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BACKGROUND: Social media platforms are increasingly being used by stakeholders to generate, access, and share health-related information and experiences. Lung cancer is the most common cancer, impacting > 2 million patients globally. This observational study utilized a social listening approach to analyze social media trends and gain insights into stakeholder perceptions of lung cancer. METHODS: This social media study retrospectively collated data from open access blogs, forums, and social networking sites. Social media posts were collected between June 2019-May 2020 from 14 European countries. Using social media aggregator tools, posts comprising lung cancer and non-small cell lung cancer-specific terms were extracted. Manual and automated relevancy algorithms filtered the extracted information to provide the relevant dataset. This contextualized dataset was further mined to generate the final data for analysis. RESULTS: Of 1360 conversations analyzed, 42% were generated by patients/caregivers and 14% by healthcare professionals (HCPs). A majority of patients were 51-70 years old (approximately 50%) and 91% (n = 500/550) had late-stage cancer. Treatment (35%) and disease awareness (30%) were among the most discussed topic of the patient journey. Although the overall treatment sentiment was neutral, chemotherapy was the treatment type with the highest associated negative sentiment (28%); fewer negative sentiments were associated with immunotherapy (9%) and targeted therapy (2%), due to perceptions of longer survival outcomes and fewer side effects. In conversations that discussed clinical endpoints, "survivability" and "overall survival" (47 and 30%, respectively; n = 539) were most frequently mentioned by stakeholders. HCPs mostly used technical terms, whereas patients and caregivers used colloquial terms such as "getting rid of cancer". Emotional wellness was identified to have a huge impact on quality of life in lung cancer. Delay or treatment cancellations due to COVID-19, lack of effective treatments and funding, and lack of empathy by physicians emerged as the key unmet needs among patients/caregivers. CONCLUSIONS: Social listening proved to be an effective tool to explore stakeholders' perceptions and their key unmet needs, typically not available in published literature or databases, and provides HCPs with valuable insights into the distress, doubts, and needs of lung cancer patients and caregivers.
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COVID-19 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mídias Sociais , Idoso , Carcinoma Pulmonar de Células não Pequenas/terapia , Humanos , Neoplasias Pulmonares/terapia , Pessoa de Meia-Idade , Qualidade de Vida , Estudos RetrospectivosRESUMO
INTRODUCTION: Anti-vascular endothelial growth factors (anti-VEGFs) are considered standard of care therapy for diabetic macular oedema (DME). This study examined treatment patterns and outcomes in patients with DME treated with anti-VEGF therapy. METHODS: Using anonymized electronic medical record data collected from three UK sites, this retrospective cohort study assessed rates of anti-VEGF intravitreal injections in adults with treatment-naïve DME who received their first treatment between 1 September 2010 and 31 July 2018. The proportion of patients with at least one interval of at least 12 weeks between injections; the distribution of injection intervals; the discontinuation rates; and the number of anti-VEGF injection-, injection-free- and total visits were assessed during the first and second years of treatment. RESULTS: Overall, 1606 patient eyes with DME were included, with no minimum follow-up. During the first and second year of treatment, 63.2% and 73.1% of eyes had at least one anti-VEGF injection interval of at least 12 weeks, respectively. In the first and second years of treatment, the mean (standard deviation) numbers of injections were 7.7 (1.9) and 5.6 (2.2), with 14.2 (5.7) and 13.4 (6.4) total clinic visits, and 6.6 (5.0) and 7.8 (5.8) injection-free visits, respectively. In total, 27.8% of patient eyes discontinued treatment during the first 2 years. CONCLUSIONS: The high number of clinic visits and high discontinuation rates demonstrate a significant unmet need for a treatment to enable sustainable extended injection intervals, while maintaining visual acuity. This could improve patient adherence and health-related quality of life for patients with DME.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Adulto , Inibidores da Angiogênese/uso terapêutico , Retinopatia Diabética/complicações , Retinopatia Diabética/tratamento farmacológico , Humanos , Edema Macular/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer. METHODS: Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15-3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated. RESULTS: Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 µg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90%. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 µg/ml, with 62.7% sensitivity and 91.1% specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively). CONCLUSIONS: Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.
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Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Fibronectinas/sangue , Adiponectina/sangue , Adulto , Idoso , Índice de Massa Corporal , Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Leptina/sangue , Modelos Logísticos , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Examine the efficacy of a competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate receptor antagonist, selurampanel (BGG492), in the human photostimulation model. METHODS: Patients with epilepsy and a generalized epileptiform electroencephalography response to intermittent photic stimulation (photoparoxysmal response or PPR; diagnosed ≥ 6 months prior to initial study dosing) were enrolled in a phase II, multicenter, single-blind, within-subject, placebo-controlled proof-of-concept (PoC) study. PPR was used as a biomarker to assess the efficacy and safety of BGG492 in three cohorts (cohorts I-III received BGG492 50, 100, and 15 mg, respectively). Primary endpoints were to evaluate the efficacy of single oral BGG492 doses in abolishment of PPR or a relevant reduction of the standardized photoparoxysmal response (SPR), and to evaluate time of onset and duration of response. Secondary endpoints were to evaluate maximal SPR reduction, determine the pharmacokinetic profile of BGG492, explore the pharmacokinetic/pharmacodynamic relationship, and evaluate the safety and tolerability of BGG492. RESULTS: Ten patients were enrolled, with three participating twice, that is, in two cohorts (n = 13). Treatment with BGG492 resulted in abolition of PPR in seven of 13 patients in a dose-dependent manner: three, three, and one patient in cohorts I-III, respectively. All patients showed treatment-related reductions of SPR range of at least three steps in at least one eye condition (eye closure, eyes closed, or eyes open). Generally, onset of the suppressive effect appeared to be within 1-2 h post-BGG492 dose and continued in three patients at the 50- and 100-mg doses for 29-33 h. Most common adverse events across the BGG492-treated groups were headache and nasopharyngitis (three patients each), followed by dizziness, fatigue, and diarrhea (two patients each). SIGNIFICANCE: The dose-dependent positive effect of BGG492 on the PPR and SPR in patients with photosensitive epilepsy in this proof-of-concept study supports further investigation of AMPA receptor antagonists in large-scale phase III trials.
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Anticonvulsivantes/uso terapêutico , Epilepsia Reflexa/tratamento farmacológico , Estimulação Luminosa/efeitos adversos , Quinazolinonas/uso terapêutico , Adolescente , Adulto , Idoso , Anticonvulsivantes/farmacocinética , Área Sob a Curva , Estudos de Coortes , Relação Dose-Resposta a Droga , Eletroencefalografia , Epilepsia Reflexa/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Quinazolinonas/farmacocinética , Método Simples-Cego , Adulto JovemRESUMO
BACKGROUND: Graft-versus-host disease (GVHD) is the major cause of short- and long-term morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Treatment options beyond corticosteroid therapy remain limited, and prolonged treatment often leads to impaired quality of life (QoL). A better understanding of the needs and experiences of patients with GVHD is required to improve patient care. OBJECTIVE: The aim of this study is to explore different social media (SM) channels for gathering and analyzing the needs and experiences of patients and other stakeholders across 14 European countries. METHODS: We conducted a retrospective analysis of SM data from the public domain. The Talkwalker social analytics tool collected data from open-access forums, blogs, and various social networking sites using predefined search strings. The raw data set derived from the aggregator tool was automatically screened for the relevancy of posts, generating the curated data set that was manually reviewed to identify posts that fell within the predefined inclusion and exclusion criteria. This final data set was then used for the deep-dive analysis. RESULTS: A total of 9016 posts relating to GVHD were identified between April 2019 and April 2021. Deduplication and relevancy checks resulted in 325 insightful posts, with Twitter contributing 250 (77%) posts; blogs, 49 (15%) posts; forums, 13 (4%) posts; Facebook, 7 (2%) posts; and Instagram and YouTube, 4 (1%) posts. Patients with GVHD were the primary stakeholders, contributing 63% of all SM posts. In 234 posts, treatment was the most discussed stage of the patient journey (68%), followed by symptoms (33%), and diagnosis and tests (21%). Among treatment-related posts (n=159), steroid therapy was most frequently reported (54/159, 34%). Posts relating to treatment features (n=110) identified efficacy (45/110, 41%), side effects (38/110, 35%), and frequency and dosage (32/110, 29%), as the most frequently discussed features. Symptoms associated with GVHD were described in 24% (77/325) of posts, including skin-related conditions (49/77, 64%), dry eyes or vision change (13/77, 17%), pain and cramps (16/77, 21%), and fatigue or muscle weakness (12/77, 16%). The impacts of GVHD on QoL were discussed in 51% (165/325) of all posts, with the emotional, physical and functional, social, and financial impacts mentioned in 69% (114/165), 50% (82/165), 5% (8/165), and 2% (3/165) of these posts, respectively. Unmet needs were reported by patients or caregivers in 24% (77/325) of analyzed conversations, with treatment-related side effects being the most common (35/77, 45%) among these posts. CONCLUSIONS: SM listening is a useful tool to identify medical needs. Treatment of GVHD, including treatment-related side effects, as well as its emotional and physical impact on QoL, are the major topics that GVHD stakeholders mention on SM. We encourage a structured discussion of these topics in interactions between health care providers and patients with GVHD. TRIAL REGISTRATION: Not applicable.
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OBJECTIVE: To evaluate treatment patterns and outcomes of patients in the United States who received antivascular endothelial growth factor (anti-VEGF) agents for wet age-related macular degeneration (AMD). DESIGN: Retrospective study PARTICIPANTS: Patients with wet AMD. METHODS: Using the Intelligent Research in Sight Registry, we studied patients with wet AMD who received ≥1 anti-VEGF injection, who were ≥50 years old, and with ≥1.5 years of follow-up. Patients were grouped based on follow-up duration (in years): ≥1.5 (cohort 1), ≥2.5 (cohort 2), and ≥3.5 (cohort 3). RESULTS: Patient characteristics were similar between treatment groups. 36.8%, 34.5%, and 39.2% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had an injection interval <8 weeks in length at the end of year 1. Results were similar at year 2 and 3. In cohorts 1-3, visual acuity (VA) changes from baseline ranged from 0.3 to 0.7 (year 1), -1.3 to -1.7 (year 2), and -2.8 to -3.1 (year 3) Early Treatment Diabetic Retinopathy Study letters. By the end of year 3, 41%, 39%, and 42% of ranibizumab, aflibercept, and all anti-VEGF eyes, respectively, had discontinued treatment (no injection for >6 months). CONCLUSION: Approximately one-third of eyes had injection intervals <8 weeks in length at the end of year 1. VA was slightly better at the end of year 1 and declined after the first year despite treatment. By the end of year 3, more than one-third of eyes had discontinued treatment. Given the high treatment burden, wet AMD patients may benefit from more durable approaches that require less frequent dosing.
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Ranibizumab , Degeneração Macular Exsudativa , Humanos , Pessoa de Meia-Idade , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Fatores de Crescimento Endotelial/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Estudos Retrospectivos , Injeções Intravítreas , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular , Sistema de Registros , Proteínas Recombinantes de FusãoRESUMO
Deregulation of the endothelin system, comprised of endothelin-1 (ET-1), its isoforms (ET-2 and ET-3) and their receptors (ET(A)R and ET(B)R), is under investigation in various types of human cancer. ET-1 has been suggested to participate in breast cancer development and progression, while Big ET-1, its biological precursor, has also been found elevated in breast cancer patients. In the present study, we investigated plasma ET-1 and Big ET-1 levels in patients with suspicious mammographic lesions, in order to assess their potential application as diagnostic biomarkers in the early estimation of breast disease. The study consisted of 94 patients (Group A to 30 patients with invasive ductal carcinoma: Group B, 30 with ductal carcinoma in situ; and group C, 34 with papilloma or ductal hyperplasia), who underwent an image-guided vacuum-assisted breast biopsy, and 30 healthy controls (group D). ET-1 and Big ET-1 plasma levels were measured with enzyme-linked immunosorbent assay. ET-1 levels did not exhibit significant differences between patients and healthy controls (Group A to 0.92 fmol/mL; Group B: 0.90 fmol/mL; Group C: 0.66 fmol/mL; and Group D: 0.86 fmol/mL). In contrast, Big ET-1 levels were significantly higher in patients with invasive or in situ carcinoma compared to healthy controls (Group A: 0.69 fmol/mL; Group B, 0.62 fmol/mL; and group D: 0.39 fmol/mL; p < 0.001 and p < 0.01). Plasma Big ET-1 may provide a useful tool for the early detection of invasive or noninvasive ductal breast cancer. The utilization of such a diagnostic tool would greatly assist in the modern management of breast cancer.
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Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Endotelina-1/sangue , Precursores de Proteínas/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/sangue , Carcinoma Intraductal não Infiltrante/diagnóstico , Detecção Precoce de Câncer , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e EspecificidadeRESUMO
This review examined patterns of systemic anticancer treatment in patients with HR+ /HER2- metastatic breast cancer in real-world clinical practice in Europe since 2016 to assess whether they reflect clinical guidelines and recent changes in available treatment options. We identified 30 publications for inclusion. In studies evaluating patients up to the end of 2017, endocrine therapy predominated, with endocrine monotherapy typically used in 45-65 % of patients. More recent studies suggested that use of cyclin-dependent kinase 4/6 inhibitor therapy has gained ground since European approval in late 2016, with two studies reporting first-line use in over 55 % of patients. Chemotherapy was typically used first line in 25-45 % of patients, although current guidelines recommend endocrine therapy in the absence of a visceral crisis. In conclusion, our review suggests that the most recent treatment developments for patients with HR+ /HER2 - metastatic breast cancer are being reflected in the changing treatment patterns seen in real-world practice.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptor ErbB-2 , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Europa (Continente)RESUMO
Background: Despite a wealth of real-world data on metastatic breast cancer (mBC), insights into the lived experience are lacking. This study aimed to explore how the lived experience of mBC is described on social media. Methods: A predefined search string identified posts relevant to the lived experience of mBC from Twitter, patient forums, and blogs across 14 European countries. The final data set was analyzed using content analysis. Results: A total of 76,456 conversations were identified between November 1, 2018, and November 30, 2020. Twitter was the most commonly used social media platform across all 76,456 conversations from the raw data set (n = 61,165; 80%). Automated and manual relevancy checks followed by a final random sampling filter identified 820 conversations for content analysis. The majority of data from the raw data set was generated from the United Kingdom (n = 31,346; 41%). From this final data set, 61% of posts were authored by patients, 15% by friends and/or family members of patients, and 14% by caregivers. A total of 686 conversations described the patient journey (n = 686/820; 84%); 64% of these (n = 439) concerned breast cancer treatment, with approximately 40% of discussions regarding diagnosis and tests (n = 274/686) and less than 20% of discussions surrounding disease management (n = 123/686; 18%). Key themes relating to a lack of effective treatment, prolonged survival and associated quality of life, debilitating consequences of side effects, and the social impacts of living with mBC were identified. Conclusions: The findings from this study provided an insight into the lived experience of mBC. While retrospective data collection inherently limits the amount of demographic or clinical information that can be obtained from the population sample, social media listening studies offer training to healthcare professionals in communication, the importance of quality of life, organization of healthcare, and even the design of clinical trials. As new targeted therapies are gradually incorporated into clinical practice, innovative technologies, such as social media listening, have the potential to support regulatory procedures and drug toxicity monitoring, as well as provide the patient voice in the regulation of new and existing medicines.
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BACKGROUND: Cutaneous melanoma is an aggressive malignancy that is proposed to account for 90% of skin cancer-related mortality. Individuals with melanoma experience both physical and psychological impacts associated with their diagnosis and treatment. Health-related information is being increasingly accessed and shared by stakeholders on social media platforms. OBJECTIVE: This study aimed to assess how individuals living with melanoma across 14 European countries use social media to discuss their needs and provide their perceptions of the disease. METHODS: Social media sources including Twitter, forums, and blogs were searched using predefined search strings of keywords relating to melanoma. Manual and automated relevancy approaches filtered the extracted data for content that provided patient-centric insights. This contextualized data was then mined for insightful concepts around the symptoms, diagnosis, treatment, impacts, and lived experiences of melanoma. RESULTS: A total of 182,400 posts related to melanoma were identified between November 2018 and November 2020. Following exclusion of irrelevant posts and using random sampling methodology, 864 posts were identified as relevant to the study objectives. Of the social media channels included, Twitter was the most commonly used, followed by forums and blogs. Most posts originated from the United Kingdom (n=328, 38%) and Spain (n=138, 16%). Of the relevant posts, 62% (n=536) were categorized as originating from individuals with melanoma. The most frequently discussed melanoma-related topics were treatment (436/792, 55%), diagnosis and tests (261/792, 33%), and remission (190/792, 24%). The majority of treatment discussions were about surgery (292/436, 67%), followed by immunotherapy (52/436, 12%). In total, 255 posts discussed the impacts of melanoma, which included emotional burden (n=179, 70%), physical impacts (n=61, 24%), effects on social life (n=43, 17%), and financial impacts (n=10, 4%). CONCLUSIONS: Findings from this study highlight how melanoma stakeholders discuss key concepts associated with the condition on social media, adding to the conceptual model of the patient journey. This social media listening approach is a powerful tool for exploring melanoma stakeholder perspectives, providing insights that can be used to corroborate existing data and inform future studies.
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PURPOSE: The effectiveness of intravitreal anti-vascular endothelial growth factor agents is usually lower in real world settings compared with randomized clinical trials (RCTs), often limiting the use of real-world evidence (RWE) in regulatory and healthcare decisions. The current analysis aimed to develop and validate an algorithm to explain the difference in outcomes between RWE studies and RCTs in patients with neovascular age-related macular degeneration. METHODS: The algorithm was developed using ranibizumab real world data (RWD) from the US and validated on Australian and UK RWD. A decision model was developed using machine learning principles, in which the model learns how to partition the most influential factors (out of 59 variables) so that they maximally relate to the change in visual acuity (VA) over 12 months. RESULTS: The algorithm identified baseline VA <73 Early Treatment Diabetic Retinopathy Study letters, presence of baseline subretinal fluid, and administration of three loading doses by Day 90 from drug initiation as the characteristics with the greatest impact on VA at month 12. When applying the different criteria, RWE outcomes became similar to those obtained in known RCTs. CONCLUSION: Machine learning techniques can be used to classify real world cohorts and identify subsets of patients who benefit to the same extent as that reported in RCTs. This methodology may support the translation of clinical trial findings to treatment performance in the clinical practice setting.
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Inibidores da Angiogênese , Degeneração Macular , Austrália , Seguimentos , Humanos , Injeções Intravítreas , Aprendizado de Máquina , Degeneração Macular/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/uso terapêuticoRESUMO
OBJECTIVES: To study the effect of repeated retinal thickness fluctuations during the anti-VEGF therapy maintenance phase in neovascular age-related macular degeneration (nAMD). METHODS: Data were extracted from electronic medical records of 381 nAMD patients, aged ≥50 years; baseline VA ≥33 and ≤73 letters; ≥24 months' follow-up and ≥2 optical coherence tomography (OCT) measurements. OCT scans were analysed using an artificial intelligence algorithm that quantified the volumes of intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachments (PED) and central subfield thickness (CSFT). IRF, SRF and PED were summed to obtain total fluid (TF). The standard deviation (SD) of IRF, SRF, PED, CSFT and TF was computed and categorised into quartiles (SD-Q). Relationships between SD-Qs for each OCT feature and VA change was tested using generalised estimating equations and linear regression. RESULTS: By Month 24, compared to SD-Q1, eyes in SD-Q2, SD-Q3, and SD-Q4 for IRF, SRF, PED, CSFT and TF showed greater VA losses. Eyes in SD-Q4 of TF were 9.4 letters worse compared to eyes in Q1 (95% Confidence Interval: -12.9 to -6.0). The frequency of clinic visits with IRF and SRF present on OCT scans by quartiles of CSFT was lower in eyes with least fluctuation (Q1) compared to eyes with the most fluid fluctuation (Q4) (median [IQR] IRF: 0.3 [0.0-0.7] versus 0.8 [0.5-1.0]; SRF: 0.0 [0.0-0.5] versus 0.6 [0.3-1.0]). CONCLUSIONS: Greater fluctuations in retinal fluid volumes during the maintenance phase of anti-VEGF treatment in nAMD is associated with worse VA by 2 years.
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Inteligência Artificial , Degeneração Macular Exsudativa , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Humanos , Injeções Intravítreas , Ranibizumab/uso terapêutico , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológicoRESUMO
PURPOSE: Characterize real-world baseline visual acuity (VA) and anti-vascular endothelial growth factor (VEGF) treatment patterns in neovascular age-related macular degeneration patients in 2012-2015. DESIGN: Retrospective, multicenter, noninterventional real-world evidence study. PARTICIPANTS: A total of 98 821 eyes from 79 885 patients receiving intravitreal anti-VEGF therapy. METHODS: Anonymized patient data routinely collected over 5 years were extracted from 58 United States centers to a central database using an electronic medical records system. MAIN OUTCOME MEASURES: Baseline VA, VA change from baseline, treatment frequencies, annual anti-VEGF injections, bilateral treatment frequencies, annual total clinic visits, and noninjection clinic visits. RESULTS: Baseline characteristics were comparable across years. Baseline VAs (Mean±standard deviation [SD] Early Treatment Diabetic Retinopathy Study [ETDRS] letters) were similar for 2012, 2013, and 2014 (53.6±23.3, 53.2±23.4, and 53.1±23.6, respectively), but was lower for 2015 (50.7±24.4). In eyes with 4-year follow-up, VA changes from baseline (ETDRS letters) were least squares means of +1.1 (95% confidence interval [CI], 1.0;1.3), -1.3 (95%CI, -1.5;-1.0), and -3.1 (95%CI, -3.5;-2.7), and -5.2 (95%CI, -6.0;-4.3) for years 1-4. Mean±SD number of injections was 7.5±1.9, 6.7±2.1, 6.6±2.3, and 6.4±2.3 for years 1-4. By year 4, 36.7% of eyes had ≤8-week dosing intervals (q8w) and 21.2% had ≥12-week dosing intervals. Eyes treated q8w increased 40% from Year 1 (32.4%) to Year 4 (45.3%). Baseline bilateral treatment frequency was 6.1%. Of the patients treated bilaterally, 32.0% received the first treatment in the better-seeing eye, and 68.0% received first treatment in an eye with vision the same as or worse than the fellow-eye. This trend was evident across all index years. CONCLUSIONS: This real-world study describes the treatment burden, initiation and monitoring patterns, and VA outcomes at a scale and timeframe that has not been previously reported. In this cohort, baseline VA was similar for the index years 2012-2014, but lower for 2015. In patients with 4-year follow-up, both VA and injection frequency declined, whereas the proportion of eyes treated more frequently than the recommended q8w interval increased. The reduction in dosing intervals may be a consequence of intensification of treatment due to year-on-year VA loss and disease progression.
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Ranibizumab/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/epidemiologiaRESUMO
BACKGROUND/OBJECTIVES: To investigate the association between optical coherence tomography (OCT) markers of lesion activity and changes in visual acuity (VA) during anti-vascular endothelial growth factor (anti-VEGF) therapy of eyes diagnosed with neovascular age-related macular degeneration (nAMD); and how VA and OCT markers are considered in physicians' decision to retreat with anti-VEGFs. SUBJECTS/METHODS: Retrospective, non-comparative, non-randomised cohort study involving electronic medical record data collected from 1190 patient eyes with nAMD diagnosis at two sites in the United Kingdom. Two sub-cohorts consisting of 321 and 301 eyes, respectively, were selected for analyses. RESULTS: In 321 eyes, absence of IRF or SRF at ≥2 clinic visits resulted in a gain of five ETDRS letters from baseline, compared with two letters gained in eyes with <2 clinic visits with absence of IRF (p = 0.006) or SRF (p = 0.042). Anti-VEGF treatment was administered at 421 clinic visits, and 308 visits were without treatment. Comparing treatment visits with non-treatment visits, the maximum difference in frequency of OCT markers of lesion activity were for intraretinal fluid (IRF; 24% versus 5%) and subretinal fluid (SRF; 32% versus 5%). Pigment epithelial detachment (PED) was reported in 58% of treatment visits compared with 36% in non-treatment visits. VA loss was not a consistent trigger for retreatment as it was present in 63% of injection visits and in 49% of non-injection visits. CONCLUSIONS: Retreatment decision making is most strongly influenced by the presence of IRF and SRF and less by the presence of PED or VA loss.
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Degeneração Macular , Ranibizumab , Inibidores da Angiogênese/uso terapêutico , Estudos de Coortes , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Retratamento , Estudos Retrospectivos , Tomografia de Coerência Óptica , Reino Unido , Acuidade VisualRESUMO
AIM: The aim of this study was to evaluate three axes: the sympathetic system (adrenaline and noradrenaline), surgical stress-related endocrine factors (prolactin, cortisol, insulin, glucose and growth hormone) and inflammatory cytokines (IL-1alpha, IL-1beta and IL-6) during excisional breast biopsy under local anesthesia (EBBLA). PATIENTS AND METHODS: On 14 women undergoing EBBLA, all the aforementioned molecules were measured in peripheral venous blood samples prior (baseline), during (at 10 and 30 minutes), at the end of EBBLA (46+/-9 minutes) and one hour after its end. RESULTS: Serum growth hormone glucose and cortisol were found elevated at the 10th and 30th minute and at the end of EBBLA. Serum prolactin increased only at the 30th minute. Of notice, none of the measured parameters was found elevated one hour after the end of biopsy. Concerning adrenaline, noradrenaline and interleukins, no significant changes were documented. CONCLUSION: During EBBLA, significant stress-related endocrine events arise. However, no significant sympathetic / cytokine triggering was noted.
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Anestesia Local , Biópsia/psicologia , Doenças Mamárias/patologia , Sistema Imunitário/metabolismo , Sistemas Neurossecretores/metabolismo , Estresse Psicológico/metabolismo , Adulto , Doenças Mamárias/psicologia , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Hidrocortisona/sangue , Sistema Imunitário/imunologia , Insulina/sangue , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Pessoa de Meia-Idade , Sistemas Neurossecretores/imunologia , Prolactina/sangue , Estresse Psicológico/imunologiaRESUMO
Treat and extend (T&E) is a standard treatment regimen for treating neovascular age-related macular degeneration (nAMD) with anti-vascular endothelial growth factors (anti-VEGFs), but the treatment intervals attained are not well documented. This retrospective, non-comparative, non-randomised study of eyes with nAMD classified treatment interval sequences in a T&E cohort in Australia using Electronic Medical Records (EMR) data. We analysed data from 632 treatment-naïve eyes from 555 patients injected with ranibizumab, aflibercept or unlicensed bevacizumab between January 2012 and June 2016 (mean baseline age 78.0). Eyes were categorised into non-overlapping clusters of interval sequences based on the first 12 months of follow-up. We identified 523 different treatment interval sequences. The largest cluster of 197 (31.5%) eyes attained an 8-week treatment interval before dropping to a shorter frequency, followed by 168 (26.8%) eyes that did not reach or attained a single 8-week interval at the end of the study period. A total of 65 (10.4%) and 83 (13.3%) eyes reached and sustained (≥2 consecutive injection intervals of the same length) an 8 and 12 weekly interval, respectively. This study demonstrates highly individualised treatment patterns in the first year of anti-VEGF therapy in Australia using T&E regimens, with the majority of patients requiring more frequent injections than once every 8 weeks.
RESUMO
PURPOSE: To assess the long-term comparative effectiveness of ranibizumab versus switching to aflibercept in neovascular age-related macular degeneration (nAMD). DESIGN: A 24-month, retrospective, comparative, nonrandomized, matched cohort study. PARTICIPANTS: Patients with nAMD initiated on ranibizumab who remained (nonswitchers) or who switched to aflibercept (switchers) captured from a United States electronic medical records database between July 1, 2011 and October 12, 2014. METHODS: Patient eyes were matched for baseline age, baseline visual acuity (VA), VA at month 3, and duration of follow-up. Matching ratio was 1:2 (switchers: nonswitchers) where possible and 1:1 otherwise. MAIN OUTCOME MEASURES: The primary outcome was VA change from baseline (first injection of ranibizumab) to month 24. Secondary end points were standardized area under the curve of VA change; patient eyes (%) gaining or losing ≥5, ≥10, or ≥15 letters, or with VA of >73 letters at month 24; number of injections and monitoring visits; and analysis of preswitch characteristics. RESULTS: A total of 454 switchers and 750 matched nonswitchers were included. The adjusted difference in mean VA change from baseline to month 24 for switchers to nonswitchers was 0.02 letters (95% confidence interval [CI], -1.63 to 1.68). The upper bound 95% CI (1.68) was below the predefined noninferiority margin of 5 letters. Switchers had a significantly higher annualized number of mean total visits compared with nonswitchers (10.0 vs. 9.0 for year 1; 8.7 vs. 7.4 for year 2), a higher number of injection visits (8.4 vs. 6.7 for year 1; 7.0 vs. 5.1 for year 2), but a lower number of monitoring-only visits (1.6 vs. 2.3 for year 1; 1.7 vs. 2.3 for year 2). During the preswitch period, switchers had a higher number of injection visits (7.6 vs. 6.5), fewer monitoring-only visits (1.5 vs. 2.2), and comparable total visits (9.1 vs. 8.7). Visual acuity change from baseline to switch was similar between switchers and nonswitchers (adjusted least squares mean difference, -1.36 letters; 95% CI, -2.76 to 0.05). CONCLUSIONS: Switching patients from ranibizumab to aflibercept resulted in no difference in VA change compared with those maintained on ranibizumab only. The lower retreatment rate in nonswitchers compared with switchers post switch does not support the view of a longer treatment efficacy.
Assuntos
Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Relação Dose-Resposta a Droga , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Degeneração Macular Exsudativa/diagnósticoRESUMO
BACKGROUND: A 6-week, multicenter, randomized, double-blind, parallel-group study was conducted in patients with COPD to compare lung function improvements of tiotropium, 18 microg qd, plus formoterol, 12 microg bid, to salmeterol, 50 microg bid, plus fluticasone, 500 microg bid. METHODS: Following a screening visit, subjects entered a run-in period in which they received regular ipratropium. At randomization, patients were assigned to either tiotropium plus formoterol or salmeterol plus fluticasone. After 6 weeks of treatment, a 12-h lung function profile was obtained. The coprimary end points were FEV(1) area under the curve for the time period 0 to 12 h (AUC(0-12)) and peak FEV(1). RESULTS: A total of 729 patients were screened, and 605 patients were randomized and treated. A total of 592 patients (baseline FEV(1), 1.32 +/- 0.43 L/min [+/-SD]) were included in the analysis. After 6 weeks, the 12-h lung function profiles in the group receiving tiotropium plus formoterol were superior to those in the group receiving salmeterol plus fluticasone (mean difference in FEV(1) AUC(0-12), 78 mL [p = 0.0006]; mean difference in FVC AUC(0-12), 173 mL, p < 0.0001). Also, peak responses were in favor of tiotropium plus formoterol (difference in peak FEV(1), 103 mL [p < 0.0001]; difference in peak FVC, 214 mL [p < 0.0001]), as were FEV(1) and FVC at each individual time point after dose (p < 0.05). Predose FVC was significantly higher with the bronchodilator combination, while predose FEV(1) and rescue medication use did not differ significantly between groups. Both treatments were well tolerated. CONCLUSIONS: Tiotropium plus formoterol was superior in lung function over the day compared to salmeterol plus fluticasone in patients with moderate COPD. Long-term studies in patients with severe COPD are warranted to assess the relative efficacy of different treatment combinations. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00239421.
Assuntos
Albuterol/análogos & derivados , Androstadienos/administração & dosagem , Broncodilatadores/administração & dosagem , Etanolaminas/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Derivados da Escopolamina/administração & dosagem , Idoso , Albuterol/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Fluticasona , Volume Expiratório Forçado , Fumarato de Formoterol , Humanos , Masculino , Pessoa de Meia-Idade , Xinafoato de Salmeterol , Brometo de Tiotrópio , Resultado do TratamentoRESUMO
BACKGROUND: Stereotactic vacuum-assisted breast biopsy (VABB) is used for the assessment of non-palpable mammographic lesions. This study aims to evaluate stress- and anxiety-related endocrine responses during VABB. MATERIALS AND METHODS: VABB (11 G, Fischer's table) was performed on 22 women. Serum adrenaline, noradrenaline, prolactin, cortisol, growth hormone, glucose and insulin were measured prior to, during (at 10 and 30 minutes), at the end of and one hour after VABB. RESULTS: Baseline serum adrenaline and noradrenaline were above the normal range in 14/22 and 13/22 patients, respectively. Baseline serum growth hormone, insulin, prolactin, cortisol were above the normal range in <10% of patients. At all time points, serum prolactin and cortisol exhibited a significant increase from baseline values. Serum noradrenaline and growth hormone were found elevated at the end of and one hour after VABB. CONCLUSION: Immediately before VABB, women are frequently stressed expecting the forthcoming biopsy. The further hormone increase which follows VABB may be attributed to surgical trauma.
Assuntos
Biópsia/métodos , Doenças Mamárias/patologia , Estresse Fisiológico/sangue , Vácuo , Glicemia/análise , Doenças Mamárias/diagnóstico , Epinefrina/sangue , Feminino , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Insulina/sangue , Pessoa de Meia-Idade , Norepinefrina/sangue , Prolactina/sangueRESUMO
PURPOSE: The goal of this study was to investigate the effect of siponimod treatment re-initiation on the initial negative chronotropic effects and cardiac rhythm after variable drug discontinuation periods. METHODS: This partially double-blind, randomized, placebo-controlled study was conducted in healthy subjects. Siponimod doses (0.5-4.0 mg) and placebo were evaluated in combination with drug discontinuation periods ranging from 48 to 192 hours. Twelve-lead Holter ECGs were performed from 1.5 hours before until 24 hours after single-dose re-initiation. Atrioventricular blocks (AVBs) and sinus pauses (RR >2 seconds) were categorized according to dose level, discontinuation period, and resting and nonresting hours. FINDINGS: Of the enrolled 138 subjects, 117 were evaluated. Demographic and baseline characteristics were comparable between the treatment groups. Subjects rechallenged at the combination of 4 mg/192 hours (highest investigated dose and longest discontinuation period [7 missed doses]) exhibited the highest decrease in pooled, placebo-adjusted heart rate (HR) of 14.53 beats/min. The magnitude of the negative chronotropic effect of siponimod re-initiation was dependent on both dose and duration of treatment discontinuation. Regardless of the dose, the placebo-adjusted HR reduction at re-initiation of drug treatment after up to 96 hours of drug discontinuation remained <10 beats/min. Except for 1 outlier for HR decrease under the 96-hour/placebo combination, no outliers were observed for any combination up to and including the 96-hour discontinuation periods. Most of the AVBs and sinus pauses were observed during nocturnal hours concurrent with increased vagal tone. All detected AVBs and sinus pauses were asymptomatic and not considered clinically relevant. IMPLICATIONS: Siponimod could be safely re-initiated without retitration after drug discontinuation periods up to 96 hours. Retitration is required if patients miss ≥ 4 consecutive doses.