Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review.

The alarming spread and impact of multidrug-resistant Candida auris infections alongside the limited therapeutic options have prompted the development of new antifungals. These promising agents are currently in different stages of development, offering novel dosing regimens and mechanisms of action. A systematic search in MEDLINE, EMBASE, Web of Science, and Scopus up to 27 June 2022 was conducted to find relevant articles reporting data of in vitro activity and in vivo efficacy of investigational antifungals against C. auris. These included new additions to existing antifungal classes (rezafungin and opelconazole), first-in-class drugs such as ibrexafungerp, manogepix/fosmanogepix, olorofim and tetrazoles (quilseconazole, oteseconazole and VT-1598), as well as other innovative agents like ATI-2307, MGCD290 and VL-2397. From 592 articles retrieved in the primary search, 27 met the eligibility criteria. The most studied agent was manogepix/fosmanogepix (overall MIC90: 0.03 mg/L), followed by ibrexafungerp (overall MIC90: 1 mg/L) and rezafungin (overall MIC mode: 0.25 mg/L), while VT-1598 and ATI-2307 were the least explored drugs against C. auris. All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential.

Localized gallbladder perforation: a systematic review of treatment and prognosis.

BACKGROUND: The optimal management of localized gallbladder perforation (Neimeier type II) has yet to be defined. The aim of this systematic review was to identify factors associated with improved patient outcomes. METHODS: Systematic review of studies that described the management of Neimeier type II perforation, reported complications of the first intervention, necessity of added interventions, resolution of the pathology, and days of hospital stay were included. The search strategy was conducted in EMBASE, Mayo Journals, MEDLINE, SCOPUS, and Web of Science (December 2020) RESULTS: A total of 122 patients (53% male) from case reports, series, and cohorts were included for analysis. In total 56 (46%) and 44 (36%)patients were treated with open and laparoscopic cholecystectomy respectively. Overall risk of bias was moderate. The need for another intervention was higher in the laparoscopic group (5 vs 17, p=<0.001) as well as prevalence of complications (4 vs 16, p=<0.001), but lower for days of hospital stay (median days 5. vs 15, p = 0.008) against open cholecystectomy. Preoperative percutaneous catheter drainage did not influence outcome. CONCLUSION: Open cholecystectomy has a lower need for further surgical procedures and postoperative complications, but a longer hospital stay. These outcomes did not vary with preoperative percutaneous drainage. The effect of timing of cholecystectomy did not influence the outcomes.

Does current evidence on disease-modifying antirheumatic drugs for psoriatic arthritis reinforce an effect on radiographic progression? Results from a systematic review and meta-analysis.

This study aims to estimate the effect of synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) on radiographic progression and quality of life in adult patients with psoriatic arthritis. A comprehensive search was performed using MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials (CCRCT). Clinical trials comparing DMARDs with placebo for ≥ 12 weeks were included. The meta-analysis was conducted with a random-effects model using mean differences (MD). A total of 16 trials with overall moderate quality of evidence were included. Exposure to a biologic agent reduced radiographic progression at 24 weeks of treatment (MD: - 0.66; [95% CI - 0.97 to - 0.34]; P < .00001; I2 = 100%). The reduction of the baseline score was more than two times higher for TNF blockers compared with IL-17 and IL-12/IL-23 inhibitors (MD: - 0.94 vs - 0.41). Improvement in health-related quality of life scores was observed in biologic-treated populations (MD: - 0.21; [95% CI - 0.25 to - 0.18]; P < .00001; I2 = 97%). No sufficient data were available regarding conventional synthetic agents. Our data analyses suggest a better control of radiological damage with bDMARDs, as compared to placebo, after 24 weeks of treatment. However, the accuracy of these results in real life are jeopardized by the exceedingly high level of heterogeneity exhibited within and across included studies, and the true intervention effect cannot be determined with confidence. Further research is required to assess long-term outcomes and to control heterogeneity in the evaluation of treatments for psoriatic arthritis. PROSPERO registration number: CRD42019122223. Key Points • Radiographic progression is not the primary outcome for most efficacy studies in psoriatic arthritis; hence, baseline data are substantially diverse in major clinical trials. • The best available evidence on this particular outcome is currently at a moderate risk of bias. • Existing reports of the effect of DMARDs on structural damage must be taken with caution. • Further research is required to assess long-term outcomes and to control heterogeneity between studies.

Prevalence of Diabetes and Hypertension and Their Associated Risks for Poor Outcomes in Covid-19 Patients.

Coronavirus disease 2019 (Covid-19) has affected millions of people and may disproportionately affect those with hypertension and diabetes. Because of inadequate methods in published systematic reviews, the prevalence of diabetes and hypertension and associated risks of poor outcomes in Covid-19 patients are unknown. We searched databases from December 1, 2019, to April 6, 2020, and selected observational peer-reviewed studies in English of patients with Covid-19. Independent reviewers extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence. We included 65 (15 794 participants) observational studies at moderate to high risk of bias. Overall prevalence of diabetes and hypertension was 12% (95% confidence interval [CI], 10-15; n = 12 870; I 2: 89%), and 17% (95% CI, 13-22; n = 12 709; I 2: 95%), respectively. In severe Covid-19, the prevalence of diabetes and hypertension were 18% (95% CI, 16-20; n = 1099; I 2: 0%) and 32% (95% CI, 16-54; n = 1078; I 2: 63%), respectively. Unadjusted relative risk for intensive care unit admission and mortality were 1.96 (95% CI, 1.19-3.22; n = 8890; I 2: 80%; P = .008) and 2.78 (95% CI, 1.39-5.58; n = 2058; I 2: 75%; P = .0004) for diabetics; and 2.95 (95% CI, 2.18-3.99; n = 1737; I 2: 0%; P < .001) and 2.39 (95% CI, 1.54-3.73; n = 3107; I 2: 66%; P < .001) for hypertensives. Neither diabetes (1.50; 95% CI, 0.90-2.50; n = 1991; I 2: 74%; P = .119) nor hypertension (1.48; 95% CI, 0.99-2.23; n = 2023; I 2: 69%; P = .058) was associated with severe Covid-19. In conclusion, the risk of intensive care unit admission and mortality for patients with diabetes or hypertension who developed Covid-19 is increased compared with those without these comorbidities. PROSPERO REGISTRATION NUMBER: CRD42020176582.

[Association of family typology and dysfunction in families with adolescents from a Mexican population]. / Asociación de tipología familiar y disfuncionalidad en familias con adolescentes de una población mexicana.

OBJECTIVE: To determine the association between family typology and dysfunction in families with adolescents in a Mexican population. DESIGN: Cross-sectional observational study. SETTING AND POPULATION: A total of 437 families in a Mexican population with adolescents attending a public high school. MAIN MEASUREMENTS: Determination of family typology (Mexican Family Medicine Council and Consensus) and family function (family APGAR) in adolescents and their parents/guardians. Identification of families with concordant perceptions among members (Cohen kappa), in which the association between typology and perception of family dysfunction was determined (odds ratio [OR]). RESULTS: The types of families are associated with family function by kinship, physical presence in the home and the level of family poverty. From the perception of the adolescent, the types are associated with: simple nuclear (OR 0.5, 95% CI 0.3-0.8), extended single parent (OR 1.9, 95% CI 1.03-3.5), integrated nucleus (OR 0.6, 95% CI 0.4-0.9), low family poverty (OR 0.5, 95% CI 0.3-0.8), and high family poverty (OR 5.3, 95% CI 1.5-18.6). From the perception of the tutor: the single parent (OR 1.9, 95% CI 1.09-3.4), and high family poverty (OR 2.9, 95% CI 1.1-7.7). There were 259 families with concordant perception of family function/dysfunction with a κ=0.189, determining that the types associated are: simple nuclear (OR 0.4, 95% CI 0.2-0.7), single-parent (OR 1.7, 95% CI 0.80-3.8), integrated nucleus (OR 0.5, 95% CI 0.3-0.8), non-integrated nucleus (OR 1.9, 95% CI 1.09-3.5), and high family poverty (OR 13.8, 95% CI 1.7-108.5). CONCLUSION: The family types with adolescents associated with family dysfunction are single-parent families with a non-integrated nucleus and high family poverty, and as protective factors, the simple nuclear and integrated nucleus.