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Insufficient information is available regarding the administration of anticoagulants, specifically direct oral anticoagulants, in individuals with cirrhosis awaiting liver transplantation. In this report, we present a case of a 66-year-old male with atrial fibrillation treated with dabigatran who received idarucizumab prior to orthotopic liver transplantation. Hemostatic status was monitored throughout the procedure with both conventional hemostatic tests and point-of-care viscoelastic hemostatic assays. The patient suffered an intraoperative myocardial infarction, which could be related to the use of idarucizumab.

The principle objective of a diagnosis is not to categorise symptoms, or group a combination of signs or clinical symptoms in a coherent way, but to cure a patient or improve their quality of life. Diagnoses that are technically correct, but do not seek this objective may become unnecessary labels which convert healthy people, or those who do not consider themselves to be sick, into patients. We propose a limitation of the diagnostic effort in order to reduce the iatrogenic consequences of these unnecessary labels or diagnoses, a new imperative which, in Kantian terms, can be expressed as: examine and treat your patients in such a way that, at the very least, the effects of your actions always improve the quality of their lives.

Background Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function. Methods The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV 1 ) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV 1 , forced vital capacity (FVC) and FEV 1 /FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point. Results Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8–8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV 1 z-score was − 2.0 (0.7) with 44.7% ( n  = 155) having an FEV 1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV 1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV 1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load. Conclusion There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function. Trial registration ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.

Background We investigated risk factors for sustained virological non-suppression (viral load ≥ 1000 copies/ml on two tests 48 weeks apart) among children and adolescents accessing HIV care in public sector clinics in Harare, Zimbabwe and Blantyre, Malawi. Methods Participants were enrolled between 2016 and 2019, were aged 6–19 years, living with HIV, had chronic lung disease (FEV z-score < -1) and had taken antiretroviral therapy (ART) for at least six months. We used multivariate logistic regression to identify risk factors for virological non-suppression after 48 weeks, among participants who were non-suppressed at enrolment. Results At enrolment 258 participants (64.6%) were on first-line ART and 152/347 (43.8%) had virological non-suppression. After 48 weeks 114/313 (36.4%) were non-suppressed. Participants non-suppressed at baseline had almost ten times higher odds of non-suppression at follow-up (OR = 9.9, 95%CI 5.3–18.4, p  < 0.001). Of those who were non-suppressed at enrolment, 87/136 (64.0%) were still non-suppressed at 48 weeks. Among this group non-suppression at 48 weeks was associated with not switching ART regimen (adjusted OR = 5.55; 95%CI 1.41–21.83); p  = 0.014) and with older age. Twelve participants switched regimen in Zimbabwe and none in Malawi. Conclusions Viral non-suppression was high among this group and many with high viral load were not switched to a new regimen, resulting in continued non-suppression after 48 weeks. Further research could determine whether improved adherence counselling and training clinicians on regimen switches can improve viral suppression rates in this population. Trial registration Secondary cohort analysis of data from BREATHE trial (Clinicaltrials.gov NCT02426112 ).

Background Human immunodeficiency virus (HIV)-related chronic lung disease (CLD) among children is associated with substantial morbidity, despite antiretroviral therapy. This may be a consequence of repeated respiratory tract infections and/or dysregulated immune activation that accompanies HIV infection. Macrolides have anti-inflammatory and antimicrobial properties, and we hypothesised that azithromycin would reduce decline in lung function and morbidity through preventing respiratory tract infections and controlling systemic inflammation. Methods/design We are conducting a multicentre (Malawi and Zimbabwe), double-blind, randomised controlled trial of a 12-month course of weekly azithromycin versus placebo. The primary outcome is the mean change in forced expiratory volume in 1 second (FEV 1 ) z-score at 12 months. Participants are followed up to 18 months to explore the durability of effect. Secondary outcomes are FEV 1 z-score at 18 months, time to death, time to first acute respiratory exacerbation, number of exacerbations, number of hospitalisations, weight for age z-score at 12 and 18 months, number of adverse events, number of malaria episodes, number of bloodstream Salmonella typhi infections and number of gastroenteritis episodes. Participants will be followed up 3-monthly, and lung function will be assessed every 6 months. Laboratory substudies will be done to investigate the impact of azithromycin on systemic inflammation and on development of antimicrobial resistance as well as impact on the nasopharyngeal, lung and gut microbiome. Discussion The results of this trial will be of clinical relevance because there are no established guidelines on the treatment and management of HIV-associated CLD in children in sub-Saharan Africa, where 80% of the world’s HIV-infected children live and where HIV-associated CLD is highly prevalent. Trial registration ClinicalTrials.gov, NCT02426112 . Registered on 21 April 2015.

Strawberries have a thin epidermis and a high respiration rate. The use of edible coatings containing chitosan nanoparticles (CSNPs) and propolis (P) has been effective in preserving the shelf life and antioxidant capacity of various fruit and vegetable products. The present research evaluated the effect of coatings with CSNPs and P on the quality, antioxidant compounds, and antioxidant capacity of strawberries. The specific coatings that were evaluated were chitosan (CS), CS+CSNPs33%, CS + CSNPs + P10%, CS + CSNPs + P20%, CS + CSNPs + P30%, and a control with no coating. The variables were weight loss, firmness, total soluble solids (TSS), color, phenols, total flavonoids, antioxidant capacity, and sensory characteristics. An ANOVA and a Tukey test (p ≤ 0.05) were used to analyze the data. Strawberries covered with CS + CSNPs + P10% showed the lowest weight loss (9.77%), while those covered with CS + CSNPs + P20% had the greatest firmness (4.96 N). CS + CSNPs + P coatings at 10%, 20%, and 30% concentrations maintained the antioxidant compounds and antioxidant capacity in the evaluated fruit (28.49 mg GAE g−1, 554.61 μg quercetin g−1, and 92.48% DPPH, respectively). The application of nanostructured coatings did not modify the sensory characteristics of the fruit. Coatings with CSNPs and/or P could therefore be a viable alternative for preserving the quality and antioxidant capacity of strawberries.

This article analyses the evolution and geographic distribution of the rural unrest that prevailed during the years of the Second Spanish Republic (1931–1936), a period characterised by political instability and social conflict. The number of provincial strikes recorded in the forestry and agricultural industries and complied by the Ministry of Labour and Social Welfare constitute the primary source of the study. Based on this information, maps of the regional and provincial distribution of the agricultural unrest have been created for the republican period. The results reveal that, contrary to the traditional belief which confines the rural unrest of this period to the geographic areas of the latifundios (large estates), Spanish agriculture, in all its diversity, was hit by collective disputes. Although the areas of the latifundios were most affected by the agricultural reform of 1932, the data show that the extension of the unrest in the Spanish countryside was also the result of the refusal of the landowners to accept and apply the new republican collective bargaining agreement. The number of strikes increased during the period 1931–1933, fell between 1934 and 1935, and increased again during the months of the Popular Front (February to July 1936).

Background Currently, in the scientific literature there is a great interest on the study of strategies to implement patient-centered care. One of the main tools for this is the therapeutic relationship. Some studies suggest that the perception of the environment in which the treatment takes place can influence the perception of its quality, but this is not explored in physical therapy. For all these reasons, the aim of this study was to understand the influence of the environment in which physical therapy treatment takes place on the patients’ perception of the quality of the patient-centered therapeutic relationship in public health centers in Spain. Methods A qualitative study analysed thematically using a modified grounded theory approach. Data collection used semistructured interviewing during focus groups. Results We conducted four focus groups. The size of the focus groups ranged from six to nine participants. In total, 31 patients participated in these focus groups. Participants described a series of specific experiences and perceptions relating to the environment, which they felt were influential in the establishment of therapeutic patient-centered relationships, including six physical factors (Architectural barriers, Furniture, Use of the computer, Physical space, Ambiet conditions, and Privacy) and six organizational factors (Patient-physical therapist ratio, Treatment interruptions, Social factors, Continuity with the professional, Lack of professional autonomy, and Coordination or communication among team members). Conclusion The results of this study highlight environmental factors that affect the quality of the therapeutic patient-centered relationship in physical therapy from the patient’s point of view, and emphasize the need for physical therapists and administrators to underline the need to review these factors and take them into account in their service delivery.

HIV-associated chronic lung disease (HCLD) in children is associated with small airways disease, is common despite antiretroviral therapy (ART), and is associated with substantial morbidity. Azithromycin has antibiotic and immunomodulatory activity and may be effective in treating HCLD through reducing respiratory tract infections and inflammation. To determine whether prophylactic azithromycin is effective in preventing worsening of lung function and in reducing acute respiratory exacerbations (AREs) in children with HCLD taking ART. This double-blind, placebo-controlled, randomized clinical trial (BREATHE) was conducted between 2016 and 2019, including 12 months of follow-up, at outpatient HIV clinics in 2 public sector hospitals in Malawi and Zimbabwe. Participants were randomized 1:1 to intervention or placebo, and participants and study personnel were blinded to treatment allocation. Participants included children aged 6 to 19 years with perinatally acquired HIV and HCLD (defined as forced expiratory volume in 1 second [FEV1] z score < -1) who were taking ART for 6 months or longer. Data analysis was performed from September 2019 to April 2020. Once-weekly oral azithromycin with weight-based dosing, for 48 weeks. All outcomes were prespecified. The primary outcome was the mean difference in FEV1 z score using intention-to-treat analysis for participants seen at end line. Secondary outcomes included AREs, all-cause hospitalizations, mortality, and weight-for-age z score. A total of 347 individuals (median [interquartile range] age, 15.3 [12.7-17.7] years; 177 boys [51.0%]) were randomized, 174 to the azithromycin group and 173 to the placebo group; 162 participants in the azithromycin group and 146 placebo group participants had a primary outcome available and were analyzed. The mean difference in FEV1 z score was 0.06 (95% CI, -0.10 to 0.21; P = .48) higher in the azithromycin group than in the placebo group, a nonsignificant difference. The rate of AREs was 12.1 events per 100 person-years in the azithromycin group and 24.7 events per 100 person-years in the placebo groups (hazard ratio, 0.50; 95% CI, 0.27 to 0.93; P = .03). The hospitalization rate was 1.3 events per 100 person-years in the azithromycin group and 7.1 events per 100 person-years in the placebo groups, but the difference was not significant (hazard ratio, 0.24; 95% CI, 0.06 to 1.07; P = .06). Three deaths occurred, all in the placebo group. The mean weight-for-age z score was 0.03 (95% CI, -0.08 to 0.14; P = .56) higher in the azithromycin group than in the placebo group, although the difference was not significant. There were no drug-related severe adverse events. In this randomized clinical trial specifically addressing childhood HCLD, once-weekly azithromycin did not improve lung function or growth but was associated with reduced AREs; the number of hospitalizations was also lower in the azithromycin group but the difference was not significant. Future research should identify patient groups who would benefit most from this intervention and optimum treatment length, to maximize benefits while reducing the risk of antimicrobial resistance. ClinicalTrials.gov Identifier: NCT02426112.