2 Minute Medicine Rewind May 18, 2020

Early estimates of the indirect effects of the COVID-19 pandemic on maternal and child mortality in low-income and middle-income countries: a modelling study

1. In three separate models, it was found that the combination of decreased health care access, food availability, and the economic impacts (both intentional and unintentional) of COVID-19 may lead to between 250,000 to 1,157,000 additional child deaths and 12,200 to 56,700 maternal deaths over 6 months globally.

Evidence Rating: 3 (Average)

Historically, decreased access to food, increased unemployment, redistribution and shortages of healthcare personnel and equipment, lower buying power, and lack of infrastructure for domestic development of medical and pharmaceutical supplies in low and middle income countries (LMICs) have led to decreases in reproductive, maternal, and child health (RMNCH) services. Subsequently, there has been evidence to suggest decreased access to these services during previous outbreaks, such as in the case of the Ebola Virus and SARS, leading to potentially increased mortality rates in affected populations. In this study, researchers estimated the additional maternal and under-5 child deaths in 118 LMICs resulting from COVID-19 caused by disruptions to healthcare coverage and reduced food access. The Lives Saved Tool (LiST), a tool historically used to estimate additional mortality was employed, and researchers used a framework that broke down healthcare coverage into 4 contributing parts: availability of healthcare workers, availability of supplies and equipment, demand for health services, and access to health services. The tool also took into account changes in food access and economic disruption, as modelled by proportion of children who are wasted (low weight for height). In the least severe scenario, modelled by small reductions in healthcare coverage (i.e., 9.8-18.5%) and a 10% increase in wasting, an estimated 253,500 additional child deaths and 12,200 additional maternal deaths was estimated over 6 months. Over 12 months, 417,000 additional child deaths and 24,400 maternal deaths were projected. Results were grimmer in models predicting severe disruption (39.3-51.9% healthcare coverage reduction, and wasting increase of 50%), with a staggering 1,786,400 child deaths and 113,400 maternal deaths over 12 months. These results emphasize the ability of diseases to cause great suffering beyond their immediate pathology, as even the conservative estimates of the study yield mortality rates comparative to that of the currently confirmed worldwide death toll. The findings of this study may serve to better inform future policy changes and healthcare behavior, and encourage proactive decision making in these sectors to mitigate these potential losses.

Effect of Internet vs Face-to-Face Cognitive Behavior Therapy for Health Anxiety

1. Internet-delivered cognitive behavioral therapy for patients with health anxiety was found to be noninferior to face-to-face CBT.

Evidence Rating: 1 (Excellent)

Health anxiety is a common and often chronic mental health problem, and affects a significant portion of the population. Current first line therapy involves face-to-face cognitive behavior therapy (CBT), and though this method is often found to be an effective management strategy, constant face-to-face CBT incurs significant costs, requires greater commitment (standard is weekly appointments over 3 months), and may be out of reach to populations with reduced healthcare availability and accessibility. As an increasing number of health services are being paired with virtual alternatives, researchers sought to investigate whether internet delivered CBT is a noninferior alternative to face-to-face therapy. In this randomized noninferiority clinical trial, 204 adult patients with a principal diagnosis of DSM-5 somatic symptom disorder or illness anxiety disorder were recruited between 2014 and 2017 and were assigned randomly to either receive internet delivered CBT (ICBT) or face-to-face CBT over 12 weeks. Response to treatment, as the primary outcome, was measured by change in health anxiety over the treatment period as measured by the Health Anxiety Inventory (HAI). Interestingly, therapists were spending 10 minutes per patient per week in the ICBT treatment group, versus 45.6 minutes in the face-to-face CBT. Despite this, in the intention-to-treat analysis, ICBT was found to be noninferior to individual face-to-face CBT, as the estimated difference in effect over the treatment period was 0.00 points on the primary outcome (HAI), and the upper limit of the 1-sided 95% CI was 1.98, within the noninferiority margin of 2.25. There were no significant differences in rates of adverse outcomes between either group. In further health economic analysis, it was estimated that the net societal cost per patient was $3584 lower in ICBT versus face-to-face CBT. Study findings are highly supportive of the implementation of ICBT into regular practice as an effective alternative to face-to-face CBT for health anxiety.

An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

1. Findings from a cohort in Bergamo, Italy indicate a roughly 30-fold increase in the incidence of Kawasaki-like disease associated with the SARS-CoV-2 outbreak.

2. Pediatric patients diagnosed with Kawasaki-like disease post COVID-19 were more likely to have a more severe form of the disease, and had higher rates of cardiac involvement, Kawasaki Disease Shock Syndrome, and macrophage activation syndrome (MAS).

Evidence Rating: 3 (Average)

Kawasaki disease is an idiopathic acute vasculitis primarily affecting children under the age of five. Classically, patients present with prolonged fever, cervical lymphadenopathy, non-exudative conjunctivitis, polymorphic rash, and hand and feet changes, such as erythema. Although the mortality rate of the condition is relatively low at rough 1%, and often self-limiting, severe complications can arise from the disease, such as Kawasaki Disease Shock Syndrome (KDSS), macrophage activation syndrome (MAS) arrhythmias and myocardial infarction. In this observational cohort study, researchers sought to characterize an increase in incidence of Kawasaki-like disease coinciding with SARS-CoV-2 outbreak in Bergamo, Italy, an epicentre of the pandemic. The data of all child patients diagnosed with Kawasaki-like disease at a pediatric unit was reviewed between 2015 to 2020, and divided into two groups: group 1 denoting patients presenting before the beginning of the SARS-CoV-2 epidemic, and group 2 denoting patients presenting afterward. In addition to incidence, researchers investigated rates of serious adverse outcomes such as KDSS, cardiac involvement, MAS, and need for adjunctive steroid treatment. Group 1 consisted of 19 patients diagnosed between Jan 2015 to Feb 2020, and Group 2 consisted of 10 patients diagnosed between Feb 18 to April 20, 2020, eight of whom were IgG positive for SARS-CoV-2 antibodies. The difference in incidence between group 2 was calculated to be 30 times greater than group 1 (i.e., 10 vs. 0.3 per month). Patients in group 2 were also observed to have significantly higher rates (all p<0.01) of more severe form of the disease, (80% of patients requiring adjunctive steroid treatment versus 15.7% in group 1), KDSS (50% vs. 0%), MAS (50% vs. 0%), cardiac involvement (60% vs. 10.5%). Despite a small sample size, study findings draw reasonable speculation into an association between COVID-19 and Kawasaki-like disease, as increases in disease incidence, severity, and complications were observed. Study findings would suggest similar increases in Kawasaki-like disease incidence in other pandemic epicentres.

Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial

1. For patients who underwent elective surgery and were at moderate to high risk of venous thromboembolism, pharmaco-thromboprophylaxis with low molecular weight heparin alone was noninferior to a combination of pharmaco-thromboprophylaxis and graduated compression stockings.

Evidence Rating: 1 (Excellent)

Venous thromboembolism (VTE) is associated with significant mortality and morbidity worldwide. For patients undergoing elective surgical procedures, graduated compression stockings (GCS) in addition to pharmaco-thromboprophylaxis are currently the standard practice for prevention of VTE. As the effectiveness of GCS have been brought into question in recent years, researchers conducted an open-labelled, multicentre, randomised, controlled, non-inferiority trial with 1905 adult elective surgical inpatients assessed at being moderate to high risk of VTE to investigate the necessity of GCS as a preventative measure for VTE. Patients were randomly assigned to receive pharmaco-thromboprophylaxis alone with low molecular weight heparin (LMWH) or pharmaco-thromboprophylaxis with GCS. Primary outcome out interest was the rate of deep vein thrombosis (DVT) in both groups as confirmed by imaging, or symptomatic pulmonary embolism within 90 days. Secondary outcomes were quality of life, compliance with GCS and LMWH, lower limb complications resulting from GCS application, bleeding complications, adverse reactions to LMWH, and all-cause mortality. Intention to treat analysis revealed a risk difference of 0.3% (95% CI, -0.65% to 1.26%), as the primary event was observed in 1.7% of the no GCS group and 1.4% in the GCS group receiving standard care. These findings were well within the predefined margin of non-inferiority of 3.5% (P<0.001). No significant differences in quality of life or other secondary outcomes were reported. Although further studies must be carried out to expand generalizability of findings, these findings suggest that GCS inclusion is an unnecessary component of current standard practice for VTE patients who undergo elective surgical procedures.

Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

1. Administration of hydroxychloroquine was not associated with significantly higher rates of recovery in patients with mild to moderate COVID-19

2. Adverse events, primarily gastrointestinal symptoms, were more common in the group receiving hydroxychloroquine.

Evidence Rating: 2 (Good)

Amidst the global rush to find an approved pharmacologic agent for the treatment of COVID-19, hydroxychloroquine has gained international attention. However, the evidence supporting its clinical efficacy is limited, and often confined to case studies. In this multicenter, open label, randomized controlled trial, researchers enrolled 150 patients with mild to moderate laboratory COVID-19 to further investigate the clinical efficacy of the drug.  Patients were randomly assigned to either receive standard care alone, or to the treatment group to receive a loading dose of 1200mg daily (for 3 days) and maintenance dose of 800mg daily of hydroxychloroquine. Patients with moderate and severe disease were assigned to a treatment regimen of two and three weeks, respectively. Primary outcome was negative conversion of SARS-CoV-2 by 28 days, and secondary outcome was probability of negative conversion at 4,7,10,14, or 21 days. Adverse events were also recorded to reassess the safety profile of the drug. Intention to treat analysis revealed no significant difference in rates of negative conversion between the treatment and standard care group. Of the 109 patients that achieved negative conversion, the probability of negative conversion by 28 days in the standard of care plus hydroxychloroquine group was 85.4% (95% confidence interval 73.8% to 93.8%), and standard of care group (81.3%, 71.2% to 89.6%), with a between groups difference of was 4.1% (95% confidence interval –10.3% to 18.5%). Likewise, secondary outcome analysis of the two groups yielded similar results, as the two groups recorded similar rates of conversion at multiple time points. Thirty percent of patients in the treatment group had adverse events versus just 9% in the standard care group, though the most common events were not serious in nature and confined to gastrointestinal symptoms such as diarrhea.

Image: PD

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