2 Minute Medicine Rewind December 20, 2021

SARS-CoV-2 vaccination and myocarditis or myopericarditis: Population based cohort study

1. mRNA-1273 (Moderna) vaccination was associated with a significantly increased risk of myocarditis/myopericarditis in the Danish population.

2. BNT162b2 (Pfizer-BioNTech) vaccination was associated with a significantly increased risk of myocarditis/myopericarditis among female participants only.

3. The absolute rate of myocarditis/myopericarditis after SARS-CoV-2 vaccination was low.

Evidence Rating Level: 2 (Good)

Myocarditis and myopericarditis can result in chronic heart failure or death. Previous research has suggested an association between SARS-CoV-2 vaccination and myocarditis/myopericarditis. This association is thought to occur especially after the second booster dose of mRNA vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). To date, no publicly available controlled cohort studies have examined this association in a complete population. Consequently, this Denmark-based prospective cohort study explored this association further using population-based registers containing data on vaccinations, hospital admissions, and results of laboratory assays of blood samples. A total of 4,931,775 individuals, aged 12 years or older, were followed from October 1, 2020 to October 5, 2021. The primary outcome, myocarditis or myopericarditis, was defined as a combination of increased troponin levels, a hospital diagnosis, and a hospital stay lasting more than 24 hours. Follow up time before vaccination was compared with follow up time 0-28 days from the day of vaccination for both first and second doses. During follow up, 269 participants developed myocarditis/myopericarditis, of whom 196 (73%) were male. Of 3,482,295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis/myopericarditis within 28 days of vaccination (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. Among 498,814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis/myopericarditis within 28 days of vaccination (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. It was concluded that mRNA-1273 (Moderna) vaccination was associated with a significantly increased risk of myocarditis/myopericarditis in the Danish population, while BNT162b2 (Pfizer-BioNTech) vaccination was associated with a significantly increased risk among female participants only. However, the absolute rate of myocarditis/myopericarditis after SARS-CoV-2 vaccination was low. Further studies may explore this association in smaller subgroups.

Factors associated with undertriage in patients classified by the need to visit a hospital by telephone triage: A retrospective cohort study

1. Old age, diabetes mellitus, dementia, and a history of cerebral infarction were associated with undertriage.

Evidence Rating Level: 2 (Good)

Prehospital telephone triage systems help patients determine their need for a hospital visit and play a key role in managing patient flow and hospital workload. In Tokyo, Japan, a private after-hours house call (AHHC) medical service was recently established. This service provides telephone consultations, classifying patients into two of five categories laid out in pre-defined telephone triage protocols, namely “need to visit a hospital within 1 hour (orange)” and “need to visit a hospital within 6 hours (yellow).” Previous research on AHHC medical services have explored their efficiency, quality, and safety. However, it is unclear if patients’ present and past histories cause undertriage, especially in patients who are classified under orange and yellow categories by telephone triage. Consequently, this retrospective cohort study investigated factors associated with undertriage by comparing patients assessed as being appropriately triaged with those assessed as being undertriaged. All patients who used a single AHHC medical service in Tokyo, Japan and were classified by telephone triage into either orange or yellow categories between November 1, 2019 and November 30, 2020 were included. Following home consultation, AHHC doctors classified patients as Grade 1 (treatable with over-the-counter medications), 2 (requires hospital or clinic visit), or 3 (requires ambulance transportation). Patients classified as Grades 2 or 3 were defined as appropriately triaged or undertriaged, respectively. A total of 10,742 eligible patients were identified, of which 10,479 (97.6%) were appropriately triaged and 263 (2.4%) were undertriaged. Multivariable logistic regression analyses revealed patients aged 16–64, 65–74, and ≥ 75 years (adjusted odds ratio [OR], 2.40 [95% confidence interval {CI} 1.71–3.36], 8.57 [95% CI 4.83–15.2], and 14.9 [95% CI 9.65–23.0], respectively; those with diabetes mellitus (2.31 [95% CI 1.25–4.26]); those with dementia (2.32 [95% CI 1.05–5.10]); and those with a history of cerebral infarction (1.98 [95% CI 1.01–3.87]) were more likely to be undertriaged. These findings may guide how telephone triage protocols in Tokyo, Japan may be modified to reduce undertriaging.

Effect of values affirmation on reducing racial differences in adherence to hypertension medication: The HYVALUE randomized clinical trial

1.  A values affirmation intervention did not improve hypertension medication adherence or blood pressure among Black versus White patients with uncontrolled hypertension.

2. A values affirmation intervention was associated with higher patient activation for managing their own health.

Evidence Rating Level: 1 (Excellent)

In the United States, Black individuals have a higher prevalence of uncontrolled hypertension than White individuals. Furthermore, rates of adherence to hypertension medication are lower in Black individuals than White individuals. Stereotype threat, defined as the fear or anxiety of confirming a negative stereotype about one’s social group, may contribute to ethnic and racial differences in medication adherence. Values affirmation interventions ask patients to reflect on and write about values of importance to them and have been found to be helpful for targeting stereotype threat, improving patient-provider communication, and reducing racial disparities. The Hypertension and Values (HYVALUE) randomized clinical trial examined whether a values affirmation writing exercise disrupted negative effects of stereotype threat and improves hypertension medication adherence among self-identified non-Hispanic Black vs. White patients. Of 20,777 eligible patients with uncontrolled hypertension who were taking antihypertensive medications, a total of 960 were enrolled between February 1, 2017 and December 31, 2019. Participants were randomly assigned to an intervention or a control writing exercise delivered immediately before a clinic appointment. From a list of 11 values, intervention patients wrote about their most important values while control patients wrote about their least important values. Hypertension medication adherence was measured using pharmacy fill data at baseline, 3 months, and 6 months. Secondary outcomes included systolic and diastolic blood pressure (BP) and patient activation to manage their health. Of 960 patients, 474 (286 women [60.3%]; 256 Black patients [54.0%]; mean [SD] age, 63.4 [11.9] years) were randomly assigned to the intervention group and 486 (288 women [59.3%]; 272 Black patients [56.0%]; mean [SD] age, 62.8 [12.0] years) to the control group. Baseline medication adherence was lower (318 of 482 [66.0%] vs 331 of 412 [80.3%]) and mean (SE) BP higher among Black patients compared with White patients (systolic BP, 140.6 [18.5] vs 137.3 [17.8] mm Hg; diastolic BP, 83.9 [12.6] vs 79.7 [11.3] mm Hg). Compared with baseline, pharmacy fill adherence did not differ between intervention and control groups at 3 months (odds ratio [OR], 0.91 [95% CI, 0.57-1.43]) or at 6 months (OR, 0.86 [95% CI, 0.53-1.38]). There were also no treatment effect differences in pharmacy fill adherence by patient race (Black patients at 3 months: OR, 1.08 [95% CI, 0.61-1.92]; at 6 months: OR, 1.04 [95% CI, 0.58-1.87]; White patients at 3 months: OR, 0.68 [95% CI, 0.33-1.44]; at 6 months: OR, 0.55 [95% CI, 0.24-1.27]). In adjusted models, patient activation was higher in intervention patients than in control patients (mean difference, 2.3 [95% CI, 0.1-4.5]). Values affirmation may equip patients with resources to overcome stereotype threat but does not address structural discrimination.

Effect of treatment of clinical seizures vs. electrographic seizures in full-term and near-term neonates: A randomized clinical trial

1. When compared with treatment of clinical seizures alone, anticonvulsant treatment of electrographic seizures was not associated with reduced rates of neurodevelopment impairment or mortality in full-term or near-term neonates.

2. Treatment of clinical seizures alone was associated with improved cognitive outcomes at 2 years.

Evidence Rating Level: 1 (Excellent)

Seizures are the most common manifestation of neonatal encephalopathy. Neonatal seizures are associated with an increased risk of impaired neurodevelopment, including post-neonatal epilepsy, cognitive and motor deficits, and behavioural problems. As most neonatal seizures are subclinical, bedside neuromonitoring with amplitude-integrated EEG (aEEG) has been widely adopted in NICUs. Phenobarbital is considered first-line treatment for neonatal seizures. However, research has shown that phenobarbital and several other anticonvulsants are relatively ineffective and potentially cause apoptotic neurodegeneration when administered during critical periods of brain development. These drugs also tend to suppress clinical seizures more than electrical ones. There is ongoing debate about whether all electrographic neonatal seizures, even those without a clinical correlate, should be treated or if the treatments themselves contribute to neurological disruption and injury. Consequently, this randomized clinical trial investigated if drug treatment of all clinically and electrographically detected seizures, compared with the treatment of clinically detected seizures alone, reduced neurodevelopmental morbidity and mortality in encephalopathic term or near-term neonates. Participants were recruited between 2012 and 2016 and included neonates with encephalopathy at 35 weeks’ gestation or more and younger than 48 hours old. Neonates were randomized to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Participants were followed up until 2 years of age. The primary outcome was death or severe disability at 2 years of age. A total of 86 neonates were included in each group. Ten of 86 (9%) neonates in ESG and 4 of 86 (4%) in CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). Cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, −6.5 [95% CI, −1.2 to −11.8]; P = .01). This study concluded that treating electrographic and clinical seizures did not significantly reduce morbidity or mortality in a heterogenous group of neonates. Future research should focus on more effective anticonvulsant therapy.

Randomized controlled trial comparing 1-year outcomes of low-energy femtosecond laser-assisted cataract surgery versus conventional phacoemulsification

1. Low-energy FLACS resulted in less endothelial cell count loss post-operatively compared with conventional phacoemulsification.

2. Patients receiving low-energy FLACS had significantly higher aqueous prostaglandin, IL-6, IL-8, and INF-γ levels, leading to greater anterior chamber inflammation on the first day after surgery.

3. Patients’ subjective surgical experiences did not differ considerably between low-energy FLACS and conventional phacoemulsification.

Evidence Rating Level: 1 (Excellent)

Femtosecond laser-assisted cataract surgery (FLACS) is a safe and effective procedure and is quickly becoming an alternative to conventional phacoemulsification. Previous research comparing these techniques have primarily used observational cohort designs. This randomized controlled trial compared 1-year clinical outcomes of low-energy FLACS versus conventional phacoemulsification in the same patient. A total of 85 patients were randomized to receive FLACS in one eye and conventional phacoemulsification in the other eye. Clinical data, including phacoemulsification energy parameters, uncorrected and corrected distance visual acuities, manifest refraction spherical equivalent, central corneal thickness, endothelial cell count, anterior chamber flare, and post-operative complications were obtained for 1 year. Aqueous humor was collected for analysis and patient-reported outcomes on surgical experiences were evaluated. Compared with conventional phacoemulsification, low-energy FLACS had significantly less endothelial cell count reduction at 3 months (1.5 ± 0.3% vs. 7.0 ± 2.4%; P < 0.01) and 1 year (8.2 ± 2.8% vs. 11.2 ± 3.6%; P = 0.03). There were no significant differences in other clinical factors. FLACS resulted in significantly higher aqueous prostaglandin (PGE)₂ (P < 0.01), interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.03), and interferon (IFN)-γ (P = 0.04) concentrations and greater anterior chamber flare at 1 day (P = 0.02). Patients’ subjective surgical experiences, including duration of procedure and perceived inconvenience, did not differ considerably between groups. Study findings improve understanding of FLACS, further highlighting its comparability to conventional phacoemulsification.

Image: PD

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