2 Minute Medicine Rewind June 28, 2021

Relation of severe COVID-19 in Scotland to transmission-related factors and risk conditions eligible for shielding support: REACT-SCOT case-control study

1. Very high risk individuals that qualified for shielding interventions from COVID-19 were still at elevated risk for developing a severe infection.

2. Recent hospital exposures were the greatest risk factor for developing a case of severe COVID-19, among patients eligible for shielding interventions.

Evidence Rating Level: 3 (Average)

Towards the beginning of the COVID-19 pandemic, Scotland’s public health authorities created a list of conditions they deemed to be at moderate and very high risk for contracting the virus. For instance, patients that have had blood or bone marrow cancer, or patients on immunosuppression therapies, fell under the very high risk category. These high risk individuals and their households qualified for “shielding” interventions, such as free food and medication delivery services. The aim of this case-control study was to evaluate the shielding programme’s effectiveness by comparing the incidence of severe COVID-19 infections among shielded and non-shielded individuals, and identifying factors that increased the likelihood of severe COVID-19 within the shielding group. All 178,578 COVID-19 cases found in Scotland (from March 2020 to February 2021) were matched to 10 controls who had never been diagnosed with COVID-19, and shared the same sex and 1-year age range. They were classified into no risk, moderate risk, and very high risk categories. Out of the 212,702 individuals qualified for shielding, 2.9% received a diagnosis of COVID-19, 0.2% entered critical care, and 0.7% died. When compared to the no risk category, the severe COVID-19 rate ratio was 3.21 (95% CI 3.01-3.41, p < 0.001) for moderate risk and 6.3 (95% CI 5.8-6.8, p < 0.001) for very high risk (shielding eligible) patients. Within the shielding category, solid organ transplant patients were at the great risk, with a rate ratio of 13.4 (95% CI 9.6-18.8, p < 0.001). In terms of risk factors, a greater number of adults in a household, but not kids, was associated with higher risk for a severe infection within the shielding group. The strongest risk factor was recent hospital exposure, with a rate ratio of 6.0 (95% CI 4.7-7.7, p < 0001), with 45% of serious cases from shielding individuals having a recent hospital exposure. Overall, patients in the shielded category did experience higher risk for a severe COVID-19 infection, with the number of adults in a household and hospital transmissions being potential contributing factors to the elevated risk.

Epidemiologic analysis of chilblains cohorts before and during the COVID-19 pandemic

1. The incidence of chilblains increased during the COVID-19 pandemic, but chilblains cases were only weakly associated with COVID-19 infection, with only 2.0% of patients testing positive for COVID-19.

Evidence Rating Level: 2 (Good)

Chilblains refer to lesions of the skin related to inflammation from cold, damp conditions. During the start of the COVID-19 pandemic, dermatologists noticed an uptick in cases of chilblains, which presented within the 30 days after COVID-19 infection was confirmed in patients. This retrospective cohort study based aimed to determine the incidence of chilblains in the first 9 months of the pandemic, and assess whether a correlation between chilblains cases and COVID-19 infection existed. Data from Northern California’s medical records (with 4.4 million patients) were analyzed to track COVID-19 and chilblains cases. The study dates were from March to December of 2020 to encompass the pandemic months, and March to December of the years 2016-2019 to act as controls. The study found that the incidence of chilblains cases was higher during the pandemic. There were 780 cases in the 9 pandemic months, and 539 in the 36 month control period: This translated to an annual incidence of 28.6 per 100,000 person-years (95% CI 26.8-30.4) during the pandemic and 5.2 (95% CI 4.8-5.6) before the pandemic. However, the incidence of chilblains was higher in youth 13-19 years of age, whereas the highest COVID-19 incidence rate came from adults 20-59 years of age. When examining differences by race, the highest chilblains incidence rates were in Asian Americans (42.5, 95% CI 37.7-47.8), but the highest COVID-19 incidence was found in the Latinx population (62.5, 95% CI 61.9-63.1). The correlation coefficient for the chilblains and COVID-19 infection association was 0.18 (p = 0.01), which was determined to be a weak association. Only 2.0% of chilblains patients had a positive test result for COVID-19 within 6 weeks of chilblains diagnosis. Overall, although the incidence of chilblains increased drastically during the pandemic, the correlation between chilblains cases and COVID-19 infection is weak, with very few chilblains patients contracting COVID-19. The increased incidence could therefore be due to behavioural changes as a result of the lockdown, as opposed to being a secondary effect of COVID-19 infection.

Depression as a risk factor for incident ischemic stroke among HIV‐Positive veterans in the Veterans Aging Cohort Study

1. Depression was associated with elevated risk for ischemic stroke in veterans living with HIV, particularly in those under 60 years of age.

2. Factors that contributed to this association included alcohol use disorders, cocaine use, and antidepressant use.

Evidence Rating Level: 3 (Average)

Patients with HIV tend to have fewer of the common risk factors for ischemic stroke and other cerebrovascular events, such as hypertension or Type 2 Diabetes, meaning that there may be other important factors that increase stroke risk in the HIV population. For example, depression has been shown to be associated with stroke risk, and depression is also strongly associated with HIV status. The current study examined whether clinically diagnosed depression was a factor for increased stroke risk in the HIV population, and specifically in a cohort of veterans living with HIV. The study population consisted of patients 106,333 patients from the Veterans Aging Cohort Study, with 1 HIV-positive veteran matched to 2 HIV-negative veterans (33,528 HIV-positive and 72,805 HIV-negative veterans). Median follow-up was 9.2 years (interquartile range 5.2-11.5 years). Overall, the prevalence of depression was similar between HIV-positive and negative individuals (19.5% and 18.8% respectively). Upon adjusting for sociodemographic factors, there was a 22% greater risk of stroke in HIV-positive veterans with depression than without depression (hazards ratio 1.22, 95% CI 1.07-1.38, p = 0.003). This association persisted after adjusting for As age increases, this association declines, and is no longer statistically significant for patients 60 years and older. Furthermore, the association was not significant after controlling for antidepressant use (HR 1.16, 95% CI 1.00-1.36, p = 0.055), as well as alcohol use disorders and cocaine use. In conclusion, there is an elevated risk for ischemic stroke associated with depression in the HIV-positive veteran population, especially for individuals under the age of 60.

Restrictive versus liberal fluid resuscitation strategy, influence on blood loss and hemostatic parameters in mild obstetric hemorrhage: An open-label randomized controlled trial. (REFILL study)

1. Using a restrictive fluid resuscitation strategy for early to mild post-partum hemorrhage yielded similar hemodynamic outcomes as a liberal fluid resuscitation strategy.

Evidence Rating Level: 1 (Excellent)

Postpartum hemorrhage (PPH) is a leading cause of maternal death internationally. Currently, the PPH guidelines set by the Royal College of Obstetricians and Gynecologists outline a liberal fluid resuscitation strategy, recommending administration of twice the blood volume lost. However, Dutch guidelines note that no evidence is available for providing more fluids than the lost volume. Restrictive fluid resuscitation has been proposed, since it has been effective in other areas of medicine, although no other randomized controlled trials (RCTs) have been done assessing the best fluid administration strategy for PPH. Therefore, the current RCT based in the Netherlands aimed to compare liberal versus restrictive fluid resuscitation in PPH patients. The study population consisted of women undergoing both vaginal and caesarean deliveries, with at least 500 mL blood loss. 130 patients were in the restrictive group, receiving 0.75-1.0 times the lost blood volume, and 119 patients were in the liberal group, receiving 1.5-2.0 times the lost volume. The primary outcome assessed was progression to 1000 mL blood loss. Overall, fewer patients in the restrictive group reached 1000 mL blood loss than the liberal group (39.2% versus 51.3%), but this was not a statistically significant result (difference of -12.0%, 95% CI -24.3% to 0.3%, p = 0.057). The mean blood loss was similar, with 1182 (SD 761) mL in the restrictive group and 1242 (SD 621) mL in the liberal group (p = 0.5). There was also no difference in hemoglobin levels at 1 hour and 24 hours after fluid administration, and no difference in coagulopathy or need for blood products. In conclusion, implementing a restrictive fluid resuscitation policy may be more effective at preventing progression to 1000 mL blood loss, but did not do so significantly in this study.

Postoperative radiotherapy in pIIIA-N2 Non–Small Cell Lung Cancer after resection and chemotherapy

1. Postoperative radiotherapy for pIIIA-N2 non-small cell lung cancer did not improve disease-free survival or overall survival, but did improve locoregional recurrence-free survival.

Evidence Rating Level: 1 (Excellent)

The use of postoperative radiotherapy (PORT) has been correlated with increased survival for non-small cell lung cancer (NSCLC) patients, particularly the pN2 NSCLC subtype. However, it is unclear if PORT is associated with prolonged survival in pIIIA-N2 NSCLC patients, including patients who receive adjuvant chemotherapy. The current phase 3 randomized controlled trial aimed to determine the effect of PORT on disease-free survival (DFS) for pIIIA-N2 NSCLC patients, after having undergone a complete resection and 4 cycles of adjuvant chemotherapy. This was a single institution study based in China, with 140 patients receiving PORT and 170 patients in the observation group. PORT was done within 6 weeks after the last chemotherapy cycle, and the median follow-up was 46.0 (95% CI 41.9-51.4) months. Overall, no significant difference was found in disease-free survival between the two groups: The median DFS was 22.1 (95% CI 14.8-29.3) months for the PORT group and 18.6 (95% CI 14.3-23.0) months for the observation group. After 3 years, the DFS was 40.5% and 32.7% respectively. Additionally, overall survival was not significantly different between the PORT and observation cohorts (3-year overall survival of 78.3% and 82.8% respectively, hazards ratio 1.02, 95% CI 0.68-1.52, p = 0.93), but the locoregional recurrence-free survival rates were greater in the PORT group (66.5% versus 59.7%, HR 0.71, 95% CI 0.51-0.97, p = 0.03). No adverse events from the radiotherapy were observed. In conclusion, the use of PORT did not improve disease-free survival or overall survival, but was associated with an improvement in locoregional recurrence-free survival.

Image: PD

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