1. Starting at an index eGFR of 80 and below, there is an association with adverse outcomes including all-cause mortality, cardiovascular outcomes, and kidney failure, with higher relative hazards in younger adults aged 18-39 years.
Evidence Rating Level: 2 (Good)
Currently, the diagnosis of chronic kidney disease (CKD) depends on the estimated glomerular filtration rate (eGFR) being sufficiently low, less than 60 mL/min/1.73m2. However, eGFR diminishes with age, such that younger individuals will typically have eGFR over 100. It is unclear whether modest decreases in eGFR are associated with morbidity and mortality. Therefore, this retrospective study based in Ontario, Canada examined the correlation between modest eGFR reductions and adverse outcomes in a population based cohort stratified by age. The population included any adult between 18 and 65 years, with one or more serum creatinine lab measurement between 2008 and 2020, with no history of kidney-related disease. The index serum creatinine values were grouped into increments of 10 for the analysis. Reference eGFR values were based on mean values from other population cohort studies: 100-110 for age 18-39 years, 90-100 for 40-49 years, and 80-90 for 50-65 years. The adverse outcomes examined were all-cause mortality, any cardiovascular outcome, or kidney failure (dialysis or kidney transplant). In total, there were 8,703,871 adults in the final cohort, with 3,834,657 aged 18-39 years. The results showed that 18.0% of those aged 18-39 years were below the reference eGFR values, 18.8% for those aged 40-49, and 17.0% for those aged 50-65. For any adverse outcome, the youngest cohort had the highest adjusted hazards ratios and lowest crude incidence rates at each eGFR increment below reference values. Starting at eGFR 80-90, the gap between hazard ratios widened between the youngest and older age groups as eGFR decreased. At a modest eGFR reduction of 70-80, the 18-39 age cohort had a higher hazard ratio of 1.42 (95% CI 1.35-1.49) and lower crude incidence (4.39 events per 1000 person-years), compared to the 40-49 cohort (HR 1.13, 95% CI 1.10-1.16, crude incidence 9.61 per 1000 person-years) and 50-65 cohort (HR 1.08, 95% CI 1.07-1.09, crude incidence 23.4 per 1000 person-years). This pattern was similar when analyzing each of the adverse outcomes individually as well. Therefore, this study demonstrates that modest eGFR reductions at <80 are associated with adverse outcomes, with higher hazards, particularly in the youngest age cohort of 18-39 years.
1. High-definition cathodal direct current stimulation (HD C-tDCS) is a feasible and tolerable treatment for acute ischemic stroke (AIS) patients ineligible for reperfusion treatment.
2. On imaging, patients treated with HD C-tDCS compared to sham had reductions of hypoperfused regions, improved penumbral salvage, and increases in quantified relative cerebral blood volume (qrCBV) early post-stimulation in a dose-response pattern.
Evidence Rating Level: 1 (Excellent)
The treatment for acute ischemic stroke (AIS) consists solely of reperfusion therapies, including IV thrombolysis and endovascular thrombectomy. However, not all patients are eligible candidates for these treatments, and they are not always effective, with only 20-30% remaining disability-free 3 months post-stroke. A proposed alternative treatment is cathodal transcranial direct current stimulation with high-definition electrode montages (HD C-tDCS). This is due to it being regionally directed therapy, in contrast to drug therapies that may have limited tissue delivery in the context of ischemia. There is also evidence from animal studies that C-tDCS salvages tissue at risk of infarction through anti-excitotoxic pathways and vasodilation. Therefore, this first in-human randomized clinical trial examined the feasibility, tolerability, and efficacy of HD C-tDCS on AIS patients ineligible for reperfusion treatment. The study population included 10 patients, within 24 hours of AIS with evidence of salvageable penumbra and cortical ischemia on imaging. There were 7 active and 3 sham patients, with 2 tiers of dose escalation: Tier 1 received 1 milliamp (mA) and tier 2 received 2 mA, both for 20 minutes. The tolerability was assessed by number of patients completing the study and a tolerability questionnaire assessing for pain, neurologic, and cutaneous symptoms. Overall, the study showed that HD C-tDCS is feasible and efficient, with a median (IQR) implementation time of 12.5 (9-15) minutes in the last 4 participants. With regards to tolerability, all patients completed the study, and only 1 patient in tier 1 noted mild skin burning. On exploratory efficacy analysis, there was a median (IQR) reduction of the hypoperfused region by 100% (46-100%) in the active group, compared to 325% (112-412%) in the sham group. As well, there was a penumbral salvage of 66% (29-80.5%) in the active group compared to 0% (0-0%) in the sham. In the early post-stimulation period, the change in quantified relative cerebral blood volume (qrCBV) was 64% (40-110%) in the active group compared to -4% (-7 to 1%) in the sham. Additionally, there was a dose-response effect where the increase in qrCBV was highest in tier 2, then tier 1, then sham. Overall, this study demonstrated that HD C-tDCS is a feasible and tolerable intervention, with potential beneficial effects when examining hypoperfused regions, penumbral salvage, and qrCBV.
1. For Black adults treated for smoking cessation, there were no differences in 7-day abstinence rates at 12, 18, and 26 weeks follow-up, when randomized to a single pharmacotherapy nicotine patch (NP) regimen, compared to a regimen with early opportunities for pharmacotherapy adaptations.
Evidence Rating Level: 1 (Excellent)
Current guidelines for smoking cessation recommend 8-12 weeks of the same pharmacotherapy even if a patient continues to smoke. However, over 2/3 of people who do not achieve abstinence in 4 weeks of pharmacotherapy do not achieve it at subsequent times. Some studies have shown that changing pharmacotherapy early in response to a failed quit attempt, regardless of what medication was switched to, can improve abstinence rates. However, the participants in these studies are predominantly white, and there are differences in smoking patterns in the Black population, including smoking fewer cigarettes daily and smoking more menthol cigarettes. Therefore, this unblinded randomized controlled trial aimed to examine the rates of abstinence, among non-Hispanic Black adults continuing with a single pharmacotherapy, or usual care (UC), versus multiple pharmacotherapy adaptation, or adapted therapy (ADT). Participants were included if they smoke between 5 and 30 cigarettes daily for 25 of the last 30 days, had an exhaled carbon monoxide (CO) of 5 ppm or more, and had a desire to quit, with no pharmacotherapy used for a quit attempt in the last 30 days. There were 196 patients randomized to UC and ADT each. The UC patients received a 24-hour 21 mg nicotine patch (NP) for 18 weeks. ADT patients received the NP for 2 weeks initially, with up to 2 pharmacotherapy adaptations, including a first switch to varenicline and second switch to bupropion+NP. Adaptations were done if CO ≥6 ppm at weeks 2 and 6 respectively. Counselling was provided to both groups. The main outcome analyzed was antabine- and anabasine-verified 7-day abstinence at 12 weeks, 18 weeks (conclusion of treatment), and 26 weeks. Overall, there were no significant differences in 7-day abstinence at any of the endpoints between UC and ADT groups. At week 12, 17.4% and 11.7% of ADT and UC patients quit respectively (odds ratio 1.58, 95% CI 0.89-2.80, p = 0.12). At week 18, 16.3% and 15.8% of ADT and UC patients quit respectively (OR 1.04, 95% CI 0.61-1.78, p = 0.89). And at week 26, 12.2% and 13.3% of patients quit respectively (OR 0.91, 95% CI 0.50-1.65, p = 0.76). In conclusion, there was no difference in abstinence rates for Black patients randomized to single pharmacotherapy for smoking cessation versus a treatment plan with 2 pharmacotherapy adaptations when needed.
Associations of childhood hearing loss and adverse childhood experiences in deaf adults
1. Amongst the deaf population, demographic factors that increase the odds of reporting adverse childhood experiences (ACEs) include: Having slight-to-moderate hearing loss, not attending a school with signing access, having a cochlear implant, and hearing loss onset at older than 5 years of age.
Evidence Rating Level:2 (Good)
Experiences of childhood trauma disproportionately affect the deaf population, at nearly double the rate of the general population. Isolation, barriers to communication, and delayed development are thought to make deaf children vulnerable to neglect and abuse. Despite this association, there is a paucity of literature examining adverse childhood experiences (ACEs) in the deaf population. Therefore, this cross-sectional study based in the USA aimed to determine demographic factors specific to the deaf community that may be associated with increased risk of ACEs before 18 years of age. There were 520 participants included, whom were recruited through social media and community-based methods and filled out a survey. The demographic factors examined included severity of hearing loss, onset of hearing loss, parent hearing status, education setting, use of cochlear implant, age of cochlear implant surgery if relevant, and signing exposure before five years old. There were 10 ACE questions and participants were categorized as having 0-1, 2+, or 4+ of the ACEs listed. Overall, the study found an association between reporting 2+ and 4+ ACEs for: Participants with slight-to-moderate hearing loss (odds ratio 5.2, 95% CI 1.8-15.0, p = 0.002 and OR 4.7, 95% CI 2.1-10.3, p <0.001 respectively), who did not attend a school with signing access (OR 2.4, 95% CI 1.4-4.1, p = 0.002 and OR 3.7, 95% CI 2.1-6.4, p < 0.001 respectively), and who receive a cochlear implant (OR 2.1, 95% CI 1.2-3.5, p = 0.005 and OR 2.6, 95% CI 1.7-4.1, p < 0.001 respectively). Those who identified as deafblind had a higher likelihood of reporting 2+ ACEs (OR 2.1, 95% CI 1.0-4.1, p = 0.040) and those with hearing loss onset older than 5 years of age had a higher likelihood of reporting 4+ ACEs (OR 2.1, 95% CI 1.1-3.9, p = 0.02). In conclusion, this study uncovered several deaf-specific demographic factors that are associated with reporting childhood ACEs.
Defunctioning stoma in anterior resection for rectal cancer does not impact anastomotic leakage: a national population-based cohort studyÂ
1. For patients with rectal cancer undergoing anterior resection (AR), the rates of anastomotic leakage (AL) and re-operation did not change when diverting ileostomy (DLI) rates increased as an intended risk mitigation strategy.
Evidence Rating Level: 2 (Good)
The standard curative treatment for cancer of the middle and upper rectum is an anterior resection (AR). An anastomotic leakage (AL) is a complication of AR, with risk factors including male gender, excess alcohol, smoking, obesity, medical comorbidities, neoadjuvant therapy, and anastomotic height. Defunctioning ileostomies (DLI) have been previously shown to mitigate the risk of a symptomatic AL. However, DLIs are permanent 25% of the time, and can have a detrimental impact on quality of life. Considering that the use of DLIs has increased, this retrospective study based in Sweden aimed to determine if the frequency of AL has decreased at the same time, hypothesizing that without clear DLI indications, there would be no reduction in AL frequency with increasing DLI use. This study included rectal cancer patients with AR done in 2007-2009 and 2016-2018, with the latter group expected to have higher rates of DLI. In total, 3948 AR procedures were done in these two periods, with 71.6% of the 2007-2009 patients receiving DLI and 76.7% of the 2016-2018 patients (p < 0.001) receiving DLI. The study found no significant decrease in incidence of AL, with 9.2% in the 2007-2009 cohort and 8.2% in the 2016-2018 cohort (p = 0.35). Furthermore, the incidence of reoperations was unaltered (4% in 2007-2009 compared to 3% in 2016-2018). When examining the cohorts together, 72% of patients with an AL had a DLI and 74% of patients without an AL had a DLI (p = 0.36). In conclusion, when more DLI procedures were done for AR patients in this population study, there was no difference in rates of AL or re-operation.
Image: PD
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