Topic
Systematic review of risk factors for non-adherence and non-persistence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection therapy for neovascular age-related macular degeneration (nAMD).
Clinical Relevance
Lack of adherence (non-adherence) or under-treatment (non-persistence) with respect to evidence from clinical trials remains a significant barrier to optimizing real-world outcomes for patients with nAMD. Contributing factors and strategies to address this are poorly understood.
Methods
Studies that reported factors for non-adherence and/or non-persistence to anti-VEGF therapy as well as studies examining strategies to improve this were included. Trial eligibility and data extraction were conducted according to Cochrane review methods. Risk of bias was assessed using the Mixed Method Assessment Tool and certainty of evidence evaluated according to the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative Research) tool. Data were collated descriptively.
Results
Of the 1284 abstract results screened, 124 articles were assessed in full and 37 studies met the inclusion criteria. Definitions of non-adherence and non-persistence varied or were not reported. Non-persistence occurred early with up to 50% of patients stopping treatment by 24 months. High rates of non-adherence were similarly reported, occurring in 32 – 95% of patients. Certainty of this finding was downgraded to moderate level due to heterogeneity in definitions used across studies. Multiple factors determine non-adherence and non-persistence, including at condition, therapy, patient, social/economic and health systems/health-care team level. Moderate quality evidence points to lower baseline vision and poorer response to treatment as condition-related variables. The effects of other factors were of lower certainty, predominantly due to small numbers and potential biases in retrospective assessment. Although many factors are non-modifiable (e.g., patient co-morbidity), other factors are potentially correctable (e.g., lack of transport or mismatched patient expectations). Evidence on strategies to improve adherence and persistence is limited, but where available, these have proven effective.
Conclusions
Awareness of factors related to poor patient adherence and persistence in nAMD could help identify at-risk populations and improve real world outcomes. Further work is required to develop uniform definitions as well as establishing high quality evidence on interventions that can be easily implemented.
BackgroundColorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI).ResultsThe final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003).ConclusionThe combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher in those subgroups of patients receiving bolus 5-FU or capecitabine-based chemotherapy plus bevacizumab, when compared to patients treated with infusional %-FU plus bevacizumab (no difference in PFS and OS). Regarding the type of cytotoxic scheme, regimens containing irinotecan and fluoropyrimidine monotherapy showed superior efficacy results when combined to bevacizumab.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2734-y) contains supplementary material, which is available to authorized users.
PAL was more effective than the other 5-HT(3)R in preventing acute and delayed CINV in patients receiving MoHE treatments, regardless of the use of concomitant corticosteroids.
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