Clinical outcome analysis of patients with multiple sclerosis - Analysis from the UK Medical Cannabis Registry.

INTRODUCTION: Whilst disease-modifying therapies are the cornerstone for treatment of multiple sclerosis (MS), there is a need to develop novel therapeutics for the symptomatic sequalae of the disease. Cannabis-based medicinal products (CBMPs) have been suggested as a potential therapy for the associated pain, spasticity, and mental health disorders. However, there is a paucity of clinical evidence on CBMPs in MS. The aim of this study is to assess changes in MS-specific and general health-related quality of life (HRQoL) outcomes alongside adverse event incidence in patients prescribed CBMPs for MS from the UK Medical Cannabis Registry (UKMCR). METHOD: Patients prescribed CBMPs for MS symptoms for longer than one month were identified from the UKMCR. The primary outcomes were changes from baseline in MS Quality of Life-54 (MSQoL-54), Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L scales at one month, three months and six months. p < 0.050 was defined as statistically significant. RESULTS: 141 patients met the inclusion criteria for the study. There was an improvement in the following subscales of the MSQoL-54 at 6 months: change in health scale, cognitive function, mental health composition, physical health, role limitations due to physical limitation and due to emotional problems, as well as social and sexual function (p < 0.050). There were also improvements in the EQ-5D-5L index value, GAD-7 and SQS (p < 0.050). 146 (103.55 %) adverse events were reported in total. Most were considered mild (n = 47; 33.33 %) and moderate (n = 72; 51.06 %). CONCLUSIONS: This preliminary analysis demonstrates a possible association with improved general health-related quality of life in those prescribed CBMPs for MS. Moreover, the results suggest that CBMPs are well-tolerated in the first 6 months of treatment. However, this must be interpreted with caution considering the limitations of the observational study design.

Statin use and mortality in patients with deep vein thrombosis. Data from the RIETE Registry.

BACKGROUND: The association between statin use and mortality in patients with deep vein thrombosis (DVT) has not been rigorously evaluated. METHODS: We used the data in the RIETE registry to examine the association between statin use and mortality at 3 months. We used mixed effects survival models accounting for clinical covariates and clustering of patients in enrolling centers. RESULTS: From January 2009 through April 2022, there were 46,440 patients with isolated DVT in RIETE (in the lower-limbs 42,291, in the upper limbs 4149). Of these, 21 % and 18 %, respectively, were using statins. Statin users were older than non-users (72 ± 12 vs. 62 ± 18 years), and more likely had diabetes, hypertension, prior myocardial infarction or ischemic stroke, or were receiving antiplatelets. The 3-month mortality rates were: 6.0 % vs. 5.8 %, respectively. On multilevel multivariable analysis, the adjusted hazard ratio (aHR) for all-cause death in statin users vs. non-users was 0.77 (95%CI: 0.69-0.86). The 3-month risk of death in statin users was significantly lower than in non-users in patients with upper-limb DVT (aHR: 0.81; 95%CI: 0.72-0.91), distal lower-limb DVT (aHR: 0.48; 95%CI: 0.32-0.72), or proximal lower-limb DVT (aHR: 0.69; 95%CI: 0.50-0.95), and in those receiving simvastatin (aHR: 0.73; 95%CI: 0.60-0.90), atorvastatin (aHR: 0.70; 95%CI: 0.59-0.85), or rosuvastatin (aHR: 0.47; 95%CI: 0.27-0.80). Major bleeding, used as a falsification endpoint, did not show an association with use of statins at 3-month follow-up. CONCLUSIONS: Statin users with isolated DVT were at significantly lower risk for death at 3 months than non-users.

Rationale and design of the NODE-303 study: evaluating the safety of symptom-prompted, self-administered etripamil for paroxysmal supraventricular tachycardia episodes in real-world settings.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common episodic arrhythmia characterized by unpredictable onset and burdensome symptoms including palpitations, dizziness, chest pain, distress, and shortness of breath. Treatment of acute episodes of PSVT in the clinical setting consists of intravenous adenosine, beta-blockers, and calcium channel blockers (CCBs). Etripamil is an intranasally self-administered L-type CCB in development for acute treatment of AV-nodal dependent PSVT in a nonmedical supervised setting. METHODS: This paper summarizes the rationale and study design of NODE-303 that will assess the efficacy and safety of etripamil. In the randomized, double-blinded, placebo-controlled, Phase 3 RAPID trial, etripamil was superior to placebo in the conversion of single PSVT episodes by 30 minutes post initial dose when administered in the nonhealthcare setting; this study required a mandatory and observed test dosing prior to randomization. The primary objective of NODE-303 is to evaluate the safety of symptom-prompted, self-administered etripamil for multiple PSVT episodes in real-world settings, without the need for test dosing prior to first use during PSVT. Secondary endpoints include efficacy and disease burden. Upon perceiving a PSVT episode, the patient applies an electrocardiographic monitor, performs a vagal maneuver, and, if the vagal maneuver is unsuccessful, self-administers etripamil 70 mg, with an optional repeat dose if symptoms do not resolve within 10 minutes after the first dose. A patient may treat up to four PSVT episodes during the study. Adverse events are recorded as treatment-emergent if they occur within 24 hours after the administration of etripamil. RESULTS: Efficacy endpoints include time to conversion to sinus rhythm within 30 and 60 minutes after etripamil administration, and the proportion of patients who convert at 3, 5, 10, 20, 30, and 60 minutes. Patient-reported outcomes are captured by the Brief Illness Perception Questionnaire, the Cardiac Anxiety Questionnaire, the Short Form Health Survey 36, the Treatment Satisfaction Questionnaire for Medication and a PSVT survey. CONCLUSIONS: Overall, these data will support the development of a potentially paradigm-changing long-term management strategy for recurrent PSVT.

Flexible, high-performance and facile PVA/cellulose/Ag SERS chips for in-situ and rapid detection of thiram pesticide in apple juice.

Flexible surface-enhanced Raman scattering (SERS) sensors have gained significant attention for their practical applications in detecting chemical and biological molecules. However, the fabrication of flexible SERS chips is often complex and requires advanced techniques. In this study, we present a simple and rapid method to design a flexible SERS chip based on polyvinyl alcohol (PVA), cellulose, and silver nanoparticles (AgNPs) using mechanical stirring and drying methods. Benefiting from the abundant hydroxide groups on cellulose, AgNPs easily adhere and distribute evenly on the cellulose surface. The combination of PVA and cellulose forms a bendable film-like SERS chip. This chip allows convenient immersion in liquid analyte samples. We demonstrate its effectiveness by using it to detect the thiram pesticide in apple juice using the "dip and dry" method, achieving an outstanding detection limit of 1.01 × 10-8 M. The Raman signals on the SERS chips exhibit high repeatability and reproducibility, with relative standard deviation values below 10%. These findings show that the flexible PVA/cellulose/Ag SERS chips is a strong candidate for real-world analysis.

Individual Effects of Alkali Element and Wire Structure on Metal Transfer Process in Argon Metal-Cored Arc Welding.

This study aimed to clarify the effect of wire structure and alkaline elements in wire composition on metal transfer behavior in metal-cored arc welding (MCAW). A comparison of metal transfer in pure argon gas was carried out using a solid wire (wire 1), a metal-cored wire without an alkaline element (wire 2), and another metal-cored wire with 0.084 mass% of sodium (wire 3). The experiments were conducted under 280 and 320 A welding currents, observed by high-speed imaging techniques equipped with laser assistance and bandpass filters. At 280 A, wire 1 showed a streaming transfer mode, while the others showed a projected one. When the current was 320 A, the metal transfer of wire 2 changed to streaming, while wire 3 remained projected. As sodium has a lower ionization energy than iron, the mixing of sodium vapor into the iron plasma increases its electrical conductivity, raising the proportion of current flowing through metal vapor plasma. As a result, the current flows to the upper region of the molten metal on the wire tip, with the resulting electromagnetic force causing droplet detachment. Consequently, the metal transfer mode in wire 3 remained projected. Furthermore, weld bead formation is the best for wire 3.

Predicting the risk of osteoporosis in older Vietnamese women using machine learning approaches.

Osteoporosis contributes significantly to health and economic burdens worldwide. However, the development of osteoporosis-related prediction tools has been limited for lower-middle-income countries, especially Vietnam. This study aims to develop prediction models for the Vietnamese population as well as evaluate the existing tools to forecast the risk of osteoporosis and evaluate the contribution of covariates that previous studies have determined to be risk factors for osteoporosis. The prediction models were developed to predict the risk of osteoporosis using machine learning algorithms. The performance of the included prediction models was evaluated based on two scenarios; in the first one, the original test parameters were directly modeled, and in the second the original test parameters were transformed into binary covariates. The area under the receiver operating characteristic curve, the Brier score, precision, recall and F1-score were calculated to evaluate the models' performance in both scenarios. The contribution of the covariates was estimated using the Permutation Feature Importance estimation. Four models, namely, Logistic Regression, Support Vector Machine, Random Forest and Neural Network, were developed through two scenarios. During the validation phase, these four models performed competitively against the reference models, with the areas under the curve above 0.81. Age, height and weight contributed the most to the risk of osteoporosis, while the correlation of the other covariates with the outcome was minor. Machine learning algorithms have a proven advantage in predicting the risk of osteoporosis among Vietnamese women over 50 years old. Additional research is required to more deeply evaluate the performance of the models on other high-risk populations.

A geospatial platform to support visualization, analysis, and prediction of tuberculosis notification in space and time.

Background: Tuberculosis has caused significant public health and economic burdens in Vietnam over the years. The Vietnam National Tuberculosis Program is facing considerable challenges in its goal to eliminate tuberculosis by 2030, with the COVID-19 pandemic having negatively impacted routine tuberculosis services at all administrative levels. While the turnaround time of tuberculosis infection may delay disease detection, high transportation frequency could potentially mislead epidemiological studies. This study was conducted to develop an online geospatial platform to support healthcare workers in performing data visualization and promoting the active case surveillance in community as well as predicting the TB incidence in space and time. Method: This geospatial platform was developed using tuberculosis notification data managed by The Vietnam National Tuberculosis Program. The platform allows case distribution to be visualized by administrative level and time. Users can retrieve epidemiological measurements from the platform, which are calculated and visualized both temporally and spatially. The prediction model was developed to predict the TB incidence in space and time. Results: An online geospatial platform was developed, which presented the prediction model providing estimates of case detection. There were 400,370 TB cases with bacterial evidence to be included in the study. We estimated that the prevalence of TB in Vietnam was at 414.67 cases per 100.000 population. Ha Noi, Da Nang, and Ho Chi Minh City were predicted as three likely epidemiological hotspots in the near future. Conclusion: Our findings indicate that increased efforts should be undertaken to control tuberculosis transmission in these hotspots.

Findings from the first colorectal cancer screening among 103 542 individuals in Vietnam with systematic review of colorectal cancer screening programs in Asia-Pacific region.

BACKGROUND: Colorectal cancer is a leading cancer incidence and cause of death worldwide and in Vietnam. Although screening is considered an effective measure to prevent and control colorectal cancer, there is no such effort in Vietnam. METHODS: Between 01 January 2018 and 31 October 2019, a population-based colorectal cancer screening program was conducted in Hanoi, Vietnam. A health advocacy campaign and follow-up phone calls were used to enroll residents aged ≥40 years old to complete an immunochemical-fecal occult blood testing. Positive immunochemical-fecal occult blood testing was followed by a colonoscopy. We also conducted a systematic review of the colorectal cancer screening programs in the Asia-Pacific region that used similar approach by searching Ovid Medline and PubMed databases. RESULTS: During study period, 103 542 individuals among 672 742 eligible residents attended the screening of whom 81.5% participants finished immunochemical-fecal occult blood testing test and the positive rate was 6.1%. The coverage rate for immunochemical-fecal occult blood testing test was 11.9%. Among 2278 individuals who underwent colonoscopy, 3.5% were histologically diagnosed with cancer, 17.8% with advanced adenomas, and 23.1% with non-advanced adenomas. Males had significantly higher detection rate of advanced adenomas, cancer or ≥ two polyps/tumor than females (P < 0.0001). The systematic review showed that in two-step modality (i.e. immunochemical-fecal occult blood testing/fecal immunochemical test and colonoscopy), the test positive was from 4.1 to 10.6%. Once colonoscopy was performed subsequently, the rate of cancer among positive participants was from 1.7 to 16.4% and that of advanced adenomas was from 7.1 to 23.1%. CONCLUSION: We showed that the two-step modality is a promising strategy for colorectal cancer screening in Vietnam that might apply to similar settings with limited resources.

Intraband dynamics of mid-infrared HgTe quantum dots.

Femtosecond pump-probe spectroscopy reveals ultrafast carrier dynamics in mid-infrared (MIR) colloidal HgTe nanoparticles with a bandgap of 2.5 µm. We observe intraband relaxation processes after photoexcitation ranging from resonant excitation up to the multi-exciton generation (MEG) regime by identifying initially excited states from atomic effective pseudopotential calculations. Our study elucidates the earliest dynamics below 10 ps in this technologically relevant material. With increasing photon energy, we find carrier relaxation times as long as 2.1 ps in the MEG regime close to the ionization threshold of the particles. For all photon energies, we extract a constant mean carrier energy dissipation rate of 0.36 eV ps-1 from which we infer negligible impact of the density of states on carrier cooling.

Movement restrictions, vaccine coverage, and reduction of the COVID-19 incidence rate in the fourth wave of the pandemic: Analysis results from 63 provinces in Vietnam.

On April 27, 2021, the fourth wave of the coronavirus disease 2019 (COVID-19) pandemic originating from the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in Vietnam. The adoption of travel restrictions, coupled with rapid vaccination and mask-wearing, is a global strategy to prevent the spread of COVID-19. Although trade-off between health and economic development are unavoidable in this situation, little evidence that is specific to Vietnam in terms of movement restrictions, vaccine coverage, and real-time COVID-19 cases is available. Our research question is whether travel restrictions and vaccine coverage are related to changes in the incidence of COVID-19 in each province in Vietnam. We used Google's Global Mobility Data Source, which reports different mobility types, along with reports of vaccine coverage and COVID-19 cases retrieved from publicly and freely available datasets, for this research. Starting from the 50th case per province and incorporating a 14-day period to account for exposure and illness, we examined the association between changes in mobility (from day 27 to 04-03/11/2021) and the ratio of the number of new confirmed cases on a given day to the total number of cases in the past 14 days of indexing (the potentially contagious group in the population) per million population by making use of LOESS regression and logit regression. In two-thirds of the surveyed provinces, a reduction of up to 40% in commuting movement (to the workplace, transit stations, grocery stores, and entertainment venues) was related to a reduction in the number of cases, especially in the early stages of the pandemic. Once both movement and disease prevalence had been mitigated, further restrictions offered little additional benefit. These results indicate the importance of early and decisive actions during the pandemic.

The Contribution of Digital Health in the Response to Covid-19 in Vietnam.

Emerging from early of 2020, the COVID-19 pandemic has become one of the most serious health crisis globally. In response to such threat, a wide range of digital health applications has been deployed in Vietnam to strengthen surveillance, risk communication, diagnosis, and treatment of COVID-19. Digital health has brought enormous benefits to the fight against COVID-19, however, numerous constrains in digital health application remain. Lack of strong governance of digital health development and deployment; insufficient infrastructure and staff capacity for digital health application are among the main drawbacks. Despite several outstanding problems, digital health is expected to contribute to reducing the spread, improving the effectiveness of pandemic control, and adding to the dramatic transformation of the health system the post-COVID era.

Occupational symptoms due to exposure to volatile organic compounds among female Vietnamese nail salon workers in Danang city.

OBJECTIVES: Nail workers are exposed to many hazardous chemicals. Despite many warnings about health problems among nail workers in other countries, data concerning exposure to chemical hazards among nail workers is still limited in Vietnam. In this study, we aimed to identify exposure to volatile organic compounds and their relationship with occupational symptoms among Vietnamese female nail salon workers. METHODS: A cross-sectional study was conducted in Danang, Vietnam, from January 2019 to September 2019. Total 42 personal passive samplers were collected to evaluate 12 substances from 21 nail workers (15 salons) twice a week. We chose one representative worker from each of the nine salons with less than six workers and two representative workers from each of the six salons with over five workers for personal sampling based on the principle of similar exposure groups. We interviewed a total of 100 nail workers in 15 salons and 100 office workers in offices adjacent to the salons to compare occupational symptoms among them. RESULTS: The commonly detected compounds in nail salons were acetone (97.6%), butyl acetate (83.3%), and ethyl acetate and ethyl methacrylate (78%). The concentration of total target VOCs was related to the number of serviced customers, the concentration of CO2 , and general ventilation used. The subjective symptoms were significantly higher for the nail workers than for the comparison subjects, that is, headache, nausea, nose irritation, skin irritation, shortness of breath, and confusion. Among 100 nail workers, nose irritation was significantly higher for nail workers who were exposed to acetone at levels exceeding the Vietnam occupational exposure limit (VOEL) adjusted with the Brief-Scala model. CONCLUSIONS: Exposure to VOCs such as acetone in nail salons results in occupational symptoms among workers.

Dielectric response function for colloidal semiconductor quantum dots.

We calculate the optical properties of InP and CdSe colloidal quantum dots (QDs) within the framework of the atomic effective pseudopotential approach and the screened configuration interaction theory. We obtain an excellent agreement with experiment with our microscopic and space-dependent screening function where the dielectric constant varies in real space with a sharp transition (width of ≈0.18 nm) from the QD material high-frequency bulk value inside the QD to the solvent or passivant high-frequency value outside. We obtain a reasonable agreement (with deviations less than 140 meV) for a computationally less demanding solvent-independent screening using the full high-frequency bulk screening, in contrast to the more commonly used reduced QD radius-dependent screening constant. We show theoretically that for QDs passivated with long-chained organic molecules, the influence of the solvent on the optical gap is in the range of 10 meV, while QDs passivated with short ligands can experience shifts in the order of 100 meV. Experiments on CdSe QDs passivated with octadecylphosphonic acid (ODPA, long-chained ligand) in two different solvents (toluene and chloroform) confirm the bandgap dependence. While the optical gap is weakly affected by the environment, the quasiparticle gap and the exciton binding energy show a strong environmental dependence. Finally, we show that the optical bandgap does not depend significantly on the crystal structure (wurtzite or zincblende) or the morphological details (faceted or "spherical" shape).

Fixed intercaval block in the setting of atrial fibrillation promotes the development of atrial flutter.

BACKGROUND: In the canine sterile pericarditis model, typically only atrial fibrillation (AF) is inducible on postoperative day 2. OBJECTIVE: In this model, we tested the hypothesis that on postoperative day 2, placing a fixed line of block (LoB) between the vena cavae critically alters the atrial substrate, favoring the induction of sustained atrial flutter (AFL) instead of AF. METHODS: In 6 sterile pericarditis dogs, sustained AF was induced by rapid atrial pacing. After terminating AF, a fixed LoB between the vena cavae was created (cryoablation), and AF reinduction was attempted. Simultaneous mapping from 400 to 420 electrodes on the right and left atrial epicardium and the interatrial atrial septum was performed during all studies. RESULTS: Before creation of the LoB, in all 6 dogs, rapid atrial pacing induced sustained AF because of a rapid (mean cycle length [CL] 110 +/- 10 ms), regular, left atrial reentrant driver, which caused fibrillatory conduction. After creation of the LoB, in 5 dogs, rapid atrial pacing now induced sustained AFL (mean CL 167 +/- 13 ms). In the 6th dog, AFL failed to develop because the left atrial driver that was induced before the LoB was still reproducibly induced despite the LoB. CONCLUSION: In this model of sustained AF, altering the substrate to create a fixed LoB between the vena cavae creates a substrate favoring the induction of AFL.

Biventricular pacing attenuates T-wave alternans and T-wave amplitude compared to other pacing modes.

BACKGROUND: The impact of altered ventricular activation, including biventricular (BV) pacing, on T-wave alternans (TWA) and arrhythmic substrates is unclear. We studied how differing ventricular activation sequence alters TWA; the interval from peak-to-end of the T-wave (TpTe) and T-wave amplitude during right (RV), left (LV), and biventricular (BV) pacing; and right atrial (RA) pacing in patients with preexisting conduction delay. METHODS AND RESULTS: We measured TWA during RA, RV, LV, and BV pacing in 33 patients receiving cardiac-resynchronization-therapy-defibrillators. TWA magnitude (V(alt)) was lower during BV than RV (P < 0.01), RA (P < 0.01), or LV pacing. As a result, BV-TWA was more often negative than RV-TWA (P < 0.01), LV-TWA, and RA-TWA, particularly when discordant between pacing modes (P < 0.01). Overall, 83% of TWA recordings were abnormal (25% indeterminate), and 17% negative. BV pacing reduced T-wave amplitude (P < 0.05) and TpTe (P < 0.005) compared to RV pacing and LV pacing (P < 0.05; P < 0.005 respectively). Notably, TWA magnitude varied linearly with T-wave amplitude for all pacing modes (P < 0.001). Over 410 +/- 252 days' follow-up, RV-TWA predicted the combined endpoint of death and ICD therapy with 86% negative predictive value (P < 0.05). BV-TWA, RA-TWA, and other repolarization indices were not predictive. CONCLUSIONS: BV pacing attenuates TWA in tandem with reduced T-wave magnitude. In these patients with baseline QRS prolongation, RV-TWA predicted events more effectively than BV-TWA and RA-TWA. Further studies are required to understand how altered ventricular activation influences repolarization dynamics and arrhythmic tendency.

Cardiac-directed expression of adenylyl cyclase VI facilitates atrioventricular nodal conduction.

OBJECTIVES: The purpose of this study was to test the hypothesis that cardiac-directed expression of adenylyl cyclase VI (AC(VI)) facilitates atrioventricular (AV) nodal conduction. BACKGROUND: Cardiac-directed expression of AC(VI), unlike other strategies to increase cyclic adenosine monophosphate generation, reduces mortality in murine cardiomyopathy. Recent reports suggest that AC(VI) expression may also protect against lethal bradycardia. METHODS: We performed immunofluorescence staining for AC(VI) in the AV node of transgenic mice. We then performed electrophysiologic studies (EPSs) using a 1.7-F octapolar catheter at the AV junction in 11 transgenic AC(VI) mice and 14 control mice. RESULTS: Immunofluorescence staining revealed increased AC(VI) expression in the AV node of transgenic mice versus controls. During EPS, AV intervals approximated PR intervals (R2 = 0.99) and related linearly to atrial-to-His intervals (R2 = 0.98; both p < 0.0001). Thus, we studied AV intervals to avoid electrocardiogram pacing artifacts and inconsistent inscription of His bundle electrograms. At baseline, AC(VI) mice had shorter AV intervals (47 +/- 9 ms) than controls (57 +/- 11 ms; p = 0.02), despite similar sinus rates. In pacing, AV intervals were shorter in AC(VI) mice than controls for a wide cycle-length range (p < 0.01). The AC(VI) mice also had shorter AV Wenckebach cycle lengths (AC(VI): 114 +/- 12 ms; control: 131 +/- 28 ms; p = 0.05) and ventriculo-atrial effective refractory periods (AC(VI): 97 +/- 21 ms; control: 127 +/- 15 ms; p = 0.05). We observed no differences between groups in sinus node function, and ventricular arrhythmias were not inducible. CONCLUSIONS: Cardiac-directed expression of AC(VI) facilitates AV nodal conduction without altering sinus node function. These results suggest the need to define a role for AC(VI) gene transfer in treating diseases of AV conduction.