Clinical outcomes and bacterial characteristics of carbapenem-resistant Klebsiella pneumoniae complex among patients from different global regions (CRACKLE-2): a prospective, multicentre, cohort study

Background: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a global threat. We therefore analysed the bacterial characteristics of CRKP infections and the clinical outcomes of patients with CRKP infections across different countries. Methods: In this prospective, multicentre, cohort study (CRACKLE-2), hospitalised patients with cultures positive for CRKP were recruited from 71 hospitals in Argentina, Australia, Chile, China, Colombia, Lebanon, Singapore, and the USA. The first culture positive for CRKP was included for each unique patient. Clinical data on post-hospitalisation death and readmission were collected from health records, and whole genome sequencing was done on all isolates. The primary outcome was a desirability of outcome ranking at 30 days after the index culture, and, along with bacterial characteristics and 30-day all-cause mortality (a key secondary outcome), was compared between patients from China, South America, and the USA. The desirability of outcome ranking was adjusted for location before admission, Charlson comorbidity index, age at culture, Pitt bacteremia score, and anatomical culture source through inverse probability weighting; mortality was adjusted for the same confounders, plus region where relevant, through multivariable logistic regression. This study is registered at ClinicalTrials.gov, NCT03646227, and is complete. Findings: Between June 13, 2017, and Nov 30, 2018, 991 patients were enrolled, of whom 502 (51%) met the criteria for CRKP infection and 489 (49%) had positive cultures that were considered colonisation. We observed little intra-country genetic variation in CRKP. Infected patients from the USA were more acutely ill than were patients from China or South America (median Pitt bacteremia score 3 [IQR 2–6] vs 2 [0–4] vs 2 [0–4]) and had more comorbidities (median Charlson comorbidity index 3 [IQR 2–5] vs 1 [0–3] vs 1 [0–2]). Adjusted desirability of outcome ranking outcomes were similar in infected patients from China (n=246), South America (n=109), and the USA (n=130); the estimates were 53% (95% CI 42–65) for China versus South America, 50% (41–61) for the USA versus China, and 53% (41–66) for the USA versus South America. In patients with CRKP infections, unadjusted 30-day mortality was lower in China (12%, 95% CI 8–16; 29 of 246) than in the USA (23%, 16–30; 30 of 130) and South America (28%, 20–37; 31 of 109). Adjusted 30-day all-cause mortality was higher in South America than in China (adjusted odds ratio [aOR] 4·82, 95% CI 2·22–10·50) and the USA (aOR 3·34, 1·50–7·47), with the mortality difference between the USA and China no longer being significant (aOR 1·44, 0·70–2·96). Interpretation: Global CRKP epidemics have important regional differences in patients’ baseline characteristics and clinical outcomes, and in bacterial characteristics. Research findings from one region might not be generalisable to other regions. Funding: The National Institutes of Health

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p =.02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p =.032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0–2.6, p =.04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0–11.3, p =.05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Human Immunodeficiency Virus and Hepatitis C Virus in Cardiothoracic Transplantation and Mechanical Circulatory Support

Patients infected with human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV) or hepatitis B virus (HBV) have traditionally been considered high-risk recipients for transplantation. Recent advances have had a significant effect on the potential transplant candidacy of these patients. This review highlights the major issues associated with cardiothoracic transplantation in individuals who are infected with HIV and/or HCV

Impact of COVID-19 in solid organ transplant recipients.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exploded onto the world stage in early 2020. The impact on solid organ transplantation (SOT) has been profound affecting potential donors, candidates, and recipients. Importantly, decreased donations and the pressure of limited resources placed on health care by the pandemic also disrupted transplant systems. We address the impact of COVID-19 on organ transplantation globally and review current understanding of the epidemiology, outcomes, diagnosis, and treatment of COVID-19 in SOT recipients

Successful treatment of a disseminated infection with extensively drug‐resistant Klebsiella pneumoniae in a liver transplant recipient with a fosfomycin‐based multidrug regimen

Donor‐derived infections with multidrug‐resistant gram‐negative bacteria are associated with poor outcomes, in part because of limited treatment options. Here, we describe a case of donor‐derived, disseminated infection with colistin‐resistant, carbapenemase‐producing Klebsiella pneumoniae in a liver transplant recipient that was cured with addition of intravenous fosfomycin to a multidrug regimen, in conjunction with aggressive surgical source control. Intravenous fosfomycin represents a promising adjunctive agent for use in treatment of extensively drug‐resistant infections in immunocompromised hosts.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134238/1/tid12578_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134238/2/tid12578.pd

Husband's and wife's culture participation and their levels of education: A case of male-dominance

Contains fulltext : 28411.pdf (publisher's version ) (Open Access)In this study we seek to broaden the debate on women and class analysis to married women’s and men's educational attainment, and its impact on cultural behaviour. Analogous to the earlier discussion, the question is raised whether the husband's education dominates his wife’s behaviour. First, to examine spouses' interdependent cultural behaviour, we apply a simultaneous equation model. Our analysis, based on longitudinal data from Dutch household surveys, shows some evidence of a declining male dominance across cohorts. The findings also suggest that the total effect of the wife's education on her husband’s cultural behaviour has increased over time. Second, we apply diagonal reference models to study educationally mixed couples more elaborately by testing several interaction effects. Although both women’s and men’s relative positions are associated with a differential sahence of the spouse’s education, there is no evidence indicating that the lower educated spouse is primarily 'borrowing' from his or her higher educated partner. Instead of such a 'status maximimization' effect the higher educated spouse adapts more strongly to the lower educated spouse. In particular, women in the oldest cohort seem to be characterized by this 'status minimization'. The theoretical implications of these findings are discussed

Controle de Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae) com reguladores de crescimento de insetos Control of Anticarsia gemmatalis hübner (Lepidoptera: Noctuidae) larvae with insect growth regulators

A lagarta-da-soja, Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae), é uma praga importante na cultura da soja no Brasil. Este estudo teve como objetivo avaliar diferentes inseticidas, reguladores de crescimento, para o controle dessa praga. Os inseticidas diflubenzuron (15g i.a. ha-1), lufenuron (7,5g i.a. ha-1), metoxifenozide (21,6g i.a. ha-1) e teflubenzuron (7,5g i.a. ha-1) foram aplicados com pulverizador costal de precisão, equipado com pontas tipo leque 110, 02, numa pressão de 1 bar e volume de calda de 100l ha-1. No dia da aplicação dos inseticidas, as plantas de soja (cv. Fundacep 33) estavam com 0,90m de altura, no estádio R3.1, e infestação média de 95 lagartas pequenas e de 33 lagartas grandes por dois metros de fileira. A eficiência dos inseticidas foi determinada através da contagem do número de lagartas vivas pequenas e grandes aos 0, 2, 4, 7 e 10 dias após a aplicação (DAA); da percentagem de desfolha aos 15 DAA e da produção de grãos. Foi observado efeito de choque do inseticida metoxifenozide tanto em lagartas pequenas quanto em grandes. Os inseticidas diflubenzuron, lufenuron e teflubenzuron controlaram eficientemente as lagartas a partir de 4 DAA. As infestações de lagartas nas parcelas testemunhas aumentaram a desfolha em 75,8% e reduziram produtividade para 2371 kg ha-1. Nas parcelas tratadas com inseticidas desfolha variou de 34,7% a 50,7% e a produtividade entre 3255kg ha-1 e 3585kg ha-1.<br>The velvetbean caterpillar, Anticarsia gemmatalis Hübner (Lepidoptera: Noctuidae), is an important soybean pest in Brazil. This study aimed to evaluate growth regulators insecticides. A precision sprayer equipped with 110 02 nozzles, working at a constant pressure of 1 bar and volume of 100 liters per hectare was used to apply the insecticide treatments (diflubenzuron at 15g a.i. per hectare, lufenuron at 7.5 g a.i. per hectare, metoxyfenozide at 21.6g a.i. per hectare and teflubenzuron at 7.5g a.i. per hectare). Applications when plants were 0.90m height, in the R3.1 growth stage, and the number of small larvae was 95, while that of large larvae was 33 per two meters of row. The number of live larvae at 0, 2, 4, 7 and 10 days after application, the defoliation at 15 days after application and grain yield were evaluated. The fastest control of large and small larvae was obtained with metoxyfenozide at 2 days after application. The insecticides diflubenzuron, lufenuron and teflubenzuron efficiently controlled of large and small larvae, but only at 4 days after application. Larval infestations in non-treated plots resulted in significant defoliation and yield losses when compared to plots treated with insecticides

Assignment of a gene (NEMI) for autosomal dominant nemaline myopathy to chromosome I

Nemaline myopathy (NEM) is a neuromuscular disorder characterized by the presence, in skeletal muscle, of nemaline rods composed at least in part of α-actinin. A candidate gene and linkage approach was used to localize the gene (NEM1) for an autosomal dominant form (MIM 161800) in one large kindred with 10 living affected family members. Markers on chromosome 19 that were linked to the central core disease gene, a marker at the complement 3 locus, and a marker on chromosome 1 at the α-actinin locus exclude these three candidate genes. The family was fully informative for APOA2, which is localized to 1q21-q23. NEM1 was assigned to chromosome 1 by close linkage for APOA2, which is localized to 1q21-q23. NEM1 was assigned to chromosome 1 by close linkage to APOA2, with a lod score of 3.8 at a recombination fraction of 0. Recombinants with NGFB (1p13) and AT3 (1q23-25.1) indicate that NEM1 lies between 1p13 and 1q25.1. In total, 47 loci were investigated on chromosomes 1, 2, 4, 5, 7–11, 14, 16, 17, and 19, with no indications of significant linkage other than to markers on chromosome 1