Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan

The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient’s disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts’ opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2–3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3–4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence.

Perbandingan Interval Training dan Circuit Training terhadap Peningkatan Daya Tahan Anaerobik SSB Putra Mororejo U-16

The purpose of this study was to determine the effect of interval training and circuit training on the anaerobic endurance of soccer players on the SSB Putra Mororejo U-16 team. The method in this research is an experimental research design with a Quasi Experiment Design with a pretest-posttest control group design. The instrument used to measure anaerobic endurance is the Running-based Anaerobic Sprint Test (RAST). The sample of this study was 20 players of SSB Putra Mororejo who were divided into two groups, namely the interval training group and the circuit training group. The results of the paired sample t-test concluded that there was an effect of treatment interval training and circuit training on anaerobic endurance. In the independent sample t test, interval training was more effective in increasing anaerobic endurance than circuit training. This is evidenced by the data obtained that the increase in interval training has a percentage increase of 40.96% and circuit training has an increased percentage of 24.96%. Based on the results of the study, it can be concluded that interval training is more effective than circuit training in an effort to increase anaerobic endurance. Keywords: interval training, circuit training, anaerobic endurance. Abstrak Tujuan penelitian ini adalah untuk mengetahui pengaruh interval training dan circuit training terhadap daya tahan anaerobik pemain sepak bola pada tim SSB Putra Mororejo U-16. Metode dalam penelitian ini adalah eksperimen dengan desain penelitian Quasi Eksperimen Design dengan pretest-posttest control group design. Instrument yang digunakan untuk mengukur daya tahan anaerobik adalah Running-based Anaerobic Sprint Test (RAST). Sampel dari penelitian ini adalah 20 pemain SSB Putra Mororejo yang dibagi dalam dua kelompok yaitu kelompok interval training dan circuit training. Hasil uji paired sample t-test disimpulkan bahwa ada pengaruh treatment interval training dan circuit training terhadap daya tahan anaerobik. Pada uji independent sample t test, interval training lebih efektif dalam upaya peningkatan daya tahan anaerobik daripada circuit training. Hal itu dibuktikan dengan diperolehnya data peningkatan interval training memiliki presentase peningkatan sebesar 40,96% dan circuit training memiliki peningkatan presentase sebesar 24,96%. Berdasarkan hasil penelitian dapat disimpulkan bahwa interval training lebih efektif dibandingkan circuit training dalam upaya peningkatan daya tahan anaerobik.

Vitreous Noise on Optical Coherence Tomography as an Early Finding of Brolucizumab-Related Intraocular Inflammation

We describe a case of brolucizumab-related intraocular inflammation (IOI) detected using vitreous haze on optical coherence tomography (OCT) at an early stage before the patient was aware of any symptom. A 69-year-old female presented with decreased right vision. The patient was diagnosed with pachychoroidal neovasculopathy and started intravitreal aflibercept (IVA) with a 3+ treat-and-extend strategy (TAE). Although the serous retinal detachment (SRD) disappeared after IVA treatment, the patient was managed with treatment every 4 weeks without extending the treatment interval To shorten the treatment interval, intravitreal brolucizumab (IVBr) was started 44 weeks after starting IVA treatment. After initiating IVBr treatment, the SRD completely disappeared. However, 16 weeks after starting IVBr, OCT showed noise in the vitreous cavity, which had not been seen before, and infrared images showed a black smoke-like shadow over the macula. Despite these findings, the patient had no subjective symptoms, and so IVBr was re-administered with an 8-week TAE interval. Five days after IVBr treatment, vitreous inflammatory cells were observed, and the noise in the vitreous cavity and the smoke-like shadow in the infrared image were further enhanced. We diagnosed the patient with brolucizumab-related IOI, and anti-inflammatory treatment was initiated. After extensive treatment, the vitreous opacity gradually disappeared, and the vitreous noise on OCT and the black smoke-like shadow on infrared images disappeared. IOI may have already been present 16 weeks after starting IVBr treatment, when we judged that there was no inflammation and IVBr was re-administered. When following patients receiving IVBr, IOI may be detected by OCT at an earlier stage by evaluating vitreous haze.

Concurrent Chemoradiotherapy Induces Body Composition Changes in Locally Advanced Head and Neck Squamous Cell Carcinoma: Comparison between Oral Cavity and Non-Oral Cavity Cancer

Few prospective cohort trials have evaluated the difference in treatment-interval total body composition (TBC) changes assessed by dual-energy X-ray absorptiometry (DXA) between two patient subgroups with locally advanced head and neck squamous cell carcinoma (LAHNSCC) receiving concurrent chemoradiotherapy (CCRT): oral cavity cancer with adjuvant CCRT (OCC) and non-oral cavity with primary CCRT (NOCC). This study prospectively recruited patients with LAHNSCC. Clinicopathological variables, blood nutritional/inflammatory markers, CCRT-related factors, and TBC data assessed by DXA before and after treatment were collected. Multivariate linear regression analysis identified the factors associated with treatment-interval changes in body composition parameters, including lean body mass (LBM), total fat mass (TFM), and bone mineral content (BMC). A total of 127 patients (OCC (n = 69) and NOCC (n = 58)) were eligible. Body composition parameters were progressively lost during CCRT in both subgroups. Extremities lost more muscle mass than the trunk for LBM, whereas the trunk lost more fat mass than the extremities for TFM. BMC loss preferentially occurred in the trunk region. Different factors were independently correlated with the interval changes of each body composition parameter for both OCC and NOCC subgroups, particularly mean daily calorie intake for LBM and TFM loss, and total lymphocyte count for BMC loss. In conclusion, treatment-interval TBC changes and related contributing factors differ between the OCC and NOCC subgroups.

Managing Resistance to Diamide Insecticides in Florida Tomato

This publication discusses optimal placement of diamide insecticides in the context of season-long insecticide rotations for management of pests of tomato. It describes the treatment interval approach to managing insecticide resistance.

The Association Between Treatment Interval and Survival in Patients With Colon or Rectal Cancer: A Systematic Review

Background Surgery for colon or rectal cancer is associated with a high incidence of complications, especially in patients with a low aerobic fitness. Those patients might benefit from a comprehensive preoperative workup including prehabilitation. However, time between diagnosis and treatment is often limited due to current treatment guidelines. To date, it is unclear whether the treatment interval can be extended without compromising survival. Methods A systematic review concerning the association between treatment intervals and survival in patients who underwent elective curative surgery for colon or rectal cancer was performed. A search up to December 2020 was conducted in PubMed, Cinahl and Embase. Original research articles were eligible. Quality assessment was performed using the Downs and Black checklist. Results Eleven observational studies were included (897 947 patients). In colon cancer, treatment intervals that were statistically significant associated with reduced overall survival or cancer-specific survival ranged between > 30 and > 84 days. In rectal cancer, only one out of four studies showed that treatment intervals > 49 days was associated with reduced cancer-specific survival. Conclusions This systematic review identified that studies investigating the association between treatment intervals and survival are heterogeneous with regard to treatment interval definitions, treatment interval time intervals and used outcome measures. These aspects need standardization before a reliable estimate of an optimal treatment interval can be made. In addition, further research should focus on establishing optimal treatment intervals in patients at high risk for postoperative complications, as particularly these patients might benefit from extended diagnosis to treatment intervals permitting comprehensive preoperative preparation.

Quantification of long-term doxorubicin response dynamics in breast cancer cell lines to direct treatment schedules

While acquired chemoresistance is recognized as a key challenge to treating many types of cancer, the dynamics with which drug sensitivity changes after exposure are poorly characterized. Most chemotherapeutic regimens call for repeated dosing at regular intervals, and if drug sensitivity changes on a similar time scale then the treatment interval could be optimized to improve treatment performance. Theoretical work suggests that such optimal schedules exist, but experimental confirmation has been obstructed by the difficulty of deconvolving the simultaneous processes of death, adaptation, and regrowth taking place in cancer cell populations. Here we present work characterizing dynamic changes in sensitivity to the chemotherapeutic doxorubicin in three breast cancer cell lines subjected to treatment schedules varying in concentration, interval between pulse treatments, and number of sequential pulse treatments. Cell populations are monitored longitudinally through automated imaging for 600-800 hours, and this data is used to calibrate a family of cancer growth models derived from the bi-exponential model which characterizes resistant and sensitive subpopulations. We identify a model incorporating both a period of growth arrest in surviving cells and a delay in the death of chemosensitive cells which outperforms the original bi-exponential growth model in Akaike Information Criterion based model selection, and use the calibrated model to quantify the performance of each drug schedule. We find that the inter-treatment interval is a key variable in determining the performance of sequential dosing schedules and identify an optimal retreatment time for each cell line which extends regrowth time by 40%-106%, demonstrating that the time scale of changes in chemosensitivity following doxorubicin exposure allows optimization of drug scheduling by varying this inter-treatment interval.