Intralesional 5-Fluorouracil for Keloids: A Systematic Review.

Keloids are benign, fibroproliferative dermal tumours, often arising after trauma, that are more common in darker skin types. Numerous therapeutic options have been employed for the treatment of keloids; however, there is no one gold standard approach. Five-fluorouracil, a potent chemotherapeutic agent, has emerged as a promising therapeutic option. Therefore, this systematic review, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focused on providing a broad overview of the use of 5-fluorouracil for the management of keloids. Forty studies (2325 patients) met inclusion criteria and investigated 5-fluorouracil for keloid management, with 19 studies (1043 patients) including a 5-fluorouracil monotherapy group. Five-fluorouracil monotherapy demonstrated consistent keloid improvement with >254 keloids injected across various anatomical regions. Five-fluorouracil monotherapy was most often compared to intralesional triamcinolone acetonide, utilizing the Patient and Observer Scar Assessment Scale and the Vancouver Scar Scale. The most common keloid parameters assessed were height, size, volume, width, length, induration, pruritus, and erythema. Five-fluorouracil monotherapy exhibited substantial improvements, with weight averages of 73% of patients experiencing >25% improvement and 67% achieving >50% improvement. Relapse rate was 16% at 27 weeks after 5-fluorouracil monotherapy treatment. Limitations included potential selection bias, language restrictions, and heterogenous data analysis among studies. Overall, our findings underscore the potential effectiveness of 5-fluorouracil monotherapy in the management of keloids, with an encouraging safety profile. Larger prospective trials are needed to determine optimal therapy or combination therapy for the management of keloids. This detailed compilation of treatment protocols, outcomes, and relapse rates stand as a valuable resource for further research and clinical applications.

The new frontline: exploring the links between moral distress, moral resilience and mental health in healthcare workers during the COVID-19 pandemic.

BACKGROUND: Global health crises, such as the COVID-19 pandemic, confront healthcare workers (HCW) with increased exposure to potentially morally distressing events. The pandemic has provided an opportunity to explore the links between moral distress, moral resilience, and emergence of mental health symptoms in HCWs. METHODS: A total of 962 Canadian healthcare workers (88.4% female, 44.6 + 12.8 years old) completed an online survey during the first COVID-19 wave in Canada (between April 3rd and September 3rd, 2020). Respondents completed a series of validated scales assessing moral distress, perceived stress, anxiety, and depression symptoms, and moral resilience. Respondents were grouped based on exposure to patients who tested positive for COVID-19. In addition to descriptive statistics and analyses of covariance, multiple linear regression was used to evaluate if moral resilience moderates the association between exposure to morally distressing events and moral distress. Factors associated with moral resilience were also assessed. FINDINGS: Respondents working with patients with COVID-19 showed significantly more severe moral distress, anxiety, and depression symptoms (F > 5.5, p < .020), and a higher proportion screened positive for mental disorders (Chi-squared > 9.1, p = .002), compared to healthcare workers who were not. Moral resilience moderated the relationship between exposure to potentially morally distressing events and moral distress (p < .001); compared to those with higher moral resilience, the subgroup with the lowest moral resilience had a steeper cross-sectional worsening in moral distress as the frequency of potentially morally distressing events increased. Moral resilience also correlated with lower stress, anxiety, and depression symptoms (r > .27, p < .001). Factors independently associated with stronger moral resilience included: being male, older age, no mental disorder diagnosis, sleeping more, and higher support from employers and colleagues (B [0.02, |-0.26|]. INTERPRETATION: Elevated moral distress and mental health symptoms in healthcare workers facing a global crisis such as the COVID-19 pandemic call for the development of interventions promoting moral resilience as a protective measure against moral adversities.

Profiles of sleep changes during the COVID-19 pandemic: Demographic, behavioural and psychological factors.

This study aimed to evaluate changes in sleep during the COVID-19 outbreak, and used data-driven approaches to identify distinct profiles of changes in sleep-related behaviours. Demographic, behavioural and psychological factors associated with sleep changes were also investigated. An online population survey assessing sleep and mental health was distributed between 3 April and 24 June 2020. Retrospective questions were used to estimate temporal changes from before to during the outbreak. In 5,525 Canadian respondents (67.1% females, 16-95 years old: Mean ± SD = 55.6 ± 16.3 years), wake-up times were significantly delayed relative to pre-outbreak estimates (p < .001, ηp2  = 0.04). Occurrences of clinically meaningful sleep difficulties significantly increased from 36.0% before the outbreak to 50.5% during the outbreak (all p < .001, g ≥ 0.27). Three subgroups with distinct profiles of changes in sleep behaviours were identified: "Reduced Time in Bed", "Delayed Sleep" and "Extended Time in Bed". The "Reduced Time in Bed" and "Delayed Sleep" subgroups had more adverse sleep outcomes and psychological changes during the outbreak. The emergence of new sleep difficulties was independently associated with female sex, chronic illnesses, being employed, family responsibilities, earlier wake-up times, higher stress levels, as well as heavier alcohol use and television exposure. The heterogeneity of sleep changes in response to the pandemic highlights the need for tailored interventions to address sleep problems.

Emerging New Psychiatric Symptoms and the Worsening of Pre-existing Mental Disorders during the COVID-19 Pandemic: A Canadian Multisite Study: Nouveaux symptômes psychiatriques émergents et détérioration des troubles mentaux préexistants durant la pandémie de la COVID-19: une étude canadienne multisite.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused global disruptions with serious psychological impacts. This study investigated the emergence of new psychiatric symptoms and the worsening of pre-existing mental disorders during the COVID-19 pandemic, identified factors associated with psychological worsening, and assessed changes in mental health service use. METHODS: An online survey was circulated between April 3 and June 23, 2020. Respondents were asked to complete mental health questionnaires based on 2 time referents: currently (i.e., during the outbreak) and in the month preceding the outbreak. A total of 4,294 Canadians between 16 and 99 years of age were subdivided based on the presence of self-reported psychiatric diagnoses. RESULTS: The proportion of respondents without prior psychiatric history who screened positive for generalized anxiety disorder and depression increased by 12% and 29%, respectively, during the outbreak. Occurrences of clinically important worsening in anxiety, depression, and suicidal ideation symptoms relative to pre-outbreak estimates were significantly higher in those with psychiatric diagnoses. Furthermore, 15% to 19% of respondents reported increased alcohol or cannabis use. Worse psychological changes relative to pre-outbreak estimate were associated with female sex, younger age, lower income, poorer coping skills, multiple psychiatric comorbidities, previous trauma exposure, deteriorating physical health, poorer family relationships, and lower exercising. Reductions in mental health care were associated with increased suicidal ideation. CONCLUSION: The worsening in mental health symptoms and the decline in access to care call for the urgent development of adapted interventions targeting both new mental disorders and pre-existing psychiatric conditions affected by the COVID-19 pandemic.

Autonomic Modulation of Cardiac Activity Across Levels of Sleep Depth in Individuals With Depression and Sleep Complaints.

OBJECTIVE: We assessed mean heart rate (HR) and HR variability (HRV) across wake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep, and across varying levels of NREM sleep depth in individuals with depression and sleep complaints. METHODS: Retrospective polysomnographic data were obtained for 25 individuals diagnosed as having depression (84% female; mean age = 33.8 ± 12.2 years) and 31 mentally healthy controls (58.1% female; mean age = 37.2 ± 12.4 years). All were free of psychotropic and cardiovascular medication, cardiovascular disease, and sleep-related breathing disorders. HR and time-domain HRV parameters were computed on 30-second electrocardiography segments and averaged across the night for each stage of sleep and wake. RESULTS: Compared with the control group, the depression group had higher HR across wake, REM, and all levels of NREM depth (F(1,51) = 6.3, p = .015). Significant group by sleep stage interactions were found for HRV parameters: SD of normal-to-normal intervals (SDNN; F(2.1,107.7) = 4.4, p = .014) and root mean square differences of successive R-R intervals (RMSSD; F(2.2,113.5) = 3.2, p = .041). No significant group difference was found for SDNN or RMSSD during wake (all, p ≥ .32). However, compared with the control group, the depression group had significantly lower SDNN in REM (p = .040) and all NREM stages (all p ≤ .045), and lower RMSSD during NREM 2 (p = .033) and NREM 3 (p = .034). CONCLUSIONS: This study suggests that the abnormalities in autonomic cardiac regulation associated with depression and sleep problems are more prominent during sleep, especially NREM sleep, than during wake. This may be due to abnormalities in parasympathetic modulation of cardiac activity.

Using heart rate profiles during sleep as a biomarker of depression.

BACKGROUND: Abnormalities in heart rate during sleep linked to impaired neuro-cardiac modulation may provide new information about physiological sleep signatures of depression. This study assessed the validity of an algorithm using patterns of heart rate changes during sleep to discriminate between individuals with depression and healthy controls. METHODS: A heart rate profiling algorithm was modeled using machine-learning based on 1203 polysomnograms from individuals with depression referred to a sleep clinic for the assessment of sleep abnormalities, including insomnia, excessive daytime fatigue, and sleep-related breathing disturbances (n = 664) and mentally healthy controls (n = 529). The final algorithm was tested on a distinct sample (n = 174) to categorize each individual as depressed or not depressed. The resulting categorizations were compared to medical record diagnoses. RESULTS: The algorithm had an overall classification accuracy of 79.9% [sensitivity: 82.8, 95% CI (0.73-0.89), specificity: 77.0, 95% CI (0.67-0.85)]. The algorithm remained highly sensitive across subgroups stratified by age, sex, depression severity, comorbid psychiatric illness, cardiovascular disease, and smoking status. CONCLUSIONS: Sleep-derived heart rate patterns could act as an objective biomarker of depression, at least when it co-occurs with sleep disturbances, and may serve as a complimentary objective diagnostic tool. These findings highlight the extent to which some autonomic functions are impaired in individuals with depression, which warrants further investigation about potential underlying mechanisms.

Rapid resolution of erythrodermic atopic dermatitis with upadacitinib: A case report.

Atopic dermatitis is a chronic inflammatory skin disease that may progress to erythroderma in severe cases. Biologic agents such as dupilumab have recently become the mainstay of systemic treatment for moderate-to-severe cases, yet many patients remain refractory to therapy. Here, we present a case of erythrodermic atopic dermatitis, resistant to prednisone and dupilumab, with remarkably rapid achievement of remission following treatment with upadacitinib, an oral selective Janus kinase 1 inhibitor.

Pityriasis rubra pilaris partially responsive to treatment with upadacitinib: A case report.

Pityriasis rubra pilaris is a rare inflammatory dermatosis characterized by orange-red confluent plaques, hyperkeratotic follicular papules, palmoplantar keratoderma, and, in some cases, erythroderma. The etiology of pityriasis rubra pilaris is unclear. This condition is often treated with oral retinoids and topical corticosteroids, and more recently, biological agents have become the mainstay of treatment. However, there is a paucity of high-quality evidence on the safety and effectiveness of these agents, and the disease often remains refractory to therapy. Herein, we present a case of pityriasis rubra pilaris with a favorable response to treatment with upadacitinib, a Janus kinase inhibitor, which has not been previously reported in the literature for the management of this condition.

Pregnancy and neonatal outcomes following malignancy in pregnancy at a tertiary care Canadian center: a retrospective chart review.

Objective: Data on pregnancy-associated cancers (PACs) are lacking. The objectives of this study were to determine the incidence of PACs and describe the characteristics and outcomes of pregnancies affected by malignancy at a single tertiary care center in Ottawa, Canada.Methods: This was a retrospective chart review of individuals with PAC at The Ottawa Hospital (TOH) between 2011-2022. Eligible cases were identified from the TOH Data Warehouse, the TOH instance of the Better Outcomes Registry & Network Ontario, and the TOH Division of Maternal Fetal Medicine's Perinates database. Chart reviews were conducted to confirm case eligibility and to extract demographic, oncologic, obstetrical, and neonatal measures. The annual incidence of PAC over the 11-year period was reported per 1000 deliveries. Descriptive statistics were used to describe the sample, including frequency (n) and proportions (%) for categorical variables and mean and standard deviation (SD) for continuous variables.Results: The final cohort included 59 individuals with PAC at TOH between 2011-2022. The annual incidence of PAC ranged from 0.47 to 1.54 per 1000 deliveries. The most common PACs were breast cancer (28.8%), Hodgkin lymphoma (10.2%), and thyroid cancer (8.5%). Common interventions during pregnancy included chemotherapy (33.9%) and surgical intervention (32.2%). A total of 19 individuals (32.2%) did not undergo PAC-related treatment during pregnancy. There were 55 livebirths (91.7%), 2 spontaneous abortions (3.3%), 3 induced abortions (5.0%), and no stillbirths. Among livebirths, the mean gestational age was 37.4 ± 2.8 weeks and the mean birthweight was 2920.3 ± 650.0 g. All neonates had reassuring 5-minute Apgar scores, 18 (32.7%) were admitted to the Neonatal Intensive Care Unit/Special Care Nursery (NICU/SCN), and 8 (14.5%) were noted to have a mild congenital abnormality.Conclusion: This study shows promising perinatal outcomes for patients with PAC and their neonates. Ongoing surveillance of PAC is needed to better inform care for this patient population.

Changes in Positive Airway Pressure Use in Adults with Sleep-Related Breathing Disorder During the COVID-19 Pandemic: A Cross-Sectional National Community-Based Survey.

Purpose: To better understand: (i) a positive airway pressure (PAP) therapy use during the pandemic, (ii) how PAP use may relate to sleep, health, and COVID-19-related outcomes, and (iii) factors associated with PAP use during the pandemic. Methods: This study is based on data collected between Apr 2020 and Jan 2021 as part of an online cross-sectional national community-based survey. The included participants were located in North America, 18 years and older, with self-reported sleep-related breathing disorder (SBD) and usage of a PAP device in the last month before the COVID-19 pandemic. Results: Of all respondents, 7.2% (41/570) stopped using PAP during the pandemic over a median time since the pandemic declaration of 62.0 days (IQR = 8.0). There were no significant differences between individuals who continued and stopped using PAP in the time elapsed since the pandemic declaration, age, sex, education level, occupational status, family income, or the proportions of individuals endorsing symptoms that could be related to COVID-19. Compared to individuals who continued using PAP, those who stopped had significantly shorter sleep time, lower sleep efficiency, and poorer sleep quality. Higher stress levels and living with someone who experienced symptoms that could be attributable to COVID-19 were independently associated with stopping PAP use. Conclusions: In this survey study, most individuals with SBD continued PAP therapy during the pandemic. However, even 7% of participants who stopped using PAP cannot be ignored. Identifying individuals at risk of discontinuing PAP treatment may help design targeted interventions for people with SBD and health professionals to improve PAP use.

Stuck in a lockdown: Dreams, bad dreams, nightmares, and their relationship to stress, depression and anxiety during the COVID-19 pandemic.

BACKGROUND: An upsurge in dream and nightmare frequency has been noted since the beginning of the COVID-19 pandemic and research shows increases in levels of stress, depression and anxiety during this time. Growing evidence suggests that dream content has a bi-directional relationship with psychopathology, and that dreams react to new, personally significant and emotional experiences. The first lockdown experience was an acute event, characterized by a combination of several unprecedent factors (new pandemic, threat of disease, global uncertainty, the experience of social isolation and exposure to stressful information) that resulted in a large-scale disruption of life routines. This study aimed at investigating changes in dream, bad dream and nightmare recall; most prevalent dream themes; and the relationship between dreams, bad dreams, nightmares and symptoms of stress, depression and anxiety during the first COVID-19 lockdown (April-May 2020) through a national online survey. METHODS: 968 participants completed an online survey. Dream themes were measured using the Typical Dreams Questionnaire; stress levels were measured by the Cohen's Perceived Stress Scale; symptoms of anxiety were assessed by Generalized Anxiety Disorder (GAD-7) scale; and symptoms of depression were assessed using the Quick Inventory of Depressive Symptomatology. RESULTS: 34% (328) of participants reported increased dream recall during the lockdown. The most common dream themes were centered around the topics of 1) inefficacy (e.g., trying again and again, arriving late), 2) human threat (e.g., being chased, attacked); 3) death; and 4) pandemic imagery (e.g., being separated from loved ones, being sick). Dream, bad dream and nightmare frequency was highest in individuals with moderate to severe stress levels. Frequency of bad dreams, nightmares, and dreams about the pandemic, inefficacy, and death were associated with higher levels of stress, as well as with greater symptoms of depression and anxiety. CONCLUSIONS: Results support theories of dream formation, environmental susceptibility and stress reactivity. Dream content during the lockdown broadly reflected existential concerns and was associated with increased symptoms of mental health indices.

Selective serotonin reuptake inhibitor use is associated with worse sleep-related breathing disturbances in individuals with depressive disorders and sleep complaints: a retrospective study.

STUDY OBJECTIVES: The effects of serotonergic agents on respiration neuromodulation may vary according to differences in the serotonin system, such as those linked to depression. This study investigated how sleep-related respiratory disturbances relate to depression and the use of medications commonly prescribed for depression. METHODS: Retrospective polysomnography was collated for all 363 individuals who met selection criteria out of 2,528 consecutive individuals referred to a specialized sleep clinic (Ottawa, Canada) between 2006 and 2016. The apnea-hypopnea index (AHI), oxygen saturation nadir, and oxygen desaturation index during REM and NREM sleep were analyzed using mixed analyses of covariance comparing 3 main groups: (1) medicated individuals with depressive disorders (antidepressant group; subdivided into the selective serotonin reuptake inhibitor and norepinephrine-dopamine reuptake inhibitor subgroups), (2) non-medicated individuals with depressive disorders (non-medicated group), and (3) mentally healthy control patients (control group). RESULTS: Individuals with depressive disorders (on antidepressants or not) had significantly higher AHIs compared to control patients (both P ≤ .007). The antidepressant group had a lower NREM sleep oxygen saturation nadir and a higher NREM sleep oxygen desaturation index than the control and non-medicated groups (all P ≤ .009). Within individuals with depressive disorders, independent of depression severity, the selective serotonin reuptake inhibitor group had a lower oxygen saturation nadir and a higher oxygen desaturation index during NREM sleep than the norepinephrine-dopamine reuptake inhibitor (both P ≤ .045) and non-medicated groups (both P < .001) and a higher NREM sleep AHI than the non-medicated group (P = .014). CONCLUSIONS: These findings suggest that the use of selective serotonin reuptake inhibitors may be associated with impaired breathing and worse nocturnal oxygen saturation in individuals with depressive disorders and sleep complaints, but this needs to be confirmed by prospective studies.

Social, financial and psychological stress during an emerging pandemic: observations from a population survey in the acute phase of COVID-19.

INTRODUCTION: The negative impacts of COVID-19 have rippled through every facet of society. Understanding the multidimensional impacts of this pandemic is crucial to identify the most critical needs and to inform targeted interventions. This population survey study aimed to investigate the acute phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress between 3 April and 15 May 2020. METHODS: 6040 participants are included in this report. A multivariate linear regression model was used to identify factors associated with stress changes (as measured by the Cohen's Perceived Stress Scale (PSS)) relative to pre-outbreak retrospective estimates. RESULTS: On average, PSS scores increased from low stress levels before the outbreak to moderate stress levels during the outbreak (p<0.001). The independent factors associated with stress worsening were: having a mental disorder, female sex, having underage children, heavier alcohol consumption, working with the general public, shorter sleep duration, younger age, less time elapsed since the start of the outbreak, lower stress before the outbreak, worse symptoms that could be linked to COVID-19, lower coping skills, worse obsessive-compulsive symptoms related to germs and contamination, personalities loading on extraversion, conscientiousness and neuroticism, left wing political views, worse family relationships and spending less time exercising and doing artistic activities. CONCLUSION: Cross-sectional analyses showed a significant increase from low to moderate stress during the COVID-19 outbreak. Identified modifiable factors associated with increased stress may be informative for intervention development. TRIAL REGISTRATION NUMBER: NCT04369690; Results.