2 Minute Medicine Rewind April 20, 2020

Association Between Visit-to-Visit Blood Pressure Variability in Early Adulthood and Myocardial Structure and Function in Later Life

1. Greater variability in visit-to-visit systolic and diastolic blood pressure readings in early adulthood is associated with adverse myocardial structure changes and impaired systolic and diastolic function.

Evidence Rating: 2 (Good)

Blood pressure (BP) control remains one of the most important modifiable risk factors for cardiovascular health. Variability in BP measurements are commonly observed and clinical practice, and recent literature has suggested that increase in variability is independently associated with greater cardiovascular disease (CVD) risk and heart failure. In this retrospective cohort study, researchers used the data of 2400 patients from the Coronary Artery Risk Development in Young Adults (CARDIA) study to expand upon prior literature and investigate the association between BP variability and myocardial structure. Blood pressure of adults aged 18 to 30 years at baseline was measured over 8 visits over a 25-year interval, and participants received echocardiograms at year 25. Exposures of interest were visit-to-visit variability in systolic (BP) and diastolic BP, and primary outcomes were indices of myocardial structure, systolic function and diastolic function as observed on echocardiogram. In concordance with previous literature,  greater visit-to-visit systolic BP variability independent of the mean (VIM) was associated with higher LV mass index (β [SE], 2.66 [0.4]; P < .001), worse diastolic function (é) (β [SE], −0.40 [0.1]; P < .001), higher LV filling pressures (E/é) (β [SE], 0.37 [0.1]; P < .001), and worse global longitudinal strain (β [SE], 0.17 [0.1]; P = .002). Standard deviations of visit-to-visit systolic BP and diastolic BP variability were 8.5, and 7.1, respectively. Similar findings were reported when analyzing variability in DBP, though there were no significant associations between variability in either BP reading with LVEF or left atrial volume. This study represents the first investigation to comprehensively demonstrate an association between long-term BP variability and cardiac remodelling, and adds to a mounting body of evidence that suggests long term BP variability may be a potential important marker for predicting long term cardiovascular health. Using visit-to-visit BP variability as a potential means of identifying at risk patients may pose opportunities for earlier lifestyle or pharmacologic interventions to reduce cardiovascular burden later in life.

Psychological Impact of the COVID-19 Pandemic on Health Care Workers in Singapore

1. In the care of COVID-19 patients in Singapore non-medically-trained hospital personnel were more likely to experience anxiety than physicians and nurses, though psychological effects were clearly present among all workers.

Evidence Rating Level: 2 (Good)

Singapore witnessed a total of 200 confirmed cases of COVID-19 by March 13, 2020, an increase from 84 over the previous month. A total of 11 cases were in critical condition but no deaths were reported. This cross-sectional, case-control study utilized self-administered questionnaires to examine the psychological impact on healthcare workers during this pandemic, comparing both medically- and non-medically-trained hospital staff. Psychological symptoms included distress, anxiety, stress, and depression. A total of 470 individuals (median [IQR] age = 31 [28-36] years, 68.3% female) participated in this study, comprised of nurses (34.3%), physicians (28.7%), allied healthcare professionals (13.8%), maintenance workers (7.7%), administrators (7.0%), clerical staff (6.4%), and technicians (2.1%). Only physicians and nurses were considered medically-trained, which is approximately 63.0% of the total sample. About 14.5% of individuals screened positive for anxiety, 8.9% for depression, 6.6% for stress, and 7.7% for concern for Posttraumatic Stress Disorder (PTSD). Adjusted prevalence ratio for anxiety was found to be higher in non-medically-trained personnel than physicians and nurses (1.85, 95% CI 1.15 to 2.99, p = 0.011). Components of the Depression, Anxiety, and Stress Scales (DASS-21) were all higher in non-medically-trained personnel. While rates were relatively low compared to those anticipated, this may be due to the lack of COVID-19-related deaths at the time of the study. Further, the knowledge of frontline medical professionals in Singapore may have served as a protective factor against some of the uncertainty that could result in stress in others. In general, though, this study suggests that all workers in healthcare are likely to experience some form of psychological consequences of this pandemic.

Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study

1. Non-pharmaceutical interventions, including border closures, quarantine and isolation, social distancing, and other changes in population behavior were associated with a reduction of COVID-19 and influenza transmission in Hong Kong

Evidence Rating: 3 (Average)

As the COVID-19 pandemic continues to progress, there continue to be varying public health measures and strategies adopted by different municipalities and nations to mitigate transmission. While some cities and countries are quick to implement lockdown measures and promote social distancing for example, others are reluctant to do so, often due to its economic implications. In this study, researchers analyzed the transmission dynamics of COVID-19 in Hong Kong, a city that was relatively quick to implement public health measures such as border entry restrictions, quarantine of cases, and population behaviour changes such as social distancing and implementation of personal protective measures. Specifically, data of laboratory confirmed cases of COVID-19 cases, in addition to influenza hospitalizations, were used to estimate the daily effective reproduction number (Rt) of COVID-19 and influenza A H1N1. Following implementation of social distancing measures and changes in population behaviours in late January, COVID-19 transmissibility estimated by Rt appeared to decline, and remain stable at the critical threshold of 1 for 8 weeks in Hong Kong until March. Interestingly however, there was a substantial decrease in influenza transmission, with a 44% (95% CI 34–53%) reduction in transmissibility, from an Rt of 1·28 (95% CI 1·26–1·30) before the beginning of the school closures to 0·72 (0·70–0·74) during the closure weeks, in which paediatric hospitalisation rates also declined during this time span. As both COVID-19 and influenza have similar modes of transmission, data from this observational study suggest that public health measures such as social distancing and isolation are effective in reducing transmissibility. Although no single measure can be identified as the most responsible for this trend, these findings reinforce the importance of the cumulative efforts taken on by governments and communities across the world currently, as they may be critical in mitigating the effects of this pandemic.

A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia

1. Oral compound SEP-363856 was found to significantly reduce PANSS score from baseline during an acute exacerbation of schizophrenia compared to placebo.

Evidence Rating: 1 (Excellent)

Currently, the treatment options for acute schizophrenia exacerbations and psychotic episodes are relatively limited, with antipsychotics that tend to block dopamine D2 receptors being first line therapy. Limited treatment options may confer challenges in clinical practice, as D2 receptor antagonists have been shown to have limited efficacy in the treatment of blunted affect and cognitive impairment, and may have undesirable side effects in patients with concomitant movement disorders. As such, there may be value in exploration of novel pharmacological therapies that work through an alternative mechanism of action. In this randomized controlled trial, researchers enrolled 120 adult patients with an acute exacerbation of schizophrenia to either receive placebo or once-daily treatment with SEP-363856, an novel agent with agonist activity of the trace amine-associated receptor 1 (TAAR1) and 5-hydroxytryptamine type 1A (5-HT1A) receptor for 4 weeks. The primary end point of interest was change from baseline in total score on the Positive and Negative Symptom Scale (PANSS), a score measuring severity of psychotic symptoms. Compared to the placebo group, the treatment group achieved a significantly greater mean reduction on the PANSS at 4 weeks, at -9.7 points and -17.2 points, respectively (least-squares mean difference, −7.5 points; 95% confidence interval, −11.9 to −3.0; P=0.001), from a baseline measurement of roughly 100 points. The SEP-363856 treatment was generally well tolerated, with somnolence and gastrointestinal symptoms being the most common adverse event, and one sudden cardiac death. While further testing in larger trials must be completed to further investigate the safety and efficacy of the drug, preliminary findings are promising in the potential discovery of a new drug for the treatment of acute exacerbations of schizophrenia where the therapeutic options have conventionally been very limited.

Association of Cigarette Smoking With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

1. Cigarette smoking was associated with increased risk of antineutrophil cytoplasmic antibody-associated vasculitis.

Evidence Rating: 3 (Average)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) confers high mortality and morbidity for affected patients and likely has a multifactorial etiology. While contribution from environmental factors have been previously documented, the association between cigarette smoking and risk of AAV is unclear. To address this knowledge gap, researchers conducted a large case-control study with a cohort of 484 patients diagnosed with AAV between 2002 to 2017, and matched with 3 randomly-selected controls based on sex, race, and age to determine the possible associations between smoking status and AAV development. Ultimately, 473 cases of AAV were matched with 1419 controls, and it was found that patients with AAV were more likely to be former (OR, 1.6; 95% CI, 1.3-2.0) or current smokers (OR, 2.7; 95% CI, 1.8-4.1), with a dose-dependent relationship between risk and pack-years of exposure (P<.001). Likewise, there was a significantly greater proportion of current or former smokers among participants with AAV (54%) than controls (42%), with an increased odds ratio of having AAV in smokers versus controls (OR, 1.7, 95% CI, 1.4-2.2). The strongest associations were found among patients with MPO-ANCA-positive disease, and weaker associations were found in patients with PR3-ANCA-positive AAV. This study represents the first large scale study investigating the association between cigarette smoking and AAV, and provides evidence to suggest smoking as a modifiable risk factor for the potential development of AAV. While pathogenic mechanisms should be further explored to provide potential therapeutic targets, this study emphasizes yet another reason for why clinicians should strongly counsel against cigarette smoking in patients.

Image: PD

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