Acute Effects of Coffee Consumption on Health among Ambulatory Adults.

BACKGROUND: Coffee is one of the most commonly consumed beverages in the world, but the acute health effects of coffee consumption remain uncertain. METHODS: We conducted a prospective, randomized, case-crossover trial to examine the effects of caffeinated coffee on cardiac ectopy and arrhythmias, daily step counts, sleep minutes, and serum glucose levels. A total of 100 adults were fitted with a continuously recording electrocardiogram device, a wrist-worn accelerometer, and a continuous glucose monitor. Participants downloaded a smartphone application to collect geolocation data. We used daily text messages, sent over a period of 14 days, to randomly instruct participants to consume caffeinated coffee or avoid caffeine. The primary outcome was the mean number of daily premature atrial contractions. Adherence to the randomization assignment was assessed with the use of real-time indicators recorded by the participants, daily surveys, reimbursements for date-stamped receipts for coffee purchases, and virtual monitoring (geofencing) of coffee-shop visits. RESULTS: The mean (±SD) age of the participants was 39±13 years; 51% were women, and 51% were non-Hispanic White. Adherence to the random assignments was assessed to be high. The consumption of caffeinated coffee was associated with 58 daily premature atrial contractions as compared with 53 daily events on days when caffeine was avoided (rate ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). The consumption of caffeinated coffee as compared with no caffeine consumption was associated with 154 and 102 daily premature ventricular contractions, respectively (rate ratio, 1.51; 95% CI, 1.18 to 1.94); 10,646 and 9665 daily steps (mean difference, 1058; 95% CI, 441 to 1675); 397 and 432 minutes of nightly sleep (mean difference, 36; 95% CI, 25 to 47); and serum glucose levels of 95 mg per deciliter and 96 mg per deciliter (mean difference, -0.41; 95% CI, -5.42 to 4.60). CONCLUSIONS: In this randomized trial, the consumption of caffeinated coffee did not result in significantly more daily premature atrial contractions than the avoidance of caffeine. (Funded by the University of California, San Francisco, and the National Institutes of Health; CRAVE ClinicalTrials.gov number, NCT03671759.).

Growing up and moving out: Migration and the demographic transition in low- and middle-income nations.

International migration has increased since 1990, with increasing numbers of migrants originating from low- and middle-income countries (LMICs). Efforts to explain this compositional shift have focused on wage gaps and other push and pull factors but have not adequately considered the role of demographic factors. In many LMICs, child mortality has fallen without commensurate economic growth and amid high fertility. This combination increases young adult populations and is associated with greater outmigration: in the poorest countries, we estimate that a one-percentage-point increase in the five-year lagged growth rate of the population of 15-24-year-olds was associated with a 15 per cent increase in all-age outmigrants, controlling for other factors. Increases in growth of young adult populations led to 20.4 million additional outmigrants across 80 countries between 1990 and 2015. Understanding the determinants of these migration shifts should help policymakers in origin and destination countries to maximize their potential positive effects.

Prospective arrhythmia surveillance after a COVID-19 diagnosis.

BACKGROUND: Cardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease. OBJECTIVE: To determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis. METHODS: Adults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations. RESULTS: A total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34-126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5-13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of <1%; one participant had a 2.8% supraventricular ectopic burden and one had a 15.4% ventricular ectopic burden. While 47 (92%) participants triggered their monitor for palpitation symptoms, 78% of these triggers were for either sinus rhythm or sinus tachycardia. CONCLUSIONS: We did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation: The I-STOP-AFib Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is the most common arrhythmia. Although patients have reported that various exposures determine when and if an AF event will occur, a prospective evaluation of patient-selected triggers has not been conducted, and the utility of characterizing presumed AF-related triggers for individual patients remains unknown. Objective: To test the hypothesis that n-of-1 trials of self-selected AF triggers would enhance AF-related quality of life. Design, Setting, and Participants: A randomized clinical trial lasting a minimum of 10 weeks tested a smartphone mobile application used by symptomatic patients with paroxysmal AF who owned a smartphone and were interested in testing a presumed AF trigger. Participants were screened between December 22, 2018, and March 29, 2020. Interventions: n-of-1 Participants received instructions to expose or avoid self-selected triggers in random 1-week blocks for 6 weeks, and the probability their trigger influenced AF risk was then communicated. Controls monitored their AF over the same time period. Main Outcomes and Measures: AF was assessed daily by self-report and using a smartphone-based electrocardiogram recording device. The primary outcome comparing n-of-1 and control groups was the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score at 10 weeks. All participants could subsequently opt for additional trigger testing. Results: Of 446 participants who initiated (mean [SD] age, 58 [14] years; 289 men [58%]; 461 White [92%]), 320 (72%) completed all study activities. Self-selected triggers included caffeine (n = 53), alcohol (n = 43), reduced sleep (n = 31), exercise (n = 30), lying on left side (n = 17), dehydration (n = 10), large meals (n = 7), cold food or drink (n = 5), specific diets (n = 6), and other customized triggers (n = 4). No significant differences in AFEQT scores were observed between the n-of-1 vs AF monitoring-only groups. In the 4-week postintervention follow-up period, significantly fewer daily AF episodes were reported after trigger testing compared with controls over the same time period (adjusted relative risk, 0.60; 95% CI, 0.43- 0.83; P < .001). In a meta-analysis of the individualized trials, only exposure to alcohol was associated with significantly heightened risks of AF events. Conclusions and Relevance: n-of-1 Testing of AF triggers did not improve AF-associated quality of life but was associated with a reduction in AF events. Acute exposure to alcohol increased AF risk, with no evidence that other exposures, including caffeine, more commonly triggered AF. Trial Registration: ClinicalTrials.gov Identifier: NCT03323099.

Emergency activations for chest pain and ventricular arrhythmias related to regional COVID-19 across the US.

Evidence that patients may avoid healthcare facilities for fear of COVID-19 infection has heightened the concern that true rates of myocardial infarctions have been under-ascertained and left untreated. We analyzed data from the National Emergency Medical Services Information System (NEMSIS) and incident COVID-19 infections across the United States (US) between January 1, 2020 and April 30, 2020. Grouping events by US Census Division, multivariable adjusted negative binomial regression models were utilized to estimate the relationship between COVID-19 and EMS cardiovascular activations. After multivariable adjustment, increasing COVID-19 rates were associated with less activations for chest pain and non-ST-elevation myocardial infarctions. Simultaneously, increasing COVID-19 rates were associated with more activations for cardiac arrests, ventricular fibrillation, and ventricular tachycardia. Although direct effects of COVID-19 infections may explain these discordant observations, these findings may also arise from patients delaying or avoiding care for myocardial infarction, leading to potentially lethal consequences.

Predictors of incident SARS-CoV-2 infections in an international prospective cohort study.

OBJECTIVE: Until effective treatments and vaccines are made readily and widely available, preventative behavioural health measures will be central to the SARS-CoV-2 public health response. While current recommendations are grounded in general infectious disease prevention practices, it is still not entirely understood which particular behaviours or exposures meaningfully affect one's own risk of incident SARS-CoV-2 infection. Our objective is to identify individual-level factors associated with one's personal risk of contracting SARS-CoV-2. DESIGN: Prospective cohort study of adult participants from 26 March 2020 to 8 October 2020. SETTING: The COVID-19 Citizen Science Study, an international, community and mobile-based study collecting daily, weekly and monthly surveys in a prospective and time-updated manner. PARTICIPANTS: All adult participants over the age of 18 years were eligible for enrolment. PRIMARY OUTCOME MEASURE: The primary outcome was incident SARS-CoV-2 infection confirmed via PCR or antigen testing. RESULTS: 28 575 unique participants contributed 2 479 149 participant-days of data across 99 different countries. Of these participants without a history of SARS-CoV-2 infection at the time of enrolment, 112 developed an incident infection. Pooled logistic regression models showed that increased age was associated with lower risk (OR 0.98 per year, 95% CI 0.97 to 1.00, p=0.019), whereas increased number of non-household contacts (OR 1.10 per 10 contacts, 95% CI 1.01 to 1.20, p=0.024), attending events of at least 10 people (OR 1.26 per 10 events, 95% CI 1.07 to 1.50, p=0.007) and restaurant visits (OR 1.95 per 10 visits, 95% CI 1.42 to 2.68, p<0.001) were associated with significantly higher risk of incident SARS-CoV-2 infection. CONCLUSIONS: Our study identified three modifiable health behaviours, namely the number of non-household contacts, attending large gatherings and restaurant visits, which may meaningfully influence individual-level risk of contracting SARS-CoV-2.

Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events.

BACKGROUND: Patients' self-reports suggest that acute alcohol consumption may trigger a discrete atrial fibrillation (AF) event. OBJECTIVE: To objectively ascertain whether alcohol consumption heightens risk for an AF episode. DESIGN: A prospective, case-crossover analysis. SETTING: Ambulatory persons in their natural environments. PARTICIPANTS: Consenting patients with paroxysmal AF. MEASUREMENTS: Participants were fitted with a continuous electrocardiogram (ECG) monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded using a button on the ECG recording device. Fingerstick blood tests for phosphatidylethanol (PEth) were used to corroborate ascertainments of drinking events. RESULTS: Of 100 participants (mean age, 64 years [SD, 15]; 79% male; 85% White), 56 had at least 1 episode of AF. Results of PEth testing correlated with the number of real-time recorded drinks and with events detected by the transdermal alcohol sensor. An AF episode was associated with 2-fold higher odds of 1 alcoholic drink (odds ratio [OR], 2.02 [95% CI, 1.38 to 3.17]) and greater than 3-fold higher odds of at least 2 drinks (OR, 3.58 [CI, 1.63 to 7.89]) in the preceding 4 hours. Episodes of AF were also associated with higher odds of peak blood alcohol concentration (OR, 1.38 [CI, 1.04 to 1.83] per 0.1% increase in blood alcohol concentration) and the total area under the curve of alcohol exposure (OR, 1.14 [CI, 1.06 to 1.22] per 4.7% increase in alcohol exposure) inferred from the transdermal ethanol sensor in the preceding 12 hours. LIMITATION: Confounding by other time-varying exposures that may accompany alcohol consumption cannot be excluded, and the findings from the current study of patients with AF consuming alcohol may not apply to the general population. CONCLUSION: Individual AF episodes were associated with higher odds of recent alcohol consumption, providing objective evidence that a modifiable behavior may influence the probability that a discrete AF event will occur. PRIMARY FUNDING SOURCE: National Institute on Alcohol Abuse and Alcoholism.

Predictors of incident viral symptoms ascertained in the era of COVID-19.

BACKGROUND: In the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission. METHODS: We conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a smartphone. We collected self-reported characteristics, exposures, and behaviors, as well as smartphone-based geolocation data. Our main outcome was incident symptoms of viral infection, defined as fevers and chills plus one other symptom previously shown to occur with SARS-CoV-2 infection, determined by daily surveys. FINDINGS: Among 14, 335 participants residing in all 50 US states and 93 different countries followed for a median 21 days (IQR 10-26 days), 424 (3%) developed incident viral symptoms. In pooled multivariable logistic regression models, female biological sex (odds ratio [OR] 1.75, 95% CI 1.39-2.20, p<0.001), anemia (OR 1.45, 95% CI 1.16-1.81, p = 0.001), hypertension (OR 1.35, 95% CI 1.08-1.68, p = 0.007), cigarette smoking in the last 30 days (OR 1.86, 95% CI 1.35-2.55, p<0.001), any viral symptoms among household members 6-12 days prior (OR 2.06, 95% CI 1.67-2.55, p<0.001), and the maximum number of individuals the participant interacted with within 6 feet in the past 6-12 days (OR 1.15, 95% CI 1.06-1.25, p<0.001) were each associated with a higher risk of developing viral symptoms. Conversely, a higher subjective social status (OR 0.87, 95% CI 0.83-0.93, p<0.001), at least weekly exercise (OR 0.57, 95% CI 0.47-0.70, p<0.001), and sanitizing one's phone (OR 0.79, 95% CI 0.63-0.99, p = 0.037) were each associated with a lower risk of developing viral symptoms. INTERPRETATION: While several immutable characteristics were associated with the risk of developing viral symptoms, multiple immediately modifiable exposures and habits that influence risk were also observed, potentially identifying readily accessible strategies to mitigate risk in the COVID-19 era.

Blocking transmembrane219 protein signaling inhibits autophagy and restores normal cell death.

Autophagy plays a vital role in tumor therapy and survival of dormant tumor cells. Here we describe a novel function of a protein known as Transmembrane 219 (TM219) as an autophagy activator. TM219 is a small membrane protein expressed in all known human tissues except the thymus. We used biochemical approaches to identify calmodulin and calmodulin dependent protein kinase II as a part of TM219 protein complex. Then, we employed in vitro reconstitution system and fluorescence anisotropy to study the requirements of TM219 to bind calmodulin in vitro. We also used this system to study the effects of a synthetic peptide derived from the sequence of the short cytoplasmic tail of TM219 (SCTT) on calmodulin-TM219 receptor interactions. We conjugated SCTT peptide with a pH Low Insertion peptide (pHLIP) for optimal cellular delivery. We finally tested the effects of SCTT-pHLIP on triple negative human breast cancer cells in three dimension culture. Our data defined a novel function of TM219 protein and an efficient approach to inhibit it.