The Global Impact of COVID-19 on Childhood Cancer Outcomes and Care Delivery - A Systematic Review.

Background: Childhood cancer represents a leading cause of death and disease burden in high income countries (HICs) and low-and-middle income countries (LMICs). It is postulated that the current COVID-19 pandemic has hampered global development of pediatric oncology care programs. This systematic review aimed to comprehensively review the global impact of COVID-19 on childhood cancer clinical outcomes and care delivery. Methods: A systematic search was conducted on PubMed, Embase, Medline, and the African Medical Index from inception to November 3, 2021 following PRISMA guidelines. A manual search was performed to identify additional relevant studies. Articles were selected based on predetermined eligibility criteria. Findings: The majority of studies reported patients with cancer and COVID-19 presenting as asymptomatic (HICs: 33.7%, LMICs: 22.0%) or with primary manifestations of fever (HICs: 36.1%, LMICs: 51.4%) and respiratory symptoms (HICs: 29.6%, LMICs: 11.7%). LMICs also reported a high frequency of patients presenting with cough (23.6%) and gastrointestinal symptoms (10.6%). The majority of patients were generally noted to have a good prognosis; however the crude mortality rate was higher in LMICs when compared to HICs (8.0% vs 1.8%). Moreover, the pandemic has resulted in delays and interruptions to cancer therapies and delays in childhood cancer diagnoses in both HICs and LMICs. However, these findings were disproportionately reported in LMICs, with significant staff shortages, supply chain disruptions, and limited access to cancer therapies for patients. Conclusions: The COVID-19 pandemic has resulted in delays and interruptions to childhood cancer therapies and delays in childhood cancer diagnoses, and disproportionately so within LMICs. This review provides lessons learned for future system-wide disruptions to care, as well as provides key points for moving forward better with care through the remainder of this pandemic. Systematic Review Registration: CRD42021266758, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=266758.

Efficacy of dextromethorphan for the treatment of depression: a systematic review of preclinical and clinical trials.

INTRODUCTION: The large percentage of adults with major depressive disorder (MDD) insufficiently responding and/or tolerating conventional monoamine-based antidepressants invites the need for mechanistically novel treatments. Convergent evidence implicates glutamatergic signaling as a potential therapeutic target in MDD. AREAS COVERED: The synthesis herein of preclinical and clinical studies indicates that dextromethorphan (DXM) is well tolerated and exhibits clinically significant antidepressant effects; DXM combined with bupropion has demonstrated replicated and relatively rapid onset efficacy in adults with MDD. DXM efficacy has been preliminarily reported in adults with bipolar depression. The combination of DXM and bupropion represents a pharmacokinetic and pharmacodynamic synergy which may account for the rapidity of action in MDD. EXPERT OPINION: The combination of DXM and bupropion is a safe, well tolerated and efficacious treatment option in adults with MDD. Priority questions are whether DXM/bupropion is uniquely effective across discrete domains of psychopathology (e.g. anhedonia, reward processing, general cognitive systems) and/or whether it is able to significantly improve patient-reported outcomes (e.g. quality of life, psychosocial functioning). The availability of ketamine/esketamine and DXM/bupropion instantiates the relevance of glutamate as a treatment target in MDD. Studies in bipolar depression with DXM/bupropion are warranted as well as in MDD with suicidality.

The Association between Selective Serotonin Reuptake Inhibitors (SSRIs) Use and the Risk of Bladder Cancer: A Nationwide Population-Based Cohort Study.

BACKGROUND: Past studies suggest mixed associations between selective serotonin reuptake inhibitor (SSRI) prescription and carcinogenic risk. There is no epidemiological study reporting on the association between SSRI use and the incidence of bladder cancer. The aim of this study is to determine whether SSRI use influences the risk of bladder cancer. METHODS: We conducted a nationwide retrospective cohort study by Taiwan's National Health Insurance Research Database from January 1, 1997 to December 31, 2013. 192,392 SSRI prescribed individuals were randomly matched 1 to 1 with 191,786 individuals who had never received any SSRIs by propensity scores match. The Cox Proportional Hazard models were conducted to examine the risk of bladder cancer between individuals prescribed SSRIs and individuals not prescribed SSRIs. RESULTS: SSRIs were associated with significant reduced risk of bladder cancer with 0.5, 1, and 2 year induction periods (adjusted hazard ratio (aHR) = 0.86, 95% CI (confidence interval) = 0.76-0.98, aHR = 0.85, 95% CI = 0.75-0.97, and aHR = 0.77, 95% CI = 0.66-0.89). When examining the effect of specific SSRI, there was significantly lower risk of bladder cancer in individuals prescribed fluoxetine (6 month induction period: aHR = 0.78, 95% CI = 0.65-0.93; 1 year induction period: aHR = 0.78, 95% CI = 0.65-0.94; 2 year induction period: aHR = 0.73, 95% CI = 0.60-0.89), paroxetine (6 month induction period: aHR = 0.78, 95% CI = 0.61-0.99; 1 year induction period: aHR = 0.79, 95% CI = 0.61-1.01; 2 year induction period: aHR = 0.72, 95% CI = 0.54-0.95), and citalopram (6 month induction period: aHR = 0.74, 95% CI = 0.53-1.03; 1 year induction period: aHR = 0.70, 95% CI = 0.50-0.99; 2 year induction period: aHR = 0.60, 95% CI = 0.41-0.88). CONCLUSIONS: Individuals prescribed fluoxetine, paroxetine, or citalopram had a reduced risk of bladder cancer in this large, cross-national database.

The Association Between Adverse Childhood Experiences and Inflammation in Patients with Major Depressive Disorder: A Systematic Review.

BACKGROUND: Replicated evidence has documented elevated levels of pro-inflammatory cytokines in populations with major depressive disorder (MDD). However, childhood trauma, a risk factor for MDD, has been separately shown to also impact inflammatory systems; its potential moderating effect on inflammation in MDD has been less frequently investigated. METHODS: We systematically searched the PubMed, Google Scholar, Scopus, Web of Science, and PsycINFO databases between database inception to June 19th, 2019 using the search string: (Childhood trauma or Adverse childhood experiences or childhood abuse or childhood rape or physical abuse or emotional abuse) AND (Inflammation or inflammatory cytokines or interleukin-6 or tumor necrosis factor-alpha or c-reactive protein) AND (Major Depressive Disorder or Depression). RESULTS: We identified nine articles that evaluated inflammatory biomarkers in MDD populations with adverse childhood experiences (ACE). Eight articles evaluated IL-6, three articles evaluated CRP, and five articles evaluated TNF-α. The strongest effects were observed for IL-6; six studies reported significantly elevated levels of IL-6 in MDD and ACE patients compared to healthy controls and/or MDD-only populations. Meanwhile, only three studies found TNF-α to be significantly elevated in the MDD and ACE cohort. In contrast, MDD-ACE populations did not exhibit significantly elevated CRP. LIMITATIONS: The methodological heterogeneity amongst studies was very high. CONCLUSION: The current review suggests that MDD and ACE subpopulations present elevated levels of IL-6 compared to MDD-only and healthy control populations. Therefore, research should consider whether elevated inflammation in MDD is just an epiphenomenon of previous ACE and whether MDD-ACE subgroups are more likely to respond to immune-inflammatory targeted intervention.

Knowledge and Attitude of Teenagers Towards Electronic Cigarettes in Karachi, Pakistan.

Introduction Studies have shown that electronic cigarettes have gained immense popularity and their use has increased dramatically all over the world. However, little is known about the knowledge and attitudes towards e-cigarettes in third world countries such as Pakistan. The aim of this study was to determine the perceptions of teenagers in Karachi regarding e-cigarettes and whether the differences in said perceptions were affected by gender and level of education. Methods We conducted a cross-sectional study in January 2017 using convenience sampling and interviewed 441 young individuals, aged 13 to 19 years, to determine their knowledge, attitudes, and practices regarding e-cigarettes. The participants were questioned about their knowledge and its source. Attitudes were judged using four and five-point Likert scales while questions regarding practices focused on single and current use. Chi-square and Mann-Whitney tests were applied to compare the knowledge, attitudes, and practices of teenagers with gender and level of schooling. Results The majority of participants knew what e-cigarettes were (n=277, 68.7%) but did not know about their contents (n=225, 55.8%) and had learned about them from either friends or the internet (n=245, 60.%). Almost half of them (n=190, 47.2%) believed that the reason for e-cigarette use was either peer pressure or to quit smoking conventional cigarettes. An overwhelming majority also stated that; it was either easy or very easy to obtain e-cigarettes (n=277, 68.7%), they would not try smoking e-cigarettes even if a good friend of theirs recommended them (n=287, 71.2%), they were not current e-cigarette smokers (n=370, 91.8%) and they would never promote e-cigarette use (n=371, 92.1%). Statistically significant differences were found with males knowing more about e-cigarettes (p=0.006) and being more common to either have smoked (p <0.001) or be current e-cigarette smokers (p <0.001). Furthermore, middle school students were more likely to have negative attitudes towards e-cigarettes believing they were more harmful (p=0.003) and more addictive (p <0.001) than conventional cigarettes. Conclusion Many people were aware of what electronic cigarettes are but still, it was evident that there was the lack of proper knowledge along with negative attitudes towards e-cigarette use among teenagers in Pakistan due to cultural and social stigmas and lack of advertising. Males and females had considerable differences in their opinions regarding e-cigarette use owing to such social practices being considered taboo by females and males having greater freedom due to patriarchal, familial and cultural systems.