2 Minute Medicine Rewind August 24, 2020

Air pollution and family related determinants of asthma onset and persistent wheezing in children: nationwide case-control study

1. Exposure to particulate matter less than 2.5 um in diameter was identified as an environmental risk factor for pediatric asthma.

2. Family related risk factors for pediatric asthma include parental asthma, maternal smoking during pregnancy, lower parental income, and lower parental educational attainment.

Evidence Rating Level: 3 (Average)

Asthma is one of the most widespread conditions affecting children around the world. In the past, genetics were considered a significant risk factor due to children of asthmatic parents being more likely to have asthma themselves. However, rapidly increasing rates of asthma indicate that environmental and societal factors may be important to consider as well. Specifically, environmental factors such as air pollution and urbanisation, and family factors such as exposure to smoking, socioeconomic status (SES), and parental income, have all been associated with pediatric asthma. The current case-control study used a nationwide approach, evaluating 3 192 785 Danish children, born between 1997 and 2014 to investigate how air pollution and family factors are associated with asthma onset and persistent wheezing. Out of these, 122 842 were identified as asthmatic, meaning they were diagnosed with asthma or received at least two asthma-related medications between the ages of 1 and 15. Each asthmatic child was matched randomly with 25 non-asthmatic controls, with the same sex and a birth date within a week. For family factors, the results showed higher rates of asthma in children whose parents also had asthma, and whose mothers had smoked while pregnant (adjusted hazard ratio 2.29, 95% CI 2.22-2.35; HR 1.20, 95% CI 1.18-1.22 respectively). As well, lower rates of asthma were found in children of parents with high income and high educational attainment (HR 0.85, 95% Ci 0.81-0.89; HR 0.72, 95% CI 0.69-0.75 respectively). In terms of air pollution, exposure to particulate matter less than 2.5 um in a diameter was the only factor to be positively associated with asthma and persistent wheezing across all models. For every increase in pollutant concentration by 5 ug/m3, the HR was 1.05 (95% CI, 1.03-1.07). Study findings reinforce existing evidence associating low SES and increased air pollution with increased incidence of asthma. 


Left atrial emptying fraction determined during atrial fibrillation predicts maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation

1. Left atrial emptying fraction was identified as an independent prognostic factor for sinus rhythm maintenance, following direct current cardioversion in atrial fibrillation patients

Evidence Rating Level: 2 (Good)

Atrial fibrillation (AF) refers to an irregular, rapid heartbeat due to improper electrical signalling in the heart’s atria. To restore sinus rhythm (SR) in AF patients, direct current cardioversion (DCCV) is often used. Although DCCV restores SR in 90% of individuals, only 70% continue to have SR maintained for 12 months afterwards. To assess the prognosis of SR maintenance, echocardiographic imaging is used to evaluate factors such as left atrium volume index (LAVI) and left atrium emptying fraction (LAEF). However, past research has focused on assessing these prognostic factors during SR, after DCCV is used to correct AF. The current prospective cohort study aimed to determine which factors are the best predictors for SR maintenance, even before DCCV is applied. The population consisted of 146 patients with persistent AF, lasting at least seven days, to be treated with DCCV. Numerous factors related to the electrical and mechanical aspects of the atria were measured through echocardiographic imaging, prior to DCCV. After 12 months, 41.8% of patients had SR maintained. The results found that LAEF was significantly greater in the SR maintenance group than the AF recurrence group (mean±SD = 30.8±8.3% vs 24.6±10.4%, p < 0.0001). Furthermore, out of all echocardiographic variables measured, only LAEF was found to be an independent predictor for SR maintenance following 12 months (odds ratio 1.046, 95% CI 1.000-1.095, p = 0.049). Overall, this study was the first to identify LAEF as an independent prognostic factor for SR maintenance 12 months after DCCV. Study findings identify LAEF as a potential prognostic factor that may aid clinicians in identifying patients who may have less success with SR maintenance after DCCV, and require additional cardiac interventions. 


Long term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial

1. Targeted intraoperative radiotherapy for breast cancer has comparable long-term cancer-related outcomes as whole breast post-operative radiotherapy, and lower mortality from other causes.

Evidence Rating Level: 1 (Excellent)

Breast cancer is one of the most common cancers worldwide, with 2 million diagnoses and 626 000 deaths in 2018 alone. The treatment for breast cancer consists usually of breast conserving surgery, known as a lumpectomy, postoperative whole breast external beam radiotherapy (ERBT). However, a new radiotherapy treatment was developed known as immediate targeted intraoperative radiotherapy (TARGIT-IORT): This is a single treatment performed immediately following the lumpectomy, while the patient is still under anesthesia. Furthermore, TARGIT-IORT is done only on target tissues to avoid affecting nearby healthy tissues and organs. In this randomized controlled trial, researchers sought to determine whether TARGIT-IORT was non-inferior to EBRT, with the primary outcomes being local recurrence of cancer after five years, as well as long-term survival. The study population consisted of women over 45 years of age, 1140 in the TARGIT-IORT group and 1158 in the ERBT group. The TARGIT-IORT group was risk adapted, meaning that if certain risks/conditions were present following the lumpectomy and TARGIT-IORT treatment, ERBT would then be performed. 80% of TARGIT-IORT patients did not receive additional ERBT. The results found 24 local recurrences in the TARGIT-IORT group and 11 in the ERBT group, which translates to a 2.11% and 0.95% recurrence rate respectively (difference is 1.16%, 90% CI 0.32-1.99). This falls under the 2.5% threshold for non-inferiority, indicating that TARGIT-IORT is not inferior to ERBT. As well, there were fewer deaths in the TARGIT-IORT group, 42 compared to 56 (3.7% versus 4.8%). For long term follow-up (the interquartile range being 7.0-10.6 years), there was no significant difference in overall survival (hazards ratio 0.82, 95% CI 0.63-1.05, p = 0.13) or breast cancer mortality (HR 1.12, 95% CI 0.78-1.60, p = 0.54). Other cause mortality was significantly lower for the TARGIT-IORT group (HR 0.59, 95% CI 0.40-0.86, p = 0.005). Overall, this study demonstrated that risk adapted immediate TARGIT-IORT has comparable long-term cancer-related outcomes as ERBT, with lower non breast-cancer related mortality. This has implications for helping physicians and patients in making informed decisions on their preferred radiotherapy treatment.


Monitoring, treatment and control of blood glucose and lipids in Ontario First Nations people with diabetes

1. Indigenous individuals with diabetes were found to have poorer blood sugar and lipid levels, as well as higher use of diabetes medications, compared to non-Indigenous patients.

2. Indigenous individuals with diabetes had lower rates of HbA1c and LDL monitoring than the general population.

Evidence Rating Level: 2 (Good)

Diabetes is a metabolic disease that leads to high blood sugar, and can result in medical complications such as cardiovascular disease and renal dysfunction. To control diabetic symptoms and prevent these complications, glycated hemoglobin (HbA1c) and low-density lipoprotein (LDL) cholesterol are measured and monitored. Current guidelines recommend routine monitoring of HbA1c every 3-6 months, and LDL levels every 1-3 years. Around the world  however, diabetes and its resulting complications disproportionately affects Indigenous populations, due to the interplay between intergenerational trauma, social status, and metabolic health, and these disparities have been hypothesized to be reflected in screening as well. The purpose of this longitudinal, retrospective cohort study was to compare the monitoring, control, and treatment of diabetes in Indigenous versus non-Indigenous individuals, in Ontario, Canada. This involved accessing health administration data from 1995 to 2015, with a sample size of 22 240 Indigenous individuals and 1 319 503 other Ontarians. In terms of monitoring, both HbA1c and LDL monitoring rates were lower in Indigenous people than other Ontarians (as low as 20% for A1c monitoring in Indigenous men aged 20-34 years). However, younger individuals had the lowest monitoring rates overall, regardless of sex or Indigenous status. After controlling for age and sex, the HbA1c level was higher for Indigenous diabetic patients (7.59%, 95% CI 7.59-7.61) compared to other Ontarian diabetic patients (7.03%, 95% CI 7.02-7.03). Furthermore, 24.7% (95% CI 23.6-25.0) and 60.3% (95% CI 59.7-61.6) of Indigenous patients had poor HbA1c and LDL levels respectively, compared to other Ontarians (12.8%, 95% CI 12.1 to 13.5 for A1c; 52.0%, 95% CI 51.1 to 52.9 for LDL). In terms of treatment, more Indigenous patients took insulin than other Ontarians (28.1% versus 15.1%) and fewer Indigenous patients took no medications (28.3% versus 40.1%). In this study, clear disparities in screening have been identified. Should this be validated by further research, future intervention via policy making may be required to address this factor contributing to poorer outcomes in Indigenous patients with diabetes. 


For-profit long-term care homes and the risk of COVID-19 outbreaks and resident deaths

1. For-profit status of long term care homes (LTCs) were not associated with the odds of a COVID-19 outbreak.

2. For-profit status was associated with increased extent of outbreak and mortality rate. 

3. Older design standards of LTCs and chain ownership were associated with poorer COVID-19 outbreak outcomes.

Evidence Rating Level: 2 (Good)

In Canada, 80% of deaths from COVID-19 have come from patients living in long-term care homes (LTCs). There are several potential reasons for this, such as the elderly population being at greater risk for COVID-19 mortality, as well as the communal living arrangements. Moreover, there is particular concern over the outbreak risk in for-profit LTCs, since past research has found them to have higher hospital admission rates, more complaints from residents, as well as poorer hand hygiene and infection control. In the province of Ontario, although all LTC residents receive public funding, the homes themselves can be operated by for-profit, non-profit, or municipal parties. The purpose of this retrospective cohort study was to investigate the relationship between for-profit status and COVID-19 related outcomes in Ontario LTCs. Specifically, the primary outcome was risk of COVID-19 outbreak (at least 1 infected individual) extent of outbreak (the number of infected individuals), and death. Covariates analyzed included chain ownership, age of the home’s design standards, and COVID-19 outbreaks in the surrounding region. In total, the study included 623 LTCs in Ontario during the epidemic’s peak (March to May 2020). The results found that for-profit status was not associated with the odds of a COVID-19 outbreak (odds ratio 0.96, 95% CI 0.61-1.49, with non-profit LTCs as the reference). However, for-profit status was associated with the extent of an outbreak (risk ratio 1.96, 95% CI 1.26-3.05) and death (RR 1.78, 95% CI 1.03-3.07). Furthermore, older design standards were associated with the odds of an outbreak, extent of an outbreak, and death (OR 1.55, 95% CI 1.01-2.38; RR 1.88, 95% CI 1.27-2.79; RR 2.08, 95% CI 1.28-3.36 respectively). Chain ownership was also associated with outbreak extent and death (RR 1.84, 95% CI 1.08-3.15; RR 1.89, 95% CI 1.00-3.59 respectively). Overall, this study has implications for policy recommendations to improve for-profit LTCs’ abilities to handle outbreaks, such as by upgrading facilities to modern standards and addressing issues that stem from chain ownership.

Image: PD

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