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Background: There is currently no validated tool available for assessing the potential significance of pharmacist interventions in Vietnam., Aim: This study aimed to translate the CLEO tool from French into Vietnamese, validate the Vietnamese version, and demonstrate its feasibility in daily practice., Method: The CLEO tool was translated into Vietnamese (CLEO VN ) using a 5-step process by bilingual experts. A total of 100 scenarios were compiled from clinical cases from nine hospitals evaluated by seven clinical pharmacists to determine inter-rater reliability and 30 out of 100 scenarios were re-evaluated one month later to determine test-retest reliability. Reliability was quantified using the intra-class correlation coefficient (ICC). A 20-item questionnaire on a 7-point Likert scale assessed the tool's appropriateness, acceptability, precision, and feasibility., Results: Inter-rater reliability was good for clinical dimension (ICC A,1  = 0.71), excellent for economic dimension (ICC A,1  = 0.86), and fair for organizational/operational dimension (ICC A,1  = 0.56). Test-retest reliability scores were excellent for clinical (I̅C̅C̅ A,1  = 0.79), excellent for economic (I̅C̅C̅ A,1  = 0.84), and fair for organizational/operational (I̅C̅C̅ A,1  = 0.56). The tool was rated as appropriate (mean = 5.86; SD = 1.03), acceptable (mean = 5.19; SD = 1.12), precise (mean = 5.71; SD = 1.17), and feasible (mean = 5.05; SD = 1.24). The maximum time required to evaluate an intervention was three minutes., Conclusion: The CLEO VN tool was successfully translated and validated for reliability, appropriateness, acceptability, precision, and feasibility. It will be suitable to evaluate the value of clinical pharmacy interventions., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5 x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself., (© 2024 Orthopaedic Research Society.)

Objective: Extracorporeal CPR (E-CPR) has been primarily limited to the in-hospital setting. A few systems around the world have implemented pre-hospital mobile E-CPR in the form of a dedicated cardiac vehicle fitted with specialised equipment and clinicians required for the performance of E-CPR on-scene. However, evidence of the outcomes and cost-effectiveness of mobile E-CPR remain to be established. We evaluated the cost-effectiveness of a hypothetical mobile E-CPR vehicle operated by Queensland Ambulance Service in the state of Queensland, Australia., Methods: We adapted our published mathematical model to estimate the cost-effectiveness of pre-hospital mobile E-CPR relative to current practice. In the model, a specialised cardiac vehicle with mobile E-CPR capability is deployed to selected OHCA patients, with eligible candidates receiving pre-hospital E-CPR in-field and rapid transport to the closest appropriate centre for in-hospital E-CPR. For comparison, non-candidates receive standard ACLS from a conventional ambulance response. Cost-effectiveness was expressed as Australian dollars ($, 2021 value) per quality-adjusted life year (QALY) gained., Results: Pre-hospital mobile E-CPR improves outcomes compared to current practice at a cost of $27 323 per QALY gained. The cost-effectiveness of pre-hospital mobile E-CPR is sensitive to the assumption around the number of patients who are the targets of the vehicle, with higher patient volume resulting in improved cost-effectiveness., Conclusions: Pre-hospital E-CPR may be cost-effective. Successful implementation of a pre-hospital E-CPR programme requires substantial planning, training, logistics and operational adjustments., (© 2024 Australasian College for Emergency Medicine.)

Camptothecin (CPT) is an important alkaloid used for anticancer treatment. It is mainly produced by two endangered and overharvested Camptotheca acuminata and Nothapodytes nimmoniana plants. Endophytic fungi are promising alternative sources for CPT production. In the present study, fungi residing within explants of Ixora chinensis were isolated and their CPT-producing capability of their endophytes was verified via thin-layer chromatography, high-performance liquid chromatography, liquid chromatography/high resolution mass spectrometry, and nuclear magnetic resonance analyses and compared with standards. In addition, MTT and sulforhodamine B assays were selected to test the anticancer effect. The endophytic fungi collection of 62 isolates were assigned to 11 genera, with four common genera ( Diaporthe , Phyllosticta , Colletotrichum , and Phomopsis ) and seven less common genera ( Penicillium , Botryosphaeria , Fusarium , Pestalotiopsis , Aspergillus , and Didymella ). Moreover, the anticancer activity of extracts was assessed against human lung carcinoma (A549). Among eight potential extracts, only Penicillium sp. I3R2 was found to be a source of CPT, while the remaining seven extracts have not been discovered potential secondary compounds. Thus, other prominent endophytic fungi might be potential candidates of phytochemicals with anticancer properties., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Research into suicide-related out-of-hospital cardiac arrests (OHCA) using OHCA registries is scant. A more complete understanding of methods, patient characteristics, and outcomes is essential to inform prehospital management strategies and public health interventions., Methods: Included were all OHCA attended by Queensland Ambulance Service (Australia) paramedics between 1 January 2007 and 31 December 2020, where suicide-related causes could be identified. Age- and sex-standardized incidence rates were calculated. Suicide methods, patient characteristics, and survival outcomes were described. Factors associated with survival outcomes were investigated., Results: Seven thousand three hundred and fifty-six suicide-related OHCA cases were included. The incidence rates increased from 9.0 per 100,000 population in 2007 to 12.4 in 2020. The incidence rates for males were four times those for females; however, incidence rates for females have increased faster than for males. Hanging was the most common suicide method (63%). Twenty-three percent of patients received resuscitation attempts by paramedics. Among those, the rates of return of spontaneous circulation (ROSC) sustained to hospital arrival, survival to hospital discharge, and survival to 30 days were 28.6, 8.5, and 8.0%, respectively. Over time, the rates of ROSC upon hospital arrival increased, whereas the rates of survival to discharge and 30-day survival remained stable., Conclusion: The incidence of prehospital-identified suicide-related OHCA in Queensland has increased over time. The prognosis of suicide-related OHCA is poor. Prevention measures should focus on early identification and treatment of individuals having a high risk of suicide. Emergency medical services need to have sufficient training for telecommunicators and paramedics in suicide risk assessment and identification.

Purpose: This study aims to investigate the prevalence of presbyphonia among older adults who report voice complaints., Method: We conducted a systematic search of five medical databases to identify studies that reported on presbyphonia as the cause of voice disorders in older adults. The pooled prevalence was calculated using random-effects models and presented as percentages with 95% confidence intervals (CI). The degree of heterogeneity among studies was assessed using I 2 statistics. Subgroup analyses were performed to identify the sources of heterogeneity., Results: Out of 764 abstracts from five libraries, 11 studies were included in this systematic review. The pooled prevalence of presbyphonia among older adults with voice disorders is 17.78% (95% CI [12.69, 23.51]). We conducted a subgroup analysis on studies that used laryngeal visualization to confirm the diagnosis for all patients and found that the prevalence of presbyphonia was lower in studies with unrestrictive inclusion criteria (12.84%, 95% CI [8.38, 18.08]) compared to studies with restricted inclusion criteria (22.59%, 95% CI [14.49, 31.88])., Conclusions: This study suggests that voice disorders in older adults have multiple causes, not predominantly presbyphonia. Overestimation of presbyphonia prevalence occurs if certain diagnoses are excluded at recruitment. This study emphasizes the importance of recognizing the diverse underlying etiologies of dysphonia in older adults; therefore, comprehensive examination and accurate diagnosis are crucial., Supplemental Material: https://doi.org/10.23641/asha.24263029.

Despite their promise, circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection face challenges in test performance, due mostly to the limited abundance of ctDNA and its inherent variability. To address these challenges, published assays to date demanded a very high-depth sequencing, resulting in an elevated price of test. Herein, we developed a multimodal assay called SPOT-MAS (screening for the presence of tumor by methylation and size) to simultaneously profile methylomics, fragmentomics, copy number, and end motifs in a single workflow using targeted and shallow genome-wide sequencing (~0.55×) of cell-free DNA. We applied SPOT-MAS to 738 non-metastatic patients with breast, colorectal, gastric, lung, and liver cancer, and 1550 healthy controls. We then employed machine learning to extract multiple cancer and tissue-specific signatures for detecting and locating cancer. SPOT-MAS successfully detected the five cancer types with a sensitivity of 72.4% at 97.0% specificity. The sensitivities for detecting early-stage cancers were 73.9% and 62.3% for stages I and II, respectively, increasing to 88.3% for non-metastatic stage IIIA. For tumor-of-origin, our assay achieved an accuracy of 0.7. Our study demonstrates comparable performance to other ctDNA-based assays while requiring significantly lower sequencing depth, making it economically feasible for population-wide screening., Competing Interests: VN VTCN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN HTN is affiliated with Gene Solutions. The author has no other competing interests to declare, ND NNTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TMQP is affiliated with Gene Solutions. The author has no other competing interests to declare, GN GTHN is affiliated with Gene Solutions. The author has no other competing interests to declare, TN TDN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTTT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV, TP, TJ, VN, HN, TN, QD, TD, AT, VN, VN, LH, QT, TP, TH, BN, TN, TN, DP, BP, TV, TN, TT, MT, NT, TL, TT, MD, HB, VK, TP, DT, TL, TP, ML, VC, TD No competing interests declared, TN THHN is affiliated with Gene Solutions. The author has no other competing interests to declare, LH LAKH is affiliated with Gene Solutions. The author has no other competing interests to declare, TT THT is affiliated with Gene Solutions. The author has no other competing interests to declare, DV DHV is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TMTT is affiliated with Gene Solutions. The author has no other competing interests to declare, MN MNN is affiliated with Gene Solutions. The author has no other competing interests to declare, TV TTVV is affiliated with Gene Solutions. The author has no other competing interests to declare, AN ANN is affiliated with Gene Solutions. The author has no other competing interests to declare, TT TTT is affiliated with Gene Solutions. The author has no other competing interests to declare, VT VUT is affiliated with Gene Solutions. The author has no other competing interests to declare, ML MPL is affiliated with Gene Solutions. The author has no other competing interests to declare, TD TTD is affiliated with Gene Solutions. The author has no other competing interests to declare, TP TVP is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HDN is affiliated with Gene Solutions. The author has no other competing interests to declare, DN DSN holds equity in Gene Solutions.DSN is affiliated with Gene Solutions. The author has no other competing interests to declare, DT DKT is affiliated with Gene Solutions. The author has no other competing interests to declare, HT HST is affiliated with Gene Solutions. The author has no other competing interests to declare, HG HG holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HG who is inventor on the patent application (USPTO 17930705).HG is affiliated with Gene Solutions. The author has no other competing interests to declare, HN HNN holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for HNN who is inventor on the patent application (USPTO 17930705).HNN is affiliated with Gene Solutions. The author has no other competing interests to declare, MP MDP holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for MDP who is inventor on the patent application (USPTO 17930705).MDP is affiliated with Gene Solutions. The author has no other competing interests to declare, LT LST holds equity in Gene Solutions. The funder Gene Solutions provided support in the form of salaries for LST who is inventor on the patent application (USPTO 17930705).LST is affiliated with Gene Solutions. The author has no other competing interests to declare, (© 2023, Nguyen, Nguyen et al.)

Aim: Awareness of heart attack symptoms may enhance health-seeking behaviour and prevent premature deaths from out-of-hospital cardiac arrest (OHCA). We sought to investigate the impact of a national awareness campaign on emergency medical service (EMS) attendances for chest pain and OHCA., Methods: Between January 2005 and December 2017, we included registry data for 97,860 EMS-attended OHCA cases from 3 Australian regions and dispatch data for 1,631,217 EMS attendances for chest pain across 5 Australian regions. Regions were exposed to between 11 and 28 months of television, radio, and print media activity. Multivariable negative binomial models were used to explore the effect of campaign activity on the monthly incidence of EMS attendances for chest pain and OHCA., Results: Months with campaign activity were associated with an 8.8% (IRR 1.09, 95% CI: 1.07, 1.11) increase in the incidence of EMS attendances for chest pain and a 5.6% (IRR 0.94, 95% CI: 0.92, 0.97) reduction in OHCA attendances. Larger intervention effects were associated with increasing months of campaign activity, increasing monthly media spending and media exposure in 2013. In stratified analyses of OHCA cases, the largest reduction in incidence during campaign months was observed for unwitnessed arrests (IRR 0.93, 95% CI: 0.90, 0.96), initial non-shockable arrests (IRR 0.93, 95% CI: 0.90, 0.97) and arrests occurring in private residences (IRR 0.95, 95% CI: 0.91, 0.98)., Conclusion: A national awareness campaign targeting knowledge of heart attack symptoms was associated with an increase in EMS use for chest pain and a reduction in OHCA incidence and may serve as an effective primary prevention strategy for OHCA., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ZN, JF and JB are editorial board members of Resuscitation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plasmids are essential source material for production of biological drugs, vaccines and vectors for gene therapy. They are commonly formulated as frozen solutions. Considering the cost associated with maintenance of cold chain conditions during storage and transport, there is a significant need for alternative methods for stabilization of plasmids at ambient temperature. The objective of these studies was to identify a film-based formulation that preserved transfection efficiency of plasmids at 25 °C. A model plasmid, pAAVlacZ, was used for these studies. Transfection efficiency and agarose gel electrophoresis were utilized to assess bioactivity and changes in physical conformation of plasmid during storage. An amino acid, capable of sustaining a positive charge while supporting an alkaline environment within the film matrix, preserved transfection efficiency for 9 months at 25 °C. Addition of sugar and a plasticizer to the formulation preserved the plasmid in an amorphous state and improved handling properties of the film. The manner in which excipients were incorporated into bulk formulations and environmental humidity in which films were stored significantly impacted transfection efficiency of plasmid in the rehydrated solution. Taken together, these results suggest that plasmids can be stored for extended periods of time without refrigeration within a film matrix., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: The deliberate inhalation of volatile substances for their psychotropic properties is a recognised public health issue that can precipitate sudden death. This study aimed to describe the epidemiological characteristics and survival outcomes of patients with out-of-hospital cardiac arrests following volatile substance use., Methods: We conducted a retrospective cohort analysis of all out-of-hospital cardiac arrest attended by the Queensland Ambulance Service over a ten-year period (2012-2021). Incidents were extracted from the Queensland Ambulance Service cardiac arrest registry, which collects clinical information using the Utstein-style guidelines and linked hospital data., Results: During the study period, 52,102 out-of-hospital cardiac arrests were attended, with 22 (0.04%) occurring following volatile substance use. The incidence rate was 0.04 per 100,000 population, with no temporal trends identified. The most commonly used product was deodorant cans (19/22), followed by butane canisters (2/22), and nitrous oxide canisters (1/22). The median age of patients was 15 years (interquartile range 13-23), with 14/22 male and 8/22 Indigenous Australians. Overall, 16/22 patients received a resuscitation attempt by paramedics. Of these, 12/16 were bystander witnessed, 10/16 presented in an initial shockable rhythm, and 9/16 received bystander chest compressions. The rates of event survival, survival to hospital discharge, and survival with good neurological outcome (Cerebral Performance Category 1-2) were 69% (11/16, 95% CI 41-89%), 38% (6/16, 95% CI 15-65%) and 31% (5/16, 11-59%), respectively. Eight patients in the paramedic-treated cohort that used hydrocarbon-based products were administered epinephrine during resuscitation. Of these, none subsequently survived to hospital discharge. In contrast, all six patients that did not receive epinephrine survived to hospital discharge, with 5/6 having a good neurological outcome., Conclusion: Out-of-hospital cardiac arrest following volatile substance use is rare and associated with relatively favourable survival rates. Patients were predominately aged in their adolescence with Indigenous Australians disproportionately represented.

Traumatic joint injuries are common, leading to progressive tissue degeneration and the development of osteoarthritis. The post-traumatic joint experiences a pro-inflammatory milieu, initiating a subtle but deteriorative process in cartilage tissue. To prevent or even reverse this process, our group previously developed a tissue-penetrating methacrylated hyaluronic acid (MeHA) hydrogel system, crosslinked within cartilage to restore and/or protect the tissue. In the current study, we further optimized this approach by investigating the impact of biomaterial molecular weight (MW; 20, 75, 100 kDa) on its integration within and reinforcement of cartilage, as well as its ability to protect tissue degradation in a catabolic state. Indeed, the low MW MeHA integrated and reinforced cartilage tissue better than the high MW counterparts. Furthermore, in a 2 week IL-1β explant culture model, the 20 kDa MeHA demonstrated the most protection from biphasic mechanical loss, best retention of proteoglycans (Safranin O staining), and least aggrecan breakdown (NITEGE). Thus, the lower MW MeHA gels integrated better into the tissue and provided the greatest protection of the cartilage matrix. Future work will test this formulation in a preclinical model, with the goal of translating this therapeutic approach for cartilage preservation.

Purpose: Voice disorders significantly impair the ability to communicate effectively and reduce the quality of life in older adults; however, its prevalence has not been well established. The aim of our research was to investigate the prevalence and associated factors of voice disorders among the older population., Method: Five medical databases were systematically searched for studies that reported the prevalence of voice disorders in older adults. The overall prevalence was exhibited in proportions and 95% confidence intervals (CIs) utilizing random-effects models. Heterogeneity was measured using I 2 statistics., Results: Of 930 articles screened, 13 fulfilled the eligibility criteria, including 10 studies in community-based settings and three in institutionalized settings. An overall prevalence of voice disorders in older adults was estimated to be 18.79% (95% CI [16.34, 21.37], I 2 = 96%). Subgroup analysis showed a prevalence of 33.03% (95% CI [26.85, 39.51], I 2 = 35%) in institutionalized older adults, which was significantly higher than that in the community-based older adults with 15.2% (95% CI [12.65, 17.92], I 2 = 92%). Some factors that influenced the reported prevalence were identified, including types of survey, the definition of voice disorders, sampling methods, and the mean age of the population among included studies., Conclusions: The prevalence of voice disorders in the older population depends on various factors but is relatively common in older adults. The findings of this study accentuate the necessity for researchers to standardize the protocol for reporting geriatric dysphonia as well as for older adults to express their voice-related problems so that they will receive appropriate diagnosis and treatment.

Introduction Lymph node (LN) metastasis happens even in early gastric cancer (GC) even in LN stations that are not adjacent to the primary tumor. Total or subtotal gastrectomy (TG or sTG) can be performed in the middle third of the GC if the negative proximal margin is maintained. These procedures differed in the extent of LN dissection; therefore, oncology considerations must be taken into consideration when selecting the appropriate procedure. Methods This was a cross-sectional study involving 98 patients suffering from middle-third GC. The metastatic lymph nodes (mLN) ratio was calculated in each case by the ratio between the number of mLN and the number of total LNs retrieved. We compare the difference in the total LN retrieved, number of mLN, and rate of positive LN (N+) between the two groups TG and sTG. Results The majority of patients had advanced GC (82.7% pT2-4). About 65.3% of patients had metastasis LN. The events of LN metastasis and skipped LN metastasis happened even in tumors contained in the submucosal layer. The metastasis rates in each LN station were also increasing in correlation with the depth of tumor invasion. For LN station No. 2, 4sa, 10, 11d (which are not mandatory) in sTG, the rate of mLN was 0% for the pT1-3 tumor, regardless of tumor longitudinal location. The rate of mLN for each station was higher in adjacent stations of the tumor (No. 1-3-5-7 in lesser curvature, No. 4sb-4d-6 in greater curvature, No.1-3-4sb in the anterior wall, No. 3-7-12a in the posterior wall). The total LN retrieved, number of mLN, and rate of positive LN were statistically higher in the TG group compared to the sTG group. However, the mean mLN ratios between the two groups were comparable (p = 0.116). Conclusion In accordance with the macroscopic and microscopic characteristics, we observed a stratified distribution of mLN in the middle third of the GC. With these early results, sTG combined with standard lymphadenectomy was an acceptable treatment for T1-T3 middle-third GC in terms of mLN distribution. Total No. 4sb LN dissection might also be reserved in gastrectomy for T1-T3 GC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Vu Tuan Anh et al.)

Objective: This study presents the proportion of adults with intellectual disability using psychotropic medications including antipsychotics, antidepressants, anxiolytics, hypnotics and sedatives, and psychostimulants., Methods: A search was performed in PubMed, Embase, PsycINFO, Web of Science, and Scopus up to 31 December 2021. Articles were included if they reported the proportion of adults with intellectual disability using psychotropic medications. Frequency of use was estimated using a random effects meta-analysis. Meta-regression analysis was used to assess the association between study-level characteristics and variability in estimates, when heterogeneity was considerable., Results: Twenty-four articles were included in pooled analysis. The pooled prevalence of psychotropic medications was 41% (95% confidence interval: 35-46%). Pooled prevalences of subclasses were as follows: antipsychotics 31% (27-35%), antidepressants 14% (9-19%), anxiolytics 9% (4-15%), hypnotics/sedatives 5% (2-8%), and psychostimulants 1% (1-2%). Heterogeneity was considerable between studies, except for psychostimulants. There was no significant association between assessed characteristics and variability in prevalence estimates., Conclusion: Two-fifths of adults with intellectual disability were prescribed psychotropic medications. Antipsychotics and antidepressants were used by one-third and one-seventh of adults, respectively. There was considerable variability between studies, and further investigation is required to determine the source of variability. More studies are needed to better characterise prescribed psychotropic medications, including effectiveness and adverse effects, to ensure appropriate use of these drugs.

Background: ST-segment elevation myocardial infarction (STEMI) is a common cause of out-of-hospital cardiac arrest (OHCA). For these patients, urgent angiography and revascularization is an important treatment goal. There is a lack of data on the prognosis of STEMI patients after OHCA, who are diagnosed and treated by paramedics prior to hospital transport for primary percutaneous coronary intervention (PCI). Methods: Included were adult STEMI patients identified and treated by paramedics in Queensland (Australia) from January 2016 to December 2019, transported to a hospital for primary PCI, and receiving primary PCI. Patients were grouped into those with resuscitated OHCA and those without OHCA. Clinically-important time intervals, angiographic and clinical profiles, and survival were described. Results: Patients with OHCA had longer time intervals from prehospital STEMI identification to reperfusion than those without OHCA (median 97 versus 87 mins, p  = 0.001). The former had higher rates of cardiac arrhythmia history (50.5 versus 12.4%, p  < 0.001), classified low left ventricular ejection fraction on admission (64.9 versus 50.1%, p  = 0.006), and cardiogenic shock (5.2 versus 1.2%, p  = 0.011) than the latter. A significantly higher proportion of patients with OHCA had multiple diseased vessels (16.9 versus 8.3%, p  = 0.005). In-hospital, 30-day, and one-year mortality was low, being 4.1%, 4.1% and 5.2%, respectively, for STEMI patients with OHCA. The corresponding figures for those without OHCA were 1.6%, 1.8% and 3.3%, respectively. Conclusions: Survival in paramedic-identified STEMI patients treated with primary PCI following OHCA resuscitation was high. Rapid angiography and reperfusion are critical in these patients.

Background: In a cohort of adults with intellectual disability who were followed for up to 16-years, we investigated characteristics associated with frequent emergency department (ED) presentations, hospitalisation, and psychiatric care., Method: Community-dwelling adults with intellectual disability residing in Queensland, Australia, were followed from 1999 to 2015. Healthcare presentations were extracted from administrative databases. Adults who presented frequently were identified and characteristics associated with frequent presentations were identified., Results: Data from 445 adults were analysed. Chronic disease and challenging behaviour were associated with frequent ED presentations (adjusted odds ratio = 1.8, 95% confidence interval = 1.1-3.0 and aOR = 2.2, 95% CI = 1.2-3.9 respectively). Chronic disease and severe/profound intellectual disability were associated with frequent hospitalisations (aOR = 1.9, 95% CI = 1.2-3.2 and aOR = 2.0, 95% CI = 1.2-3.3 respectively). Psychotropic medication use was associated with frequent psychiatric presentations (aOR = 1.9, 95% CI = 1.0-3.4)., Conclusions: Adults at high risk of frequent healthcare presentations should be identified for programmes of optimising health system use, and potentially improving health care quality., (© 2022 John Wiley & Sons Ltd.)

Background: Extracorporeal cardiopulmonary resuscitation (E-CPR) is a method of CPR that passes the patient's blood through an extracorporeal membrane oxygenation (ECMO) device to provide mechanical haemodynamic and oxygenation support in cardiac arrest patients who are not responsive to conventional CPR (C-CPR). E-CPR is being adopted rapidly worldwide despite the absence of high quality trial data and its substantial cost. Published cost-effectiveness data for E-CPR are scarce., Methods: We developed a mathematical model to estimate the cost-effectiveness of E-CPR relative to C-CPR in adult patients with refractory out-of-hospital cardiac arrest (OHCA). The model was a combination of a decision tree for the acute treatment phase and a Markov model for long-term periods. Cost-effectiveness was evaluated from the Australian health system perspective over lifetime. Cost-effectiveness was expressed as Australian dollars (AUD, 2021 value) per quality-adjusted life year (QALY) gained. Variables were parameterised using published data. Probabilistic and univariate sensitivity analyses were performed., Results: The incremental cost-effectiveness ratio (ICER) of E-CPR was estimated to be AUD 45,716 per QALY gained over lifetime (95% uncertainty range 22,102-292,904). The cost-effectiveness of E-CPR was most sensitive to the outcome of the therapy., Conclusion: E-CPR has median ICER that is below common accepted willingness-to-pay thresholds. Local factors within the health care system need to be considered to determine the feasibility of implementing an effective E-CPR program., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

The lymphatic system has been proposed to play a crucial role in preventing the development and progression of osteoarthritis (OA). As OA develops and progresses, inflammatory cytokines and degradation by-products of joint tissues build up in the synovial fluid (SF) providing a feedback system to exacerbate disease. The lymphatic system plays a critical role in resolving inflammation and maintaining overall joint homeostasis; however, there is some evidence that the lymphatics can become dysfunctional during OA. We hypothesized that the functional mechanics of lymphatic vessels (LVs) draining the joint could be directly compromised due to factors within SF derived from osteoarthritis patients (OASF). Here, we utilized OASF and SF derived from healthy (non-OA) individuals (healthy SF (HSF)) to investigate potential effects of SF entering the draining lymph on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractile activity of rat femoral LVs (RFLVs) ex vivo. Dilutions of both OASF and HSF containing serum resulted in a similar LEC migratory response to the physiologically endothelial basal medium-treated LECs (endothelial basal medium containing serum) in vitro. Ex vivo, OASF and HSF treatments were administered within the lumen of isolated LVs under controlled pressures. OASF treatment transiently enhanced the RFLVs tonic contractions while phasic contractions were significantly reduced after 1 h of treatment and complete ceased after overnight treatment. HSF treatment on the other hand displayed a gradual decrease in lymphatic contractile activity (both tonic and phasic contractions). The observed variations after SF treatments suggest that the pump function of lymphatic vessel draining the joint could be directly compromised in OA and thus might present a new therapeutic target., (Copyright © 2022 by ASME.)

Background: To date, there is no conclusive evidence that transcutaneous neuromuscular electrical stimulation (TNMES) benefits patients with post-stroke dysphagia (PSD). In addition, the optimal TNMES electrode placement has not been well-established. This systematic review and meta-analysis were conducted to investigate these two research gaps. Methods: Five major databases were systematically searched for randomized controlled trials (RCTs) through January 2022. Effect sizes were computed using Hedges’ g statistic, which were then entered into the random-effects model to obtain pooled effect estimates. Results: Twenty-four RCTs met the eligibility criteria. On the improvement of swallowing function, TNMES alone was not superior to conventional swallowing therapies (CSTs); combined therapy of TNMES and CSTs significantly surpassed CSTs alone (standardized mean difference (SMD) = 0.91, 95% confidence interval (95% CI): 0.68 to 1.14, p < 0.0001; I2 = 63%). Moreover, significant pooled effect sizes were observed in subgroups with horizontal electrode placement above the hyoid bone (SMD = 0.94, 95% CI: 0.72 to 1.16; I2 = 0%) and horizontal electrode placement just above and below the hyoid bone (SMD = 0.87, 95% CI: 0.59 to 1.14; I2 = 0%). The largest pooled effect size was observed in the subgroup that individualized electrode placement according to dysphagia evaluation (SMD = 1.65, 95% CI: 0.38 to 2.91; I2 = 90%). Conclusion: TNMES should be used in combination with CSTs for PSD. Horizontal electrode placement should target suprahyoid muscles or both suprahyoid and thyrohyoid muscles.

Background: The association between ambient air pollution (AAP) and the risk of Rheumatoid arthritis (RA) remains debatable. We conducted a population-based cohort study to investigate the association between exposure to AAP and the risk of RA in Taiwan. Methods: We analyzed and combined the longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality-Monitoring Database (TAQMD), which were in line with the residential areas. We calculated the RA incidence rates per 10,000 person-years exposed to each quartile of PM2.5 or PM10 concentrations or RH. Hazards regression was conducted to analyze the associations between exposure to each quartile of PM2.5 and PM10 concentrations and the risk of developing RA. The hazard ratios of RA were analyzed between participants exposed to annual average concentrations of PM2.5 and PM10. All the hazard ratios of RA were stratified by gender and adjusted for age and relative humidity (RH). A p-value < 0.05 was considered statistically significant. Results: Among 722,885 subjects, 9338 RA cases were observed. The analyses adjusted for age, gender, and humidity suggested an increased risk of developing RA in the exposure to PM2.5 in the last quartile (Q4) with the adjusted hazard ratio (aHR) was 1.053 (95%CI: 1.043 to 1.063). Conclusion: Our study suggests that exposure to PM2.5 is associated with an increased risk of RA. The finding has implications for policymaking to develop coping strategies to confront AAP as a risk factor for RA.

Aim: To determine the epidemiological characteristics, temporal trends and survival outcomes of OHCAs precipitated by chemical asphyxiation., Methods: We conducted a retrospective cohort analysis of OHCAs attended by paramedics in Queensland, Australia between 2011 and 2020. Patients were classified into two groups depending on the asphyxiating agent involved; simple (argon, carbon dioxide, helium, liquified petroleum gas, nitrogen) and systemic (carbon monoxide, cyanides, hydrogen sulfide, methemoglobin-inducing substances, smoke inhalation). Incidence rates, characteristics and outcomes were described for the entire cohort and independently for each group, with the groups then compared. Temporal trends of asphyxiant utilisation were also described., Results: During the study period, 50,669 OHCAs were attended, with 551 (1.1%) attributable to chemical asphyxiation. The incidence rate was 1.1 per 100,000 population with no significant temporal changes. Suspected suicide was the primary cause of exposure (-95.8%), with systemic asphyixants the dominant agent reported in comparison to simple agents (66.4% vs 33.6%). Over the 10-year period, events precipitated by carbon monoxide decreased by 26.2% (p for trend < 0.001), helium remained unchanged (p for trend = 0.302) and incidents involving nitrogen increased by 28.7% (p for trend < 0.001). Overall, 14.2% (78/551) of the study cohort received a resuscitation attempt by paramedics with 6.4% of these incidents witnessed and 2.6% involving patients presenting in a shockable rhythm. Survival rates were low, with 6.4% surviving the index event, and 1.3% surviving to hospital discharge with a normal neurocognitive function., Conclusion: OHCA precipitated by chemical asphyxiation is relatively infrequent and associated with poor survival outcomes., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

This study aimed to synthesize frailty prevalence among community-dwelling older adults in Asia and identify factors influencing prevalence estimates. Five electronic databases were searched by 29 April 2022, including representative samples of community-dwelling adults who were aged 60 years and older and lived in Asia. Cross-sectional or national longitudinal population-based cohort studies completed with validated instruments were selected. Twenty-one studies with 52,283 participants were included. The pooled prevalence rate of frailty was 20.5% (95% CI = 15.5% to 26.0%). The estimated frailty prevalence was 14.6% (95% CI = 10.9% to 18.8%) while assessed by the Fried frailty phenotype, 28.0% (95% CI = 21.3% to 35.3%) by the Cumulative Frailty Index, 36.4% (95% CI = 33.6% to 39.3%) by the Study of Osteoporotic Fractures (SOF) index, and 46.3% (95% CI = 40.1% to 52.4%) by the Clinical Frailty Scale (p < 0.01). Subgroup analysis in studies using the Fried’s phenotype tool found that frailty prevalence was increased with older age (p = 0.01) and was higher in those who were single (21.5%) than in married participants (9.0%) (p = 0.02). The study results supported a better understanding of frailty prevalence in different geographical distributions and provide references for health policy decision-making regarding preventing frailty progression in older adults.

Background: This systematic review and meta-analysis aimed to estimate the pooled prevalence of dysphagia in older adults, subgrouping by recruitment settings and varying dysphagia assessment methods., Methods: Five major databases were systematically searched through January 2022. A random-effects model for meta-analysis was conducted to obtain the pooled prevalence., Results: Prevalence of dysphagia in the community-dwelling elderly screened by water swallow test was 12.14% (95% CI: 6.48% to 19.25%, I 2 = 0%), which was significantly lower than the combined prevalence of 30.52% (95% CI: 21.75% to 40.07%, I 2 = 68%) assessed by Standardized Swallowing Assessment (SSA) and volume-viscosity swallow test (V-VST). The dysphagia prevalence among elderly nursing home residents evaluated by SSA was 58.69% (95% CI: 47.71% to 69.25%, I 2 = 0%) and by the Gugging Swallowing Screen test (GUSS) test was 53.60% (95% CI: 41.20% to 65.79%, I 2 = 0%). The prevalence of dysphagia in hospitalized older adults screened by the 10-item Eating Assessment Tool was 24.10% (95% CI: 16.64% to 32.44%, I 2 = 0%), which was significantly lower than those assessed by V-VST or GUSS tests of 47.18% (95% CI: 38.30% to 56.14%, I 2 = 0%)., Conclusions: Dysphagia is prevalent in the elderly, affecting approximately one in three community-dwelling elderly, almost half of the geriatric patients, and even more than half of elderly nursing home residents. The use of non-validated screening tools to report dysphagia underestimates its actual prevalence.

Mesenchymal stromal cells (MSCs) have shown promise as osteoarthritis (OA) treatments; however, effective translation has been limited by high variability and heterogeneity of MSCs, suboptimal delivery strategies, and poor understanding of critical quality and potency attributes. Furthermore, most pre-clinical studies of MSC therapeutics for OA have focused on delaying OA development and not on treating established OA, which brings added clinical relevance. Thus, the objective of the current study was to assess the effects of sodium alginate microencapsulation on human MSC (hMSC) secretion of immunomodulatory cytokines in an OA microenvironment and therapeutic efficacy in treating established OA. A Medial Meniscal Transection (MMT) pre-clinical model of OA was implemented. Three weeks post-surgery, after OA was established, intra-articular injections of encapsulated hMSCs or nonencapsulated hMSCs were administered. Six weeks post-surgery, microstructural changes in the knee joint were quantified using microCT. Encapsulated hMSCs reduced articular cartilage degeneration and subchondral bone remodeling. A multiplexed immunoassay panel was used to profile the in vitro secretome of hMSCs in response to IL-1β. Nonencapsulated hMSCs showed an indiscriminate increase in all cytokines in response to IL-1β while encapsulated hMSCs showed a targeted secretory response with increased expression of pro-inflammatory (IL-1β, IL-6, IL-7, IL-8), anti-inflammatory (IL-1RA), and chemotactic (G-CSF, MDC, IP10) cytokines. These data show that sodium alginate microencapsulation can modulate hMSC paracrine signaling and enhance the therapeutic efficacy of the hMSCs in treating established OA. This cytokine profile provides a foundation for the identification of key factors affecting the overall potency of hMSC therapeutics for OA. STATEMENT OF SIGNIFICANCE: While there has been considerable interest in material based MSC encapsulation for treatment of OA, there are critical gaps in our translational understanding of these biomaterial-based technologies for OA. More specifically, previous studies have several important limitations: (1) they have been largely focused on preventing OA development, which limits their translational utility and (2) little prior work has been done to delineate potential routes/mechanisms by which material encapsulation alters MSC therapeutic action. In our manuscript, we aimed to fill these gaps in knowledge by testing the hypotheses that: (1) hMSC encapsulation can attenuate established disease progression, which is a more clinically relevant scenario and (2) hMSC encapsulation significantly changes the secreted paracrine factors from hMSCs., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Survival from out-of-hospital traumatic cardiac arrest (TCA) is poor. Regional variation exists regarding epidemiology, management and outcomes. Data on prognostic factors are scant. A better understanding of injury patterns and outcome determinants is key to identifying opportunities for survival improvement., Methods: Included were adult (≥18 years) out-of-hospital TCA due to blunt, penetrating or burn injury, who were attended by Queensland Ambulance Service paramedics between 1 January 2007 and 31 December 2019. We compared the characteristics of patients who were pronounced dead on paramedic arrival and those receiving resuscitation from paramedics. Intra-arrest procedures were described for attempted-resuscitation patients. Survival up to 6 months postarrest was reported, and factors associated with survival were investigated., Results: 3891 patients were included; 2394 (61.5%) were pronounced dead on paramedic arrival and 1497 (38.5%) received resuscitation from paramedics. Most arrests (79.8%) resulted from blunt trauma. Motor vehicle collision (42.4%) and gunshot wound (17.7%) were the most common injury mechanisms in patients pronounced dead on paramedic arrival, whereas the most prevalent mechanisms in attempted-resuscitation patients were motor vehicle (31.3%) and motorcycle (20.6%) collisions. Among attempted-resuscitation patients, rates of transport and survival to hospital handover, to hospital discharge and to 6 months were 31.9%, 15.3%, 9.8% and 9.8%, respectively. Multivariable model showed that advanced airway management (adjusted OR 1.84; 95% CI 1.06 to 3.17), intravenous access (OR 5.04; 95% CI 2.43 to 10.45) and attendance of high acuity response unit (highly trained prehospital care clinicians) (OR 2.54; 95% CI 1.25 to 5.18) were associated with improved odds of survival to hospital handover., Conclusions: By including all paramedic-attended patients, this study provides a more complete understanding of the epidemiology of out-of-hospital TCA. Contemporary survival rates from adult out-of-hospital TCA who receive resuscitation from paramedics may be higher than historically thought. Factors identified in this study as associated with survival may be useful to guide prognostication and treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Significance: Changes in interstitial fluid clearance are implicated in many diseases. Using near-infrared (NIR) imaging with properly sized tracers could enhance our understanding of how venous and lymphatic drainage are involved in disease progression or enhance drug delivery strategies., Aim: We investigated multichromatic NIR imaging with multiple tracers to assess in vivo microvascular clearance kinetics and pathways in different tissue spaces., Approach: We used a chemically inert IR Dye 800CW (D800) to target venous capillaries and a purified conjugate of IR dye 680RD with 40 kDa PEG (P40D680) to target lymphatic capillaries in vivo. Optical imaging settings were validated and tuned in vitro using tissue phantoms. We investigated multichromatic NIR imaging's utility in two in vivo tissue beds: the mouse tail and rat knee joint. We then tested the ability of the approach to detect interstitial fluid perturbations due to exercise., Results: In an in vitro simulated tissue environment, free dye and PEG mixture allowed for simultaneous detection without interference. In the mouse tail, co-injected NIR tracers cleared from the interstitial space via distinct routes, suggestive of lymphatic and venous uptake mechanisms. In the rat knee, we determined that exercise after injection transiently increased lymphatic drainage as measured by lower normalized intensity immediately after exercise, whereas exercise pre-injection exhibited a transient delay in clearance from the joint., Conclusions: NIR imaging enables simultaneous imaging of lymphatic and venous-mediated fluid clearance with great sensitivity and can be used to measure temporal changes in clearance rates and pathways.

Objective: International guidelines recommend amiodarone for out-of-hospital cardiac arrest (OHCA) in refractory ventricular fibrillation (VF). While early appropriate interventions have been shown to improve OHCA survival, the association between time to amiodarone and survival remains to be established., Methods: Included were adult OHCA in refractory VF, between January 2015 and December 2019, who received a resuscitation attempt with amiodarone from Queensland Ambulance Service paramedics. Patient characteristics and survival outcomes were described. Factors associated with survival were investigated, with a focus on time from arrest to amiodarone administration. Optimal time window for amiodarone administration was determined, and factors influencing whether amiodarone was given within the optimal time window were examined., Results: A total of 502 patients were included. The average (range) time from arrest to amiodarone was 25 (4-83) min. Time to amiodarone was negatively associated with survival (adjusted odds ratio 0.93 for event survival; 95% confidence interval 0.89-0.97). The optimal time window for amiodarone was within 23 min following arrest. Patients receiving amiodarone within the optimal time had significantly better survival than those receiving it outside this window (event survival 38.3% vs 20.6%, P < 0.001; discharge survival 25.5% vs 9.7%, P < 0.001; 30-day survival 25.1% vs 9.7%, P < 0.001). Paramedic response time (adjusted odds ratio 0.96; 95% confidence interval 0.92-0.99) and time from arrest to intravenous access (0.71; 0.67-0.76) were independent factors determining whether patients received amiodarone within the optimal time., Conclusions: Earlier amiodarone administration was associated with improved survival. Strategies aimed at reducing delay to amiodarone administration have the potential to improve outcome., (© 2021 Australasian College for Emergency Medicine.)

Background: Spatiotemporal analysis of out-of-hospital cardiac arrest (OHCA) risk is essential to design targeted public health strategies. Such information is lacking in the state of Queensland and Australia more broadly., Methods: We developed a spatiotemporal Bayesian model accounting for spatial and temporal dimensions, space-time interactions, and demographic factors. The model was fit to data of all OHCA cases attended by paramedics in Queensland between January 2007 and December 2019. Parameter inference was performed using the integrated nested Laplace approximation method. We estimated and thematically mapped area-year risk of OHCA occurrence for all 78 local government areas (LGAs) in Queensland., Results: We observed spatial variability in OHCA risk among the LGAs. Areas in the north half of the state and two areas in the south exhibited the highest risk; whereas OHCA risk was lowest in the west and south west parts of the state. Demographic factors did not have significant impact on the heterogeneity of risk between the LGAs. An overall trend of modestly decreasing risk of OHCA was found., Conclusions: This study identified areas of high OHCA risk in Queensland, providing valuable information to guide public health policy and optimise resource allocation. Further research is needed to investigate the specifics of the areas that may explain their risk profile., (© 2021 The Author(s).)

Tuberculosis (TB) exhibits considerable spatial heterogeneity, occurring in clusters that may act as hubs of community transmission. We evaluated the impact of an intervention targeting spatial TB hotspots in a rural region of Ethiopia. To evaluate the impact of targeted active case finding (ACF), we used a spatially structured mathematical model that has previously been described. From model equilibrium, we simulated the impact of a hotspot-targeted strategy (HTS) on TB incidence ten years from intervention commencement and the associated cost-effectiveness. HTS was also compared with an untargeted strategy (UTS). We used logistic cost-coverage analysis to estimate cost-effectiveness of interventions. At a community screening coverage level of 95 % in a hotspot region, which corresponds to screening 20 % of the total population, HTS would reduce overall TB incidence by 52 % compared with baseline. For UTS to achieve an equivalent effect, it would be necessary to screen more than 80 % of the total population. Compared to the existing passive case detection strategy, the HTS at a CDR of 75 percent in hotspot regions is expected to avert 1,023 new TB cases over ten years saving USD 170 per averted case. Similarly, at the same CDR, the UTS will detect 1316 cases over the same period saving USD 3 per averted TB case. The incremental-cost effectiveness-ratio (ICER) of UTS compared with HTS is USD 582 per averted case corresponding to 293 more TB cases averted at an additional cost of USD 170,700. Where regional TB program spending was capped at current levels, maximum gains in incidence reduction were seen when the regional budget was shared between hotspots and non-hotspot regions in the ratio of 40% : 60%. Our analysis suggests that a spatially targeted strategy is efficient and cost-saving, with the potential for significant reduction in overall TB burden., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: Patients that experience an out-of-hospital cardiac arrest in the context of a paramedic-identified ST-segment elevation myocardial infarction are a unique cohort. This study identifies the survival outcomes and determinants of survival in these patients., Methods: A retrospective analysis was undertaken of all patients, attended between 1 January 2013 and 31 December 2017 by the Queensland Ambulance Service, who had a ST-segment elevation myocardial infarction identified by the attending paramedic prior to deterioration into out-of-hospital cardiac arrest. We described the 'survived event' and 'survived to discharge' outcomes of patients and performed univariate analysis and multivariate logistic regression to identify factors associated with survival., Results: In total, 287 patients were included. Overall, high rates of survival were reported, with 77% of patients surviving the initial out-of-hospital cardiac arrest event and 75% surviving to discharge. Predictors of event survival were the presence of an initial shockable rhythm (adjusted odds ratio 8.60, 95% confidence interval (CI) 4.16-17.76; P  < 0.001) and the administration of prehospital medication for subsequent primary percutaneous coronary intervention (adjusted odds ratio 2.54, 95% CI 1.17-5.50; P  = 0.020). These factors were also found to be associated with survival to hospital discharge, increasing the odds of survival by 13.74 (95% CI 6.02-31.32; P  < 0.001) and 6.96 (95% CI 2.50-19.41; P  < 0.001) times, respectively. The administration of prehospital fibrinolytic medication was also associated with survival in a subgroup analysis., Conclusion: This subset of out-of-hospital cardiac arrest patients was found to be highly salvageable and responsive to resuscitative measures, having arrested in the presence of paramedics and presented with an identified reversible cause., (© The European Society of Cardiology 2020.)

Moral outrage shapes fundamental aspects of social life and is now widespread in online social networks. Here, we show how social learning processes amplify online moral outrage expressions over time. In two preregistered observational studies on Twitter (7331 users and 12.7 million total tweets) and two preregistered behavioral experiments ( N = 240), we find that positive social feedback for outrage expressions increases the likelihood of future outrage expressions, consistent with principles of reinforcement learning. In addition, users conform their outrage expressions to the expressive norms of their social networks, suggesting norm learning also guides online outrage expressions. Norm learning overshadows reinforcement learning when normative information is readily observable: in ideologically extreme networks, where outrage expression is more common, users are less sensitive to social feedback when deciding whether to express outrage. Our findings highlight how platform design interacts with human learning mechanisms to affect moral discourse in digital public spaces., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Field identification and treatment of ST-segment elevation myocardial infarction (STEMI) by paramedics is an important component of care for these patients. There is a paucity of studies in the setting of paramedic-identified STEMI. This study investigated mortality and factors associated with mortality in a large state-wide prehospital STEMI sample. Methods: Included were adult STEMI patients identified and treated with reperfusion therapy by paramedics in the field between January 2016 and December 2018 in Queensland, Australia. 30-day and one-year all-cause mortality was compared between two prehospital reperfusion pathways: prehospital fibrinolysis versus direct referral to a hospital for primary percutaneous coronary intervention (direct percutaneous coronary intervention [PCI] referral). For prehospital fibrinolysis patients, factors associated with failed fibrinolysis were investigated. For direct PCI referral patients, factors associated with mortality were examined. Results: The 30-day mortality was 2.2% for prehospital fibrinolysis group and 1.8% for direct PCI referral group ( p  = 0.661). One-year mortality for the two groups was 2.7% and 3.2%, respectively ( p  = 0.732). Failed prehospital fibrinolysis was observed in 20.1% of patients receiving this therapy, with male gender and history of heart failure being predictors. For direct PCI referral group, low left ventricular ejection fraction (LVEF) on admission and cardiogenic shock prior to PCI were predictors of both 30-day and one-year mortality. Aboriginal and Torres Strait Islander status, and impaired kidney function on admission, were associated with one-year but not 30-day mortality. Being overweight was associated with lower 30-day mortality. Conclusions: Mortality in STEMI patients identified and treated by paramedics was low, and the prehospital fibrinolysis treatment pathway was effective with a mortality rate comparable to that of patients undergoing primary PCI. Key words: prehospital; Queensland; cardiac reperfusion; STEMI.

Post-stroke spasticity impedes patients' rehabilitation progress. Contradictory evidence has been reported in using Botulinum Neurotoxin type A (BoNT-A) to manage post-stroke lower extremity spasticity (PLES); furthermore, an optimum dose of BoNT-A for PLES has not yet been established. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to identify the efficacy and optimal dose of BoNT-A on PLES. "Meta" and "Metafor" packages in R were used to analyze the data. Hedges' g statistic and random effect model were used to calculate and pool effect sizes. Twelve RCTs met the eligibility criteria. Muscle tone significantly improved in week four, week eight, and maintained to week twelve after BoNT-A injection. Improvements in functional outcomes were found, some inconsistencies among included studies were noticed. Dosage analysis from eight studies using Botox® and three studies using Dysport® indicated that the optimum dose for the commonest pattern of PLES (spastic plantar flexors) is medium-dose (approximately 300U Botox® or 1000 U Dysport®). BoNT-A should be regarded as part of a rehabilitation program for PLES. Furthermore, an optimal rehabilitation program combined with BoNT-A management needs to be established. Further studies should also focus on functional improvement by BoNT-A management in the early stage of stroke.

Adrinandra megaphylla Hu is a medicinal plant belonging to the Adrinandra genus, which is well-known for its potential health benefits due to its bioactive compounds. This study aimed to assemble and annotate the chloroplast genome of A. megaphylla as well as compare it with previously published cp genomes within the Adrinandra genus. The chloroplast genome was reconstructed using de novo and reference-based assembly of paired-end reads generated by long-read sequencing of total genomic DNA. The size of the chloroplast genome was 156,298 bp, comprised a large single-copy (LSC) region of 85,688 bp, a small single-copy (SSC) region of 18,424 bp, and a pair of inverted repeats (IRa and IRb) of 26,093 bp each; and a total of 51 SSRs and 48 repeat structures were detected. The chloroplast genome includes a total of 131 functional genes, containing 86 protein-coding genes, 37 transfer RNA genes, and 8 ribosomal RNA genes. The A. megaphylla chloroplast genome indicated that gene content and structure are highly conserved. The phylogenetic reconstruction using complete cp sequences, matK and trnL genes from Pentaphylacaceae species exhibited a genetic relationship. Among them, matK sequence is a better candidate for phylogenetic resolution. This study is the first report for the chloroplast genome of the A. megaphylla.

Background: Hepatectomy is always a challenge to surgeons and requires an appropriate approach for specific tumors to achieve effective complication management. Selective hepatic pedicle clamping is more considerable strategy when comparing with total hepatic pedicle clamping in the balance between reducing blood loss and transfusion with causing the hepatic parenchyma damages (two main complications affecting liver resection result)., Objectives: In this study, we aim to describe the application of selective hepatic inflow vascular occlusion (SHIVO) and anatomical anterior approach in liver resection and evaluate the results, focusing on intraoperative and postoperative complications., Methods: We enrolled 72 patients who underwent liver resection with SHIVO at Viet Duc University Hospital in 4-year period (2011-2014) and then followed up all of them until June 2020 (in 52.6 ± 33 months; range, 2-105 months) or up to the time of death. All the patients were diagnosed with primary or secondary liver cancer, and their future remnant liver volume measured on 64-slice CT scan (dm 3 ) to body weight (kg) > 0.8% (for right hepatectomy). Perioperative parameters were collected and analyzed., Results: The average operation time was 196.2 ± 62.2 minutes, and blood loss was 261.4 ± 202.9 ml; total blood transfusion proportion during and after surgery was 16.7%. Complications accounted for 44.5% of patients in which pleural effusion was the most common one (41.7%). There were no liver failure and biliary fistula after surgery. No deaths were recorded during 30 days postoperatively. Average hospital stay was 11.4 ± 3.7 days. Blood transfusions during the operation and major liver resection were the factors significantly affecting the percentage of complications after liver surgery in our study. In the last follow-up evaluation, 44 patients were dead and 28 patients were alive, in which 7 with recurrence and 21 without recurrence. The overall survival rate was 38.9%., Conclusion: SHIVO in anatomical liver resection is a safe and feasible approach to help resect precisely targeted tumors and manage several complications in liver resection., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Khai Viet Ninh et al.)

Background: The health impacts of temperatures are gaining attention in Australia and worldwide. While a number of studies have investigated the association of temperatures with the risk of cardiovascular diseases, few examined out-of-hospital cardiac arrest (OHCA) and none have done so in Australia. This study examined the exposure-response relationship between temperatures, including heatwaves and OHCA in Brisbane, Australia., Methods: A quasi-Poisson regression model coupled with a distributed lag non-linear model was employed, using OHCA and meteorological data between 1 January 2007 and 31 December 2019. Reference temperature was chosen to be the temperature of minimum risk (21.4°C). Heatwaves were defined as daily average temperatures at or above a heat threshold (90th, 95th, 98th, 99th percentile of the yearly temperature distribution) for at least two consecutive days., Results: The effect of any temperature above the reference temperature was not statistically significant; whereas low temperatures (below reference temperature) increased OHCA risk. The effect of low temperatures was delayed for 1 day, sustained up to 3 days, peaking at 2 days following exposures. Heatwaves significantly increased OHCA risk across the operational definitions. When a threshold of 95th percentile of yearly temperature distribution was used to define heatwaves, OHCA risk increased 1.25 (95% CI 1.04 to 1.50) times. When the heat threshold for defining heatwaves increased to 99th percentile, the relative risk increased to 1.48 (1.11 to 1.96)., Conclusions: Low temperatures and defined heatwaves increase OHCA risk. The findings of this study have important public health implications for mitigating strategies aimed at minimising temperature-related OHCA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)