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Abstract Background Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model. Methods The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2–4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted. Results Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses. Conclusion In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population.

Abstract Introduction Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. Methods Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. Results In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P

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).

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.

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.

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.

Die doel van hierdie artikel is om die fiktiewe voorstelling van vroue in twee van Sharai Mukonoweshuro se romans, naamlik Ndakagara Ndazviona en Akafuratidzwa Moyo, te verken. Tradisionele Shona verwagtinge van hoe ’n vrou moet optree, skryf die rolle voor wat van vroue verwag word om in die samelewing te speel. In ’n koloniale konteks soos die voormalige Rhodesië het kolonialisme wette in die gewoontereg bedink wat vroue verder gedegradeer het tot sosiale posisies soortgelyk aan dié van minderjariges. Hoewel die nasionalistiese stryd in wese bedoel was om vryheid te waarborg vir alle Swart mense, ongeag van geslag, het die manlike elites Swart vroue as hul minderwaardige ‘ander‘ gekonstrueer. In hierdie artikel word geargumenteer dat Sharai Mukonoweshuro se romans worstel met hierdie manlik-goedgekeurde stereotipes. Maar, soos getoon word, Mukonoweshuro se wyse van weerstand teen vroulike stereotipes is ambivalent; die skrywer skep jong vroue wat die patriargie aan die een kant uitdaag, en aan die ander kant, ou vroue wat die ondenkbare doen om hulle eie seuns te vergiftig.