Prolonged acute mechanical ventilation and hospital bed utilization in 2020 in the United States: implications for budgets, plant and personnel planning

<p>Abstract</p> <p>Background</p> <p>Adult patients on prolonged acute mechanical ventilation (PAMV) comprise 1/3 of all adult MV patients, consume 2/3 of hospital resources allocated to MV population, and are nearly twice as likely to require a discharge to a skilled nursing facility (SNF). Their numbers are projected to double by year 2020. To aid in planning for this growth, we projected their annualized days and costs of hospital use and SNF discharges in year 2020 in the US.</p> <p>Methods</p> <p>We constructed a model estimating the relevant components of hospital utilization. We computed the total days and costs for each component; we also applied the risk for SNF discharge to the total 2020 PAMV population. The underlying assumption was that process of care does not change over the time horizon. We performed Monte Carlo simulations to establish 95% confidence intervals (CI) for the point estimates.</p> <p>Results</p> <p>Given 2020 projected PAMV volume of 605,898 cases, they will require 3.6 (95% CI 2.7–4.8) million MV, 5.5 (95% CI 4.3–7.0) million ICU and 10.3 (95% CI 8.1–13.0) million hospital days, representing an absolute increase of 2.1 million MV, 3.2 million ICU and 6.5 million hospital days over year 2000, at a total inflation-adjusted cost of over $64 billion. Expected discharges to SNF are 218,123 (95% CI 177,268–266,739), compared to 90,928 in 2000.</p> <p>Conclusion</p> <p>Our model suggest that the projected growth in the US in PAMV population by 2020 will result in annualized increases of more than 2, 3, and 6 million MV, ICU and hospital days, respectively, over year 2000. Such growth requires careful planning efforts and attention to efficiency of healthcare delivery.</p

Ocular medicines in children: the regulatory situation related to clinical research

<p>Abstract</p> <p>Background</p> <p>Many ocular medications are prescribed for paediatric patients, but the evidence for their rational use is very scant. This study was planned to compare the availability and the licensing status of ocular medications marketed in Italy, the United Kingdom (UK), and the United States of America (USA) related to the amount of published and un-published RCTs testing these drugs in the paediatric population.</p> <p>Methods</p> <p>A quantitative analysis was performed to evaluate the number of ocular medications with a paediatric license in Italy, the UK, and the USA. A literature search was also performed in MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) on ophthalmic pharmacological therapy in children aged < 18 years, published up to December 2010. A search in the international clinical trial registries, the list of paediatric investigation plans (PIPs) approved by European Medicines Agency (EMA), and the table of medicines with new paediatric information approved by Food and Drug Administration (FDA) was also performed.</p> <p>Results</p> <p>In all, of 197 drugs identified, 68 (35%) single drugs are licensed for paediatric use at least in one considered country, while 23 (12%) were marketed in all three countries. More specifically, in Italy 43 single drugs (48% of those marketed) had a paediatric license, while 39 (64%) did in the UK and 22 (54%) did in the USA. Only 13 drugs were marketed with a paediatric license in all countries.</p> <p>The percentage of drugs licensed for paediatric use and for which at least one RCT had been performed ranged between 51% in Italy and 55% in the USA. No published RCTs were found for 11 (48%) drugs licensed for paediatric use in all three countries. In all, 74 (35%) of the retrieved RCTs involved mydriatic/cycloplegic medications.</p> <p>A total of 62 RCTs (56% completed) on 46 drugs were found in the international clinical trial registries. Cyclosporin and bevacizumab were being studied in many ongoing trials. Twenty-six drugs had new paediatric information approved by FDA based on new paediatric clinical trials, while only 4 PIPs were approved by EMA.</p> <p>Conclusions</p> <p>There is a pressing need for further research and clinical development in the pediatric ophthalmic area, where effective up-to-date treatments, and additional research and education on use in children, remain priorities.</p

Imipenem resistance of Pseudomonas in pneumonia: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Pneumonia, and particularly nosocomial (NP) and ventilator-associated pneumonias (VAP), results in high morbidity and costs. NPs in particular are likely to be caused by <it>Pseudomonas aeruginosa </it>(PA), ~20% of which in observational studies are resistant to imipenem. We sought to identify the burden of PA imipenem resistance in pneumonia.</p> <p>Methods</p> <p>We conducted a systematic literature review of randomized controlled trials (RCT) of imipenem treatment for pneumonia published in English between 1993 and 2008. We extracted study, population and treatment characteristics, and proportions caused by PA. Endpoints of interest were: PA resistance to initial antimicrobial treatment, clinical success, microbiologic eradication and on-treatment emergence of resistance of PA.</p> <p>Results</p> <p>Of the 46 studies identified, 20 (N = 4,310) included patients with pneumonia (imipenem 1,667, PA 251; comparator 1,661, PA 270). Seven were double blind, and 7 included US data. Comparator arms included a β-lactam (17, [penicillin 6, carbapenem 4, cephalosporin 7, monobactam 1]), aminoglycoside 2, vancomycin 1, and a fluoroquinolone 5; 5 employed double coverage. Thirteen focused exclusively on pneumonia and 7 included pneumonia and other diagnoses. Initial resistance was present in 14.6% (range 4.2-24.0%) of PA isolates in imipenem and 2.5% (range 0.0-7.4%) in comparator groups. Pooled clinical success rates for PA were 45.2% (range 0.0-72.0%) for imipenem and 74.9% (range 0.0-100.0%) for comparator regimens. Microbiologic eradication was achieved in 47.6% (range 0.0%-100.0%) of isolates in the imipenem and 52.8% (range 0.0%-100.0%) in the comparator groups. Resistance emerged in 38.7% (range 5.6-77.8%) PA isolates in imipenem and 21.9% (range 4.8-56.5%) in comparator groups.</p> <p>Conclusions</p> <p>In the 15 years of RCTs of imipenem for pneumonia, PA imipenem resistance rates are high, and PA clinical success and microbiologic eradication rates are directionally lower for imipenem than for comparators. Conversely, initial and treatment-emergent resistance is more likely with the imipenem than the comparator regimens.</p

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Campylobacter concisus from chronic inflammatory bowel diseases stimulates IL-8 production in HT-29 cells

Abstract The emerging pathogen Campylobacter concisus has been isolated from patients with gastrointestinal diseases; however, it is also present in the gut of healthy individuals. The aim of this study was to compare IL-8 production in HT-29 cells after infection with C. concisus from different gastrointestinal disease phenotypes. Additionally, to investigate whether differentiation of isolates in genomospecies (GS1 and GS2) or presence of the zot gene, encoding the Zot toxin, affects IL-8 production. A total of 37 C. concisus isolates from patients with microscopic colitis (n = 20), ulcerative colitis (n = 5), Crohn’s disease (n = 5), diarrhoea (n = 2) and from healthy controls (n = 5) were used. Intestinal HT-29 cells were infected and incubated for 24 h. Supernatants were subsequently removed and analysed for IL-8 by MILLIPLEX. All isolates were able to stimulate IL-8 production and IL-8 levels were higher than in non-infected HT-29 cells. No difference was observed between disease phenotypes or GS1 and GS2, whereas presence of the zot gene showed a tendency towards higher IL-8 production. Further investigations in other inflammatory and physiological models are needed to conclude whether C. concisus strains from different gastrointestinal disease phenotypes differ in pathogenic potential and play a part in gastrointestinal disease