Initial evaluation of the relationship between maximal axial vertebra rotation and the rotation deformity in adolescent idiopathic scoliosis.

PURPOSE: This study evaluated the relationship between maximal axial vertebra rotation (maxAVR) and other clinical and radiological indexes, compared to apical vertebra rotation (AVR) in idiopathic adolescent scoliosis (AIS). METHODS: Forty consecutive patients of AIS with Cobb angle of major curve > 40° were included. They were scanned by an EOS imaging system and had trunk rotational angle (TRA) measured by scoliometer. The correlation between variables was assessed using Pearson's correlation coefficient and loaded onto a meta-analysis model. RESULTS: There were (34 girls and 6 boys) with an average age of 13.8 ± 1.6 years. AVR was maxAVR in only 47.5% (19/40) cases of the major curves and 42.3% (11/26) cases of the minor curves. The correlation between maxAVR and TRA was significantly higher than the correlation between AVR and TRA for the MT curves (p = 0.0001) and TL/L curves (p = 0.0001). On multivariate regression analysis, the magnitude of maxAVR showed a significant correlation with TRA (p = 0.0002), Cobb angle (p = 0.001), and coronal deformity angular ratio (C-DAR) (p = 0.027). CONCLUSIONS: The apical vertebra was not the most rotated in most cases. The correlation between maxAVR and TRA was significantly higher than the correlation between AVR and TRA. Moreover, the maxAVR was multivariately related to TRA, Cobb angle, and C-DAR. LEVEL OF EVIDENCE: Level II, diagnostic.

Plant crude extracts containing oligomeric hemagglutinins protect chickens against highly Pathogenic Avian Influenza Virus after one dose of immunization.

Highly pathogenic avian influenza viruses (HPAIV) have been responsible for causing several severe outbreaks across the world. To protect poultry farms and to prevent the possible spread of new influenza pandemics, vaccines that are both efficacious and low-cost are in high demand. We produced stable, large hemagglutinin H5 oligomers in planta by the specific interaction between S•Tag and S•Protein. H5 oligomers combined via S•Tag::S•Protein interaction in plant crude extracts induced strong humoral immune responses, strong neutralizing antibody responses, and resistance in chickens after challenge with a wild type HPAIV H5 virus strain. In all three parameters, plant crude extracts with H5 oligomers induced better responses than crude extracts containing trimers. The neutralizing antibodies induced by by two-dose and one dose immunization with an adjuvanted crude extract containing H5 oligomer protected vaccinated chickens from two lethal H5N1 virus strains with the efficiency of 92% and 100%, respectively. Following housing vaccinated chickens together with ten non-immunized chickens, only one of these chickens had detectable levels of the H5N1 virus. To facilitate the easy storage of a candidate vaccine, the H5 oligomer crude extracts were mixed with adjuvants and stored for 3.5 and 5.5 months at 4 °C, and chickens were immunized with these crude extracts. All these vaccinated chickens survived after a lethal H5N1 virus challenge. H5 oligomer crude extracts are comparable to commercial vaccines as they also induce strong virus-neutralizing immune responses following the administration of a single dose. The cost-effective production of plant crude extract vaccine candidates and the high stability after long-term storage will enable and encourage the further exploration of this technology for veterinary vaccine development.

Impact of pharmacist-initiated educational interventions on improving medication reconciliation practice in geriatric inpatients during hospital admission in Vietnam.

WHAT IS KNOWN AND OBJECTIVE: Unintentional medication discrepancies (UMDs) are common in geriatric patients during care transitions, resulting in frequent undesirable consequences. Medication reconciliation could be a useful practice to prevent or ameliorate UMD. However, this practice in Vietnamese hospitals has not been well established or standardized. This study aims to determine the effect of pharmacist-initiated educational interventions on improving medication reconciliation practice. METHODS: This prospective 6-month pre-and post-study was conducted in two internal medicine wards in a Vietnamese 800-bed public hospital. Pharmacists provided training and short-term support to physicians on medication reconciliation. Primary outcome measures were the proportions of patients with at least one UMD at admission. Secondary outcome measures were the proportions of patients with preventable adverse drug events (pADEs) score ≥0.1 due to these UMDs. Odds ratio and 95% confidence intervals were assessed based on a multivariate logistic regression model. RESULTS AND DISCUSSION: One hundred fifty-two patients were recruited in the pre-intervention phase, and 146 in the post-intervention phase. Following the intervention, the proportion of geriatric patients with ≥1 UMD at admission significantly decreased from 55.3 to 25.3 % (ORadj 0.255, 95% CI: 0.151-0.431). Similarly, the proportion of patients with a pADE ≥0.1 at admission reduced from 44.1 to 11.6% [ORadj 0.188, 95% CI: 0.105-0.340] post-intervention. WHAT IS NEW AND CONCLUSION: Our pharmacist-initiated educational interventions have demonstrated the ability to produce substantial improvement in medication reconciliation practice, reducing UMDs and potential harm. Our approach may provide an alternate option to implement medication reconciliation for jurisdictions with limited healthcare resources.

Implementing clinical pharmacy activities in hospital setting in Vietnam: current status from a national survey.

BACKGROUND: Clinical pharmacy activities have evolved over the past decades contributing to all stages of the patient care process, especially in the hospital setting. However, these practice roles may differ to a significant extent depending on the healthcare policy of countries. In Vietnam, the magnitude of adopting clinical pharmacy activities in hospital settings throughout the country is still unknown since these activities have been implemented. This study aimed to ascertain the current status of clinical pharmacy activities performed within the Vietnamese hospital setting. METHODS: A nation-wide survey was conducted from December 2017 to January 2018. Two online questionnaires, one for the Heads of Pharmacy Department and one for clinical pharmacists, were designed based on the national legal regulations about implementing clinical pharmacy activities in the hospital setting. These questionnaires were sent to all hospitals and healthcare facilities with a department of pharmacy. RESULTS: A total of 560 Heads of Pharmacy and 574 clinical pharmacists participated in the study, representing a response rate of 41.2%. Among the participating hospitals, non-patient specific activities were implemented widely across all hospital classes, with pharmacovigilance, medication information, and standard operating procedures development implemented in ≥88% of all hospitals. In contrast, there was a significant variation in the level of implementation of patient-specific activities among hospital classes. With activities such as medication counselling, monitoring of adverse drug reactions, and obtaining patient's medication histories provided at a considerably lower level in between 49 and 57% of hospitals. CONCLUSION: Clinical pharmacy activities have been initiated in most of the surveyed hospitals. In general, clinical pharmacy is more established in higher-class hospitals in Vietnam. However, the current implementation status is focused on non-patient-specific activities, while patient-oriented activities remained insufficiently established.

Implementation and Evaluation of Clinical Pharmacy Services on Improving Quality of Prescribing in Geriatric Inpatients in Vietnam: An Example in a Low-Resources Setting.

Purpose: Geriatric inpatients generally have a high risk of drug-related problems (DRP) in prescribing following hospital admission, which are likely to cause negative clinical consequences. This is particularly evident in developing countries such as Vietnam. Therefore, clinical pharmacy service (CPS) aims to identify and resolve these DRPs to improve the quality use of medicines in the older population following hospital admission. Patients and Methods: The study was conducted as a prospective, single-center study implemented at a general public hospital in Hanoi. Patients aged ≥60 years with at least three chronic diseases admitted to the Internal Medicine Department between August 2020 and December 2020 were eligible to be enrolled. A well-trained clinical pharmacist provided a structured CPS to identify any DRP in prescribing for each patient in the study. Clinical pharmacist interventions were then proposed to the attending physicians and documented in the DRP reporting system. Results: A total of 255 DRP were identified in 185 patients during the study period. The most frequent types of DRP were underuse (21.2%), dose too high (12.2%), and contraindication (11.8%). There was a very high rate of approval and uptake by the physicians regarding the interventions proposed by the clinical pharmacist (82.4% fully accepted and 12.5% partially accepted). Of the interventions, 73.4% were clinically relevant (pADE score ≥0.1). In general, 9 out of 10 physicians agreed that CPS has significant benefits for both patients and physicians. Conclusion: Improving clinical pharmacy services can potentially have a positive impact on the quality of prescribing in elderly inpatients. These services should officially be implemented to optimize the quality use of medicines in this population group in Vietnam.

Inappropriate supply of antibiotics for common viral infections by community pharmacies in Vietnam: A standardised patient survey.

Background: This study aimed to evaluate the appropriateness of antibiotic dispensing of private pharmacies in Vietnam. Methods: Standardised patient surveys were conducted in randomly selected community pharmacies across 40 districts in Vietnam. Four clinical scenarios were represented by patient actors: (a) an adult requesting treatment for a sibling with a viral upper respiratory tract infection (URTI), (b) a parent requesting treatment for a child with acute diarrhoea, (c) an adult making a direct antibiotic request, and (d) an adult presenting with an antibiotic prescription. We calculated the proportion of interactions that resulted in inappropriate supply of antibiotics and patient advice. Predictors of inappropriate antibiotic supply were assessed. Findings: Patient actors attended 949 pharmacies, resulting in 1266 clinical interactions. Antibiotics were inappropriately supplied to 92% (291/316) of adults requesting treatment for URTI symptoms, 43% (135/316) for children with acute diarrhoea symptoms and to 84% (267/317) of direct request for antibiotics. Only 49% of pharmacies advised patients regarding their antibiotic use. Female actors were more likely to be given antibiotics than male actors for URTI (aOR 2·71, 1·12-6·60) but not for diarrhoeal disease. Pharmacies in northern Vietnam were more likely than those in southern Vietnam to supply antibiotics without a prescription: for adult URTI (aOR=5·8, 95% CI: 2·2-14·9) and childhood diarrhoea (aOR=3·5, 95% CI: 2·0-6·0) symptoms, but less likely to dispense for direct antibiotics request. Interpretation: Inappropriate antibiotic supply was common in Vietnamese private pharmacies. Multifaceted measures are urgently needed to achieve WHO's global action plan for the optimal use of antimicrobials. Funding: This study was funded by a grant from the Australian Department of Foreign Affairs and Trade.

Unintentional Medication Discrepancies at Admission Among Elderly Inpatients with Chronic Medical Conditions in Vietnam: A Single-Centre Observational Study.

BACKGROUND: Elderly patients are at high risk of unintentional medication discrepancies during transition of care as they are more likely to have multiple comorbidities and chronic diseases that require multiple medications. OBJECTIVE: The aim of the study was to assess the frequency of unintentional medication discrepancies and identify the associated risk factors and potential clinical impact of them in elderly inpatients during hospital admission. PATIENTS AND METHODS: A prospective observational study was conducted from July to December 2018 in an 800-bed geriatric hospital in Hanoi, North Vietnam. Patients over 60 years of age, admitted to one of selected internal medicine wards, taking at least one chronic medication before admission, and staying at least 48 h were eligible for enrollment. Medication discrepancies of chronic medications before and after admission of each participant were identified by a pharmacist using a step-by-step protocol for the medication reconciliation process. The identified discrepancies were then classified as intentional or unintentional by an assessment group comprising a pharmacist and a physician. A logistic regression model was used to identify risk factors of medication discrepancies. RESULTS: Among 192 enrolled patients, 328 medication discrepancies were identified, with 87 (26.5%) identified as unintentional. Nearly a third of enrolled patients (32.3%) had at least one unintentional medication discrepancy. The most common unintentional medication discrepancy was omission of drugs (75.9% of 87 medication discrepancies). The logistic regression analysis revealed a positive association between the number of discrepancies at admission and the type of treatment wards. CONCLUSIONS: Medication discrepancies are common at admission among Vietnamese elderly inpatients. This study highlights the importance of obtaining a comprehensive medication history at hospital admission and supports implementing a medication reconciliation program to reduce the negative impact of medication discrepancy, especially for the elderly population.

Effects of Size and Surface Properties of Nanodiamonds on the Immunogenicity of Plant-Based H5 Protein of A/H5N1 Virus in Mice.

Nanodiamond (ND) has recently emerged as a potential nanomaterial for nanovaccine development. Here, a plant-based haemagglutinin protein (H5.c2) of A/H5N1 virus was conjugated with detonation NDs (DND) of 3.7 nm in diameter (ND4), and high-pressure and high-temperature (HPHT) oxidative NDs of ~40-70 nm (ND40) and ~100-250 nm (ND100) in diameter. Our results revealed that the surface charge, but not the size of NDs, is crucial to the protein conjugation, as well as the in vitro and in vivo behaviors of H5.c2:ND conjugates. Positively charged ND4 does not effectively form stable conjugates with H5.c2, and has no impact on the immunogenicity of the protein both in vitro and in vivo. In contrast, the negatively oxidized NDs (ND40 and ND100) are excellent protein antigen carriers. When compared to free H5.c2, H5.c2:ND40, and H5.c2:ND100 conjugates are highly immunogenic with hemagglutination titers that are both 16 times higher than that of the free H5.c2 protein. Notably, H5.c2:ND40 and H5.c2:ND100 conjugates induce over 3-folds stronger production of both H5.c2-specific-IgG and neutralizing antibodies against A/H5N1 than free H5.c2 in mice. These findings support the innovative strategy of using negatively oxidized ND particles as novel antigen carriers for vaccine development, while also highlighting the importance of particle characterization before use.

Immunization with Plant-Derived Multimeric H5 Hemagglutinins Protect Chicken against Highly Pathogenic Avian Influenza Virus H5N1.

Since 2003, H5N1 highly pathogenic avian influenza viruses (HPAIV) have not only caused outbreaks in poultry but were also transmitted to humans with high mortality rates. Vaccination is an efficient and economical means of increasing immunity against infections to decrease the shedding of infectious agents in immunized animals and to reduce the probability of further infections. Subunit vaccines from plants are the focus of modern vaccine developments. In this study, plant-made hemagglutinin (H5) trimers were purified from transiently transformed N. benthamiana plants. All chickens immunized with purified H5 trimers were fully protected against the severe HPAIV H5N1 challenge. We further developed a proof-of-principle approach by using disulfide bonds, homoantiparallel peptides or homodimer proteins to combine H5 trimers leading to production of H5 oligomers. Mice vaccinated with crude leaf extracts containing H5 oligomers induced neutralizing antibodies better than those induced by crude leaf extracts containing trimers. As a major result, eleven out of twelve chickens (92%) immunized with adjuvanted H5 oligomer crude extracts were protected from lethal disease while nine out of twelve chickens (75%) vaccinated with adjuvanted H5 trimer crude extracts survived. The solid protective immune response achieved by immunization with crude extracts and the stability of the oligomers form the basis for the development of inexpensive protective veterinary vaccines.

Magnetic Field-Sensitive Radical Pair Dynamics in Polymethylene Ether-Bridged Donor-Acceptor Systems.

Donor-acceptor systems forming exciplexes are versatile models for the study of magnetic field effects (MFEs) on charge recombination reactions. The MFEs originate from singlet-triplet interconversion within transient radical ion pairs (RIPs), which exist in a dynamic equilibrium with the exciplexes. Here, we describe the synthesis and MFEs of the chain-linked N,N-dimethylaniline (DMA)/9-methylanthracene (MAnt) donor-acceptor system MAnt-(CH2) n -O-CH2-CH2-DMA for n = 6, 8, 10, and 16. The MFEs are found to increase with increasing chain length. Effects as large as 37.5% have been observed for the long-chain compound with n = 16. The solvent dependence of the MFEs at magnetic field intensity 75 mT is reported. For the range of solvent static dielectric constants εs = 6.0-36.0, the MFEs go through a maximum for intermediate polarities, for which the direct formation of RIPs prevails and their dissociation and reencounter are balanced. Field-resolved measurements (MARY spectra) are reported for solutions in butyronitrile. The MARY spectra reveal that for n = 8, 10, 16, the average exchange interaction is negligible during the coherent lifetime of the radical pair. However, singlet-triplet dephasing broadens the lineshape; the shorter the linker, the more pronounced this effect is. For n = 6, a dip in the fluorescence intensity reveals a nonzero average exchange coupling of the order of ±5 mT. We discuss the field-dependence in the framework of the semiclassical theory taking spin-selective recombination, singlet-triplet dephasing, and exchange coupling into account. Singlet recombination rates of the order of 0.1 ns-1 and various degrees of singlet-triplet dephasing govern the spin dynamics. In addition, because of a small free energy gap between the exciplex and the locally excited fluorophore quencher pair, a fully reversible interconversion between the RIP, exciplex, and locally excited fluorophore is revealed by spectrally resolved MFE measurements for the long-chain systems (n = 10, 16).

Effects of Preferential Solvation Revealed by Time-Resolved Magnetic Field Effects.

External magnetic fields can impact recombination yields of photoinduced electron transfer reactions by affecting the spin dynamics in transient, spin-correlated radical pair intermediates. For exciplex-forming donor-acceptor systems, this magnetic field effect (MFE) can be investigated sensitively by studying the delayed recombination fluorescence. Here, we investigate the effect of preferential solvation in microheterogeneous solvent mixtures on the radical pair dynamics of the system 9,10-dimethylanthracene (fluorophore)/N,N-dimethylaniline (quencher) by means of time-resolved magnetic field effect (TR-MFE) measurements, wherein the exciplex emission is recorded in the absence and the presence of an external magnetic field using time-correlated single photon counting (TCSPC). In microheterogeneous environments, the MFE of the exciplex emission occurs on a faster time scale than in iso-dielectric homogeneous solvents. In addition, the local polarity reported by the exciplex is enhanced compared to homogeneous solvent mixtures of the same macroscopic permittivity. Detailed analyses of the TR-MFE reveal that the quenching reaction directly yielding the radical ion pair is favored in microheterogeneous environments. This is in stark contrast to homogeneous media, for which the MFE predominantly involves direct formation of the exciplex, its subsequent dissociation to the magneto-sensitive radical pair, and re-encounters. These observations provide evidence for polar microdomains and enhanced caging, which are shown to have a significant impact on the reaction dynamics in microheterogeneous binary solvents.