Combination therapies with monoclonal antibodies (mAbs) enhance therapeutic activity and may circumvent drug resistance. However, these studies present bioanalytical challenges for ligand-binding ...assays (LBAs). Recent MS-based protein quantification offers an alternative for bioanalysis.
A hybrid LC-MS/MS assay was developed to simultaneously measure human serum concentrations of two mAbs. Anti-idiotypic reagents that did not work in LBAs were successfully used for mAb affinity capture enrichment. Stable isotope-labeled peptide internal standards were employed. The mAb quantification involved measuring a signature CDR peptide derived from each mAb as a surrogate. Selected clinical samples were successfully analyzed.
The multiplexed LC-MS/MS method provided a powerful quantitative tool for clinical PK assessment of co-administered mAbs without the requirement for stringent affinity capture reagents.
This review aimed to gather recent studies that could identify the specificities in the relationship between urbanization and alcohol use epidemiology in the current century.
Although we find lower ...rates of alcohol use among adolescents in urban environments than in rural ones, this difference tends to diminish until it disappears by the time they reach adulthood. In addition to excessive marketing and increased accessibility, several urban environment characteristics have been related to alcohol use. First, problematic alcohol use is linked to stress and mental health problems like depression and anxiety, which are common in metropolitan areas. Second, alcohol use behaviors are influenced by homelessness, loneliness, and deprivation in megacities, where female and male individuals have presented more similar alcohol use behaviors (i.e. gender convergence). Third, treatment levels for alcohol use disorders are very low.
There is a new epidemiological wave of alcohol consumption in large urban centers, largely influenced by advertisement and marketing. Social and psychological risk factors and subpopulations of interest were identified for preventive interventions in large urban centers (i.e. advertisement regulation). In addition, increasing the availability of treatment, including specific medications for alcohol use disorder, should be strongly encouraged.
Diabetic macular edema (DME) is a major cause of visual impairment and its treatment is a public health challenge. Even though anti-angiogenic drugs are the gold-standard treatment, they are not ...ideal and subthreshold laser (SL) remains a viable and promising therapy in selected cases. The aim of this study was to evaluate its efficacy in a real-life setting.
Retrospective case series of 56 eyes of 36 patients with center-involving DME treated with SL monotherapy. Treatment was performed in a single session with the EasyRet® photocoagulator with the following parameters: 5% duty cycle, 200-ms pulse duration, 160-µm spot size and 50% power of the barely visible threshold. A high-density pattern was then applied to the whole edematous area, using multispot mode. Best corrected visual acuity (BCVA) and optical coherence tomography (OCT) data were obtained at baseline and around 3 months after treatment.
Fifty-six eyes of 36 patients were included (39% women, mean age 64.8 years old); mean time between treatment day and follow-up visit was 14 ± 6 weeks. BCVA (Snellen converted to logMAR) was 0.59 ± 0.32 and 0.43 ± 0.25 at baseline and follow-up, respectively (p = 0.002). Thirty-two percent had prior panretinal photocoagulation (p = 0.011). Mean laser power was 555 ± 150 mW and number of spots was 1,109 ± 580. Intraretinal and subretinal fluid (SRF) was seen in 96 and 41% of eyes at baseline and improved in 35 and 74% of those after treatment, respectively. Quantitative analysis of central macular thickness (CMT) change was performed in a subset of 23 eyes, 43% of which exhibited > 10% CMT reduction post-treatment.
Subthreshold laser therapy is known to have RPE function as its main target, modulating the activation of heat-shock proteins and normalizing cytokine expression. In the present study, the DME cases associated with SRF had the best anatomical response, while intraretinal edema responded poorly to laser monotherapy. BCVA and macular thickness exhibited a mild response, suggesting the need for combined treatment in most patients. Given the effect on SRF reabsorption, subthreshold laser therapy could be a viable treatment option in selected cases.
Advances in Vitreoretinal Surgery Ribeiro, Lucas; Oliveira, Juliana; Kuroiwa, Dante ...
Journal of clinical medicine,
10/2022, Letnik:
11, Številka:
21
Journal Article
Recenzirano
Odprti dostop
Advances in vitreoretinal surgery provide greater safety, efficacy, and reliability in the management of the several vitreoretinal diseases that benefit from surgical treatment. The advances are ...divided into the following topics: scleral buckling using chandelier illumination guided by non-contact visualization systems; sclerotomy/valved trocar diameters; posterior vitrectomy systems and ergonomic vitrectomy probes; chromovitrectomy; vitreous substitutes; intraoperative visualization systems including three-dimensional technology, systems for intraoperative optical coherence tomography, new instrumentation in vitreoretinal surgery, anti-VEGF injection before vitrectomy and in eyes with proliferative diabetic retinopathy, and new surgical techniques; endoscopic surgery; the management of subretinal hemorrhages; gene therapy; alternative techniques for refractory macular hole; perspectives for stem cell therapy and the prevention of proliferative vitreoretinopathy; and, finally, the Port Delivery System. The main objective of this review is to update the reader on the latest changes in vitreoretinal surgery and to provide an understanding of how each has impacted the improvement of surgical outcomes.
Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of ...two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody; n = 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses; n = 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses; n = 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.).
To report the long-term anatomical and visual outcomes of intravitreal bevacizumab (IVB) monotherapy in naive choroidal neovascularisation (CNV) caused by myopia.
Retrospective analysis of naive CNV ...secondary to myopia that underwent antivascular endothelial growth factor monotherapy was performed. Collected data included demographic details, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last visit. Secondary outcomes included change in visual acuity, number of injections and adverse events.
Thirty-three eyes of 31 subjects with a mean age of 51.48±16.4 years were included. The mean follow-up was 66.47 months. 27 eyes had type 2 CNV and the rest seven eyes had type 1 CNV. The mean number of IVB injections per eye was 4.9. Mean visual acuity at baseline reduced from 0.65±0.33 logMAR units (Snellen equivalent=20/89) to 0.73±0.50 logMAR units (20/107) at final follow-up (p=0.003). The mean central macular thickness decreased from 309.31±86 µm at baseline to 267.5±70.89 µm at the last visit (p=0.03). However, visual acuity was maintained (±1 line of baseline) in 13 eyes (39.4%), ≥2 line improvement in nine (27.3%) eyes and more than two lines worsening in 11 eyes (33.3%). Foveal atrophy was observed at baseline and last visit in 6 (12.5%) and 14 (29.1%), respectively (p=0.007). No systemic adverse events were observed.
IVB monotherapy is safe and effective for long-term treatment of CNV secondary to myopia in real life.
Additional statistical tests (multiple comparisons with Bonferroni correction after linear mixed model estimation) were performed to verify difference in measurements before and after positive or ...negative contact lens wearing. ...we tested the same eye with a negative or positive contact lens, and this represented another method to reduce the possible effect of accommodative capacity. In the present study, contact lens wear did not significantly change the OCT measurements for CT and RT in emmetropic eyes. ...precise CT and RT measurements could be obtained in contact lens wearers, without the need to remove them before the OCT imaging.
(1) Background: Attention-deficit/hyperactivity disorder (ADHD) is typically treated with stimulant medications, which may lead to several adverse effects. Recent animal studies have shown that ...caffeine can improve the symptoms of ADHD. This systematic review and meta-analysis sought to evaluate the effect of caffeine on ADHD symptoms in children. (2) Methods: PubMed, Embase, and Cochrane databases were searched for randomized controlled trials comparing caffeine with placebo in children, comparing overall symptoms of ADHD, inattention, hyperactivity, and impulsivity. (3) Results: We included seven RCTs in the systematic review for qualitative assessment, with 104 patients aged 5 to 15 years. Four of these studies (n = 76) were included in the meta-analysis. After qualitative analysis, four studies indicated no improvement in any of the ADHD symptoms compared with placebo. One study showed improvement in ADHD symptoms based on 1 of 5 scales applied. One study indicated significant improvement in general symptoms, inattention, and hyperactivity. One study indicated improvement in sustained attention but a worsening of impulsivity. In contrast, when using a quantitative analysis of the general symptoms of ADHD, the data showed no significant difference when comparing placebo with caffeine (standardized mean difference −0.12; 95% CI −0.44 to 0.20; p = 0.45; I2 = 0%). (4) Conclusion: overall, the totality of the evidence suggests no significant benefit of caffeine over placebo in the treatment of children with ADHD.
The COVID-19 pandemic has had a heavy impact on daily life, leading to physical and psychosocial consequences. Nowadays, clinicians and health researchers are particularly interested in describing ...and facing the long-term effects of COVID-19, also known as "long-COVID syndrome". Pandemic fatigue has been defined as a cluster of demotivation, tiredness, and psychological effects that emerge gradually over time after the infection or through the adoption of the recommended measures to combat it. In this study, we report the findings of a large survey conducted in South America involving 1448 participants (mean age: 33.9 ± 11.2 years old) from Argentina, Bolivia, Uruguay, Peru, and Paraguay. An online survey was launched through the common social media based on a specific assessment aimed to detect the prevalence of pandemic fatigue and associated factors. Socio-demographic characteristics, medical, and personal information were collected; the Pandemic Fatigue Scale (PFS) and the Coronavirus Anxiety Scale (CAS) were also administered. We found mid-levels of pandemic fatigue among respondents (21.7 ± 7.95 score at PFS) as well as significant anxiety related to the COVID-19 pandemic (1.56 ± 2.76 score at CAS). In addition, pandemic fatigue was significantly associated with the experience of the loss of a relative/friend due to COVID-19, anxiety related to the infection, and reliance on social media as a primary source of information on the pandemic. Vaccination significantly reduced the levels of fatigue among respondents. Our findings may add to the international debate regarding the long-term health consequences of the COVID-19 pandemic and strategies to manage them in the general population of South America.
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