2 Minute Medicine Rewind August 19, 2024

Suvorexant for reduction of delirium in older adults after hospitalization

1. In this randomized clinical trial of adults, the use of suvorexant compared with placebo was associated with decreased rates of delirium, although this difference was not statistically significant. 

Evidence Rating Level: 1 (Good)

Delirium is defined as a disturbed level of consciousness or cognition which often comes on acutely, triggered by a primary condition, and is commonly seen in the elderly population.  It can be divided into three categories: hyperactive, hypoactive, and mixed, with symptoms differing between them. Insomnia impacts delirium, so suvorexant, an orexin receptor antagonist and thus a sleep-promoting medication, was tested to see if it helps delirium prevention, especially in older adults after hospitalization. This randomized double-blind controlled trial was conducted at 50 hospitals in Japan and included individuals between the ages of 65 to 90 years who were at high risk for delirium and had been hospitalized. Individuals were excluded from the study if they developed delirium during the screening period, were taking psychotropic drugs, and had a history of drug or alcohol abuse, among a few others. A total of 203 participants were randomly assigned 1:1 to either receive 15 mg of suvorexant or placebo taken at bedtime for 5-7 days. If a participant developed delirium between randomization and the first dose of the medication, they were not to be given trial medication. Of the participants, 101 received suvorexant (mean [SD] age, 81.5 [4.5]; years) and 102 received placebo (mean [SD] age, 82.0 [4.9] years). At baseline, 189 participants (93.1%) had mild cognitive impairment, and 38 participants (18.7%) had a history of delirium. There was a lower percentage of delirium in the suvorexant group compared to the placebo group (17 of 101 [16.8%] vs 27 of 102 [26.5%]), however, these results are not statistically significant (-8.7% [95% CI, -20.1% to 2.6%]; P = .13). In further comparisons, suvorexant had a stronger benefit in patients with mild dementia (11 of 48 [22.9%] vs 18 of 40 [45.0%]; difference, -22.1% [95% CI, -40.8% to -2.2%]). Individuals with the hypoactive subtype did not have a strong treatment effect (6 of 101 [5.9%] for suvorexant vs 5 of 102 [4.9%] for placebo) whereas the hyperactive and mixed subtypes had a strong benefit (11 [10.9%] for suvorexant vs 22 [21.6%] for placebo). In this randomized clinical trial, suvorexant-treated participants had lower rates of delirium compared to placebo-treated patients, however this is not statistically significant.  

Continued homelessness and depressive symptoms in older adults 

1. In a cohort of adults experiencing homelessness at baseline, there was a significantly higher chance of experiencing depressive symptoms in the individuals who experienced continued homelessness compared to those who regained housing. 

Evidence Rating Level: 2 (Good) 

The prevalence of depression is higher among people experiencing homelessness; however, the directionality is unclear. The goal of this study was to understand the association between housing status and depressive symptoms in adults experiencing homelessness. The study recruited participants aged 50 or older who were experiencing homelessness between July 2013 and June 2014. Individuals were eligible to participate if they were experiencing homelessness as defined by the HEARTH (Homeless Emergency Assistance and Rapid Transition to Housing) Act, able to speak English, provide informed consent, and met the age criteria. The Hearth act defines someone as experiencing homelessness if they do not have an established address, are staying in a place not used for sleeping, fleeing domestic violence, or at risk of losing their house in the upcoming 2 weeks. Depressive symptoms were measured as the main outcome through the Center for Epidemiologic Studies-Depression (CES-D) scale, a short self-assessment. Test scores ranged from 0 to 3, with higher scores meaning higher depression severity.  A total of 450 participants, mean [SD] age, 58.5 (5.2) years, were included. Of these individuals, the mean (SD) number of chronic conditions was 1.5 (1.4) and 21.0% (96 people) reported experiencing some type of abuse in the past 6 months. The study was observed for 1640 person-years, wherein participants continued experiencing homelessness for 880 person-years (57.1%) and being housed for 715 person-years (44.3%). During a follow-up visit, 304 (78.0%) participants were housed while 332 (85.1%) were experiencing homelessness. The mean (SD) CES-D score was 18.4 (12.5), while a total of 226 participants (51.1%) had significant depressive symptoms, and 164 participants (36.4%) exhibited moderate to severe symptoms. Overall, in this cohort study of adults aged 50 or older who were experiencing homelessness at baseline, continued homelessness was associated with a higher odds of depressive symptoms compared to adults regaining housing. 

Vitamin B12 status and the risk of developing sepsis in patients with bacterial infection: a prospective observational cohort study 

1. In a cohort of adult patients who presented to the emergency department with a bacterial infection, there was an association between an elevated methylmalonic acid (MMA) concentration and developing sepsis. 

2. No association was found between holotranscobalamin (HTC) and concentrations of B12 in the development of sepsis in adults with bacterial infections. 

Evidence Rating Level: 1 (Excellent) 

Sepsis remains a prevalent cause of death in ICUs, with millions of incidences worldwide. A common risk factor for infection is malnutrition, with increasing indication that deficiency in vitamins increases susceptibility. Some previous studies have suggested a link between vitamin B12 deficiency, occurring in over 20% of people over 60, and inflammation. As B12 deficiency is only expected to increase with higher prevalence of plant-based diets as well as aging populations, this study aims to examine the relationship between B12 deficiency and sepsis, with the hope of increasing levels reducing potential cases of sepsis. In this single centre prospective observational cohort study based out of the University Hospital Zurich, B12 levels were evaluated by holotranscobalamin (HTC), B12 and methylmalonic acid (MMA), common indicators of B12 found in the body, and was compared to development of sepsis. Adult patients with fever in the emergency department (ED) and a quick Sequential Organ Failure Assessment score (qSOFA) of ≤1 who gave consent were enrolled, and subsequently had a blood sample taken and analysed for sepsis. Positive screening resulted in inclusion in the study, with B12 levels evaluated. The study analyzed 99 patient who met the criteria, of which 4 were receiving B12 supplementation, and 20 were deemed high risk of malnutrition. A total of 29 patients developed sepsis with an HTC concentration of 10 pmol/L lower (61 vs 71) in these patients (p=0.319) compared to those who did not develop sepsis. Concentrations of B12 and MMA for the sepsis group were 384 ng/L and 217 nmol/L respectively, compared to the non-sepsis group of 421 ng/L and 150 nmol/L, with p scores of 0.541 and 0.018 respectively. Statistically, while HTC and B12 were not indicators, increased MMA showed increased likelihood of developing sepsis. By taking blood samples as soon as the patient entered the ED, levels were able to be accurately assessed before treatments could alter levels of B12. Some limitations include low sample size and low diversity as most patients were white Europeans who have a lower prevalence of vitamin B12 deficiency. Overall, this prospective cohort study found that individuals who self-reported higher frequency and longer length of daytime napping were associated with an increased PD risk. While no causal connection could be established in the MR analysis due to low sample size, larger studies should be conducted to further determine the link between B12 deficiency and sepsis.

Renin–angiotensin system inhibitors and risk of hepatocellular carcinoma among patients with hepatitis B virus infection

1. In a cohort of patients with hepatitis B virus infection in China, the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were associated with a decreased risk of developing hepatocellular carcinoma and liver-related mortality, compared to the use of calcium channel blockers (CCBs) or thiazide diuretics (THZs).

Evidence Rating Level: 2 (Good) 

Chronic hepatitis B virus (HBV) affects hundreds of million people globally and has been a public health concern globally. Although advances have been made in treatments, HBV infection has remained a common cause of liver-related morbidity and mortality. There have been beliefs suggesting that the renin-angiotensin-aldosterone system (RAS) plays a key role in liver fibrosis, the precursor to liver cirrhosis. The most commonly used antihypertensive medications include RAS inhibitors (RASi), angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), both of which may be linked to a reduction in liver-related mortality. With this in mind, the goal of this study was to understand the association between the use of ACEIs or ARBs and the risk of developing hepatocellular carcinoma (HCC) and liver-related mortality, compared with the use of calcium channel blockers (CCBs) or thiazide diuretics (THZs). To achieve this goal, a propensity score-matched cohort study design was used to compare the risk of developing HCC in patients with an HBV infection who were started on ACEIs/ARBs with those started on CCBs/THZs. The primary outcome was new development of HCC, while the secondary outcome was liver-related mortality. Between the study period of January 1, 2012, and December 31, 2022, a total of 32 692 individuals with HBV infection who started ACEI/ARBs or CCBs/THZs were identified, with the median age of 58 (interquartile range [IQR] 49-68) years. Of these patients, 10 364 (31.7%) started on ACEIs/ARBs while 22 328 (68.3%) started on CCBs/THZs. During a mean follow-up period of 2.3 years, the incidence rates per 1000 person-years were 4.11 (95% CI 3.34-5.05) and 5.94 (95% CI 5.01-7.04) in the ACEIs/ARBs group and CCBs/THZs group respectively. Compared to starting CCBs/THZs, initiating ACEIs/ARBs was associated with a decreased risk of liver-related mortality (HR 0.77; 95% CI 0.64-0.93). The use of ACEIs/ARBs was associated with a smaller risk of developing incident HCC (HR 0.66, 95% CI 0.50-0.86), new-onset liver cirrhosis (HR 0.81, 95% CI 0.70-0.94) and liver-related mortality (HR 0.77, 95% CI 0.64-0.93). In a cohort study of patients with HBV infection, the use of ACEIs/ARBs, compared to the use of CCBs/THZs was associated with a decreased risk of new HCC development and liver-related deaths. 

Daytime napping and the incidence of Parkinson’s disease: a prospective cohort study with Mendelian randomization 

1. In this UK Biobank prospective cohort study, an increased frequency of self-reported daytime napping along with the duration of accelerometer measurements were associated with an increased risk of Parkinson’s Disease (PD). 

2. Although an association was found, there was no causal relationship between frequency of naps and PD risk in the Mendelian randomization (MR) analysis 

Evidence Rating Level: 1 (Excellent) 

Parkinson’s Disease (PD) is a severe neurological condition that is both the second most prevalent and fastest growing neurodegenerative disease since 1990. This study aims to examine the link between PD and daytime napping, a common lifestyle habit for the elderly, for which previous studies have been inconclusive in association. Aiming to overcome previous study design limitations, self-reported and accelerometer measured napping data of 393,302 people was pooled from UK Biobank. Prospective observational analysis, polygenic risk score (PRS) and Mendelian randomization (MR) were used to examine the link between daytime napping and PD. The participants in the study had a mean age of 56.27 years, with a median follow up of 12.18 years. 57.1% said they rarely napped, 37.7% sometimes napped, and 5.2% usually napped. The more frequent nappers had higher rates of other poor health factors, such as smoking and obesity, and were higher age and more likely to be male with lower socioeconomic status. After adjustment of covariates, those with more frequent napping had a higher risk of PD. Those who napped sometimes had a 13% increased prevalence of PD (HR, 1.13; 95% CI, 1.03–1.23; P = 0.009), and those who frequently napped had a 33% increased risk of PD (HR, 1.33; 95% CI, 1.14–1.55; P = 0.001) relative to those who did not nap. Some factors of the naps that increased risk were length, specifically, naps over an hour saw a 54% increase (HR, 1.54; 95% CI, 1.11–2.16; P = 0.01), and time of day in which the nap took place, with morning naps not showing an increased risk. However, the MR analysis showed no reciprocal causal relationship between PD and frequency of napping, although this part of the study faced issues of lower sample sizes. Additionally, no interaction was observed between napping and PRS for PD risk, with a potential being the Lew body pathological burden. The observational study confirms previous studies findings of increased risk of PD with higher rates of napping. Some limitations include potential unknown cofounders, and latency for REM sleep disorders being up to 10 years, and the study being predominately those of European descent. Overall, while the MR analysis did not show evidence, increased PD risk was seen among people who reported daytime napping.

Image: PD

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