Avoiding a lost decade—an interim update

All sovereign debt restructurings are inherently messy, expensive, exasperating, time-consuming, and contentious.These are the familiar pathologies in the international system to resolve unsustainable sovereign debts. But the period since the onset of the Covid-19 crisis has revealed (to use a term we all learned during pandemic lockdowns) several new co-morbidities.These include a breakdown in the ability of the major external creditor groups (traditional Paris Club lenders, non-Paris Club bilateral creditors like China and bondholders) to coordinate their debt relief efforts, the increasingly diverse nature of the private-sector entities holding claims against a debtor state, and the total absence of any mechanisms—statutory or contractual—that can be used to ensure that the sacrifices made by the vast majority of claimants and official sector sponsors in the economic recovery process cannot be exploited by the uncooperative few. © The Author(s) 2023. Published by Oxford University Press.

Efficacy of home respiratory culture kits in people with cystic fibrosis

Background: Respiratory cultures are an important part of clinical care for people with cystic fibrosis (CF). Telemedicine visits during the COVID-19 pandemic have not allowed for routine collection. To address this, the University of Michigan Adult Cystic Fibrosis Program mailed home culture kits to patients. We hypothesized that results from home sputum samples would be consistent with prior cultures obtained in sputum collected in clinic but that self-collected throat swabs would provide false-negative results. We also sought to determine percentage return rate. Method(s): Adults with CF were sent culture kits containing a specimen cup and a throat swab. Patients had the choice to submit either sample for processing. Medical personnel provided written instructions with the culture kits and, on occasion, instructed patients on proper collection techniques via phone. Samples were then refrigerated for up to 24 hours before a delivery service returned the specimen to a University of Michigan laboratory for analysis. Data collected from December 2020 to December 2021 (N = 77) included percentage return rate, result, source, and presence of microorganisms. Pairwise culture data of samples collected in clinic versus home-collected samples within 1 yearwere included in the analysis. Descriptive statistics and Cohen kappa correlation coefficients were computed for all culture data and subgroups (Table 1A-E). Result(s): Of 77 culture kits returned, 46 had corresponding clinic samples collected using the same method, and the remaining 21 were collected using different methods (throat swab vs sputum sample). Overall, approximately 200 kits were mailed to patients, with a return rate of 38.5%. A similar percentage of positive culture results was obtained with same method of collection: sputum and throat samples (Table 1C, D, E), although the discordance rate between cultures collected in clinic and at home ranged from approximately 10% to 30%. Correlation between clinic and home culture data was generally good throughout, except for clinic Table 1 ( 115): Analysis of respiratory culture results for (A) all cultures, (B) different collection, and (C, D, E) same collection method. *p < 0.05. Cohen kappa correlation coefficient between groups: poor agreement <0.20;fair agreement = 0.21-0.40;moderate agreement = 0.41-0.60;good agreement = 0.61-0.80;very good agreement = 0.81-1.00. PsA = Pseudomonas aeruginosa;Staph = Staphylococcus aureus.(Table Presented)versus home throat swabs, probably because of a lowevent rate in the small sample size. Conclusion(s): The data suggest that, overall, clinic and home culture kits provide similar positive results, although discordance in specific culture results was common. This may be due to natural fluctuations from culture to culture in people with CF. A limitation of this study is that the cultures being compared in our study were not completed on the same day. Nevertheless, our data also indicate that collection technique may influence results for certain microorganisms. How these differences might influence antibiotic selection and treatment outcomes in the era of telemedicine requires more investigation. The return rate was found to be relatively low, demonstrating the need for interventions to improve patient outreach and compliance.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved

Eosinophilic fasciitis triggered by intensive exercise

A 59-year-old white female who was previously fit and well, developed gradual tightening and thickening of the skin on her forearms progressing to the abdomen, chest and lower legs associated with restricted movement. She also noticed bruise-like patches on her trunk. There were no systemic symptoms and no history of Raynaud syndrome. Since the beginning of the COVID-19 lockdown, the patient had engaged in increasing amounts of exercise compared with normal;this included yoga once weekly for 75 min, high-intensity interval training for 20 min on alternate days, running three times weekly for 45 min, lifting 2.5 kg weights for the arms every day and regular long walks. Examination showed a 'groove' sign on her forearms and a peau d'orange appearance of the skin with a woody induration and hardness on palpation. Symmetrical and circumferential involvement on the forearms and lower legs and bruise-like indurated patches on the abdomen were noted. Differential diagnoses included eosinophilic fasciitis (EF), morphoea, EF/morphoea overlap, scleroderma, scleromyxoedema and nephrogenic systemic fibrosis. Blood investigations showed an eosinophilia of 1.2 x 109 cells L-1, erythrocyte sedimentation rate of 31 mm h-1, a C-reactive protein of 20 mg L-1 and negative autoimmune and viral serology. She underwent two incisional biopsies down to fascia. The first was taken from the back, which showed an interstitial inflammatory cell infiltrate composed of lymphocytes, plasma cells and very occasional eosinophils. The subcutaneous septa were minimally thickened. The second biopsy taken from the left forearm showed striking thickening of the subcutaneous septa, with an associated inflammatory cell infiltrate, composed predominantly of lymphocytes and plasma cells. This process was deeper and more established than that seen in the biopsy from the trunk. The appearances were clearly those of a sclerosing process of the dermis and subcutis and consistent with eosinophilic fasciitis. Our diagnosis was EF with morphoea overlap and she was treated with oral methotrexate 15 mg weekly and oral prednisolone 50 mg once daily (weight 60 kg), reducing the dose by 5 mg every 2 weeks. An 80% improvement was seen in functionality within 3 months, but the skin remained tight and thickened and therefore the patient was referred for phototherapy [ultraviolet A 1 (UVA1)] as combination therapy. We present a rare case of EF, which appears to have been triggered by intensive exercise. Other causes include insect bites, radiation, infections (Mycoplasma and Borrelia) and paraneoplastic. Haematological associations have been seen, including aplastic anaemia and lymphoma. Treatment options for EF include prednisolone, UVA1/psoralen + UVA, immunosuppressive systemic agents (including ciclosporin and methotrexate), biological agents (including infliximab and rituximab) and physiotherapy.

HAND OSTEOARTHRITIS: INVESTIGATING PAIN EFFECTS in A RANDOMISED PLACEBO-CONTROLLED FEASIBILITY STUDY of ESTROGEN-CONTAINING THERAPY (HOPE-E): REPORT on the PRIMARY FEASIBILITY OUTCOMES

Background: There is an unmet need for new treatments for hand osteoarthri-tis (OA). Symptomatic hand OA is more common in women and its incidence increases round the age of menopause. Pre-clinical, epidemiological and post hoc studies in Hormone Replacement Therapy (HRT) trials implicate estrogen defciency as of likely importance in OA aetiopathogenesis. No clinical trials of HRT have been carried out in hand OA to date. The licensed HRT Duavive (conjugated estrogens + SERM bazedoxifene) was selected on its potential for efficacy and tolerability. Objectives: We set out to determine the feasibility and acceptability of this form of HRT in post-menopausal women with hand OA, to generate proof of concept data and refne methods for a full study. Methods: ISRCTN12196200. Females aged 40-65 yrs and 1-10yrs after fnal menstrual period with hand OA fulflling ACR criteria and 2+ painful hand joints were recruited. Eligibility incorporated best practice for HRT prescription but did not require menopausal symptoms. Recruitment was at 3 sites in primary/secondary care, including directly from the community. Design was parallel group, double-blind 1:1 randomisation of Duavive or placebo, orally once daily for 24 weeks, then weaning for 4 weeks before stopping. Routes and rates of recruitment and the acceptability of randomisation, medication (compliance, retention), and proposed outcomes were measured, and the likelihood of unblinding. Measures related to hand pain and function, menopause symptoms and joint appearance. Patient and Public Involvement actively informed study rationale, design and materials. An end of study questionnaire and 2 participant focus groups provided further acceptability data. Results: Recruitment was for 12/possible 18 months, interrupted due to COVID-19. Some study procedures were modifed to allow reopening whilst collecting all primary outcomes. 434 enquiries/referrals were received, leading to 96 telephone pre-screens, of which 33 gave written informed consent and attended face to face screening. 28/33 screened (85%) were eligible and randomised. The highest number of randomisations was from study web presence (n=7) followed by SMS text from GP surgeries (n=5). Of 401 not proceeding, 250 (62%) were ineligible, most commonly due to contraindicated medication, followed by medical contraindication, whilst 55 (14%) decided not to take part, for reasons including not wanting to take a hormone-based drug or difficulty attending study visits. Retention and compliance were excellent. All 28 participants completed all study follow ups, with only 3 withdrawals from treatment due to AEs, 2 of these at week 24 and all in the placebo arm. There were no serious AEs. High levels of completeness of all study outcome measures were achieved. Bang's blinding index suggested that participants/investigators were well blinded. There were overall high/good levels of satisfaction with taking part in the study. 26/28 (92%) would recommend taking part to others with hand OA (irrespective of study arm). Many found the fexibility offered by a combination of remote and face to face visits (due to the pandemic) attractive. Additional insights from focus groups were to include hand stiffness as well as pain measures but to reduce the overall number of questions. Conclusion: Despite COVID-19 and a reduced recruitment period, this study recruited sufficient numbers to assess feasibility outcomes. Randomisation of eligible people and retention rates were high. A mixture of remote and face to face visits due to COVID-19 probably improved recruitment and retention and was supported by participants, who were generally satisfed with the study design and medication. The study provided useful insight and improvements that would be incorporated into a future study. Overall, this feasibility study showed that with clear messaging on eligibility and a defned recruitment strategy, recruitment and retention to a study testing this treatment is possible.

Potential of the triad of fatty acids, polyphenols, and prebiotics from cucurbita against COVID-19 in diabetic patients: A review

Though the scientific community of the entire world has been struggling to create preventive and therapeutic drugs for coronavirus disease 2019 (COVID-19), the role of nutraceuticals has been hitherto neglected. Established role of fatty acids and polyphenols in combating lifestyle disease can be harnessed to play a significant role in the prevention of this disease. The synergistic effect of these phytonutrients and prebiotics is anticipated to prove beneficial for prevention as well as attenuation of COVID-19 infection. Presence of fatty acids, polyphenols and prebiotics in vegetables from the Cucurbitaceae family makes them an attractive choice for being used as a nutritional supplement during COVID-19. These are known to attenuate the excessive immune response which may prove to be beneficial in preventing and mitigating COVID-19. Use of prebiotics to promote the growth of probiotics has also been recommended for the prevention and cure of COVID-19. However, no such report exists in literature that throws light on such role of cucurbita plants. The present review focuses on the role of the triad of fatty acids, prebiotics and polyphenols present in cucurbita plants in controlling systemic inflammation and endothelial damage, the two main etiopathological factors involved in COVID-19. Cucurbita plants are rich in all these components and their inclusion in diet would be an effective strategy to combat COVID-19. The main focus of the review is to discuss the role of various components of the plants of Cucurbita family, taken as dietary component, in prevention and control of the ongoing pandemic COVID19.

Impaired systemic oxygen extraction relates to reduced exercise capacity in post-covid-19 long hauler syndrome

Introduction: Following acute coronavirus 2019 (COVID-19) disease, at least 10% of patients report some form of residual limitation, most commonly dyspnea and fatigue. These COVID-19 “long haulers” experience symptoms that are largely unexplained by pulmonary function testing (PFT), echocardiogram and chest computed tomography (CT). Using invasive cardiopulmonary exercise testing, this pilot study characterized exercise limitation in 5 patients with persistent symptoms 1 year following mild COVID-19 illness. Methods: Following written informed consent, data were obtained in accordance with an IRBapproved protocol entailing placement of radial and pulmonary arterial catheters for pressure monitoring and blood sampling prior to and during maximum upright incremental exercise. Rest and exercise pulmonary hemodynamics, ventilation and gas exchange were recorded. Aerobic exercise capacity was estimated by peak O2 consumption (VO2 ). Results: All patients had normal biventricular and valvular function on resting echocardiogram, no evident parenchymal lung disease on CT, and normal PFTs. Resting mean pulmonary arterial pressure was ≤20 mmHg for all patients with pulmonary vascular resistance <3 Woods units. At maximum exercise, all patients exhibited normal respiratory, cardiac output (% predicted), and total pulmonary vascular resistance responses, but demonstrated clearly depressed aerobic capacity (peak VO2 <80% predicted). Reduced peak VO2 was associated with impaired systemic O2 extraction as indicated by an arterial-venous O2 content difference (adjusted for hemoglobin) of <80% (Figure 1). Conclusion: This case series provides preliminary evidence that reduced peak aerobic capacity among long haulers is primarily attributable to a peripheral (i.e., impaired systemic O2 extraction), rather than central cardiopulmonary, limitation. These results suggest that systemic microcirculatory dysfunction contributes to exercise limitation.

Avoiding a lost decade-sovereign debt workouts in the post-Covid era

In the late summer of 2020, Ecuador and Argentina each concluded restructurings of their foreign currency bonds. These were not the first post-Covid era sovereign debt workouts;they were the last pre-Covid sovereign debt restructurings. Both countries had been in debt distress before the pandemic began and, somewhat ominously, the financial terms of the two debt restructurings may have been framed without regard to the longer-term consequences of the Covid crisis. © The Author(s) (2020). Published by Oxford University Press. All rights reserved.