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Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study

CNS Drugs. 2023 Nov 24. doi: 10.1007/s40263-023-01050-3. Online ahead of print.

ABSTRACT

BACKGROUND: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up.

OBJECTIVE: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine.

METHODS: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed.

RESULTS: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events.

CONCLUSIONS: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.

PMID:37999868 | DOI:10.1007/s40263-023-01050-3

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Health-related quality of life in long-term early-stage breast cancer survivors compared to general population in Korea

J Cancer Surviv. 2023 Nov 24. doi: 10.1007/s11764-023-01482-2. Online ahead of print.

ABSTRACT

PURPOSE: This study assessed health-related quality of life (HRQoL) of long-term breast cancer (BC) survivors diagnosed at early stages and compare with cancer-free, age-matched women.

METHODS: The study population included BC survivors diagnosed with ductal carcinoma in situ (DCIS) or breast cancer stages I-II, who had undergone lumpectomy/mastectomy, with time since diagnosis ranging from 9 to 16 years. Survey was conducted at two tertiary hospitals in 2020. Data for cancer-free female controls was randomly drawn from a population-based survey and age-, education-matched with 1 case: 3 controls ratio. Self-reported HRQoL was assessed using EQ-5D with five dimentions. EQ-5D utility index score was calculated. Difference in EQ-5D score was evaluated using the Tobit regression model with adjustment for other covariates.

RESULTS: Of 273 survivors. 88% and 12% underwent mastectomy and lumpectomy, respectively. The mean (standard deviation, SD) age at survey was 57.3 (8.5) years old. BC survivors reported significantly more problems performing daily activities (11% vs. 5%, p < 0.001), pain/discomfort (46% vs. 23%, p < 0.001), and anxious/depressed feelings (44% vs. 8%, p < 0.001) relative to the controls. Difference in EQ-5D score between BC survivors and the general population was higher in older age groups. The overall EQ-5D score of BC survivors was statistically lower than that of the control subjects (adjusted [Formula: see text]=0.117, p < 0.001).

CONCLUSION: Long-term BC survivors who survived beyond ten years post-diagnosis experience more pain, anxiety, and distress, leading to an overall poorer HRQoL.

IMPLICATIONS FOR CANCER SURVIVORS: This study suggest the importance of follow-up care, particularly focusing on pain, anxiety, and distress management to enhance the HRQoL of long-term BC survivors.

PMID:37999857 | DOI:10.1007/s11764-023-01482-2

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Passive air sampling of VOCs, O3, NO2, and SO2 in the large industrial city of Ulsan, South Korea: spatial-temporal variations, source identification, and ozone formation potential

Environ Sci Pollut Res Int. 2023 Nov 24. doi: 10.1007/s11356-023-31109-z. Online ahead of print.

ABSTRACT

Concerns about volatile organic compounds (VOCs) have increased due to their toxicity and secondary reaction with nitrogen oxides (NOX) to form ozone (O3). In this study, passive air sampling of VOCs, O3, NO2, and SO2 was conducted in summer, fall, winter, and spring from 2019 to 2020 at six industrial and ten urban sites in Ulsan, the largest industrial city in South Korea. Over the entire sampling period, the concentration of toluene (mean: 8.75 μg/m3) was the highest of the 50 target VOCs, followed by m,p-xylenes (4.52 μg/m3), ethylbenzene (4.48 μg/m3), 3-methylpentane (4.40 μg/m3), and n-octane (4.26 μg/m3). Total (Σ50) VOC levels did not statistically differ between seasons, indicating that large amounts of VOCs are emitted into the atmosphere throughout the year. On the other hand, O3, NO2, and SO2 exhibited strong seasonal variation depending on the meteorological conditions and emission sources. The spatial distribution of Σ50 VOCs, NO2, and SO2 indicated that industrial complexes were major sources in Ulsan, while O3 had the opposite spatial distribution. Using a positive matrix factorization model, five major sources were identified, with industrial effects dominant. Aromatic compounds, such as m,p,o-xylenes, toluene, and 1,2,4-trimethylbenzene, significantly contributed to O3 formation. The VOC/NO2 ratio and O3 concentrations suggested that reducing VOC emissions is more effective than reducing NO2 emissions in terms of preventing the secondary formation of O3. The findings of this study allow for a better understanding of the relationship between VOCs, O3, NO2, and SO2 in industrial cities.

PMID:37999843 | DOI:10.1007/s11356-023-31109-z

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Comparison of Efficacy and Safety Between Drug-Coated Balloons Versus Drug-Eluting Stents in the Treatment of De Novo Coronary Lesions in Large Vessels: A Study-Level Meta-Analysis of Randomized Control Trials

Cardiovasc Drugs Ther. 2023 Nov 24. doi: 10.1007/s10557-023-07526-0. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-coated balloons (DCB) can be used as an alternative to drug-eluting stents (DES) in patients with de novo small vessel coronary artery disease. This study aims to assess the efficacy and safety of solely using DCB versus DES in percutaneous coronary intervention (PCI) for de novo coronary lesions in large vessels.

METHOD: A database search was conducted using PubMed, EMBASE, Cochrane Library, and http://Clinicaltrials.gov for trials comparing DCB only with DES in treating de novo coronary lesions in large vessels. Efficacy outcomes included coronary angiography (CAG), follow-up minimal lumen diameter (MLD), and late luminal loss (LLL). Safety outcomes included target lesion failure [TLF: cardiac death, myocardial infarction (MI), target lesion revascularization (TLR)] and their individual components.

RESULTS: We included seven randomized control trials (RCTs) with 816 patients, of which 422 and 394 patients were in the DCB and DES groups, respectively. MLD measured during the 6-12 months follow-up in the DCB group was statistically significantly smaller than in the DES group (MD -0.21, 95% CI -0.34 to -0.07, P = 0.003, I2 = 52%). LLL measured at 6-12 months follow-up was statistically significantly lower in the DCB group than in the DES group (MD -0.13, 95% CI -0.22 to -0.05, P = 0.003, I2 = 60%). TLF, cardiac death, MI, and TLR, were not statistically significantly different between the two groups.

CONCLUSION: Use of DCB was associated with less LLL at 6-12 months than DES and was not associated with any increase in adverse clinical events. This data suggests DCB are as effective in treating de novo coronary lesions in large vessels as DES.

PMID:37999833 | DOI:10.1007/s10557-023-07526-0

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Causal relationship between depression and aging: a bidirectional two-sample Mendelian randomization study

Aging Clin Exp Res. 2023 Nov 24. doi: 10.1007/s40520-023-02596-4. Online ahead of print.

ABSTRACT

BACKGROUND: The causal relationship and the direction of the effect between depression and aging remain controversial.

METHODS: We used a bidirectional two-sample Mendelian randomization analysis to examine the relationship between depression and age proxy indicators. We obtained pooled statistics from genome-wide association studies (GWAS) on depression and the age proxy indicators. We employed five MR analysis methods to address potential biases and ensure robustness of our results, with the inverse variance weighted (IVW) method being the primary outcome. We also conducted outlier exclusion using Radial MR, MRPRESSO, and MR Steiger filters. Additionally, sensitivity analyses were performed to assess heterogeneity and pleiotropy.

RESULTS: Our MR analysis revealed that depression causally leads to shortened telomere length (β = – 0.014; P = 0.038), increased frailty index (β = 0.076; P = 0.000), and accelerated GrimAge (β = 0.249; P = 0.024). Furthermore, our findings showed that the frailty index (OR = 1.679; P = 0.001) was causally associated with an increased risk of depression. Additionally, we found that appendicular lean mass (OR = 0.929; P = 0.000) and left-hand grip strength (OR = 0.836; P = 0.014) were causally associated with a reduced risk of depression. Sensitivity analyses demonstrated the robustness of our findings.

CONCLUSIONS: Our study provides evidence that depression contributes to the accelerated aging process, resulting in decreased telomere length, increased frailty index, and accelerated GrimAge. Additionally, we found that the frailty index increases the risk of depression, while appendicular lean mass and left-handed grip strength reduce the risk of depression.

PMID:37999829 | DOI:10.1007/s40520-023-02596-4

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Effect of preoperative single-dose methylprednisolone administration on early postoperative pain following retrograde intrarenal surgery

Int Urol Nephrol. 2023 Nov 24. doi: 10.1007/s11255-023-03875-9. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effect of preoperative single-dose methylprednisolone use on postoperative early pain after retrograde intrarenal surgery (RIRS).

METHODS: Patients who had 10-20 mm solitary kidney stones and underwent RIRS procedures were included in this prospective cohort study between February 2022 and May 2023. Patients who were administered methylprednisolone at a dose of 1 mg/kg preoperatively were included in group 1 (n: 31), and the other first 90 patients who met the inclusion criteria and did not receive methylprednisolone before surgery were included in group 2 (n: 90). Demographic data, features of stone, postoperative pain at 1, 6, 12, 18, and 24 hour, the need for analgesics, changes in serum glucose levels, and the prevalence of postoperative fever were compared.

RESULTS: Age, sex, stone laterality, localization, size, Hounsfield Unit, modified Satava scores, stone-free status, duration of the RIRS procedure, and duration of the ureteral access sheath were found to be similar between groups. Visual Analog Scale (VAS) scores at postoperative 1, 6, 12, 18, and 24 h were found to be statistically significantly lower in group 1 (p = .001, p = .001, p = .001, p = .001, and p = .001, respectively). Similarly, postoperative analgesic requirements were found to be significantly lower in group 1 (p = .048) with a similar postoperative fever rate and changes in serum glucose levels between groups.

CONCLUSION: Giving a single dose of methylprednisolone at a dose of 1 mg/kg preoperatively for the RIRS procedure is safe and effective at preventing early pain and the need for analgesics after the RIRS procedure.

PMID:37999826 | DOI:10.1007/s11255-023-03875-9

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Application of statistical methodology for the optimization of L-glutaminase enzyme production from Streptomyces pseudogriseolus ZHG20 under solid-state fermentation

J Genet Eng Biotechnol. 2023 Nov 24;21(1):138. doi: 10.1186/s43141-023-00618-2.

ABSTRACT

BACKGROUND: Actinomycetes are excellent microbial sources for various chemical structures like enzymes, most of which are used in pharmaceutical and industrial products. Actinomycetes are preferred sources of enzymes due to their high ability to produce extracellular enzymes. L-glutaminase has proven its essential role as a pharmaceutical agent in cancer therapy and an economic agent in the food industry. The current study aimed to screen the potent L-glutaminase producer and optimize the production media for maximum enzyme yield using one factor at a time (OFAT) approach and statistical approaches under solid-state fermentation (SSF).

RESULTS: Out of 20 actinomycetes strains isolated from rhizosphere soil, 5 isolates produced extracellular L-glutaminase. One isolate was chosen as the most potent strain, and identified as Streptomyces pseudogriseolus ZHG20 based on 16S rRNA. The production and optimization process were carried out under SSF, after optimization using OFAT method, the enzyme production increased up to 884.61 U/gds. Further, statistical strategy, response surface methodology (RSM), and central composite design (CCD) were employed for the level optimization of significant media component (p < 0.05), i.e., wheat bran, sesame oil cake, and corn steep liquor which are leading to increase 3.21-fold L-glutaminase production as compared to unoptimized media.

CONCLUSIONS: The presented investigation reveals the optimization of various physicochemical parameters using OFAT and RSM-CCD. Statistical approaches proved to be an effective method for increasing the yield of extracellular L-glutaminase from S. pseudogriseolus ZHG20 where L-glutaminase activity increased up to 1297.87 U/gds which is 3.21-fold higher than the unoptimized medium using a mixture of two solid substrates (wheat bran and sesame oil cake) incubated at pH 7.0 for 6 days at 33 °C.

PMID:37999820 | DOI:10.1186/s43141-023-00618-2

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Reference values for Jamar+ digital dynamometer hand grip strength in healthy adults and in adults with non-communicable diseases or osteoarthritis: the Norwegian Tromsø study 2015-2016

Eur J Ageing. 2023 Nov 24;20(1):44. doi: 10.1007/s10433-023-00791-w.

ABSTRACT

Hand grip strength (HGS) is a key indicator of intrinsic capacity and has shown good predictive ability for morbidity and mortality. Reference values from normative populations are valuable, and such data from the Norwegian population are scarce. Normative values for the digital Jamar+ dynamometer are largely lacking.HGS was assessed in the Norwegian Tromsø study, survey 7 in 2015-2016 for 7824 participants (9324 invited) aged 40+ using a Jamar+ digital dynamometer, and three measurements for each hand were performed following the Southampton protocol. To account for non-response, full Tromsø population data, by age, education and sex, were collected from registry data from microdata.no, a service from Statistics Norway, and were then used as post-stratification weights, to provide standardized HGS values. HGS was higher in men than in women and inversely associated with age. Men and women with a history of non-communicable diseases had lower HGS than those without these conditions, while osteoarthritis was associated with lower HGS only among men. Lower height was associated with lower HGS, especially at younger ages in men. This article provides up-to-date references values for HGS in the community-dwelling population aged 40+ with or without osteoarthritis or non-communicable diseases, in Tromsø, Norway. These reference values will guide clinicians and researchers.

PMID:37999814 | DOI:10.1007/s10433-023-00791-w

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Comparative evaluation of effect of nisin-incorporated ethylenediamine tetraacetic acid and MTAD on endodontic biofilm eradication, smear layer removal, and depth of sealer penetration

Clin Oral Investig. 2023 Nov 24. doi: 10.1007/s00784-023-05285-8. Online ahead of print.

ABSTRACT

OBJECTIVES: To comparatively evaluate the nisin-incorporated ethylenediamine tetraacetic acid (N-EDTA) and MTAD on cytotoxicity, endodontic biofilm eradication potential, smear layer removal ability, and sealer penetration depth.

MATERIALS AND METHODS: N-EDTA was prepared and characterized using high-performance liquid chromatography (HPLC). Minimum inhibitory, minimum bactericidal, and minimum biofilm inhibitory concentration (MBC, MIC, and MBIC) were determined on Enterococcus faecalis (E. faecalis) strain. The cytocompatibility of N-EDTA and MTAD was evaluated using 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay. Dentin specimens (n = 88 for antibacterial analysis, n = 170 for sealer penetration depth) were prepared and subjected to the classical irrigating strategy and obturation, respectively. The scanning electron microscopic evaluation (SEM) was done for the evaluation of biofilm disruption and smear layer removal. Confocal laser scanning microscopy (CLSM) evaluation was done for determining percentage of bacterial viability and sealer penetration depth. Statistical analysis of one-way ANOVA and Tukey’s HSD post hoc tests for bacterial viability and Kruskal-Wallis test and Mann-Whitney test for smear layer removal and depth of penetration were done with the significance level set at p < 0.05.

RESULTS: MTAD and N-EDTA showed cytocompatibility without any statistical differences from each other. For N-EDTA, the MIC and MBC values were 12.5 μg/ml (1:8), and MBIC values were 36 μg/ml. Biofilm disruption and killed bacterial percentage of N-EDTA was statistically higher than MTAD, whereas both the materials showed similar efficacy in the removal of the smear layer and sealer penetration depth.

CONCLUSION: N-EDTA had negligible cytotoxicity with similar smear layer removal ability, sealer penetration, and better antibiofilm potential than MTAD.

CLINICAL RELEVANCE: N-EDTA can serve as a viable alternative endodontic irrigant.

PMID:37999802 | DOI:10.1007/s00784-023-05285-8

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Efficacy of pulsed electromagnetic field therapy on pain and physical function in patients with non-specific low back pain: a systematic review

Wien Med Wochenschr. 2023 Nov 24. doi: 10.1007/s10354-023-01025-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Non-specific low back pain is a common and clinically significant condition with substantial socioeconomic implications. Pulsed electromagnetic field (PEMF) therapy has shown benefits in pain reduction and improvement of physical function in patients with pain-associated disorders like osteoarthritis. However, studies had heterogeneous settings. The aim of this study was to assess the effects of PEMF on pain and function on patients with non-specific low back pain.

METHODS: A systematic literature search of randomized controlled trials in PubMed, MEDLINE, EMBASE, Cochrane Library, and PEDro was performed (from inception until 15/5/2023). Outcome measures assessed pain and function.

RESULTS: Nine randomized controlled trials with 420 participants (n = 420) were included. The studies compared PEMF vs. placebo-PEMF, PEMF and conventional physical therapy vs. conventional physical therapy alone, PEMF and conventional physical therapy vs. placebo-PEMF and conventional physical therapy, PEMF vs. high-intensity laser therapy (HILT) vs. conventional physical therapy, and osteopathic manipulative treatment (OMT) and PEMF vs. PEMF alone vs. placebo-PEMF vs. OMT alone. Five of the nine included studies showed statistically significant pain reduction and improvement in physical function in comparison to their control groups (p < 0.05). There was substantial heterogeneity among the groups of the study, with a wide range of duration (10-30 min), treatments per week (2-7/week), applied frequencies (3-50 Hz), and intensities (2mT-150mT). No serious adverse event had been reported in any study. The included studies showed solid methodological quality, with an overall score of 7.2 points according to the PEDro scale.

CONCLUSION: PEMF therapy seems to be a safe and beneficial treatment option for non-specific low back pain, particularly if used as an addition to conventional physical therapy modalities. Future research should focus on standardized settings including assessment methods, treatment regimens, frequencies, and intensities.

PMID:37999784 | DOI:10.1007/s10354-023-01025-5