2 Minute Medicine Rewind December 9, 2024

Chocolate intake and risk of type 2 diabetes: prospective cohort studies

1. In three cohort studies, higher consumption of chocolate was significantly associated with a decreased risk of type 2 diabetes (T2D). 

2. More specifically, participants who consumed dark chocolate weekly had a significant lower risk of T2D. No such associations were found for milk chocolate. 

Evidence Rating Level: 1 (Excellent) 

Type 2 diabetes (T2D) is one disease that has increased in prevalence significantly over the last decades and is further expected to grow in the next 20 years. T2D is characterized by insulin resistance and impaired insulin secretion and may have several downstream complications such as renal failure or impaired vision. Previous research has shown an association between high consumption of flavonoids and a decreased risk of T2D. Chocolate is one of the most commonly consumed flavonoids, however, there is not much research comparing chocolate consumption and T2D risk. To address this knowledge gap, three prospective cohort studies were used to investigate the association between chocolate intake and risk of T2D and change in body weight. The studies included the Nurses’ Health Study (NHS), Nurses’ Health Study II, and Health Professionals Follow-Up Study (HPFS). The participants’ diets were assessed every four years using a semiquantitative food frequency questionnaire. Other information collected in the questionnaires included lifestyle factors like physical activity and medical conditions. T2D was self-reported in the follow-up questionnaires. To identify changes in body weight, participants self-reported their weight at baseline and in the follow-up questionnaires. The total chocolate intake analysis included 192 208 participants (63 798 in NHS, 88 383 women in HSII, and 40 027 men in HPFS) while the chocolate subtype analysis included 111 654 participants (39 400 women in NHS, 58 187 women in NHSII, and 14 067 men in HPFS). Throughout the study periods, 18 862 people were diagnosed with incident T2D. However, there was no significant association between overall chocolate consumption and the risk of T2D. Compared to participants who never ate chocolate, those who consumed ≥5 servings/week of any chocolate had a 10% (95% CI 2% to 17%; P trend=0.07) decreased risk of T2D. In the chocolate subtype analysis, 4771 people reported incident T2D. Among participants who consumed 5 or more servings of dark chocolate/week, there was a 21% lower rate of T2D compared with those who did not or rarely ate dark chocolate (P trend = 0.006). The consumption of milk chocolate was not significantly associated with T2D risk. Milk chocolate consumption was positively associated with weight gain. Overall, these findings show that consumption of dark chocolate was associated with a decreased risk of T2D, however, the same cannot be said about milk chocolate.

 

Psilocybin therapy for clinicians with symptoms of depression from frontline care during the COVID-19 pandemic 

1. In this randomized clinical trial, psilocybin therapy for PTSD, depression, and burnout was associated with a sustained decrease in depression symptoms in front-line workers during the COVID-19 pandemic. 

Evidence Rating Level: 1 (Excellent) 

Throughout the pandemic, healthcare workers experienced a variety of psychological symptoms including burnout, depression, and posttraumatic stress disorder (PTSD). Previous studies have shown improvements in mental health through the use of psilocybin in the context of psychological support. Stemming from earlier research, this double-blind randomized clinical trial had the goal of investigating if psilocybin could improve burnout, PTSD, and depression symptoms in US clinicians. The study included physicians, nurses, and advanced practice practitioners (APPs) who were recruited through online newsletters and a study website. Each respective intervention episode consisted of 2 preparation sessions, 1 medication session, and 3 integration sessions. The first dose was either 25 mg of psilocybin or 100 mg of niacin for the experimental and control group respectively. The main outcome of interest was a change in depression symptoms from baseline to day 28. Looking at the results, a total of 30 US clinicians (15 female and 15 male, mean [rage] age of 38 [29-60] years) were included in the study. These participants were equally split using randomization techniques into the psilocybin and control groups. The mean change in the Montgomery-Asberg Depression Rating Scale (MADRS) score was -21.33 (7.84) and -9.33 (7.32) in the psilocybin and control group respectively (mean difference -12.00 [95% CI, -17.67 to -6.33; P<.001). A decrease in the MADRS score means improvement. The mean change in the Stanford Professional Fulfillment Index (SPFI) scores showed a decrease in burnout symptoms in the psilocybin group but not the niacin group (mean [SD] score change, -6.40 [5.00] vs -2.33 [5.97]; P = .05). According to the mean post-traumatic stress disorder checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5) scores, there was a larger decrease in PTSD symptoms in the psilocybin group than the niacin group from baseline to follow-up (-16.67 [15.04] vs -6.73 [10.69]). Overall, in this randomized clinical trial, there was a significant association between psilocybin therapy and a decrease in depression symptoms among front-liner healthcare workers during the COVID-19 pandemic.

 

Fostamatinib for hospitalized adults with COVID-19 and hypoxemia 

1. In this randomized clinical trial, fostamatinib did not increase the number of days oxygen-free in adults hospitalized with COVID-19 and hypoxemia compared to the placebo. 

Evidence Rating Level: 1 (Excellent) 

Although there are many novel and effective treatments for COVID-19, mortality due to hypoxemia remains high. Fostamatinib is an oral spleen tyrosine kinase inhibitor that is approved for the treatment of chronic immune thrombocytopenia. Fostamatinib blocks the activation of neutrophils, macrophages, and platelets, all of which contribute to inflammation in COVID-19. The previous phase 2 study showed that fostamatinib was safe and effective in treating patients with COVID-19. Thus, this phase 3 trial aimed to examine the effects of fostamatinib on oxygen-free days in the hospital in adults hospitalized for COVID-19 and subsequent hypoxemia. The fostamatinib trial was rolling at the same time as 2 other trials. During that time, the participants were randomly assigned to either fostamatinib, TXA-127, TRV-027, or placebo. If assigned to this trial, participants were randomized 1:1 to either fostamatinib or placebo. Included in the trial were patients aged 18 years or older who were hospitalized for SARS-CoV-2 infection. To properly assess the effect of fostamatinib on hypoxemia, the main outcome was oxygen-free days, while secondary outcomes included all-cause mortality, and alive and free of respiratory failure. After assessing eligibility, and assigning to the other 2 trials, a total of 400 participants (median age, 68 years [IQR, 58-76 years]) were included in the study. Of these individuals, 199 were assigned to the fostamatinib group and 201 to the placebo group. The mean (SD) number of oxygen-free days was 13.4 (12.4) and 14.2 (12.1) in the fostamatinib and placebo group respectively (unadjusted mean difference, -1.26 days [95% CI, -3.52 to 1.00 days]; adjusted odds ratio (AOR), 0.82 [95% credible interval (Crl), 0.58-1.17]). When further comparing the groups, mortality occurred in 22 of 195 patients in the fostamatinib group (11.3%) while only 16 of 197 were in the placebo group (8.1%; AOR, 1.44; 95% Crl, 0.72-2.90). The fostamatinib group experienced a greater proportion of patients with elevated aspartate aminotransferase (AST) levels (23 [11.6%]) compared to the placebo group (11 [5.5%]; AOR, 2.28; 95% Crl, 1.07-4.84). The results show that fostamatinib was not effective at increasing the number of days alive and free from oxygen supplementation or decreasing all-cause mortality.

 

Efficacy of melatonin for prolonged disorders of consciousness: a double-blind, randomized clinical trial

1. In this randomized clinical trial studying patients with prolonged disorder of consciousness (DoC), melatonin increased the level of consciousness in unresponsive wakefulness syndrome (UWS) patients. 

Evidence Rating Level: 1 (Excellent) 

Prolonged disorder of Consciousness (DoC) is a condition caused by brain injury, consisting of impaired arousal and/or awareness for longer than 4 weeks. Prolonged DoC is further categorized into 2 subsets: unresponsive wakefulness syndrome (UWS), where patients show no signs of awareness, and minimally conscious state (MCS), where patients exhibit minimal signs of awareness. Damage to the brainstem affects patients with DoC ability to sleep impacting recovery, as consistent sleep has been associated with better prognosis in patients with DoC. While some neuromodulation techniques and pharmacological interventions are currently used as treatments, their scopes and effectiveness are limited. Melatonin is a critical hormone involved in sleep regulation, with minimal side effects and dependency. There is a gap in research studying the effects of melatonin alone on individuals with prolonged DoC. To address this, the study used Electroencephalography (EEG), a cortical processing assessment tool, to examine the effects of melatonin on patients with DoC, with additional sleep patterns and behavioural assessments. This randomized, double-blind, parallel-group, placebo-controlled outpatient trial involved 46 participants divided into the melatonin group (n=24) and the placebo group (n=22). Patients with UWS showed better improvement in the melatonin group than in the placebo group (Fgroup*time = 6.86, P = 0.032; Fgroup = 4.03, P = 0.045; Ftime = 13.61, P < 0.001). This improvement was especially notable in visual scores (Fgroup*time = 7.03, P = 0.030; Fgroup = 4.90, P = 0.027). Patients in a UWS state in the melatonin group showed a higher relative spectral density in the alpha band of the frontal lobe compared to those in the placebo group (Ftime-mel = 4.55, P = 0.033). Some limitations of the study were its small sample size affecting generalizability, and lack of dosage variability. Overall, while not applicable to all DoC patients, those in the UWS category saw improved consciousness levels through regular melatonin use.

 

Assessment of inflammatory biomarkers and incident atrial fibrillation in older adults 

1. In a cohort of individuals aged 65 years or older, 5 biomarkers including IL-6, hsCRP, WBC, sTNFR1, and sIL-2R⍺ were significantly associated with an increased risk of developing atrial fibrillation (AF). 

2. After adjusting for other inflammatory biomarkers simultaneously, all except one of the observed biomarker associations (IL-6) lost significance. 

Evidence Rating Level: 1 (Excellent) 

Atrial fibrillation (AF) is the most common sustained arrhythmia, estimated to increase in prevalence in the next few years. Individuals with AF tend to have a greater risk of developing heart failure, stroke, and mortality. Although it is known that myocardial and systemic inflammation occurs in AF, many anti-inflammatory agents have not been tested for AF prevention. The goal of this study was to evaluate the associations of 9 inflammatory biomarkers (soluble CD14 (sCD14), interleukin 6 (IL-6), high sensitivity C reactive protein (hs-CRP), white blood cell count (WBC), soluble CD163 (sCD163), IL-18, IL-1 receptor antagonist, soluble tumor necrosis factor receptor 1 (sTNFR1), and soluble interleukin 2 receptor alpha (sIL-2R⍺)) with AF individually and jointly. The study included 5726 participants (median age 72 years). Of these individuals, 1836 developed AF over a median follow-up period of 11.5 years. After adjusting the inflammatory biomarkers, there was a significant association for IL-6, hazard ratio (HR), 1.14 (95% CI, 1.07-1.21), hs-CRP, HR, 1.05 (95% CI, 1.01-1.09); white blood cell count, HR, 1.18 (95% CI, 1.04-1.35), sTNFR1, HR, 1.21 (95% CI, 1.05-1.39), sIL-2R⍺, HR, 1.16 (95% CI, 1.05-1.29). On the other hand, sCD14, sCD163, IL-18, and IL-1 showed no association with AF. After concurrent adjustment, IL-6 was the only biomarker that was still significantly associated with AF (HR, 1.17 (95% CI, 1.07-1.26)), showing a 17% increased incidence risk. Overall, in this cohort study of older adults, 5 inflammatory biomarkers had a significant association with atrial fibrillation development, while the remaining 4 did not. These findings highlight the potential of IL-6 as a promising strategy for preventing AF.  

Image: PD

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