Purpose Patients undergoing radiotherapy for head and neck cancers often experience radiation dermatitis, which is typically managed by applying topical moisturizers. A silicone-based polymer film with antibacterial properties, StrataXRT, has been developed to mitigate radiation-induced side effects. We sought to determine the efficacy of StrataXRT compared with standard moisturizers in reducing the incidence of severe radiation dermatitis in patients with head and neck malignancies. Materials and methods We conducted a retrospective analysis of patients treated with StrataXRT compared with historical controls using conventional moisturizers (largely Aquaphor®) via a clinical informatics approach. Propensity score matching was used to control for dosimetric properties: mean skin dose, maximum skin dose, and the surface area receiving 40 Gy or higher. The endpoint was grade 2+ radiation dermatitis, measured using Common Terminology Criteria for Adverse Events or CTCAE, in 171 patients treated with StrataXRT, compared with 171 matched patients treated with a standard moisturizer. Multivariable Cox regression was performed to estimate the association between StrataXRT and standard moisturizer while adjusting for confounding clinical variables. Results In the multivariable Cox regression, the hazard ratio was 0.61 (95% CI (0.37, 1.0), p=0.049) with a relative reduction in the risk of grade 2+ radiation dermatitis of 36.5% with the use of StrataXRT compared with standard moisturizers. The absolute risk reduction with StrataXRT was 14.5%, which translates to a number needed to treat of seven patients to prevent one occurrence of grade 2+ radiation dermatitis. Conclusions Patients benefited from StrataXRT, with a significant reduction in the incidence of grade 2+ radiation dermatitis throughout the course of treatment. This study supports the adoption of a novel topical agent providing barrier protection in the form of a film-forming gel to reduce acute radiation dermatitis in head and neck cancer patients.
ABSTRACT Introduction This study evaluates our new EHR‐integrated patient portal for asthma care (PAC) management module for parents of children with asthma. The module includes a previsit asthma intake questionnaire via the portal. The parent answers are integrated into the provider's clinic progress note to support clinical decision‐making. Our goals were to measure the functionality and usability of the PAC module and to understand facilitators and barriers to its use for parents. Methods Parents of children ages 0–11 years old ( n = 45) completed the PAC module's asthma intake questionnaires prior to their upcoming pediatric pulmonology clinic visit. To assess functionality, provider progress notes were manually reviewed to measure the amount of key asthma‐related data captured. Differences in percent data captured with and without the PAC module were compared. Electronic surveys capture demographics, usability data (the System Usability Scale [SUS]), and open‐ended experiential feedback about the module. Analysis included descriptive statistics for demographics and usability, as well as the constant comparative method for open‐ended feedback. Results The PAC module at this early stage of design significantly improved the capture of key asthma data in physician notes, increasing from 77% to 92% ( p < 0.001). The average SUS score (83.8) indicated high usability. Favorable aspects of the module that were identified included time savings and ease of use. Conclusion Our PAC module enhanced data capture of key asthma management elements and demonstrated high parental usability. We will continue to refine the module through an iterative approach based on end‐user feedback, with future expansion planned for broader patient populations.
Abstract Background: The western Russell’s viper (Daboia russelii) is widely distributed in South Asia, and geographical venom variation is anticipated among distant populations. Antivenoms used for Russell’s viper envenomation are, however, raised typically against snakes from Southern India. The present study investigated and compared the venom proteomes of D. russelii from Sri Lanka (DrSL) and India (DrI), the immunorecognition of Indian VINS Polyvalent Antivenom (VPAV) and its efficacy in neutralizing the venom toxicity. Methods: The venoms of DrSL and DrI were decomplexed with C18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol. Results: DrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A2 (PLA2) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately. Conclusion: Considering that a large amount of venom can be injected by Russell’s viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.
This study aimed to evaluate the effectiveness of an educational intervention (Safe D.U.M.P) to improve the knowledge, attitude, and practice regarding the return and disposal of unused medications. Community-dwelling adults in Malaysia who could understand English were recruited from two healthcare events. Participants were asked to fill out the validated Return and Disposal of Unused Medications (ReDiUM) questionnaire (pre-intervention), view six educational intervention posters on how to dispose of unused medications (Safe D.U.M.P), then answer the ReDiUM questionnaire immediately after viewing the posters (post-intervention). A total of 390 out of 456 participants participated (response rate=85.5%). Most were female (71%) with a median age of 42 years. The overall knowledge of participants significantly increased from 60% to 80% (p<0.001). However, no improvement was seen regarding their overall attitude and practice. This outcome was as expected as it may be more difficult to improve attitude and practice (when compared to knowledge) with a single educational session.
The venom proteome of Hydrophis curtus (synonym: Lapemis hardwickii) from Penang, Malaysia was investigated with nano-electrospray ionization-liquid chromatography tandem mass spectrometry (ESI-LCMS/MS) of the reverse-phase high-performance liquid chromatography (HPLC) venom fractions. Thirty distinct protein forms were identified as toxins from ten families. The three major protein families were phospholipase A2 (PLA2, 62.0% of total venom proteins), three-finger toxin (3FTX, 26.33%) and cysteine-rich secretory protein (CRiSP, 9.00%). PLA2 comprises diverse homologues (11 forms), predominantly the acidic subtypes (48.26%). 3FTX composed of one short alpha-neurotoxin (SNTX, 22.89%) and four long alpha-neurotoxins (LNTX, 3.44%). Both SNTX and LNTX were lethal in mice (intravenous LD50 = 0.10 and 0.24 μg/g, respectively) but the PLA2 were non-lethal (LD50 >1 μg/g). The more abundant and toxic SNTX appeared to be the main driver of venom lethality (holovenom LD50 = 0.20 μg/g). The heterologous Sea Snake Antivenom (SSAV, Australia) effectively cross-neutralized the venom (normalized potency = 9.35 mg venom neutralized per g antivenom) and the two neurotoxins in vivo, with the LNTX being neutralized more effectively (normalized potency = 3.5 mg toxin/g antivenom) than SNTX (normalized potency = 1.57 mg/g). SSAV immunorecognition was strong toward PLA2 but moderate-to-weak toward the alpha-neurotoxins, indicating that neutralization of the alpha-neurotoxins should be further improved.
Background The success of interprofessional collaboration in healthcare services requires a paradigm shift in the training of future health profession practitioners. This study aimed to develop and validate an instrument to measure Student Acceptance of Interprofessional Learning (SAIL) in Malaysia, and to assess this attribute among medical and pharmacy students using a prescribing skills training workshop. Methods The study consisted of two phases. In Phase 1, a 10-item instrument (SAIL-10) was developed and tested on a cohort of medical and pharmacy students who attended the workshop. In Phase 2, different cohorts of medical and pharmacy students completed SAIL-10 before and after participating in the workshop. Results Factor analysis showed that SAIL-10 has two domains: “facilitators of interprofessional learning” and “acceptance to learning in groups”. The overall SAIL-10 and the two domains have adequate internal consistency and stable reliability. The total score and scores for the two domains were significantly higher after students attended the prescribing skills workshop. Conclusions This study produced a valid and reliable instrument, SAIL-10 which was used to demonstrate that the prescribing skills workshop, where medical and pharmacy students were placed in an authentic context, was a promising activity to promote interprofessional learning among future healthcare professionals.
Gel filtration chromatography and gel electrophoresis revealed minimal protein degradation in lyophilized antivenoms which were 2-year expired (Hemato Polyvalent, Neuro Polyvalent; Thailand) and 18-year expired (Hemato Bivalent, Neuro Bivalent; Taiwan). All expired antivenoms retained immunological binding activity, and were able to neutralize the hemotoxic or neurotoxic as well as lethal effects of the homologous snake venoms. The findings show that antivenoms under proper storage conditions may remain relatively stable beyond the indicated shelf life.
The aim of our study was to develop and validate the return and disposal of unused medications (ReDiUM), as there are currently no validated tools available (worldwide) to assess this. The ReDiUM was developed by an expert panel. It was then administered to community-dwelling adults, who could understand English, at baseline and 2 weeks later. A total of 338/354 participants agreed to participate (response rate = 95.4%). Flesch reading ease was 60. The overall Cronbach's α was 0.703 (range = 0.609-0.762). At test-retest, κ values ranged from 0.244 to 0.523. Median total knowledge score was 60% (interquartile range = 40% to 70%). The majority of participants (94.4%) knew that improper drug disposal has harmful effects on the environment. However, their knowledge was low (11.2%) regarding the disposal of pressurized metered-dose inhalers in the garbage. The ReDiUM was found to be a valid and reliable instrument to assess the knowledge, attitude, and practice on the ReDiUM in Malaysia.
The venom proteome of wild Pakistani Russell's viper (Daboia russelii) was investigated through nano-ESI-LCMS/MS of the reverse-phase HPLC fractions. A total of 54 venom proteins were identified and clustered into 11 protein families. Phospholipase A(2) (PLA(2), 63.8%) and Kunitz-type serine protease inhibitor (KSPI, 16.0%) were most abundant, followed by snake venom serine protease (SVSP, 5.5%, mainly Factor V activating enzyme), vascular endothelial growth factor (VEGF, 4.3%), snake venom metalloproteinase (SVMP, 2.5%, mainly Factor X activating enzyme) and phosphodiesterase (PDE, 2.5%). Other minor proteins include cysteine-rich secretory protein (CRiSP), snake venom C-type lectin/lectin-like protein (snaclec), nerve growth factor, L-amino acid oxidase and 5'-nucleotidase. PLA(2), KSPI, SVSP, snaclec and SVMP are hemotoxic proteins in the venom. The study indicated substantial venom variation in D. russelii venoms of different locales, including 3 Pakistani specimens kept in the USA. The venom exhibited potent procoagulant activity on human plasma (minimum clotting dose = 14.5 ng/ml) and high lethality (rodent LD50 = 0.19 mu g/g) but lacked hemorrhagic effect locally. The Indian VINS Polyvalent Antivenom bound the venom immunologically in a concentration-dependent manner. It moderately neutralized the venom procoagulant and lethal effects (normalized potency against lethality = 2.7 mg venom neutralized per g antivenom). Biological significance: Comprehensive venom proteomes of D. russelii from different locales will facilitate better understanding of the geographical variability of the venom in both qualitative and quantitative terms. This is essential to provide scientific basis for the interpretation of differences in the clinical presentation of Russell's viper envenomation. The study revealed a unique venom proteome of the Pakistani D. russelii from the wild (Indus Delta), in which PLA(2) predominated (similar to 60% of total venom proteins). The finding unveiled remarkable differences in the venom compositions between the wild (present study) and the captive specimens reported previously. The integration of toxicity tests enabled the correlation of the venom proteome with the envenoming pathophysiology, where the venom showed potent lethality mediated through coagulopathic activity. The Indian VINS Polyvalent Antivenom (VPAV) showed binding activity toward the venom protein antigens; however the immunorecognition of small proteins and PLA(2)-dominating fractions was low to moderate. Consistently, the antivenom neutralized the toxicity of the wild Pakistani Russell's viper venom at moderate efficacies. Our results suggest that it may be possible to enhance the Indian antivenom potency against the Pakistani viper venom by the inclusion of venoms from a wider geographical range including that from Pakistan into the immunogen formulation.
Snake venoms are one of the most complicated drug targets due to the complex nature of their toxin proteins, which can be highly variable across different species or even within the same species. This study aimed to unravel the compositional details, pharmacological activities and immunological responses of the venoms of medically important snake species in Asia and Africa, including 15 major cobras (Naja) species found in the world for insights into the improvement of antivenom treatment. The venoms were first decomplexed using C18-reverse-phase high performance liquid chromatography, and the protein fractions were trypsin-digested, followed by nano-ESI liquid chromatography-tandem mass spectrometry and data mining. Denovovenom-gland transcriptomes of selected species were also analyzed to enhance the deep profiling of the venom proteomes. The venom/toxin toxicity (neurotoxicity and lethality) and the neutralization were tested exvivo (chick biventer-cervicis nerve-muscle model) and invivo(mouse model). Modified venom immunogen with enriched short neurotoxins was used to raise experimental horse anti-cobra antserum to test for neutralization efficacy improvement. Cobra venoms exhibit a high degree of plasticity, displaying a diverse composition of neurotoxins that correlated strongly with the venom toxicity. Notably, the Pakistani black cobra (Najanaja), Thai monocled cobra (Najakaouthia), Philippines spitting cobra (Najaphilippinensis) and Egyptian cobra (Najahaje) have highly lethal venoms (LD 50 = 0.1-0.3 µg/g) driven by the abundant alpha-neurotoxins (>25% of total venom proteins). This has important medical implication as it influences the effectiveness of antivenoms and the choice thereof. Further protein purification study, toxin-specific characterization through isolated nerve-muscle preparations and in vivo neurotoxicity mouse model revealed that the short three-finger alpha-neurotoxins are the culprit lethal components. Unfortunately, they were consistently weak in immunoreactivity evidenced by poor immunorecognition on enzyme-linked immunosorbent assay (ELISA), and they were poorly neutralized by antivenoms available in the region. Using a revised immunization protocol where venom immunogen was enriched with neurotoxins, the antisera raised experimentally from horses showed promising neutralization efficacy against the different cobra venoms including those with abundant short-chain neurotoxins. Together, in-depth venom protemics combined with pharmacological study and immunological innovation may pave the path to improve treatment for snakebite envenomation.
The 1^(st) Asia-Pacific Conference on Problem-Based Learning, (APC-PBL, generic) was held in Hong Kong in 1999. In the following year, the National University of Singapore organised the 1^(st) ASEAN Conference on PBL in Health Sciences. The conference was well attended by academics and practitioners from the Asia-Pacific region and a pro-tem committee was set up to form an Asia-Pacific Association for PBL in Health Sciences. Consequently, the following conference was renamed the 2^(nd) Asia-Pacific Conference for PBL in Health Sciences (APC-PHS), held in 2001 in Kuala Lumpur, Malaysia. At the 3^(rd) APC-PHS, held in Taipei, Taiwan (2002), it was decided to hold the Association Conference biennially. After several attempts, the Association was finally registered in Malaysia in 2003, as the Asia-Pacific Association on PBL in Health Sciences (APA-PHS). The first "official" Executive Committee (2004-06), was formalised at the formal inaugural at the 4^(th) APC-PHS held in Manila, Philippines (2004). Since then, biennial conferences have been held in Surabaya, Indonesia (2006) and Kuala Lumpur, Malaysia (2008). At the 2008 meeting, another milestone in the journey of PBL in the Asia-Pacific region was reached: the proposed merger of the two PBL conferences, i.e., APC-PBL and APC-PHS, was formally agreed. The 1^(st) Asia-Pacific Joint Conference on PBL (APJC-PBL) was held in Taipei, Taiwan (2010), followed by Shanghai, China (2012) and Phuket, Thailand (2014). This paper documented the journey of APA-PHS in aiming to strive for excellence in innovative education for health-science professionals in the Asia-Pacific region with a special emphasis on PBL philosophy.
The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation.