How do free healthcare policies impact on utilization of maternal and child health services in fragile settings? Evidence from a controlled interrupted time-series analysis in Burkina Faso.

Burkina Faso has implemented a nationwide free healthcare policy (gratuité) for pregnant and lactating women and children under five since April 2016. Studies have shown that free healthcare policies can increase healthcare service use. However, the emerging COVID-19 pandemic, escalating insecurity, and the political situation in recent years might have affected the implementation of such policies. No studies have looked at whether the gratuité maintained high service use under such changing circumstances. Our study aimed to assess the effects of gratuité on the utilization of facility-based delivery and curative care of children under five in light of this changing context. We employed a controlled interrupted time series analysis using data from the Health Management Information System and annual statistical reports of 2,560 primary health facilities from January 2013 to December 2021. We focused on facility-based deliveries and curative care for children under five, with antenatal care and curative care for children over five as non-equivalent controls. We employed segmented regression with the generalized least square model, accounting for autocorrelation and monthly seasonality. The monthly utilization rate among children under five compared to those above five (controls) immediately increased by 111.19 visits per 1,000 children (95% CI: 91.12; 131.26) due to the gratuité. This immediate effect declined afterwards with a monthly change of 0.93 per 1,000 children (95% CI: -1.57, -0.29). We found no significant effects, both immediate and long-term, on the use of maternal care services attributable to the gratuité. Our findings suggest that free healthcare policies can be instrumental in improving healthcare, yet more comprehensive strategies are needed to maintain healthcare utilization. Our findings reflect the overall situation in the country, while localised research is needed to understand the effect of insecurity and the pandemic at the local level, and the effects of gratuité across geographies and socio-economic statuses.

A Non-Hemadsorbing Live-Attenuated Virus Vaccine Candidate Protects Pigs against the Contemporary Pandemic Genotype II African Swine Fever Virus.

African swine fever (ASF) is a highly contagious and severe hemorrhagic transboundary swine viral disease with up to a 100% mortality rate, which leads to a tremendous socio-economic loss worldwide. The lack of safe and efficacious ASF vaccines is the greatest challenge in the prevention and control of ASF. In this study, we generated a safe and effective live-attenuated virus (LAV) vaccine candidate VNUA-ASFV-LAVL3 by serially passaging a virulent genotype II strain (VNUA-ASFV-L2) in an immortalized porcine alveolar macrophage cell line (3D4/21, 50 passages). VNUA-ASFV-LAVL3 lost its hemadsorption ability but maintained comparable growth kinetics in 3D4/21 cells to that of the parental strain. Notably, it exhibited significant attenuation of virulence in pigs across different doses (103, 104, and 105 TCID50). All vaccinated pigs remained healthy with no clinical signs of African swine fever virus (ASFV) infection throughout the 28-day observation period of immunization. VNUA-ASFV-LAVL3 was efficiently cleared from the blood at 14-17 days post-infection, even at the highest dose (105 TCID50). Importantly, the attenuation observed in vivo did not compromise the ability of VNUA-ASFV-LAVL3 to induce protective immunity. Vaccination with VNUA-ASFV-LAVL3 elicited robust humoral and cellular immune responses in pigs, achieving 100% protection against a lethal wild-type ASFV (genotype II) challenge at all tested doses (103, 104, and 105 TCID50). Furthermore, a single vaccination (104 TCID50) provided protection for up to 2 months. These findings suggest that VNUA-ASFV-LAVL3 can be utilized as a promising safe and efficacious LAV candidate against the contemporary pandemic genotype II ASFV.

A study of the impact of an interprofessional education module in Vietnam on students' readiness and competencies.

INTRODUCTION: The literature puts forward a range of challenges of interprofessional education (IPE) related to its planning, initiation, implementation, and especially to IPE assessment. The present study aims to map changes in students' readiness and interprofessional collaboration competence (IPCC) in implementing an innovative IPE module. Potential differences in impact related to the health education programs and IPCC scores resulting from self-, peer-, and tutor assessments will also be analysed. METHODS: A pre-post design was adopted. The student's readiness for interprofessional learning was assessed using the Readiness for Interprofessional Learning Scale, and the student's IPCC score was calculated based on self-, peer-, and tutor assessments with the interprofessional collaborator assessment rubric. RESULTS: Students' mean post-test readiness scores and mean post-test IPCC scores were significantly higher than the total and subscales/domain pre-test scores (p<0.01). No significant within-subject differences were observed in students' readiness total or subscale scores when comparing health educational programs. However, significant differences were observed in students' mean total IPCC scores between programs (p<0.01). Significant differences in students' average IPCC scores were found when comparing self-, peer- and tutor assessment scores in six domains (p<0.01). Also, significant correlations between peer and tutor assessment scores were observed (p<0.01). CONCLUSION: The IPE module, designed and implemented to focus on patient-centred practice within a primary care context, positively impacted students' readiness and IPCC development. These results offer insights to expand the implementation of the IPE module to all health educational programs.

Optimal allocation of resources among general and species-specific tools for plant pest biosecurity surveillance.

This paper proposes a surveillance model for plant pests that can optimally allocate resources among survey tools with varying properties. While some survey tools are highly specific for the detection of a single pest species, others are more generalized. There is considerable variation in the cost and sensitivity of these tools, but there are no guidelines or frameworks for identifying which tools are most cost-effective when used in surveillance programs that target the detection of newly invaded populations. To address this gap, we applied our model to design a trapping surveillance program in New Zealand for bark- and wood-boring insects, some of the most serious forest pests worldwide. Our findings show that exclusively utilizing generalized traps (GTs) proves to be highly cost-effective across a wide range of scenarios, particularly when they are capable of capturing all pest species. Implementing surveillance programs that only employ specialized traps (ST) is cost-effective only when these traps can detect highly damaging pests. However, even in such cases, they significantly lag in cost-effectiveness compared to GT-only programs due to their restricted coverage. When both GTs and STs are used in an integrated surveillance program, the total expected cost (TEC) generally diminishes when compared to programs relying on a single type of trap. However, this relative reduction in TEC is only marginally larger than that achieved with GT-only programs, as long as highly damaging species can be detected by GTs. The proportion of STs among the optimal required traps fluctuates based on several factors, including the relative pricing of GTs and STs, pest arrival rates, potential damage, and, more prominently, the coverage capacity of GTs. Our analysis suggests that deploying GTs extensively across landscapes appears to be more cost-effective in areas with either very high or very low levels of relative risk density, potential damage, and arrival rate. Finally, STs are less likely to be required when the pests that are detected by those tools have a higher likelihood of successful eradication because delaying detection becomes less costly for these species.

Correction: Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/44204.].

A Large Esophageal Leiomyoma: Thoraco-Laparoscopic Enucleation or Esophagectomy and Reconstruction?

BACKGROUND Esophageal leiomyoma is a rare condition, with an estimated incidence rate of 0.4% of all esophageal neoplasms. These tumors are typically small, rarely more than 5 cm. The treatment depends on symptoms and the size and location of the tumor, with enucleation as the standard treatment of esophageal leiomyomas. Esophagectomy is performed only in very few cases, such as when the tumor is too large, there are multiple leiomyomas, there is a horseshoe shape or circumference, or the tumor is inextricably adhering to the esophageal mucosa. In such complex cases, it is often difficult to perform enucleation. However, with the risks of esophagectomy and intra-thoracic anastomosis, namely reflux, stenosis, leakage, abscess, and infection, attempting to perform enucleation for these cases should still be considered. CASE REPORT We reported a case of a large, multi-lobed, circumferential esophageal thoracoabdominal leiomyoma with successfully performed enucleation and esophageal preservation. A Dor fundoplication and Witzel jejunostomy tube were also performed. Follow-up 3 months postoperatively showed no appearance of reflux or dysphagia. The postoperative esophagogram visualized no obstruction or leakage. Histopathological results gave us concrete evidence of a leiomyoma: elongated cells with eosinophilic cytoplasm and rhomboid nuclei with uniform size. CONCLUSIONS The thoraco-laparoscopic enucleation approach is the method that should be considered first in the treatment of large, multi-lobed, circumferential esophageal leiomyomas, before contemplating esophagectomy and reconstruction.

Dataset on the compounds from the leaves of Vietnamese Machilus thunbergii and their anti-inflammatory activity.

Machilus thunbergii has a history of traditional applications including treating dyspepsia, apoplexy, headaches, abdominal pain, abdominal distension, and leg edema [1]. It is also employed for alleviating allergies, inflammation, pain relief, promoting blood circulation, addressing costal chondritis, and sinusitis [2]. Research into the chemical composition of M. thunbergii has revealed the presence of lignans, flavonoids, lactones, and essential oils [1,[3], [4], [5]. While some investigations have explored the inhibitory effects of extracts and lignan compounds from this species on NO production [6], [7], [8], there has been no research into the flavonoids isolated from this plant and their potential for inhibiting NO production, given our reachable referencing. The ethyl acetate (EtOAc) soluble fraction of M. thunbergii leaves was subjected to column chromatography (CC) using silica gel and Sephadex LH-20 for compound isolation. Nuclear magnetic resonance (NMR) data primarily facilitated the determination of isolated compound structures. Anti-inflammatory activity was evaluated against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in macrophage RAW264.7 cells. Anti-inflammatory activity-guided fractionation led to the isolation of twelve secondary metabolites (1-12). The compounds were identified as quercetin (1), kaempferol (2), rhamnetin (3), quercitrin (4), hyperoside (5), reynoutrin (6), guaijaverin (7), afzelin (8), astragalin (9), rutin (10), kaempferol-3-O-rutinoside (11), and rhamnetin-3-O-rutinoside (12). Compounds 3, 5, 6, 9, 11, and 12 were isolated from M. thunbergii for the first time. Evaluation against LPS-induced NO production in macrophage RAW264.7 cells showed that 1-3 exhibited potent inhibitory activity with IC50 values of 15.45, 25.44, and 19.82 µM, respectively. Compounds 4-9 demonstrated IC50 values ranging from 42.15 to 67.42 µM, while 10-12 exhibited inactivity (IC50 > 100 µM).

A Cell-Adapted Live-Attenuated Vaccine Candidate Protects Pigs against the Homologous Strain VNUA-ASFV-05L1, a Representative Strain of the Contemporary Pandemic African Swine Fever Virus.

African swine fever (ASF) is a lethal and highly contagious transboundary animal disease with the potential for rapid international spread. Currently, there is no ASF vaccine commercially available. All infected animals must be isolated and culled immediately upon the confirmation of the presence of the virus. Studies leading to the rational development of protective ASF vaccines are urgently needed. Here, we generated a safe and efficacious live-attenuated vaccine (LAV) VNUA-ASFV-LAVL2 by serially passaging a field isolate (VNUA-ASFV-05L1, genotype II) in porcine alveolar macrophages (PAMs, 65 passages) and an immortalized porcine alveolar macrophage cell line (3D4/21, 55 passages). VNUA-ASFV-LAVL2 can efficiently replicate in both PAMs and 3D4/21 cells. It provides 100% protection, even with the low dose of 102 HAD50, to the vaccinated pigs against the challenge of contemporary pandemic ASFV field isolate. Pigs vaccinated with this LAV in a dose range of 102 to 105 HAD50 remained clinically healthy during both the 28-day observation period of immunization and the 28-day observation period of challenge. VNUA-ASFV-LAVL2 was eliminated from blood by 28 days post-inoculation (DPI), and from feces or oral fluids by 17 DPI. Although the vaccine strain in serum remained a safe and attenuated phenotype after five passages in swine, a reversion-to-virulence study using blood or tissue homogenates at peak viremia will be conducted in the future. ASFV-specific IgG antibodies and significant cellular immunity were detected in vaccinated pigs before the ASFV challenge. These results indicate that the VNUA-ASFV-LAVL2 strain is a safe and efficacious LAV against the genotype II ASFV strain responsible for current ASF outbreaks in Asia.

Effects of a low-iodine diet in post-thyroidectomy thyroid cancer patients undergoing I131 therapy at the Vietnam National Cancer Hospital.

Background: I131 therapy is regarded as an "internal surgery" (i.e., a non-invasive approach involving no incision or bleeding) that supports "external surgery" (i.e., using a scalpel) in completely eradicating the root cause of thyroid cancer. Limiting iodine intake is of paramount importance in I131 therapy. I131 therapy protocols recommend that patients follow a low-iodine diet, ideally with a maximum iodine intake of 50 µg/day for two weeks before the I131 therapy. Methods: A pre-post compassion uncontrolled clinic intervention study was conducted on a group of over 70 post-thyroidectomy thyroid cancer patients with indications for I131 therapy at the Vietnam National Cancer Hospital from December 2020 to December 2022. Aim: It aimed to assess the effects of a low-iodine diet on post-thyroidectomy thyroid cancer patients with indications for I131 therapy. Results: The study found that following the intervention, the percentage of participants at risk of mild to moderate malnutrition, as assessed by the PG-SGA tool, decreased to 4.3% from 40.0% before the intervention, with a statistically significant difference of p < 0.001. There was a considerable improvement in the low calcemia level among the study participants, with 35.7% of patients experiencing hypocalcemia prior to the intervention, which reduced to 17.1% after the intervention. This difference was statistically significant (p = 0.01). The study also revealed a urinary iodine level improvement among the study participants. Before the intervention, patients' average urinary iodine level was 14.9 ± 11.3 µg/dl. Following the intervention, it reduced to 12.7 ± 3.9 µg/dl, although this difference was not statistically significant (p = 0.29). Patients' quality of life after adhering to the low-iodine diet tended to decline; however, the change in scores before and after the intervention did not show a significant difference. Conclusion: Despite its negative impact on patients' quality of life, active nutrition counseling and intervention during the low-iodine diet contributed to the substantial improvement in the hypocalcemia level and the reduced urinary iodine level among patients, which in turn could enhance the efficacy of the subsequent I131 therapy.

In vitro and in vivo antimicrobial activity of the fungal metabolite toluquinol against phytopathogenic bacteria.

Introduction: Bacterial plant diseases cause tremendous economic losses worldwide. However, a few effective and sustainable control methods are currently available. To discover novel and effective management approaches, we screened marine fungi for their antibacterial activity against phytopathogenic bacteria in vitro and in vivo. Methods: We screened the culture broth of 55 fungal strains isolated from various marine sources (seawater, algae, and sediment) for their in vitro antibacterial activity using the broth microdilution method. Then, only the fungal strain (designated UL-Ce9) with higher antibacterial activity in vitro was tested in an in vivo experiment against tomato bacterial wilt. The active compounds of UL-Ce9 were extracted using ethyl acetate, purified by a series of chromatography, and the structure was elucidated by nuclear magnetic resonance spectroscopy. Pesticide formulations of toluquinol were prepared as soluble concentrates and wettable powder. The disease control efficacy of toluquinol formulations was evaluated against blight of rice and the bacterial wilt of tomato. Results and discussion: The culture broth of UL-Ce9 showed high antibacterial activity against Agrobacterium tumefaciens, Ralstonia solanacearum, and Xanthomonas arboricola pv. pruni in vitro, and we selected UL-Ce9 for the in vivo test. The UL-Ce9 culture broth completely suppressed the bacterial wilt of tomato at a dilution of 1:5. The phylogenetic analysis identified UL-Ce9 as Penicillium griseofulvum, and the antibacterial metabolites were revealed as patulin, gentisyl alcohol, and toluquinol, all of which were associated with the biosynthetic pathway of the mycotoxin patulin. Patulin exhibited the highest antibacterial activity against 16 phytopathogenic bacteria in vitro, followed by toluquinol and gentisyl alcohol. As patulin is toxic, we selected toluquinol to investigate its potential use as a pesticide against bacterial plant diseases. Compared with the chemicals currently being applied in agriculture (streptomycin and oxytetracycline), toluquinol formulations exhibited similar and higher control efficacies against bacterial leaf blight of rice and bacterial wilt of tomato, respectively. To the best of our knowledge, this is the first report of the antibacterial activity of toluquinol against phytopathogenic bacteria. Our results suggest that toluquinol is a potential candidate for the development of novel and effective pesticides for the management of bacterial plant diseases.

To What Extent Do Free Healthcare Policies and Performance-Based Financing Reduce Out-of-Pocket Expenditures for Outpatient services? Evidence From a Quasi-experimental Study in Burkina Faso.

BACKGROUND: Burkina Faso has been implementing financing reforms towards universal health coverage (UHC) since 2006. Recently, the country introduced a performance-based financing (PBF) program as well as user fee removal (gratuité) policy for health services aimed at pregnant and lactating women and children under 5. We aim to assess the effect of gratuité and PBF policies on facility-based out-of-pocket expenditures (OOPEs) for outpatient services. METHODS: Our study is a controlled pre- and post-test design using healthcare facility data from the PBF program's impact evaluation collected in 2014 and 2017. We compared OOPE related to primary healthcare use incurred by children under 5 and individuals above 5 to assess the effect of the gratuité policy on OOPE. We further compared OOPE incurred by individuals residing in PBF districts and non-PBF districts to estimate the effect of the PBF on OOPE. Effects were estimated using difference-in-differences models, distinguishing the estimation of the probability of incurring OOPE from the estimation of the magnitude of OOPE using a generalized linear model (GLM). RESULTS: The proportion of children under 5 incurring OOPE declined significantly from 90% in 2014 to 3% in 2017. Concurrently, mean OOPE also decreased. Differences in both the probability of incurring OOPE and mean OOPE between PBF and non-PBF facilities were small. Our difference in differences estimates indicated that gratuité produced an 84% (CI -86%, -81%) reduction in the probability of incurring OOPE and reduced total OOPE by 54% (CI 63%, 42%). We detected no significant effects of PBF, either in reducing the probability of incurring OOPE or in its magnitude. CONCLUSION: User fee removal is an effective demand-side intervention for enhancing financial accessibility. As a supply-side intervention, PBF appears to have limited effects on reducing financial burden.

Systemic chemotherapy combined with radiofrequency ablation for colorectal cancer with liver metastasis: a retrospective cohort study.

This study aims to evaluate the efficacy of systemic chemotherapy combined with radiofrequency ablation in the treatment of inoperable colorectal cancer with liver metastasis. Materials and methods: The authors conducted a retrospective cohort analysis on 30 patients diagnosed as colorectal cancer with liver metastasis who underwent systemic chemotherapy combined with radiofrequency ablation of the liver lesions from January 2017 to August 2020 at our institution. Responses was evaluated by International Working Group on Image-guided Tumor Ablation criteria, along with progression-free survival. Results: The response rate after 4 cycles and 8 cycles of chemotherapy were 73.3% and 85.2%, respectively. All patients achieved responses after of radiofrequency therapy, with the rates of complete response and partial response were 63.3% and 36.7%. The median progression-free survival was 16.7 months. After radiotherapy ablation, all patients had mild to moderate hepatic pain, 10% of patients had fever and increased liver enzymes occurred in 90% of patients. Conclusions: Systemic chemotherapy combined with radiofrequency ablation was safe and effective in colorectal cancer with liver metastasis and warrants further large-scale studies.

Primary melanoma of the rectum: a case report of a rare tumor.

Malignant melanoma has a generally poor prognosis and occurs primarily on the skin but may rarely be found in internal organs such as the small intestine, colon, or rectum. Case presentation: This report presents a case of a 78-year-old male patient with stage IV gastrointestinal melanoma, which is a rare form of melanoma. The patient received first-line pembrolizumab with a complete response. Clinical discussion: Surgery plays a crucial role in local and regional control for patients with localized stages. Immune checkpoint inhibitor therapy, including nivolumab or pembrolizumab, is a well-studied and proven effective treatment option for patients with advanced skin melanoma. In this case report, the patient with gastrointestinal melanoma also had a very good response to immunotherapy. Conclusions: Understanding gastrointestinal melanoma is still limited due to the rarity of this clinical entity. Currently, there are no standard treatment guidelines for this rare group of patients. Immune checkpoint inhibitors could be the preferred first-line therapy for patients with distant metastases.

Comparison of Four Active SARS-CoV-2 Surveillance Strategies in Representative Population Sample Points: Two-Factor Factorial Randomized Controlled Trial.

BACKGROUND: The COVID-19 pandemic is characterized by rapid increases in infection burden owing to the emergence of new variants with higher transmissibility and immune escape. To date, monitoring the COVID-19 pandemic has mainly relied on passive surveillance, yielding biased epidemiological measures owing to the disproportionate number of undetected asymptomatic cases. Active surveillance could provide accurate estimates of the true prevalence to forecast the evolution of the pandemic, enabling evidence-based decision-making. OBJECTIVE: This study compared 4 different approaches of active SARS-CoV-2 surveillance focusing on feasibility and epidemiological outcomes. METHODS: A 2-factor factorial randomized controlled trial was conducted in 2020 in a German district with 700,000 inhabitants. The epidemiological outcome comprised SARS-CoV-2 prevalence and its precision. The 4 study arms combined 2 factors: individuals versus households and direct testing versus testing conditioned on symptom prescreening. Individuals aged ≥7 years were eligible. Altogether, 27,908 addresses from 51 municipalities were randomly allocated to the arms and 15 consecutive recruitment weekdays. Data collection and logistics were highly digitized, and a website in 5 languages enabled low-barrier registration and tracking of results. Gargle sample collection kits were sent by post. Participants collected a gargle sample at home and mailed it to the laboratory. Samples were analyzed with reverse transcription loop-mediated isothermal amplification (RT-LAMP); positive and weak results were confirmed with real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Recruitment was conducted between November 18 and December 11, 2020. The response rates in the 4 arms varied between 34.31% (2340/6821) and 41.17% (2043/4962). The prescreening classified 16.61% (1207/7266) of the patients as COVID-19 symptomatic. Altogether, 4232 persons without prescreening and 7623 participating in the prescreening provided 5351 gargle samples, of which 5319 (99.4%) could be analyzed. This yielded 17 confirmed SARS-CoV-2 infections and a combined prevalence of 0.36% (95% CI 0.14%-0.59%) in the arms without prescreening and 0.05% (95% CI 0.00%-0.108%) in the arms with prescreening (initial contacts only). Specifically, we found a prevalence of 0.31% (95% CI 0.06%-0.58%) for individuals and 0.35% (95% CI 0.09%-0.61%) for households, and lower estimates with prescreening (0.07%, 95% CI 0.0%-0.15% for individuals and 0.02%, 95% CI 0.0%-0.06% for households). Asymptomatic infections occurred in 27% (3/11) of the positive cases with symptom data. The 2 arms without prescreening performed the best regarding effectiveness and accuracy. CONCLUSIONS: This study showed that postal mailing of gargle sample kits and returning home-based self-collected liquid gargle samples followed by high-sensitivity RT-LAMP analysis is a feasible way to conduct active SARS-CoV-2 population surveillance without burdening routine diagnostic testing. Efforts to improve participation rates and integration into the public health system may increase the potential to monitor the course of the pandemic. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS) DRKS00023271; https://tinyurl.com/3xenz68a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-021-05619-5.

Structure and elasticity of healthy and Alzheimer's disease cell membranes revealed by molecular dynamics simulations.

Interactions of amyloid-ß (Aß) peptides with neuronal membrane are associated with the development of Alzheimer's disease (AD). Ganglioside monosialotetrahexosylganglioside (GM1) lipids have been shown to form clusters that induce the structural conversion of Aß and promote the incorporation of Aß into the membrane via the membrane surface electrical potential. Prior to the onset of AD symptoms, GM1 clusters may not have formed but the concentration of GM1 may have already changed, and our question is whether this early concentration modification affects the structure and mechanical properties of the membrane. Using one model for healthy cell membranes and three models for AD cell membranes, we carry out 2 µs all-atom molecular dynamics simulations for each model to compare the structure and elasticity of the two membrane types. The simulations show that at the physiological concentration, 1%-3%, GM1 does not form clusters. The reduction of the GM1 lipid does not significantly alter the area per lipid, the membrane thickness, and the lipid order parameters of the AD membranes. However, the dipole potential, the bending, and twist moduli are decreased for the AD membranes. We suggest that these changes in the AD membranes are factors that could trigger the interaction and incorporation of Aß to the membranes. Finally, we show that changes in the sphingomyelin lipid concentrations do not affect the membrane structure and elasticity.

Scalable RT-LAMP-based SARS-CoV-2 testing for infection surveillance with applications in pandemic preparedness.

Throughout the SARS-CoV-2 pandemic, limited diagnostic capacities prevented sentinel testing, demonstrating the need for novel testing infrastructures. Here, we describe the setup of a cost-effective platform that can be employed in a high-throughput manner, which allows surveillance testing as an acute pandemic control and preparedness tool, exemplified by SARS-CoV-2 diagnostics in an academic environment. The strategy involves self-sampling based on gargling saline, pseudonymized sample handling, automated RNA extraction, and viral RNA detection using a semiquantitative multiplexed colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay with an analytical sensitivity comparable with RT-qPCR. We provide standard operating procedures and an integrated software solution for all workflows, including sample logistics, analysis by colorimetry or sequencing, and communication of results. We evaluated factors affecting the viral load and the stability of gargling samples as well as the diagnostic sensitivity of the RT-LAMP assay. In parallel, we estimated the economic costs of setting up and running the test station. We performed > 35,000 tests, with an average turnover time of < 6 h from sample arrival to result announcement. Altogether, our work provides a blueprint for fast, sensitive, scalable, cost- and labor-efficient RT-LAMP diagnostics, which is independent of potentially limiting clinical diagnostics supply chains.

Cost and cost-effectiveness of four different SARS-CoV-2 active surveillance strategies: evidence from a randomised control trial in Germany.

INTRODUCTION: The COVID-19 pandemic has entered its third year and continues to affect most countries worldwide. Active surveillance, i.e. testing individuals irrespective of symptoms, presents a promising strategy to accurately measure the prevalence of SARS-CoV-2. We aimed to identify the most cost-effective active surveillance strategy for COVID-19 among the four strategies tested in a randomised control trial between 18th November 2020 and 23rd December 2020 in Germany. The four strategies included: (A1) direct testing of individuals; (A2) direct testing of households; (B1) testing conditioned on upstream COVID-19 symptom pre-screening of individuals; and (B2) testing conditioned on upstream COVID-19 symptom pre-screening of households. METHODS: We adopted a health system perspective and followed an activity-based approach to costing. Resource consumption data were collected prospectively from a digital individual database, daily time records, key informant interviews and direct observations. Our cost-effectiveness analysis compared each strategy with the status quo and calculated the average cost-effective ratios (ACERs) for one primary outcome (sample tested) and three secondary outcomes (responder recruited, case detected and asymptomatic case detected). RESULTS: Our results showed that A2, with cost per sample tested at 52,89 EURO, had the lowest ACER for the primary outcome, closely followed by A1 (63,33 EURO). This estimate was much higher for both B1 (243,84 EURO) and B2 (181,06 EURO). CONCLUSION: A2 (direct testing at household level) proved to be the most cost-effective of the four evaluated strategies and should be considered as an option to strengthen the routine surveillance system in Germany and similar settings.

Population-Level Impact of Omitting Axillary Lymph Node Dissection in Early Breast Cancer Women: Evidence from an Economic Evaluation in Germany.

BACKGROUND: The American College of Surgeons Oncology Group Z0011 trial showed that complete axillary lymph node dissection (cALND) did not improve survival benefits in patients with one or two tumour-involved sentinel lymph nodes and undergoing breast conservation. Still, a considerable number of the Z0011-eligible patients continue to be treated with cALND in various countries. Given the potential economic gain from implementation of the Z0011 recommendations, we quantified population-level impacts of omitting cALND among Z0011-eligible patients in clinical practice. METHODS: This 2-year economic analysis adopted both the perspective of patients under statutory insurance and the societal perspective, using data collected prospectively from 179 German breast cancer units between 2008 and 2015. The estimation of cost savings and health gain relied on a single decision tree, which considered three scenarios: clinical practice at the baseline; actual implementation in routine care; and hypothetical full implementation in all eligible patients. RESULTS: Data for 188,909 patients with primary breast cancer were available, 13,741 (7.3%) of whom met the Z0011 inclusion criteria. The use of cALND decreased from 94.3% in 2010 to 46.9% in 2015, resulting in a gain of 335 quality-adjusted life-years and a saving of EUR50,334,756 for the society. Had cALND been omitted in all eligible patients, the total gain would have been more than double. CONCLUSIONS: The implementation of the Z0011 recommendations resulted in substantial savings and health gain in Germany. Our findings suggest that it is beneficial to introduce additional policy measures to promote further uptake of the Z0011 recommendations in clinical practice.

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.

Estimating the transmission parameters of foot-and-mouth disease in Vietnam: A spatial-dynamic kernel-based model with outbreak and host data.

Foot-and-mouth disease (FMD) affects cloven-hoofed livestock and causes devastating damages to the world's economies. Being endemic in developing countries, FMD has imposed a significant threat to the FMD-freedom status in developed countries. The globally-concerted effort to eradicate FMD at its source has faced a substantial challenge of having little knowledge about how FMD spreads in developing countries. So far, FMD virus transmission parameters have been estimated based on only a dozen actual outbreak data, mostly in Europe. Meanwhile, the fundamental north-south differences in livestock production, trading, and quarantine systems have questioned the applicability of these estimates to developing countries. In this light, we aim to narrow the knowledge gap by estimating the FMD virus transmission parameters in an endemic country, Vietnam, the world's fifth- largest pork producer. We use the spatial-dynamic kernel-based approach combined with daily FMD incursion data and FMD-host census data. The estimation also considers livestock composition and livestock quantity by species, which can influence FMD transmission. In line with existing literature, we find that cattle and buffaloes have a larger influence on disease spread than pigs, and FMD transmission depends on the herd size and the distance between susceptible and infected premises. However, our findings show FMD virus can spread over a much more ample space in our case compared with those in existing literature (25 km and 50 km versus 10 km), and the kernels have much fatter tails. This difference is likely due to the weakness in biosecurity systems, poor implementation of surveillance and quarantine measures, and bad husbandry practices such as swill feeding, which are prevalent in developing countries. Thus, our estimated kernels will be helpful for Vietnam in developing suitable biosecurity measures to contain and eradicate the FMD virus. They are also highly relevant for other countries with livestock farming practices and climate conditions similar to those in Vietnam.