Antibiotic Use in Sepsis: How and Why Less Can Really Mean More (Survival).
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ABSTRACT:
SUBMITTER: Niederman MS
PROVIDER: S-EPMC7874404 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8674610 | biostudies-literature
Project description:Over the last 10 years, there has been an explosion of literature surrounding sedation management for critically ill patients. The clinical target has moved away from an unconscious and immobile patient toward a goal of light or no sedation and early mobility. The move away from terms such as 'sedation' toward more patient-centered and symptom-based control of pain, anxiety, and agitation makes the management of critically ill patients more individualized and dynamic. Over-sedation has been associated with negative ICU outcomes, including longer durations of mechanical ventilation and lengths of stay, but few studies have been able to associate deep sedation with increased mortality.
| S-EPMC4331387 | biostudies-literature
Project description:Despite sound basis to suspect that aggressive and early administration of nutritional support may hold therapeutic benefits during sepsis, recommendations for nutritional support have been somewhat underwhelming. Current guidelines (ESPEN and ASPEN) recognise a lack of clear evidence demonstrating the beneficial effect of nutritional support during sepsis, raising the question: why, given the perceived low efficacy of nutritionals support, are there no high-quality clinical trials on the efficacy of permissive underfeeding in sepsis? Here, we review clinically relevant beneficial effects of permissive underfeeding, motivating the urgent need to investigate the clinical benefits of delaying nutritional support during sepsis.
| S-EPMC7023788 | biostudies-literature
Project description:The number of patients listed active for kidney transplantation has continued to rise over the last 10 years, leading to significantly increased wait-list time for patients awaiting kidney transplantation in the USA. This increased demand has led to a supply-demand mismatch and should prompt clinicians to seek timely solutions to improve access to available organs. Hepatitis C virus positive [HCV(+)] kidneys continue to be discarded without clear evidence that they lead to poor outcomes in the current era of highly efficacious HCV treatment with direct-acting antiviral agents (DAAs). Increased utilization of HCV(+) donor kidneys will decrease wait-list time and improve availability of donor organs. Emerging data suggests that HCV can be successfully treated with DAAs after kidney transplantation with 100% sustained virologic response rates and no significant changes from baseline kidney function. Utilization of HCV(+) donor kidneys should be considered more liberally in the era of highly effective HCV treatment. Further studies are warranted to assess the long-term effect of HCV(+) donor kidneys in transplant recipients in the new era of DAAs.
| S-EPMC5561329 | biostudies-other
Project description:Myelodysplastic syndromes (MDS) encompass a diverse group of hematologic disorders characterized by ineffective and malignant hematopoiesis, peripheral cytopenias and significantly increased risk of progression to acute myeloid leukemia (AML). The hypomethylating agents (HMA) azacitidine and decitabine induce meaningful clinical responses in a significant subset of patients with MDS. Though never compared directly with decitabine, only azacitidine has improved overall survival (OS) compared to conventional care in a randomized trial in patients with higher-risk MDS. The azacitidine regimen used in this pivotal trial AZA-001 included administration at 75 mg/m2/day for 7 consecutive days in 28-day cycles (7-0 regimen). Given the logistical difficulties of weekend administration in the 7-0 regimen, as well as in efforts to improve response rates, alternative dosing schedules have been used. In a typical 28-day cycle, administration schedules of 3, 5, 10, and (with the oral version of azacitidine) 14 and 21 days have been used in clinical trials. Most trials that evaluated alternative administration schedules of azacitidine did so in lower-risk MDS and did not directly compare to the 7-0 schedule. Given the lack of randomized prospective studies comparing the 7-0 schedule to the other regimens of azacitidine in MDS, Shapiro et al. conducted a systematic review in an attempt to answer this question. Here we place the findings of this important work in clinical context and review the current knowledge and unresolved issues regarding the impact of administration schedules of azacitidine on outcomes of patients with both lower-risk and higher-risk MDS.
| S-EPMC5796398 | biostudies-other
Project description:Perhaps the most widely studied effect to emerge from the combination of neuroimaging and human genetics is the association of the COMT-Val(108/158)Met polymorphism with prefrontal activity during working memory. COMT-Val is a putative risk factor in schizophrenia, which is characterized by disordered prefrontal function. Work in healthy populations has sought to characterize mechanisms by which the valine (Val) allele may lead to disadvantaged prefrontal cognition. Lower activity in methionine (Met) carriers has been interpreted as advantageous neural efficiency. Notably, however, studies reporting COMT effects on neural efficiency have generally not reported working memory performance effects. Those studies have employed relatively low/easy working memory loads. Higher loads are known to elicit individual differences in working memory performance that are not visible at lower loads. If COMT-Met confers greater neural efficiency when working memory is easy, a reasonable prediction is that Met carriers will be better able to cope with increasing demand for neural resources when working memory becomes difficult. To our knowledge, this prediction has thus far gone untested. Here, we tested performance on three working memory tasks. Performance on each task was measured at multiple levels of load/difficulty, including loads more demanding than those used in prior studies. We found no genotype-by-load interactions or main effects of COMT genotype on accuracy or reaction time. Indeed, even testing for performance differences at each load of each task failed to find a single significant effect of COMT genotype. Thus, even if COMT genotype has the effects on prefrontal efficiency that prior work has suggested, such effects may not directly impact high-load working memory ability. The present findings accord with previous evidence that behavioral effects of COMT are small or nonexistent and, more broadly, with a growing consensus that substantial effects on phenotype will not emerge from candidate gene studies.
| S-EPMC7028246 | biostudies-literature
Project description:BackgroundWHO Disability Assessment Schedule 2.0 (WHODAS 2.0) is a feasible tool for assessing functional disability and analysing the risk of institutionalisation among elderly patients with dementia. However, the data for the effect of education on disability status in patients with dementia is lacking. The aim of this large-scale, population-based study was to analyse the effect of education on the disability status of elderly Taiwanese patients with dementia by using WHODAS 2.0.MethodsFrom the Taiwan Data Bank of Persons with Disability, we enrolled 7698 disabled elderly (older than 65 years) patients diagnosed with dementia between July 2012 and January 2014. According to their education status, we categorised these patients with and without formal education (3849 patients each). We controlled for the demographic variables through propensity score matching. The standardised scores of these patients in the six domains of WHODAS 2.0 were evaluated by certified interviewers. Student's t-test was used for comparing the WHODAS 2.0 scores of patients with dementia in the two aforementioned groups. Poisson regression was applied for analysing the association among all the investigated variables.ResultsPatients with formal education had low disability status in the domains of getting along and social participation than did patients without formal education. Poisson regression revealed that standardised scores in all domains of WHODAS 2.0-except self-care-were associated with education status.ConclusionsThis study revealed lower disability status in the WHODAS 2.0 domains of getting along and social participation for patients with dementia with formal education compared with those without formal education. For patients with disability and dementia without formal education, community intervention of social participation should be implemented to maintain better social interaction ability.
| S-EPMC5566594 | biostudies-literature
Project description:There is a popular perception that insurance coverage will reduce overuse of the emergency department (ED). Both opponents and advocates of expanding insurance coverage under the Affordable Care Act (ACA) have made statements to the effect that EDs have been jammed with the uninsured and that paying for the uninsured population's emergency care has burdened the health care system as a result of the expense of that care. It has therefore been surprising to many to encounter evidence that insurance coverage increases ED use instead of decreasing it. Two facts may help explain this unexpected finding. First, there is a common misperception that the uninsured use the ED more than the insured. In fact, insured and uninsured adults use the ED at very similar rates and in very similar circumstances-and the uninsured use the ED substantially less than the Medicaid population. Second, while the uninsured do not use the ED more than the insured, they do use other types of care much less than the insured.
| S-EPMC5754025 | biostudies-literature
Project description:Sepsis remains a highly lethal entity resulting in more than 200 000 deaths in the USA each year. The in-hospital mortality approaches 30% despite advances in critical care during the last several decades. The direct health care costs in the USA exceed $24 billion dollars annually and continue to escalate each year especially as the population ages. The Surviving Sepsis Campaign published their initial clinical practice guidelines for the management of severe sepsis and septic shock in 2004. Updated versions were published in 2008, 2012 and most recently in 2016 following the convening of the Third International Consensus Definitions Task Force. This task force was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine to address prior criticisms of the multiple definitions used clinically for sepsis-related illnesses. In the 2016 guidelines, sepsis is redefined by the taskforce as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In addition to using the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score to more rapidly identify patients with sepsis, the task force also proposed a novel scoring system to rapidly screen for patients outside the ICU who are at risk of developing sepsis: the 'quickSOFA' (qSOFA) score. To date, the largest reductions in mortality have been associated with early identification of sepsis, initiation of a 3-hour care bundle and rapid administration of broad-spectrum antibiotics. The lack of progress in mortality reduction in sepsis treatment despite extraordinary investment of research resources underscores the variability in patients with sepsis. No single solution is likely to be universally beneficial, and sepsis continues to be an entity that should receive high priority for the development of precision health approaches for treatment.
| S-EPMC5877904 | biostudies-literature
Project description:ObjectiveThis study uses data from the largest effectiveness trial to date on treatment of co-occurring posttraumatic stress and substance use disorders, using advances in statistical methodology for modeling treatment attendance and membership turnover in rolling groups.MethodWomen receiving outpatient substance abuse treatment (N = 353) were randomized to 12 sessions of Seeking Safety or a health education control condition. Assessments were completed at baseline and at 1 week, 3, 6, and 12 months posttreatment. Outcome measures were alcohol and cocaine use in the prior 30 days captured using the Addiction Severity Index. Latent class pattern mixture modeling (LCPMM) was used to estimate attendance patterns and to test for treatment effects within and across latent attendance patterns and group membership turnover.ResultsAcross LCPMM analyses for alcohol and cocaine use, similar treatment attendance patterns emerged: Completers never decreased below an 80% probability of attendance, droppers never exceeded a 41% probability of attendance, and titrators demonstrated a 50% to 80% probability of attendance. Among completers, there were significant decreases in alcohol use from baseline to 1-week posttreatment, followed by nonsignificant increases in alcohol during follow-up. No differences between treatment conditions were detected. Titrators in Seeking Safety had lower rates of alcohol use from 1-week through 12-month follow-up compared with control participants. Droppers had nonsignificant increases in alcohol during both study phases. Cocaine use findings were similar but did not reach significance levels.ConclusionsThe impact of client self-modulation of treatment dosage and group membership composition may influence behavioral treatment outcomes among this population.
| S-EPMC3682930 | biostudies-literature