Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial
1. A shortened course of oxaliplatin-based adjuvant chemotherapy for stage III colon cancer was associated with decreased peripheral sensory neuropathy without compromising effectiveness.
Evidence Rating Level: 1 (Excellent)
FOLFOX4 regimen, which includes oxaliplatin, has proven efficacy in both the metastatic colorectal cancer setting and the adjuvant setting for resected stage III colon cancers. Peripheral neuropathy is a debilitating associated side effect of oxaliplatin-based chemotherapy. The objective of the ACHIEVE trial was to evaluate the effectiveness and safety of a shortened course of adjuvant oxaliplatin-based chemotherapy in patients with stage III colon cancer. In this open-label multicenter randomized phase III non-inferiority trial based in Japan, 1,313 patients were randomly assigned to receive either 6 months or 3 months of adjuvant chemotherapy with mFOLFOX6 or CAPOX (at physician’s discretion). Treatment regimens were repeated every two weeks for a maximum of 12 or 6 cycles, respectively. The primary efficacy endpoint was disease-free survival, and secondary endpoints included peripheral sensory neuropathy for up to 3 years and overall survival. Of 1,291 treated patients, 969 (75%) of participants received the CAPOX regimen. Researchers found that disease-free survival with 3-month therapy was not significantly different when compared to 6-month therapy (HR 0.95, 95% CI 0.76 to 1.20). The rate of any grade of peripheral neuropathy was 9.7% with 3-month therapy and 24.3% with 6-month therapy (p<0.001), with significantly lower incidences with CAPOX therapy than with mFOLFOX therapy with both durations. The findings of this study therefore indicate that a shorter duration of therapy (3 months) with oxaliplatin-containing chemotherapy may confer significantly lower rates of peripheral sensory neuropathy without compromised effectiveness.
Dual-Energy Computed Tomography Detection of Cardiovascular Monosodium Urate Deposits in Patients With Gout
1. Dual-energy computed tomography identified cardiovascular monosodium urate deposits reliably, with increased frequency of deposits found in patients with gout.
Evidence Rating Level: 2 (Good)
Hyperuricemia has been identified as a cardiovascular risk factor, and previous studies have demonstrated an association between gout and coronary heart disease. As such, there is interest in differentiating cardiovascular monosodium urate deposits from calcium deposits that may have implications in the treatment of patients with gout at risk of cardiovascular disease. To date, direct cardiovascular imaging of monosodium urate deposits using dual energy computed tomography (DECT) has not been reported on. The objective of this study was to evaluate whether DECT detection of cardiovascular monosodium urate deposits can distinguish patients with gout. This diagnostic study included 59 patients with gout and 47 controls (January 2017 to November 2018), all of whom underwent DECT for evaluation of coronary calcium scoring and monosodium urate deposition. Six cadavers were also included, for whom DECT for monosodium urate deposition evaluation was also conducted. The primary outcome was detection rate of cardiovascular (CV) monosodium urate deposits. Overall, 86.4% of patients with gout had CV monosodium urate deposits compared to 14.9% controls. Coronary calcium scoring was also significantly higher in patients with gout (900 Agatston units (AU), 95% CI 589 AU to 1211 AU) compared to controls (263 AU, 95% CI 76 AU to 451 AU) (p=0.001), and higher in patients with CV monosodium urate deposition. The findings of this study therefore suggest that DECT may be used as a modality to detect CV monosodium urate deposits, which are more prevalent in patients with gout, associated with higher coronary calcium scores, and therefore associated with higher CV risk.
Serum neurofilament light chain levels in patients with presymptomatic multiple sclerosis
1. Increased serum neurofilament light chain levels, a biomarker for neuroaxonal damage, may be associated with a prodromal or subclinical phase in the setting of multiple sclerosis (MS).
Evidence Rating Level: 3 (Average)
While most patients affected by multiple sclerosis (MS) experience initial symptoms in early adulthood, there is increasing evidence that the pathophysiologic processes contributing to the disease occur long before diagnosis. Serum neurofilament light chain (sNfL) is a sensitive biomarker for ongoing neuroaxonal degeneration. In this nested case-control study among 120 US military personnel with serum samples stores in the US Department of Defense Serum Repository, researchers compared sNfL levels in 60 cases to matched controls to assess whether sNfL levels are elevated before clinical MS onset. Researchers found that serum NfL levels were higher in case patients with MS compared with matched control samples drawn a median of 6 years (range 4 to 10 years) prior to MS clinical onset (p=0.04). Interestingly, the difference in serum sNFL levels increased as the time to case clinical onset decreased (p=0.008). Researchers also found that in comparing samples from the same case, an increase in presymptomatic sNfL levels was associated with a higher MS risk (RR for ³ 5 pg/mL increase: 7.50, 95% CI 1.72 to 32.80, p=0.007). This study therefore shows that sNfL levels were increased for years prior to the onset of clinical MS, and therefore, MS may have a prodromal phase, characterized by subclinical neuroaxonal damage.
Sacrospinus hysteropexy versus vaginal hysterectomy with uterosacral ligament suspension in women with uterine prolapse stage 2 or higher: observational follow-up of a multicentre randomised trial
1. Sacrospinous hysteropexy for uterine prolapse may be associated with a decreased incidence of anatomical recurrences of the apical compartment and/or bulge symptoms when compared to vaginal hysterectomy.
Evidence Rating Level: 2 (Good)
Worldwide, vaginal hysterectomy is the most common surgical procedure performed in the management of uterine prolapse. Few studies have compared vaginal hysterectomy with uterus-preserving procedures, however. The SAVE U (sacrospinous fixation versus vaginal hysterectomy in treatment of uterine prolapse ³2) randomized trial compared uterus preservation with hysterectomy, and found that sacrospinous hysteropexy was non-inferior to vaginal hysterectomy with suspension of the uterosacral ligaments for surgical failure of the apical compartment at 1 year of follow-up. In this study, 5-year outcomes on recurrent prolapse of the uterus or vaginal vault (apical compartment) in 204 women that underwent sacrospinous hysteropexy of vaginal hysterectomy with suspension of the uterosacral ligaments in the SAVE U trial are reported. Based on an intention-to-treat analysis, researchers found that surgical failure of the apical compartment with bothersome bulge symptoms or repeat surgery occurred in 16% of patients after sacrospinous hysteropexy as compared to 26% of patients after vaginal hysterectomy (difference -9.8%, 95% CI -20.9% to 1.2%). The per-protocol analysis showed that surgical failure in the apical compartment occurred in none of the women that underwent sacrospinous hysteropexy as compared to 5% of women that underwent vaginal hysterectomy (difference -5.1%, 95% CI -10.9% to 0.7%). Neither of these analyses achieved statistical significance. This study therefore shows that sacrospinous hysteropexy may be associated with improved long-term outcomes, with less anatomical recurrences of the apical compartment and/or bulge symptoms.
Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial
1. The use of nicotine e-cigarettes in addition to conventional nicotine patches may result in a modest improvement in smoking cessation when compared to patches alone or patches used in combination with nicotine-free e-cigarettes.
Evidence Rating Level: 2 (Good)
Nicotine replacement therapy (NRT) has been shown to reduce nicotine withdrawal symptoms in individuals trying to quit smoking. While various formulations, such as gum and nicotine patches, are available, the use of these NRT products does not allow for the rapid delivery of nicotine in the high concentrations that cigarette smokers are accustomed to. E-cigarettes, may represent an alternative NRT strategy, enabling users to obtain nicotine rapidly, in high concentrations, comparable to cigarettes. And while previously conducted studies indicate limited efficacy and effectiveness of e-cigarettes with respect to smoking cessation, the current randomized controlled trial aimed to examine whether conventional NRT combined with nicotine e-cigarette use is more effective in smoking cessation than NRT plus a nicotine-free e-cigarette, or conventional NRT alone. As part of the study, 1124 smokers age 18 years or older were randomized to receive nicotine patches only, nicotine patches plus a nicotine e-cigarette, or patches plus a nicotine-free e-cigarette. Participants were subsequently followed up for 6 months after the agreed quit date. Individuals were excluded if they had used an e-cigarette for smoking cessation for more than 1 week any time in the past year, if they were currently using smoking cessation medication, or if they were already enrolled in another smoking cessation program or study. Of note, approximately half of participants in the patches only group either withdrew from the study or were lost to follow-up. 32% and 33% of participants from the patches plus nicotine e-cigarette group and patches plus nicotine-free e-cigarette group withdrew or were lost to follow-up, respectively. Researchers found that a greater proportion of participants in the patches plus nicotine e-cigarette group, 7%, achieved carbon monoxide (CO)-verified continuous abstinence at 6 months of follow-up, when compared to those in the patches plus nicotine-free e-cigarette group (4%) and the patches only group (2%). This was, however, a modest improvement, particularly between the two e-cigarette groups (risk difference, RD 2.99, 95% CI 0.17 to 5.81). Serious adverse events occurred in 4% and 5% of participants in the patches plus nicotine e-cigarette group and patches plus nicotine-free e-cigarette group, respectively. This study therefore shows that the use of nicotine e-cigarettes in addition to conventional NRT patches may result in a modest improvement in smoking cessation when compared to patches alone or patches used in combination with nicotine-free e-cigarettes.
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