Evaluation of the early adverse effects of radiotherapy in breast cancer patients with COVID-19: Prospective single institutional study

The COVID-19 caused by the SARS-CoV-2 coronavirus is at the origin of a global pandemic. This pandemic has prompted the current health system to reorganize and rethink the care offered by health establishments. We report the early toxicity in patients infected with COVID-19 treated at the same time for early-stage breast cancer (BC). This is a monocentric prospective study of patients treated in our hospital between March 2020 and June 2020 and were diagnosed with COVID-19 infection. The inclusion criteria were to be irradiated for early-stage BC and to have a positive COVID-19 diagnosis on a PCR test and/or a lung computed tomography (CT) scan and/or suggestive clinical symptoms. Radiotherapy (RT) consisted of breast or chest wall irradiation with or without lymph node irradiation, with protocols adapted to pandemic situation. The treatment-related toxicity was graded according to the CTCAE (version 4.03). All 350 patients treated for early-stage BC were studied. Of them, 16 were presented with clinical symptoms of COVID-19 infection and of them, 12 had clinical, CT scan, and PCR confirmation. This entire cohort of 12 pts with median age of 56 (42–72) underwent their RT. During the radiotherapy, there were 9 pts presented radiation dermatitis, 8 (66%) were grade 1 and one was (8%) grade 2. Two patients with lymph nodes irradiation presented esophagitis grade 2. This prospective COVID-19 cohort, treated for early-stage BC demonstrated an acceptable toxicity profile with few low-grade adverse events. Longer follow-up is needed to confirm these findings.     

The safety of BCG revaccination: A systematic review

IntroductionRevaccination with Bacillus Calmette-Guérin (BCG) vaccine is not generally recommended due to a lack of proven efficacy of repeat doses for protection against tuberculosis. However, there is a growing interest in the use of BCG vaccine for its ‘off-target’ effects which might involve revaccination. We did a systematic review of the safety of BCG revaccination.MethodsMEDLINE (1946 to March 2020) and the BCG World Atlas (updated 2017) were searched, limiting to studies of BCG administration by the intradermal or percutaneous route. Adverse events as well as patient and vaccine characteristics were reviewed.ResultsThe search identified 388 articles, of which 24 met the inclusion criteria. These reported 22 studies comprising eight randomised trials, four case-control studies, four observational studies and six case series or reports. Overall, there was evidence for a small increase in the rate of mild local and systemic reactions. No serious adverse events were reported in immunocompetent individuals.ConclusionsEvidence to date suggests that revaccination with BCG vaccine carries minimal risk. Future studies of BCG vaccine for novel applications should report adverse event data stratified by prior BCG vaccination status.     

Exploratory assessment of treatment‐dependent random‐effects distribution using gradient functions

In analyzing repeated measurements from randomized controlled trials with mixed‐effects models, it is important to carefully examine the conventional normality assumption regarding the random‐effects distribution and its dependence on treatment allocation in order to avoid biased estimation and correctly interpret the estimated random‐effects distribution. In this article, we propose the use of a gradient function method in modeling with the different random‐effects distributions depending on the treatment allocation. This method can be effective for considering in advance whether a proper fit requires a model that allows dependence of the random‐effects distribution on covariates, or for finding the subpopulations in the random effects.     

A retrospective analysis of social media posts pertaining to COVID-19 vaccination side effects

ObjectivesWith an uprising influence of social media platforms like Twitter and Instagram a multitude of worldwide accessible information is available. Since the beginning of COVID-19 pandemic the exchange of medical information about several topics related to this infectious disease and its vaccination has increased rapidly. The purpose of this investigation was to assess the content associated with COVID-19 vaccination and its side effects and evaluate its educational quality.MethodsWe conducted this retrospective study to investigate 600 Twitter and Instagram posts by #covidvaccinesideeffects due to number of ‘likes’, comments, type of post, language, its purpose and source. In addition, posts were evaluated due to educational quality by three examiners of different educational levels.ResultsThe majority of posts showed 0 to 50 “likes” and 0 to 5 comments in English language. A comparison between Twitter and Instagram by the influence of application showed significant differences in number of posts and “likes” or comments (p < 0.05). The major post type were texts for Twitter (251; 83.7%) and videos for Instagram (104; 34.7%). While a majority of posts by #covidvaccinesideeffects report about the occurrence of side effects, the majority of them were mild and general COVID-19 vaccination feedback during the first 4 months was positive. But, only 3 to 7% were rated by “excellent” educational and validatable content. Interrater reliability between all three examiners presented a high concordance with 89% (p = 0.001).ConclusionsThis study presents an analysis of quantity and quality of social media content according to COVID-19 vaccinations and its side effects. It supports the deduction that most of the content on Twitter and Instagram is shared by patients and unclear sources and thus is limited informative. Nevertheless, influence of social media on medical information especially during COVID-19 pandemic is increasing and practitioners have to face its effect on their patients.     

How frequent are acute reactions to COVID-19 vaccination and who is at risk?

IntroductionOur objective was to describe and compare self-reported side effects of COVID-19 vaccines in the USA.MethodsA web-based registry enrolled volunteers who received a COVID-19 vaccine between March 19–July 15, 2021. We collected self-reported short-term side effects, medical consultation, hospitalization, and quality of life impact following completed vaccination regimens (Pfizer, Moderna, J&J).ResultsWe recruited 6,966 volunteers who completed their full course of vaccination (median age 48 years, IQR 35.0–62.0; 83.6% female): Pfizer 3,486; Moderna 2,857; J&J 623. Few (3.1%) sought medical care for post-vaccination side effects. Hospitalization (n = 17; 0.3%) and severe allergic reactions (n = 39; 0.6%) also were rare. Those with autoimmune disease or lung disease were approximately twice as likely to seek medical care (adjusted odds ratio (aOR) 2.01, 95% CI:1.39; 2.92 and aOR 1.70, 95% CI: 1.12; .58 respectively). 92.4% of participants reported ≥ 1 side effect (median 3), with injection site reactions (78.9%), fatigue (70.3%), headache (49.0%) reported most frequently. More side effects were reported after the second dose of two-dose vaccines (medians: 1 vs. 2 for Pfizer and 1 vs. 3 for Moderna for first and second doses respectively) versus 3 for J&J's single-dose vaccine. For the employed, the median number of workdays missed was one. Diabetics and those vaccinated against influenza were substantially less likely to report 3 or more symptoms (aOR 0.68, 95% CI: 0.56;0.82] and aOR 0.82, 95% CI: 0.73;0.93, respectively).DiscussionThe total side effect burden was, not unexpectedly, greater with two-dose regimens but all three vaccines appear relatively safe. Very few subjects reported side effects serious enough to warrant medical care or reported post-vaccination hospitalization. While these findings do not address possible long-term effects, they do inform on their short-term safety and tolerability and will hopefully provide some reassurance and positively inform the benefit-risk and pharmacoeconomic assessment for all three vaccines.See Clinicaltrials.gov NCT04368065.     

Long-term population impact of infant 10-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in adults in Finland

BackgroundLimited data are available on long-term indirect effects of ten-valent pneumococcal conjugate vaccine (PCV10) programmes. We evaluated changes in invasive pneumococcal disease (IPD) incidence, mortality, and serotype distribution in adults up to 9 years after infant PCV10 introduction.MethodsCulture-confirmed IPD cases ≥18 years (n = 5610; 85% were pneumonia) were identified through national, population-based laboratory surveillance; data were linked with population registry to conduct nationwide follow-up study. In a time-series model, we compared serotype-specific IPD incidence and associated 30-day mortality rates before and after PCV10 by using negative binomial regression models.ResultsDuring pre-PCV10 period (7/2004–6/2010), overall IPD incidence in adults ≥18 years increased yearly by 4.8%. After adjusting for trend and seasonality, the observed PCV10 serotype IPD incidence in 7/2018–6/2019 was 90% (12/100,000 person-years) lower than the expected rate without PCV10 program. Non-PCV10 serotype incidence was 40% (4.4/100,000 person-years) higher than expected; serotypes 3, 19A, 22F, and 6C accounted for most of the rate increase. However, incidence of non-PCV10 IPD levelled off by end of follow-up. The observed-expected incidence rate-ratio (IRR) was 0·7 (95 %CI 0·5–0.8) for all IPD and 0·7 (95 %CI 0·3–1·3) for IPD-associated 30-day mortality. Case-fatality proportion decreased from 11·9% to 10.0% (p < 0.01). In persons ≥65 years, the IRR was 0·7 (95 %CI 0·5–0.95).ConclusionsSignificant indirect effects were seen for vaccine-serotype IPD and for overall IPD in all adult age groups. For non-vaccine IPD, the incidence stabilized 5 years after infant PVC10 program introduction, resulting in a steady state in which non-vaccine IPD accounted for nearly 90% of overall IPD. Substantial pneumococcal disease burden remains in older adults.     

Genetic and Developmental Influences on Infant Mouse Ultrasonic Calling. III. Patterns of Inheritance in the Calls of Mice 3–9 Days of Age

Infant mice produce ultrasonic calls that may elicit retrieval by adult mice. Age-related differences and genetic effects, such as additivity and directional dominance, have been found for most call characteristics at 3 days of age. Significant maternal effects have been reported for calling rate. However, little is known about how the influence of these genetic effects changes with age. This study explored developmental-genetic patterns of inheritance of seven ultrasonic call characteristics at ages 3–9 days, from groups of mice derived from a complete 4 × 4 diallel cross. The results indicate that additive variance contributes significantly to all characteristics for all ages. Maternal effects have a small effect on call characteristics. Dominance effects decrease with age for rate, range, and length of calls, suggesting less selective pressure toward higher rates, greater range, and longer calls as pups become more competent thermoregulators.     

Human acetylator genotype: Relationship to colorectal cancer incidence and arylamine N-acetyltransferase expression in colon cytosol

Polymorphic expression of arylamine N-acetyltransferase (EC 2.3.1.5) may be a differential risk factor in metabolic activation of arylamine carcinogens and susceptibility to cancers related to arylamine exposures. Human epidemiological studies suggest that rapid acetylator phenotype may be associated with higher incidences of colorectal cancer. We used restriction fragment length polymorphism analysis to determine acetylator genotypes of 44 subjects with colorectal cancer and 28 non-cancer subjects of similar ethnic background (i.e., approximately 25% Black and 75% White). The polymorphic N-acetyltransferase gene (NAT2) was amplified by the polymerase chain reaction from DNA templates derived from human colons of colorectal and non-cancer subjects. No significant differences inNAT2 allelic frequencies (i.e., WT, M1, M2, M3 alleles) or in acetylator genotypes were found between the colorectal cancer and non-cancer groups. No significant differences inNAT2 allelic frequencies were observed between Whites and Blacks or between males and females. Cytosolic preparations from the human colons were tested for expression of arylamine N-acetyltransferase activity. Although N-acetyltransferase activity was expressed for each of the arylamines tested (i.e., p-aminobenzoic acid, 4-aminobiphenyl, 2-aminofluorene, -naphthylamine), no correlation was observed between acetylator genotype and expression of human colon arylamine N-acetyltransferase activity. Similarly, no correlation was observed between subject age and expression of human colon arylamine N-acetyltransferase activity. These results suggest that arylamine N-acetyltransferase activity expressed in human colon is catalyzed predominantly by NAT1, an arylamine N-acetyltransferase that is not regulated byNAT2 acetylator genotype. The ability to determine acetylator genotype from DNA derived from human surgical samples should facilitate further epidemiological studies to assess the role of acetylator genotype in various cancers.     

Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease

Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16).The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 g·h·l^–1, 923 g·h·l^–1 and 1300 g·h·l^–1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively.Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h^–1 in patients vs. 2.00 h^–1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls.Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.     

Anti-inflammatory activity of hamamelis distillate applied topically to the skin

Summary The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle.UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry.The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.