2 Minute Medicine Rewind November 23, 2020

Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers

1. Patients with severe COVID-19 demonstrated a unique diaphragm myopathic phenotype compared to non-COVID-19 ICU patients.

2. It is unclear whether or not myopathy is a direct result of COVID-19.

Evidence Rating Level: 2 (Good)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has well-known respiratory implications as well as extrapulmonary manifestations. Adverse effects of severe COVID-19 on respiratory muscles, however, have not been studied to-date. This study across three medical centers in the Netherlands investigated the effects of severe COVID-19 on the diaphragm in critically ill patients. Muscle specimens were collected through autopsy of 26 patients who had been hospitalized in the ICUs with severe COVID-19 (median [IQR] age = 71 [61 to 74] years, 81% male). A total of 24 of these patients had undergone invasive mechanical ventilation for a median of 12 days (IQR 6 to 25 days). Specimens from the left midcostal diaphragm were used for subsequent analyses. These patients also had higher BMIs than those without COVID-19 and were less likely to be treated with steroids. SARS-CoV-2 viral RNA was found in four patients (15.4%), localized inside diaphragm myofibers. Angiotensin-converting enzyme 2 (ACE-2) primarily localizes at the myofiber membrane, which can serve as an entry point for severe infection of the diaphragm. Further RNA sequencing determined the upregulation of 315 genes and downregulation of 281 genes in the diaphragm of COVID-19 patients compared to non-COVID-19 ICU patients. Further, epimysial and permysial fibrosis was greater than two times higher in COVID-19 diaphragms than the controls. Overall, this study demonstrated unique differences in myopathic phenotype among patients with severe COVID-19, though it is unclear whether or not diaphragm myopathy is a direct effect of SARS-CoV-2 or related to other processes. However, diaphragm weakness associated with myopathy could result in fatigue, dyspnea, and ventilator weaning failure.


Association Between Maternal Satisfaction With Breastfeeding and Postpartum Depression Symptoms

1. Increased breastfeeding satisfaction was 47% higher among mothers who were negative for postpartum depression compared to those who were positive for postpartum depression.

Evidence Rating Level: 3 (Average)

Breastfeeding and maternal health provide innumerable health benefits to newborn children. There are also many factors that can negatively impact maternal health and breastfeeding practices. This cross-sectional study from within a separate Brazil cohort study sought to investigate the relationships between postpartum depression (PPD) and maternal satisfaction with breastfeeding during the first month after birth. Across one public and one private maternity hospital, a total of 287 puerperal women were selected (M age = 29 years, range 16 to 45 years) and subsequently interviewed the week following the respective children reaching 30 days of age. The variables of interest were measured with the Maternal Breastfeeding Evaluation Scale and Edinburgh Postnatal Depression Scale. Increased breastfeeding satisfaction was defined as a score above the sample median. The prevalence of this increased satisfaction was found to be 47% higher among women who were negative for PPD compared to those positive for PPD (adjusted prevalence ratio [aPR] = 1.57, 95% CI 1.01 to 2.16, p<.047). Adjustments to this regression model included maternal age and skin color, planned pregnancy, delivery type, exclusive breastfeeding, cohabitation with father, and breastfeeding problems. Overall, this study suggests that PPD has a significant impact on maternal satisfaction with breastfeeding, which may be due to pre-existing depressive symptoms that are aggravated by breastfeeding dissatisfaction. However, this cross-sectional study is relatively limited in what it can conclude definitively. It is also worth noting that 251 (87.5%) women in this sample were negative for PPD at initial interview.


Mortality and Other Adverse Outcomes in Patients With Type 2 Diabetes Mellitus Admitted for COVID-19 in Association With Glucose-Lowering Drugs: A Nationwide Cohort Study

1. In-home glucose-lowering medications were not associated with increased mortality or complications among those with COVID-19.

Evidence Rating Level: 2 (Good)

Diabetes is one of the most common comorbidities found among patients with coronavirus disease 2019 (COVID-19), with type 2 diabetes mellitus (T2DM) negatively impacting prognosis in these people. The potential implications of glucose-lowering medications in patients with COVID-19 are currently unclear, however, with metformin showing neutral effects and insulin showing negative effects on in-hospital mortality. This observational, multisite, nationwide cohort study in Spain sought to evaluate the effects of these medications in individuals with T2DM and COVID-19. Data from 2,666 patients (M [SD] age = 74.9 [8.4] years) were initially extracted from the SEMI-COVID-19 Registry who were taking glucose-lowering drugs (1,297 monotherapy, 465 in combination with metformin). Patients using various medications were propensity score-matched. Following matching, patients taking metformin (249), dipeptidyl (105), insulin (129), metformin/dipeptidyl peptidase-4 inhibitors (127), metformin/sedum-glucose cotransporter 2 inhibitor (34), and metformin/insulin (67) were chosen. None of these in-home glucose-lowering medications were associated with in-hospital mortality, duration of stay, or the need for ICU admission. Overall, this study suggests a need for further research to explore the link between T2DM and COVID-19.


Trends in Suicidality 1 Year Before and After Birth Among Commercially Insured Childbearing Individuals in the United States, 2006-2017

1. Prevalence of suicidality increased significantly over a 12-year period among childbearing persons.

2. The prevalence of suicidality with comorbid depression or anxiety increased significantly over this same time period.

Evidence Rating Level: 2 (Good)

Suicide death is consistently a leading cause of mortality in the United States. Maternal mortality is also affected by suicidality, ranging from suicide ideation and self-harm to death. This serial cross-sectional study used data from medical claims for a commercially insured U.S. population from January 2006 to December 2017. A total of 595,237 childbearing individuals were analyzed (M [SD] age = 31.9 [6.4] years), which included 2,714 diagnoses of suicidality within one year before or after 698,239 deliveries. Approximately 63.1% were White, 12.1% were Hispanic, 8.6% were Black, 6.8% were Asian, and 9.5% had missing race/ethnicity data. From 2006 to 2017, the prevalence of suicide ideation increased from 0.1% per 100 persons to 0.5% per 100 individuals (SE = .02, p<.001). Overall suicidality prevalence increased during this time period as well (difference 0.4%, SE = .04, p<.001). Diagnoses of suicidality with comorbid psychotic or bipolar disorders increased by 10.1% in this timeframe (SE = .2, p<.001), along with comorbid depression or anxiety increasing by 1.4% (SE = .2, p<.001). The greatest increases were among those of lower socioeconomic status, non-Hispanic Black race/ethnicity, and younger chronological age. In sum, this study demonstrated a significant increase in suicidality prevalence over a 12-year period among childbearing persons. Given these trends, it is important to adequately assess for suicidality among this population and develop health policies that cater to these needs.


Death of a Partner and Risks of Ischemic Stroke and Intracerebral Hemorrhage: A Nationwide Danish Matched Cohort Study

1. Partner death was associated with both ischemic stroke and intracerebral hemorrhage in the subsequent five years, though absolute risk differences were small.

2. Risk of intracerebral hemorrhage was particularly elevated within the first 30 days following partner death.

Evidence Rating Level: 2 (Good)

Stress can have a negative impact on various systems, including but not limited to the nervous and cardiovascular systems. One particularly stressful event, among many, is the death of a partner. In the context of COVID-19, stress and the potential for the death of a partner are significantly increased. This Danish cohort study sought to investigate the relationship between death of a partner and subsequent ischemic stroke (IS) and intracerebral hemorrhage (ICH). A total of 278,758 Danish participants had experienced the death of a partner between 2002 and 2016, which were matched with cohabiting individuals matched 1:2 on age, sex, and calendar time (n = 557,516). Approximately one-third of each group were between the ages of 70 and 80 years. Follow-ups occurred for up to five years. During the study, 7,684 (2.76%) participants experienced an IS within five years of partner death (adjusted HR [aHR] = 1.11, 95% CI 1.08 to 1.14) and 1,139 (.410%) experienced an ICH (aHR = 1.13, 95% CI 1.04 to 1.23) within the five years following partner death. This association appeared to be strongest within the first 30 days following partner death (aHR = 1.66, 95% CI 1.06 to 2.61). While statistical precision was low, women, specifically, were at a higher risk during the first 30 days (aHR = 1.99, 95% CI 1.06 to 3.75). In terms of cumulative incidence, IS and ICH were both more common than those who did not experience partner death (differences, 0.1 per 1,000 and .05 per 1,000, respectively). Overall, this study suggests that partner death is a significant risk factor for IS and ICH, particularly the latter in 30 days following partner death. However, absolute risk differences were relatively small. In the context of the current pandemic, this is a noteworthy consideration that should be considered, particularly among populations at increased risk for IS and ICH.

Image: PD

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