOGY: This was an observational study based on a predesigned questionnaire, which was floated online for three months after institutional ethical approval, just after the first wave of COVID-19 in 2021, targeting HCWs of different cadres (doctors, nurses, paramedics/laboratory technicians, etc.), ages, and sexes and HCWs hailing from across the country. Questions were focused on HCW's adopted measures, the order of preference and its reasons, and concerns related to safety and efficacy. Data was collected through Google Forms (Google, Inc., Mountain View, CA) into an Excel spreadsheet (Microsoft® Corp., Redmond, WA) and analyzed by the latest Statistical Package for Social Sciences (SPSS) software (IBM SPSS Statistics, Armonk, NY) using appropriate statistics. RESULTS: The routine practice of standard precautionary measures (face mask, hand hygiene, and social distancing) and wearing a personal protective equipment (PPE) kit during the care of COVID-19-positive or COVID-19-suspected patients was adopted by the majority of HCWs, i.e., 306/312 (>98%) irrespective of cadre (p = 0.001). After the "routine measures," the most adopted measure by participant HCWs irrespective of profession, age, and gender was the consumption of allopathic drugs (n = 188; 60.26%). Anti-COVID-19 measures in the category of drugs used by healthcare providers (HCPs) were prophylactic allopathic drugs (60.26%), homeopathic drugs (11.86%), and other Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homeopathy (AYUSH)/traditional medical system drugs (11.86%). Vitamin C was the most consumed among all of the drugs for COVID-19 prophylaxis purposes. Non-drug measures espoused by the HCPs were physical exercises (46.47%), increased sleep duration (35.89%), change in dietary habits (42.62%), and spiritual measures (19.23%). CONCLUSION: The fear of COVID-19 imposed on the HCPs the obligation to use all the available preventive measures in spite of the lack of evidence on actual benefits. After the routine infection preventive measures, the most adopted measure by participant HCWs irrespective of profession, age, and gender was the consumption of prophylactic allopathic drugs (>60%), and the most non-drug preventive measures were the initiation of physical exercises and change in dietary habits. Adapting some form of physical exercise was more noted with males than females (p = 0.001), and it significantly increased with HCPs of higher age of >25 and >40 years than younger HCPs (58.6% versus 29.3%; p = 0.016). Females preferred more dietary and nutritional modifications.

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