Nosocomial Outbreak of SARS-CoV-2 in a “Non-COVID-19” Hospital Ward: Virus Genome Sequencing as a Key Tool to Understand Cryptic Transmission

Dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare institutions affects both patients and health-care workers (HCW), as well as the institutional capacity to provide essential health services. Here, we investigated an outbreak of SARS-CoV-2 in a “non-COVID-19” hospital ward unveiled by massive testing, which challenged the reconstruction of transmission chains. The contacts network during the 15-day period before the screening was investigated, and positive SARS-CoV-2 RNA samples were subjected to virus genome sequencing. Of the 245 tested individuals, 48 (21 patients and 27 HCWs) tested positive for SARS-CoV-2. HCWs were mostly asymptomatic, but the mortality among patients reached 57.1% (12/21). Phylogenetic reconstruction revealed that all cases were part of the same transmission chain. By combining contact tracing and genomic data, including analysis of emerging minor variants, we unveiled a scenario of silent SARS-CoV-2 dissemination, mostly driven by the close contact within the HCWs group and between HCWs and patients. This investigation triggered enhanced prevention and control measures, leading to more timely detection and containment of novel outbreaks. This study shows the benefit of combining genomic and epidemiological data for disclosing complex nosocomial outbreaks, and provides valuable data to prevent transmission of COVID-19 in healthcare facilities.     

Long-term survival in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Insights from a referral center in Portugal

Objectives

This study aims to assess the long-term survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients followed in a Portuguese pulmonary hypertension (PH) referral center.

Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case‒control study

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case‒control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients. We investigated whether the type of FVIII concentrate was associated with inhibitor development in nonsevere haemophilia A patients. This nested case‒control study includes 75 inhibitor patients and 223 controls, from a source population of the INSIGHT study, including all nonsevere haemophilia A patients (FVIII:C 2–40%) that were treated with FVIII concentrates in 33 European and one Australian centre. Cases and controls were matched for date of birth and cumulative number of exposure days (CED) to FVIII concentrate. A conditional logistic regression model was used to calculate unadjusted and adjusted odds ratios. No increased risk for inhibitor development was found for any type of FVIII concentrate; either when comparing recombinant FVIII concentrates to plasma-derived FVIII concentrates (adjusted odds ratio 0·96, 95% confidence interval (CI) 0·36–2·52) or for specific types of FVIII concentrates.     

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins

Objective

The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins.

Methods

Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative markers.

Results

Lipid profile analysis revealed a reduction in the plasma concentrations of cholesterol and triglycerides, which were mainly associated with a significant reduction in the plasma concentration of circulating apoB-containing lipoproteins rather than with changes in their relative chemical composition. All patients displayed a pattern A phenotype of LDL subfractions and a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P < 0.001). The switch towards predominantly larger HDL particles was due to an increase in their relative cholesteryl ester content. Excess weight loss also led to a significant decrease in the plasma concentration of oxidised LDL (∼−25%; P < 0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp-PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound Lp-PLA2.

Conclusion

Our data indicate that the weight loss induced by bariatric surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL-2 subfraction.     

COVID-19 pandemic: guidance for nuclear medicine departments

European Journal of Nuclear Medicine and Molecular Imaging -     

Handgrip Strength at Admission and Time to Discharge in Medical and Surgical Inpatients

Background and Objective: Handgrip strength is a relevant marker of functional status and is also a component of nutrition assessment. The simplicity of this measurement supports its usefulness as a tool to predict who will likely take longer to hospital discharge. The aim of this study was to quantify the association between sex‐specific handgrip strength at hospital admission and time to discharge alive. We intended to include a group of diverse diagnoses and to compare medical and surgical wards, taking into account the potential confounders’ effect of patients’ characteristics and severity of disease. Subjects and Methods: Prospective study in 2 public acute‐care general hospitals in Porto, Portugal, in 2004. Handgrip strength was evaluated using a handgrip dynamometer in a probability sample of 425 patients from medical and surgical wards. The association between baseline handgrip strength and time to discharge was evaluated using survival analysis with discharge alive as the outcome and deaths and transfers being censored. Results: In medical wards, women with high admission handgrip strength had a very short hospital stay (all had been discharged by the sixth day), and among men, patients with low handgrip strength had a particularly longer stay (approximately 50% were discharged after 15 days of hospitalization). In surgical wards, an increasing length of stay with decreasing handgrip strength quartiles was also observed in both sexes. Conclusions: Lower handgrip strength at hospital admission was associated with a longer time in the hospital, in patients of both sexes, in medical and surgical wards. Although this association was explained in part by age, height, education level, cognitive status, and disease severity, its direction remained unchanged regardless of the aforementioned factors.     

Treatment of Onychomycosis with Efinaconazole 10% Topical Solution and Quality of Life

Objective: To evaluate the benefits of efinaconazole topical solution, 10% on quality of life in onychomycosis patients. Methods: An analysis of 1,655 patients, aged 18 to 70 years, randomized to receive efinaconazole topical solution, 10%, or vehicle from two identical multicenter, double-blind, vehicle-controlled, 48-week studies evaluating safety and efficacy. The primary endpoint was complete cure rate (0% clinical involvement of target toenail, and both negative potassium hydroxide examination and fungal culture); clinical improvement defined as ≤ 10-percent improvement in nail involvement both at Week 52. Quality of life was assessed using a validated OnyCOE-t™ questionnaire. Improvement in quality of life was compared in those patients clinically and not clinically improved. Results: Efinaconazole topical solution, 10%, was significantly more effective than vehicle irrespective of QoL domain. Greatest improvement in mean score was seen in those domains with the lowest baseline scores. All mean scores in the group considered to have clinically improved with efinaconazole exceeded 80.0 at Week 52. Mean treatment satisfaction scores with efinaconazole in those patients who were clinically improved increased from 79.9 (Week 24) to 89.2 (Week 52), compared to a corresponding drop in those patients considered not improved from 65.3 to 58.0. The correlation between change in percent affected nail and change in mean domain scores was significant with efinaconazole for all domains. Limitations: A period of 52 weeks may be too brief to evaluate improvement in quality of life in onychomycosis patients. Some of the questions in the OnyCOE-t questionnaire may be more relevant than others to the study population and the onychomycosis population as a whole. Conclusion: Once-daily efinaconazole topical solution, 10%, provided statistically greater improvement in all aspects of quality of life compared to vehicle. Improvement was most marked in those patients considered clinically improved and correlated with a change in percent affected nail.Onychomycosis is a common, growing problem in dermatology practice, most frequently seen in toenails and difficult to treat successfully.1,2 It is a progressive disease, not self-healing, and occasionally the source of more widespread infection.3 Many patients suffer long-standing disease affecting several toenails.4Onychomycosis can have significant impact on the individual and other family members.5-7 The unsightly appearance of the toenail is a real concern, and often the initial reason why patients seek medical help. Indeed, the appearance of the toenail may have a more significant impact on quality of life (QoL) than the severity of the disease.8It can disrupt daily activities, negatively impact QoL, and occasionally results in significant pain and discomfort.5 The symptoms of onychomycosis and their impact on personal appearance are important determinants of patients’ perceptions of their own health. The effect of onychomycosis is greater on psychosocial than physical functioning and is directly related to the extent of nail involvement.9 Data are conflicting as to whether nail appearance or disease severity are the more important from a patient’s perspective of QoL. Area alone does not necessarily predict disease severity, and a thick nail with limited involvement may have a poor prognosis.10 Commonly reported psychosocial factors include embarrassment, low self-esteem, and social withdrawal.11The true burden of disease is unknown, but patients’ desire to have their affected nails cured is clear.5,12 Patient surveys have noted a substantial impact in several QoL domains including physical functioning (associated with foot-related activities), social functioning (affected by pain and discomfort restricting social activities and embarrassment associated with the nail appearance), and emotional well-being affected by negative feedback received from their social environment.13-15A number of disease-targeted questionnaires have been developed to assess the impact of onychomycosis and its treatment on health-related QoL. The instruments differ considerably in the extent to which they have been psychometrically tested. The generic and disease-targeted scales of most of the available questionnaires exhibit poor variability, which may limit their responsiveness to clinically important change.9 As a result; there is a lack of data to demonstrate the true QoL response to onychomycosis treatment.Improvements in QoL have been reported to correlate with the improvement or cure of infected nails.16-20 As a result, patients satisfied with their treatment had better health-related QoL;21 although patients with recurrent disease had significantly poorer QoL than those with onychomycosis for the first time that had not previously been treated.22 A significant portion of patients feel unattractive and stigmatized by onychomycosis and antimycotic therapy has been reported to result in a significant reduction of stigmatization of about 60 percent from baseline levels.23A toenail-specific questionnaire, the OnyCOE-t™, and objective clinical measures have been used to assess responsiveness of patients in a prospective onychomycosis trial.24,25 Patients were treated with terbinafine (± aggressive debridement) and comparisons made between those patients who were judged to have clinically improved and those who had not improved.The objective of this current study was to utilize this validated OnyCOE-t questionnaire to assess differences in QoL response in onychomycosis patients following treatment with efinaconazole topical solution, 10%, or vehicle. In addition, the authors compared results in those patients who were considered clinically improved (≤10% nail involvement) with those who were not clinically improved at Week 52 following active treatment, to assess the clinical meaningfulness of their results.