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Background: Concomitant fremanezumab, a calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb), and onabotulinumtoxinA (onabotA) improve treatment response compared with onabotA alone in patients with chronic migraine (CM). Methods: This was a single-center, retrospective, observational study that assessed treatment response (change over time in monthly headache days [MHD] and pain intensity [PI]) in adult patients with CM receiving fremanezumab as add-on therapy to onabotA for CM prevention. Results: In the study population ( N = 116, age 50.0 ± 13.1, female 85.3%, pre-index onabotA use 46.5 ± 34.2 months) receiving concurrent onabotA and fremanezumab for 17.5 ± 11.6 months, MHD decreased by 3.60 days (95% confidence interval [CI]: −5.26, −1.94, p < 0.001) and PI was reduced by 0.43 (95% CI: −0.77, −0.09, p = 0.012) at the final visit. Statistically significant reductions were seen in both MHD (−4.61, 95% CI: −6.84, −2.39; p < 0.001) and PI (−0.52, 95% CI: −0.84. −0.09; p = 0.017) among patients naïve to mAbs against CGRP or its receptor. No unexpected adverse events were observed. Conclusion: Concomitant fremanezumab and onabotA for CM prevention were effective at reducing the number of MHD and lessening PI, particularly in patients with difficult-to-treat CM who are naïve to mAbs against CGRP or its receptor.

Objectives: The Philippines has one of the fastest growing HIV epidemics in the world. A subtype shift from B to CRF01_AE may have contributed to the increase in cases. We undertook a genotyping and transmitted drug resistance (TDR) study to determine if the dominant subtype has any advantages in resistance and transmission. Methods: Filipinos who were treatment-naive who were living with HIV were recruited from two large government treatment hubs from March 2016 to August 2018. HIV-1 viral load, CD4 count, genotyping, and TDR testing were performed. Demographic and clinical data were collected and compared across subtypes. Results: A total of 298 Filipinos living with HIV were recruited. Median CD4 count was 143 cells/µl and HIV viral load was 2,345,431 copies/ml. Sanger-based sequencing showed 230/298 (77.2%) had subtype CRF01_AE, 41 (13.8%) subtype B, and the rest had other subtypes or recombinants. Overall TDR was 11.7%. TDR was associated with lower viral loads and no previous HIV testing. CRF01_AE had a higher likelihood of a viral load >100,000 copies/ml and having a baseline CD4 count

Abstract Background Following approval of fremanezumab for the prevention of migraine in adults, health care decision makers are interested in understanding real-world clinical characteristics and treatment patterns among patients initiating fremanezumab therapy. Methods Data were obtained for this retrospective (pre-post) study from the Veradigm Health Insights database. The study period was January 1, 2014, to June 30, 2019. Patients were included if they were aged ≥ 18 years; had ≥ 1 migraine diagnosis during the study period; and had a medication record for fremanezumab on or after diagnosis during the identification period (September 1, 2018–December 31, 2018). Treatment patterns, including adherence, persistence, and utilization of acute and preventive migraine medication prescriptions, were evaluated. Results Of 987 patients initiating fremanezumab during the study period, 738 (74.8%) were adherent to fremanezumab by proportion of days covered (PDC; ≥ 80%) and 780 (79.0%) were adherent by medication possession ratio (MPR; ≥ 80%). A total of 746 (75.6%) patients were persistent for ≥ 6 months. Quarterly fremanezumab (n = 186) was associated with higher rates of adherence versus monthly fremanezumab (n = 801) by PDC (quarterly, 91.3%; monthly, 84.9%; P

Abstract Background Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. Methods This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway–targeted mAb [CGRP mAb]). Results Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were − 7.7 (77.0%) in EM patients, − 10.1 (68.7%) in CM patients, − 10.8 (80.6%) in the MO subgroup, − 9.9 (68.3%) in the MDD subgroup, − 9.5 (66.4%) in the GAD subgroup, and − 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. Conclusions In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

Objectives: Migraine affects more than 80 million people in Western Europe. The present study evaluated disability and health‐related quality of life (HRQoL) among patients with episodic migraine (EM) and chronic migraine (CM) who had failed multiple preventive treatments. Materials and Methods: This study was an analysis of cross‐sectional, web‐based survey data from adult patients with migraine (EM and CM) from the United Kingdom, France, and Spain who had self‐reported failure of two or more preventive treatments. Patient characteristics and patient‐reported HRQoL, migraine‐related disability, healthcare resource use (HCRU), and burden of migraine were evaluated by classification (CM and EM) and country (EM only). Results: In this sample of 316 patients (United Kingdom, n = 106; Spain, n = 105; France, n = 105), 76 (24.1%) patients had CM, the mean (standard deviation [SD]) age was 39.5 (12.3) years, and 164 (51.9%) patients were female. Those patients with CM reported greater migraine‐related disability based on Migraine Disability Assessment (MIDAS) scores versus those with EM (mean [SD]: 43.8 [44.7] vs. 23.2 [28.3]), as well as greater pain‐related impact on daily activities and higher HCRU. Among patients with EM, MIDAS scores indicated disability was severe in Spain (mean [SD]: 31.6 [31.1]) and France (24.3 [31.1]) and moderate in the United Kingdom (13.8 [17.9]), while HRQoL was similar across countries. Regarding the burden of EM, higher levels of pain and symptom‐related interference with many aspects of life, including occupational functioning, were reported in the United Kingdom and Spain versus France. Conclusions: Migraine is associated with substantial disability and decreased HRQoL among patients who have failed previous preventive therapies. Although migraine burden varied by country, the results suggest high unmet needs in all countries. Appropriate treatment could reduce migraine‐related burden and HCRU among patients with difficult‐to‐treat migraine. [ABSTRACT FROM AUTHOR]

Abstract Background The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. Methods This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. Results This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were − 4.6 (36.2%) and − 4.7 (33.6%) at Month 1, − 6.7 (52.8%) and − 6.8 (48.6%) at Month 3, and − 9.2 (72.4%) and − 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from − 6.2 (21.6%) and − 8.4 (14.0%) at Month 1 to − 18.1 (63.1%) and − 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. Conclusions This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

We assessed the impact of selected pretreatment techniques, thus, vacuum-assisted osmotic dehydration (VOD), vacuum-assisted sonication (VSON) and vacuum-assisted osmosonication (VOS) on the metabolomes and quality characteristics of infrared-dried ginger slices. We found marked metabolome differences between the pretreated ginger samples, evidenced by differential amounts of 6-gingerol and 6-shogaol, total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activities. We also found distinct differences in the drying kinetics and sensory characteristics of the pretreated samples. Generally, VOS pretreatment gave the best outcomes. The VOS-pretreated samples contained the highest contents of the marker compounds, TPC, TFC and gave the best antioxidant activity. The VOS-pretreated samples also recorded the shortest drying time and exhibited the best sensory attributes. Overall, the general order observed was, VOS > VSON > VOD > control for all quality parameters examined. VOS pretreatment of ginger before drying therefore holds a great potential for large-scale industrial application.

With increasing geographic spread, frequency, and magnitude of outbreaks, dengue continues to pose a major public health threat worldwide. Dengvaxia, a dengue live-attenuated tetravalent vaccine, was licensed in 2015, but post hoc analyses of long-term data showed serostatus-dependent vaccine performance with an excess risk of hospitalized and severe dengue in seronegative vaccine recipients. The World Health Organization (WHO) recommended that only persons with evidence of past dengue infection should receive the vaccine. A test for pre-vaccination screening for dengue serostatus is needed. To develop the target product profile (TPP) for a dengue pre-vaccination screening test, face-to-face consultative meetings were organized with follow-up regional consultations. A technical working group was formed to develop consensus on a reference test against which candidate pre-vaccination screening tests could be compared. The group also reviewed current diagnostic landscape and the need to accelerate the evaluation, regulatory approval, and policy development of tests that can identify seropositive individuals and maximize public health impact of vaccination while avoiding the risk of hospitalization in dengue-naive individuals. Pre-vaccination screening strategies will benefit from rapid diagnostic tests (RDTs) that are affordable, sensitive, and specific and can be used at the point of care (POC). The TPP described the minimum and ideal characteristics of a dengue pre-vaccination screening RDT with an emphasis on high specificity. The group also made suggestions for accelerating access to these RDTs through streamlining regulatory approval and policy development. Risk and benefit based on what can be achieved with RDTs meeting minimal and optimal characteristics in the TPP across a range of seroprevalences were defined. The final choice of RDTs in each country will depend on the performance of the RDT, dengue seroprevalence in the target population, tolerance of risk, and cost-effectiveness.

An investigation into the efficient use of water as a solvent and the influence of extraction temperature, extraction time, water to leaf powder ratio, particle size, and extraction cycle on the nutraceutical and antioxidant profile of aqueous mulberry leaf extract were conducted using a single-factor experiment approach. All the assessed extracting parameters showed a significant effect on the nutraceutical compounds and antioxidant properties. The optimum extraction conditions were as follows: extraction temperature of 70°C, extraction time of 40 min, water to leaf powder ratio of 40:1 ml/g, particle size of 25 µm, and two extraction cycles. Based on these optimal conditions, chlorogenic acid (62.10 mg/g), caffeic acid (32.21 mg/g), kaempferol-7-O-glucoside (19.30 mg/g), quercetin-3-rutinose (15.69 mg/g), quercetin-3-O-glucoside (32.38 mg/g), kaempferol-3-(6-rhamnosylglucoside) (42.52 mg/g), quercetin-3-(6-malonylglucoside) (65.19 mg/g), kaempferol-3-glucoside (66.27 mg/g), kaempferol-3-(6-malonylglucoside) (50.18 mg/g), 1-deoxynojirimycin (15.58 mg/g), and gamma-aminobutyric acid (5.05 mg/g) were obtained. The optimal aqueous extract had high antioxidant properties of 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (39.98 mM/g), cupric ion reducing capacity (58.93 mM/g), 1,1-diphenyl-2-picrylhydrazyl (101.33 mM/g), and ferric reducing antioxidant power capacity (233.77 mM/g) of dried mulberry leaf extract.

Background: Concomitant fremanezumab, a calcitonin gene-related peptide (CGRP) pathway monoclonal antibody (mAb), and onabotulinumtoxinA (onabotA) improve treatment response compared with onabotA alone in patients with chronic migraine (CM). Methods: This was a single-center, retrospective, observational study that assessed treatment response (change over time in monthly headache days [MHD] and pain intensity [PI]) in adult patients with CM receiving fremanezumab as add-on therapy to onabotA for CM prevention. Results: In the study population (N = 116, age 50.0 ± 13.1, female 85.3%, pre-index onabotA use 46.5 ± 34.2 months) receiving concurrent onabotA and fremanezumab for 17.5 ± 11.6 months, MHD decreased by 3.60 days (95% confidence interval [CI]: −5.26, −1.94, p < 0.001) and PI was reduced by 0.43 (95% CI: −0.77, −0.09, p = 0.012) at the final visit. Statistically significant reductions were seen in both MHD (−4.61, 95% CI: −6.84, −2.39; p < 0.001) and PI (−0.52, 95% CI: −0.84. −0.09; p = 0.017) among patients naïve to mAbs against CGRP or its receptor. No unexpected adverse events were observed. Conclusion: Concomitant fremanezumab and onabotA for CM prevention were effective at reducing the number of MHD and lessening PI, particularly in patients with difficult-to-treat CM who are naïve to mAbs against CGRP or its receptor. [ABSTRACT FROM AUTHOR]

Patulin (PAT) is a mycotoxin produced by some Penicillium, Aspergillus, and Byssochlamys species. Rhodotorula mucilaginosa is able to degrade PAT in vivo as well as in vitro, up till date, the process and molecular mechanism(s) involved patulin degradation still remains unknown. Protein lysine crotonylation (Kcr) plays an important role in regulating chromatin dynamics, gene expression, and metabolic pathways in mammals and eukaryotes. Investigation of the Kcr changes accompanying degradation of patulin in R. mucilaginosa were observed to investigate the mechanisms of patulin inhibition. Tandem mass tag (TMT) labeling and Kcro affinity enrichment, followed by high-resolution LC-MS/MS analysis, were used to perform quantitative lysine crotonylome analysis on R. mucilaginosa. Consequently, 1691 lysine crotonylation sites in 629 protein groups were identified, among which we quantified 1457 sites in 562 proteins. Among the quantified proteins, 79 and 46 crotonylated proteins were up-regulated and down-regulated, respectively. The differentially up expressed modified proteins were mainly involved in tricarboxylic acid cycle and gluconeogenic pathway. The differentially down expressed Kcr proteins were mainly classified to ribosome and carbohydrate transport and metabolism. Bioinformatic analyses were performed to annotate the quantifiable lysine crotonylated targets. Moreover, interaction networks and high confidence domain architectures of crotonylated proteins were investigated with the aid of bioinformatic tools, and these results showed that there was an increase in the number of yeasts with crotonylated proteins. The results also provided information on the various roles of crotonylation, which are involved in PAT degradation.

Synthetic fungicides are commonly employed for the control of postharvest diseases of fruits. However, due to health concerns about the use of these chemicals, alternative control methods including biocontrol based on antagonistic yeasts are gaining in popularity. In this study, we investigated the effects of two biocontrol yeasts, Rhodotorula mucilaginosa strain 3617 and Rhodotorula kratochvilovae strain LS11, on blue mold and patulin (PAT) contamination caused by Penicillium expansum strains PY and FS7 in artificially inoculated Fuji apples stored at 20°C for 9 days. To correlate the development of the P. expansum strains in yeast-treated and untreated apples with PAT production, we quantified their biomass in the infected fruits using a recently published quantitative real-time polymerase chain reaction method based on specific primers for patF, a gene from P. expansum that is involved in PAT biosynthesis. Both yeasts significantly reduced the disease incidence caused by the two strains of P. expansum up to 5–7 days of incubation, and lowered their biomass and the progression of symptoms up to 9 days. Interestingly, both yeasts strains increased the rate of PAT production (expressed as ng patulin/μg fungal DNA) by the two pathogenic strains. Nevertheless, both biocontrol agents reduced the total PAT contamination, especially in the case of P. expansum strain FS7, the higher PAT producer of the two tested P. expansum strains. Comparing between the yeast strains, R. kratochvilovae LS11 was more effective than R. mucilaginosa 3617 for the control of P. expansum.

Background: For some years, non-governmental organisations (NGOs) and civil society have become increasingly involved in the fight against the HIV/AIDS pandemic in Africa. But even though their role is well appreciated, their actions are perceived as ineffective because of a lack of monitoring and evaluation capacity. Objective: This paper aims to describe local HIV/AIDS NGOs’ involvement in evaluation and the characteristics of this involvement. Method: Descriptive analysis of data collected in questionnaires completed by 34 NGO executives (one per NGO). Results: Most NGOs do not have the minimal conditions required for positive and effective involvement in evaluations. In addition, funding agencies’ expectations for evaluations, total human resources as well as experience as NGO are contextual factors that explain most aspects of their involvement in evaluations. Conclusion: This study provides funding agencies, NGO leaders and all those interested in developing evaluation capacity in these NGOs to understand the extent of the task in this area. They must keep in mind that there is no solution for all, but that solutions must be adapted to the developmental level of each organisation.

OBJECTIVE: The aim of this randomized controlled trial (RCT) was to investigate the effectiveness of the Stay@Work participatory ergonomics (PE) program to prevent low-back and neck pain. METHODS: A total of 37 departments were randomly allocated to either the intervention (PE) or control group (no PE). During a six-hour meeting, working groups followed the PE steps and composed and prioritized ergonomic measures aimed at preventing low-back and neck pain. Subsequently, working groups were requested to implement the ergonomic measures in the departments. The primary outcomes were low-back and neck pain prevalence and secondary outcomes were pain intensity and duration. Data were collected by questionnaires at baseline, and after 3-, 6-, 9-, and 12-months follow-up. Additionally, the course of low-back and neck pain (transitions from no symptoms to symptoms and from symptoms to no symptoms) was modeled. RESULTS: The randomization procedure resulted in 19 intervention departments (N=1472 workers) and 18 control departments (N=1575 workers). After 12 months, the intervention was not more effective than the control group in reducing the prevalence of low-back and neck pain or reducing pain intensity and duration. PE did not increase the probability of preventing low-back pain [odds ratio (OR) 1.23, 95% confidence interval (95% CI) 0.97–1.57) or neck pain (OR 1.01, 95% CI 0.74–1.40). However, PE increased the probability of recovering from low-back pain (OR 1.41, 95% CI 1.01–1.96), but not from neck pain (OR 0.95, 95% CI 0.72–1.26). CONCLUSION: PE neither reduced low-back and neck pain prevalence nor pain intensity and duration nor was it effective in the prevention of low-back and neck pain or the recovery from neck pain. However, PE was more effective in the recovery from low-back pain.