Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause
1. In this randomized controlled trial, survivors of breast cancer experienced a significant improvement in sexual function at 6 months follow-up compared to baseline after receiving first-line therapy (FLT) and either sham laser therapy (SLT) or carbon dioxide vaginal laser therapy (CLT)
2. There was no significant difference between the mean improvement of sexual function in survivors of breast cancer when comparing the CLT and SLT groups.
Evidence Rating Level: 1 (Excellent)
Genitourinary syndrome of menopause (GSM) is a persistently underdiagnosed and undertreated syndrome in breast cancer survivors. Symptoms are usually worse among survivors of breast cancer due to the antiestrogenic effects of chemotherapy, tamoxifen, and aromatase inhibitors. Estrogen-based standard treatment for GSM also remains controversial in this subset of patients. Vaginal laser therapy is a trending new therapeutic approach for GSM symptoms, but there is a paucity of high-quality evidence surrounding laser therapy. This study aimed to assess the safety and efficacy of carbon dioxide vaginal laser therapy (CLT) versus sham laser therapy (SLT). This study was a randomized controlled trial with two parallel study groups; both groups received first-line therapy (FLT) based on non-hormonal moisturizes and then were randomized to receive fractional CLT or SLT. Included were survivors of breast cancer aged over thirty years old who received aromatase inhibitors for treatment. The primary outcome measured was sexual function using the Female Sexual Function Index (FSFI). 72 participants were included in the analysis, with 35 participants randomized to CLT and 37 randomized to SLT. With respect to the primary outcome, the FSFI improved from a mean (SD) of 15.2 (7.2) points to 21.8 (8.1) points at the 6-month follow-up (P<.001). In the CLT group, the FSFI improved from 14.8 (8.8) to 20.0 (9.5), and the FSFI in the SLT group improved from 15.6 (7.0) to 23.5 (6.5) points. However, there was no significant difference between the two groups with respect to the change in sexual function as per the FSFI test at 6 months (P=.15). With respect to secondary outcomes, including multiple subjective and objective outcomes, there were no differences between the two groups at 6 month follow up in dyspareunia, Vaginal Health Index, body image, quality of life, vaginal pH, vaginal maturation index, vaginal epithelial thickness, and vaginal epithelial elasticity. Notably, there was a significant difference in tolerance between the CLT and SLT groups, as measured by the Likert scale, with the CLT group being significantly lower than the SLT group (P=.007). Overall, the findings from this study show significant improvements from baseline to 6-month follow-up in both groups, with no significant difference in the mean improvement between the CLT and SLT groups. The results suggest that vaginal laser treatment was not effective and significantly less tolerated than the sham laser treatment. A major limitation of this study is the loss of follow-up and lack of a control group without FLT, as it would have been unethical not to provide FLT to patients presenting with symptomatic GSM. This serves as an important trial adding to the growing body of evidence surrounding laser treatment for GSM in survivors of breast cancer.
Effect of Rivaroxaban vs Enoxaparin on Major Cardiac Adverse Events and Bleeding Risk in the Acute Phase of Acute Coronary Syndrome
1. In this noninferiority trial, rivaroxaban 5 mg was found to be non-inferior with respect to safety and efficacy to enoxaparin 1 mg/kg in patients presenting with acute coronary syndrome (ACS) who missed the primary reperfusion window.
2. Rivaroxaban 2.5 mg was found to be non-inferior to enoxaparin 1 mg/kg in patients presenting with respect to safety in patients presenting with ACS who missed the primary reperfusion window but was not found to be non-inferior with respect to efficacy.
Evidence Rating Level: 2 (Good)
Among patients with ischemic heart disease, patients with acute coronary syndrome (ACS) face the highest risk of death. Primary reperfusion therapy has reduced mortality, but many patients still miss the primary reperfusion window, especially in developing countries. As per current guidelines and clinical practice, enoxaparin is the preferred anticoagulant used in the acute phase of ACS. Recent studies, however, have found that rivaroxaban is non-inferior to enoxaparin in preventing thromboembolism among patients with pulmonary embolism and deep venous thrombosis. The safety and efficacy of short-term low-dose rivaroxaban in the acute phase of ACS is unknown, and this feasibility equivalence and noninferiority trial was designed to obtain data to answer this clinical question. This prospective, multicenter, open-label, active-controlled feasibility equivalence and noninferiority trial provided oral rivaroxaban and subcutaneous enoxaparin to patients with ACS who missed the primary reperfusion window. Eligible participants were randomized in a 1:1:1 ratio to receive 2.5 mg rivaroxaban, 5 mg rivaroxaban, or 1 mg/kg subcutaneous enoxaparin. The primary efficacy endpoint was a composite of major adverse cardiac events (MACE), including cardiac death, myocardial infarction, re-revascularization, or stroke during the 6-month follow-up period. The primary safety endpoint was a composite of major bleeding, clinically relevant non-major bleeding, and minor bleeding events. From January 2017 to November 2020, 2,046 patients were enrolled at 21 study centers across China. 680 patients were randomized to enoxaparin, 683 patients were randomized to rivaroxaban 2.5 mg, and 683 patients were randomized to rivaroxaban 5 mg. With respect to the primary safety endpoint, the noninferiority of rivaroxaban vs enoxaparin was reached after 6 months of follow-up (rivaroxaban 2.5 mg: HR, 0.68; 95% CI, 0.43-1.07; P = .005; rivaroxaban 5 mg: HR, 0.88; 95% CI, 0.70-1.09; P=.001). With respect to efficacy, MACEs were observed in 14 (2.1%) patients in the rivaroxaban 5 mg group, 23 patients (3.4%) in the enoxaparin group, and 16 patients (2.3%) in the rivaroxaban 2.5 mg group. The rivaroxaban 5 mg group reached noninferiority (P=.02) but the rivaroxaban 2.5 mg group did not reach noninferiority (P=.05). Overall, the findings from this study suggest that 5 mg rivaroxaban twice daily in addition to dual antiplatelet therapy (DAPT) in the acute phase of ACS for patients that missed the primary reperfusion window was non-inferior to enoxaparin in terms of bleeding risk and efficacy during 6 months of follow-up. A major limitation of this study was that the entire study population was composed of Chinese patients, and the results may not be as generalizable to other patient populations. This study provides important data and will be useful in the design of future randomized controlled trials studying enoxaparin and rivaroxaban in the acute phase of ACS.
Association of adverse respiratory events with sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors among patients with type 2 diabetes in South Korea: a nationwide cohort study
1. In this retrospective cohort study, patients with Type 2 Diabetes (T2D) using sodium-glucose cotransporter 2 inhibitors (SGLT2is) were found to have a lower incidence of adverse respiratory events than patients using dipeptidyl peptidase-4 inhibitors (DPP4is).
Evidence Rating Level: 2 (Good)
Type 2 Diabetes (T2D) shares a similar pathophysiological background with respiratory disease. Specifically, glucose levels of the airway surface liquid (ASL) influence respiratory dysfunction; low glucose levels in the ASL help prevent pulmonary infections and the exacerbation of respiratory diseases. Antidiabetic drugs reduce glucose levels, and accumulating evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2is) may offer greater benefit with respect to respiratory outcomes. SGLT2is have been found to reduce the risk of respiratory disorders, pneumonia, and respiratory failure versus dipeptidyl peptidase-4 inhibitors (DPP4is). This retrospective cohort study aimed to determine whether the use of SGLT2is is associated with the risk of adverse respiratory events among patients with T2D compared to DPP4is. Data was collected using the Health Insurance Review and Assessment Service (HIRA) database of South Korea. Patients who were newly prescribed an SGLT2i or DPP4i between January 2016 and December 2020 were identified and included in the study. The primary outcome studied was respiratory events, defined as a composite endpoint including acute pulmonary edema, ARDS, pneumonia, and respiratory failure. In total, after propensity score matching, 205,534 patients were included in each treatment group. With respect to the primary outcome, SGLT2i users displayed a lower incidence of adverse respiratory events when compared to DPP4i users (incidence rate 4.54 versus 7.54 events per 1000 person-years; rate difference: − 3.00, 95% CI − 3.44 to − 2.55). SGLT2i users had lower risks of the composite respiratory endpoint (HR 0.60, 95% CI 0.55 to 0.64), as well as acute pulmonary edema, pneumonia, and respiratory failure. The same trends persisted even after subgroup and stratified analyses, in each age, sex, history of asthma, history of COPD, history of CVD, history of CKD, and history of baseline insulin use subgroup. Overall, the findings from this study suggest that among patients with T2D, SGLT2i users had a 40% lower risk of adverse respiratory events than DPP4i users. A major limitation of this study is the homogenous patient population, as the study was completed in South Korea, which may affect the generalizability of the data. However, this study is an important addition to the growing body of evidence surrounding T2D and respiratory events and will guide further research.
Maternal mRNA covid-19 vaccination during pregnancy and delta or omicron infection or hospital admission in infants: test negative design study
1. In this retrospective cohort study, maternal vaccination with an mRNA COVID-19 vaccine series during pregnancy was highly effective against delta and moderately effective against omicron infection in infants younger than six months of age.
2. Maternal vaccination with an mRNA COVID-19 vaccine series during pregnancy was highly effective against delta and moderately effective against omicron infection requiring hospital admission in infants younger than six months of age.
Evidence Rating Level: 2 (Good)
Most cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in infants present with mild or no symptoms, but rates of admission to hospital and severe illness have been higher in infants compared with older children, especially during the first month of life. COVID-19 vaccines are effective against severe infection but are not yet licensed in infants less than 6 months old. Passive immunity for infants through the transfer of maternal antibodies after vaccination is well-established for preventing infections, and emerging evidence suggests that SARS-CoV-2 maternal vaccination may reduce the risk of SARS-CoV-2 infection and hospitalization in infants. This population-based, test-negative design study aims to evaluate the effectiveness of maternal vaccination with the mRNA COVID-19 vaccine series during pregnancy against delta and omicron SARS-CoV-2 infection and hospital admission of infants during their first six months of life. Included were infants under 6 months of age who were born between May 2021 and March 2022 and who were tested for SARS-CoV-2 between May 2021 and September 2022. Data was collected from ICES, an independent, non-profit research institute in Ontario with databases including clinical, laboratory, billing, and sociodemographic data. The primary outcome studied was a positive real-time polymerase chain reaction (PCR) test on a respiratory specimen. In total, 8809 infants met the inclusion criteria, including 99 delta cases compared to 4365 controls, and 1501 omicron cases compared to 4847 controls. Vaccine effectiveness for the primary vaccine series was 95% (95% confidence interval (CI), 88% to 98%) against delta infection and 45% (95% CI, 37% to 53%) against omicron infection. Primary plus booster vaccine effectiveness was 73% (95% CI, 61% to 80%) against omicron infection. In addition, 29 (29%) of 99 infants were admitted to the hospital because of a delta infection, and 330 (22%) of 1501 infants were admitted to the hospital because of an omicron infection. Vaccine effectiveness for the primary vaccine series was 97% (95% CI, 75% to 100%) for the delta variant and 53% (95% CI, 39% to 64%) for the omicron variant against hospital admission. Overall, the findings from this study suggest high vaccine effectiveness for maternal vaccination with the primary mRNA covid-19 vaccine against delta and omicron infections, as well as admission to hospital in infants younger than six months of age. A limitation of this study is the effect of potential confounders, such as breastfeeding, that could have differed between vaccinated and unvaccinated mothers. This study is an important addition to a growing body of evidence surrounding the efficacy of COVID-19 vaccinations, especially in the population of pregnant patients.
Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial
1. In this noninferiority trial, medial retropharyngeal lymph node (MRLN)-sparing radiotherapy was found to be noninferior with respect to local relapse-free survival when compared to standard radiotherapy encompassing all retropharyngeal lymph nodes in patients with non-metastatic nasopharyngeal carcinoma.
Retropharyngeal lymph nodes (RLN) are paired groups of lymph nodes in the suprahyoid portion of the retropharyngeal space and comprise medial (MRLN) and lateral (LRLN) groups. Due to their involvement as first echelon raining nodes for nasopharyngeal carcinoma and high proportion of involvement at initial diagnosis, complete coverage of MRLN and LRLN during radiotherapy has been the standard of care. However, radiation of the MRLN also exposes pharyngeal constrictors to a relatively high dose of radiation, and reports suggest high proportions of late dysphagia and silent aspiration, resulting in poor quality of life. Previous investigations have found that retropharyngeal lymph node involvement mainly occurs in the lateral group, and a retrospective study recently showed that exclusion of the MRLN region from elective radiotherapy still resulted in no recurrence. This noninferiority trial aimed to compare outcomes of MRLN-sparing radiotherapy versus standard radiotherapy (encompassing both MRLN and LRLN regions). Patients were randomly assigned in a 1:1 ratio to receive either MRLN-sparing radiotherapy or standard radiotherapy. The primary outcome investigated was local relapse-free survival. Between November 2017 and December 2018, 568 patients were recruited at three major hospitals in China, with 285 patients randomly assigned to the MRLN-sparing radiotherapy group and 283 patients assigned to the standard radiotherapy group. At the time of analysis, three-year visit forms were available for 540 (95.1%) of the 568 patients. With respect to the primary outcome, local recurrence was recorded for 14 (4.9%) of patients in the MRLN-sparing radiotherapy group versus 12 (4.2%) in the standard radiotherapy group, with a majority o patients developing in-field recurrences. The three-year local relapse-free survival was 95.3% (95% confidence interval, 92.8% to 97.8%) in the MRLN-sparing radiotherapy group and 95.5% (95% CI, 93.0% to 98.0%) for the standard radiotherapy group (estimated absolute difference of -.02%; P<.001). Overall, the findings from this study suggest the non-inferiority of MRLN-sparing radiotherapy in comparison to standard radiotherapy in patients with non-metastatic nasopharyngeal carcinoma with respect to local relapse-free survival. The main limitation of this study was that the nasopharyngeal carcinomas in this population were almost all caused by the Epstein-Barr virus, which may not be generalizable to different patient populations. This study is the first to study the noninferiority of MRLN-sparing radiotherapy compared to standard radiotherapy for nasopharyngeal carcinoma and will serve as a guide for the design of future randomized controlled trials.
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