1. In pregnant individuals, sickle cell trait was associated with an increased risk of stillbirth.
Evidence Rating Level: 2 (Good)
Sickle cell disease (SCD) is an inherited genetic disorder that distorts red blood cells into a crescent, or sickle, shape. SCD results when individuals have two abnormal alleles of the hemoglobin gene. Those with one abnormal allele have sickle cell trait (SCT), which is not considered a disease state because many carriers have at least 50% normal adult hemoglobin and are asymptomatic. However, it is possible for people with SCT to experience sickling of red blood cells under specific conditions (e.g. severe dehydration, hypoxia, etc.). Research has shown that individuals living with SCD who become pregnant are at increased risk of complications. However, the risk of pregnancy complications among those with SCT is unclear. Consequently, this retrospective cohort study aimed to evaluate whether there is an association between SCT and a stillbirth outcome. Information on deliveries occurring between January 1, 2010 and August 15, 2017 at 4 quaternary academic medical centers within the Penn Medicine health system in Pennsylvania was obtained. SCT and stillbirth outcomes were identified using clinical diagnosis codes recorded in the electronic health record. Other clinical complications, including cesarean deliveries, multiple gestation, pain crises, and blood transfusions, were also recorded. A total of 50 560 patients (63 334 deliveries), most of whom were aged 25 to 34 years (29 387 of 50 560 [58.1%]; mean [SD] age, 29.5 [6.1] years), were included. Of this population, 2068 patients (4.1%) with a sickle cell gene variation were identified: 164 patients (7.9%) with SCD (215 deliveries) and 1904 patients (92.1%) with SCT (2482 deliveries). After adjusting for risk factors of SCD and multiple gestation, SCT was found to be associated with an increased risk of stillbirth (adjusted odds ratio [aOR], 8.94; 95% CI, 1.05-75.79; P = .045). These findings highlight the need for clear pregnancy guidance for patients with SCT and systemic support for comprehensive coordinated care for SCT and SCD populations.
1. Preoperative intestinal dysbacteriosis was associated with higher rates of early postoperative diarrhea, infectious complications, and anastomotic leakage in colorectal cancer patients.
Evidence Rating Level: 2 (Good)
Among colorectal cancer (CRC) patients, surgical infections are a common complication, with an overall incidence of 18.9-46%. Anastomotic leakage results in prolonged hospitalization, reduced quality of life, and increased mortality. The gut microbiota plays a key role in postoperative recovery. Previous studies have shown that a low level of enteric microbial diversity correlated strongly with a higher incidence of postoperative infections and anastomotic disruption in pediatric and adult patients who underwent small intestinal resection. However, the loss of preoperative intestinal microbial diversity has not yet been directly identified as a potential risk factor for post-surgical outcomes. This prospective cohort study aimed to investigate the correlation between patterns of intestinal microbiota before surgery and postoperative complications in CRC patients. Between March 2016 and April 2019, a total of 353 patients who underwent CRC surgery were enrolled. Fecal samples were collected both at admission and at the first defecation after surgery. Patients were classified into three groups according to preoperative fecal examination results: Normal or slightly decreased intestinal microflora (Grade 1), moderate intestinal dysbacteriosis (Grade 2), and severe intestinal dysbacteriosis (Grade 3). Clinical outcomes were postoperative infections and anastomotic leakage within 30 days after surgery. At the preoperative assessment, 268 (75.9%) patients had normal or slightly decreased intestinal microflora, 58 (16.4%) patients had moderate intestinal dysbacteriosis, and 27 (7.6%) patients had severe intestinal dysbacteriosis. Patients with preoperative dysbacteriosis had a higher rate of early postoperative diarrhea (Grade 2: OR = 4.53, 95% CI 2.28–9.00; Grade 3: OR = 4.52, 95% CI 1.81–11.31), total complications (Grade 3 40.7% vs. Grade 2 25.9% vs. Grade 1 12.7%, P < 0.001), and anastomotic leakage (Grade 3 11.1% vs. Grade 2 5.2% vs. Grade 1 1.5%, P = 0.002). Consequently, preoperative dysbacteriosis may be an independent risk factor of various postoperative complications. Further research is warranted.
1. There was no difference in resolution of all COVID-19-related symptoms by day 30 between the ciclesonide and placebo groups.
2. Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 than those who were given placebo.
Evidence Rating Level: 1 (Excellent)
The SARS-CoV-2 COVID-19 pandemic is an ongoing global public health emergency. Symptoms of COVID-19 vary widely, ranging from asymptomatic to severe illness and death. Previous studies have shown that systemic dexamethasone resulted in lower 28-day mortality among patients with severe COVID-19. The role of inhaled corticosteroids, such as ciclesonide, for patients with mild to moderate coronavirus disease is less clear. This phase 3, multicenter, double-blind, randomized clinical trial explored the efficacy of a ciclesonide metered-dose inhaler (MDI) for treating non-hospitalized participants with symptomatic COVID-19 infection. Participants screened between June 11, 2020 and November 3, 2020 were randomly assigned to receive either ciclesonide MDI, 160 μg per actuation for a total of 2 actuations twice a day (total daily dose, 640 μg), or placebo for 30 days. The main outcome measure was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, fever, sore throat, muscle pain, headache, and new loss of smell or taste) by day 30. Secondary outcomes included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19. A total of 400 participants were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female). The median time to alleviation of all COVID-19–related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). Although ciclesonide did not achieve the primary efficacy end point, further research is needed to explore the role of inhaled steroids in reducing the incidence of long-term COVID-19 symptoms or post-acute sequelae of SARS-CoV-2.
1. Among patients with transient ischemic attack or ischemic stroke, elevated plasma levels of trimethyllysine were associated with cardiovascular death independent of traditional risk factors and trimethylamine N-oxide.
Evidence Rating Level: 2 (Good)
Recent work has shown that the gut microbiota may be capable of modifying the risk of developing cardiovascular disease. Specifically, the gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO), shows promise as a strong cardiovascular diagnostic or prognostic marker. Trimethyllysine is a relatively abundant posttranslational modification of protein in lysine residues in both plants and animals, which serves as a nutrient precursor of TMAO. Trimethyllysine has been associated with incident cardiovascular risks in acute coronary syndrome, independent of traditional cardiovascular risk factors and TMAO. However, few studies have examined the role of trimethyllysine in patients with stroke. This prospective cohort study examined the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with transient ischemic attack (TIA) or ischemic stroke. Information of 10 027 patients with TIA/ischemic stroke from the Third China National Stroke Registry (CNSR-III) was collected. Plasma levels of trimethyllysine were measured with mass spectrometry. Patients were followed up for clinical outcomes at 3 months, 6 months, and 1 year after onset and 1-year follow-up data for stroke outcomes were analyzed. Elevated trimethyllysine levels were found to be associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03–2.86) and all‐cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40–2.78). Trimethyllysine was associated with cardiovascular death independent of TMAO. No associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Future studies should aim to investigate the underlying mechanism between trimethyllysine and cardiovascular risk.
1. Implementation of an educational program based on Theory of Planned Behaviour improved knowledge, attitude, subjective norms, perceived behavioural control and behavioural intention relating to osteoporosis prevention among middle-aged individuals in Iran, relative to routine education on lifestyle changes.
Evidence Rating Level: 1 (Excellent)
The prevalence of chronic diseases, including osteoporosis, is increasing worldwide. It has been estimated that 20-50% of bone density changes in osteoporosis are related to lifestyle and hence, are modifiable. Consequently, osteoporosis prevention strategies include implementing educational programs focused on lifestyle modifications in the community setting. This randomized clinical trial assessed the effect of an educational program based on the Theory of Planned Behaviour (TPB), a framework used to predict health behaviours, on the osteoporosis preventative behaviours in middle-aged individuals. A total of 64 middle-aged individuals (aged 30-59 years) presenting to primary care centers affiliated with Kermanshah University in Iran were recruited and completed a researcher-made questionnaire. Participants were then randomly assigned to intervention or control groups. The intervention group (n = 32) participated in an educational program made up of six one-hour sessions designed based on TPB constructs. An emphasis was placed on using different interactive methods like group discussion and question-and-answer. The control group (n = 32) received routine education about lifestyle changes. Eight weeks after the intervention, the questionnaires were completed again. Before intervention, there was no significant difference in the mean score of knowledge, osteoporosis preventative behaviour, attitude, subjective norms, perceived behavioural control, and behavioural intention between intervention and control groups. After intervention, a significant difference was found in the mean score of knowledge, attitude, subjective norms, perceived behavioural control and behavioural intention between the cases in intervention and control groups (p<0.05). Results suggest that implementing an educational program that is compatible with culture, regional habits, and context can help to improve knowledge, behavior, attitude, norms, behavioral control, and behavioral intention as well as preventive behaviors and decrease the factors and habits that cause osteoporosis.
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