Dynamic modeling of hospitalized COVID-19 patients reveals disease state-dependent risk factors.

OBJECTIVE: The study sought to investigate the disease state-dependent risk profiles of patient demographics and medical comorbidities associated with adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. MATERIALS AND METHODS: A covariate-dependent, continuous-time hidden Markov model with 4 states (moderate, severe, discharged, and deceased) was used to model the dynamic progression of COVID-19 during the course of hospitalization. All model parameters were estimated using the electronic health records of 1362 patients from ProMedica Health System admitted between March 20, 2020 and December 29, 2020 with a positive nasopharyngeal PCR test for SARS-CoV-2. Demographic characteristics, comorbidities, vital signs, and laboratory test results were retrospectively evaluated to infer a patient's clinical progression. RESULTS: The association between patient-level covariates and risk of progression was found to be disease state dependent. Specifically, while being male, being Black or having a medical comorbidity were all associated with an increased risk of progressing from the moderate disease state to the severe disease state, these same factors were associated with a decreased risk of progressing from the severe disease state to the deceased state. DISCUSSION: Recent studies have not included analyses of the temporal progression of COVID-19, making the current study a unique modeling-based approach to understand the dynamics of COVID-19 in hospitalized patients. CONCLUSION: Dynamic risk stratification models have the potential to improve clinical outcomes not only in COVID-19, but also in a myriad of other acute and chronic diseases that, to date, have largely been assessed only by static modeling techniques.

Budget constrained machine learning for early prediction of adverse outcomes for COVID-19 patients.

The combination of machine learning (ML) and electronic health records (EHR) data may be able to improve outcomes of hospitalized COVID-19 patients through improved risk stratification and patient outcome prediction. However, in resource constrained environments the clinical utility of such data-driven predictive tools may be limited by the cost or unavailability of certain laboratory tests. We leveraged EHR data to develop an ML-based tool for predicting adverse outcomes that optimizes clinical utility under a given cost structure. We further gained insights into the decision-making process of the ML models through an explainable AI tool. This cohort study was performed using deidentified EHR data from COVID-19 patients from ProMedica Health System in northwest Ohio and southeastern Michigan. We tested the performance of various ML approaches for predicting either increasing ventilatory support or mortality. We performed post hoc analysis to obtain optimal feature sets under various budget constraints. We demonstrate that it is possible to achieve a significant reduction in cost at the expense of a small reduction in predictive performance. For example, when predicting ventilation, it is possible to achieve a 43% reduction in cost with only a 3% reduction in performance. Similarly, when predicting mortality, it is possible to achieve a 50% reduction in cost with only a 1% reduction in performance. This study presents a quick, accurate, and cost-effective method to evaluate risk of deterioration for patients with SARS-CoV-2 infection at the time of clinical evaluation.

Efficacy of tocilizumab in COVID-19: A systematic review and meta-analysis.

The efficacy of tocilizumab (TOC), monoclonal antibody against interleukin-6 (IL-6) receptor, in patients with coronavirus disease-2019 (COVID-19) patients has led to conflicting results. We performed a systematic review and meta-analysis to compare the efficacy of addition of TOC to standard of care (SOC) versus SOC in patients with COVID-19. We performed a comprehensive literature search of PubMed, Embase, Web of Science, WHO COVID, LitCOVID, and Cochrane databases. Pooled outcomes (overall mortality, need for mechanical ventilation, intensive care unit admission, and secondary infections) were compared using DerSimonian-Laird/Random-effects approach. Risk difference (RD), confidence interval (CI), and p values were generated. A total of 23 studies with 6279 patients (1897 in TOC and 4382 in SOC group, respectively) were included. The overall mortality was lower in TOC group compared to SOC group (RD: -0.06; CI: -0.12 to -0.01; p = .03). Subgroup analysis including studies with only severe cases revealed lower mortality (RD: -0.12; CI: -0.18 to -0.06; p < .01) and need for mechanical ventilation (RD: -0.11; CI: -0.19 to -0.02; p = .01) in TOC group compared to SOC group. The addition of TOC to SOC has the potential to reduce mortality and need for mechanical ventilation in patients with severe COVID-19. Randomized controlled trials are needed to validate this.

Using Therapeutic Drug Monitoring to Treat KPC-Producing Klebsiella pneumoniae Central Nervous System Infection With Ceftazidime/Avibactam.

This report describes the treatment of Klebsiella pneumoniae carbapenemase (KPC)-3-producing multidrug-resistant K. pneumoniae with ceftazidime/avibactam (CAZ-AVI) in a patient who developed postneurosurgical meningitis and bacteremia. Therapeutic drug monitoring of cerebrospinal fluid and blood samples demonstrated CAZ-AVI concentration levels 20-fold greater than the minimum inhibitory concentration in the first 60 minutes postinfusion, providing evidence for the utility of CAZ-AVI in treating KPC-Klebsiella pneumoniae central nervous system infections.

Spontaneous Pneumothorax Following COVID-19 Pneumonia.

Patient presents with dyspnea after recovering from COVID-19 pneumonia and is found to have pneumothorax. This represents an under-reported sequelae of COVID-19.

HHV-6: an unusual cause of cerebellar ataxia.

Human herpesvirus 6 (HHV-6) infection is the cause of roseola infantum in children. The reactivation of HHV-6 is associated with multiple clinical syndromes including encephalitis and myelitis, especially in haematopoietic stem cell transplant recipients. However, the virus can cause encephalitis in other immunosuppressed as well as immunocompetent individuals. We report a case of a 70-year-old woman who was immunocompromised secondary to treatment of rheumatoid arthritis with leflunomide and methotrexate. The patient presented with acute ataxia, diplopia and dysarthria. MRI brain showed an enhancing lesion in the midbrain. The diagnosis of HHV-6 encephalitis was made after HHV-6 A DNA was detected in both serum and cerebrospinal fluid. Treatment consisted of a 3-week course of intravenous ganciclovir along with physiotherapy. At a 3-month follow-up, repeat MRI brain showed a decrease in size and oedema of the lesion and the patient's neurological function was improved.

Fast-track pathway for elective caesarean section: a quality improvement initiative to promote day 1 discharge.

Enhanced recovery after surgery (ERAS) aims to improve perioperative care, hasten recovery to the normal physiological state and shorten length of stay (LoS). There is evidence that ERAS programmes following elective caesarean section (ELCS) confer benefit through faster return to physiological state and reduced LoS for mother and baby. Baseline audit of ELCS in 2013 revealed a mean LoS of 3 days. We piloted an ERAS discharge pathway promoting day 2 discharge, which rose from 5.0% to 40.2%. 19.2% of women went home on day 1. Many women fed back that they would prefer day 1 discharge. We hypothesised that a day 1 discharge pathway for low-risk women could benefit both women and services at our maternity unit. From October 2015, we developed a 'fast-track pathway' (FTP) using a Plan-Do-Study-Act approach. Between October 2015 and April 2016, we prospectively audited clinical outcomes, LoS and maternal satisfaction from all women placed on the FTP. We held regular multidisciplinary team meetings to allow contemporaneous analysis. Satisfaction was analysed by Likert scale at postoperative surveys. Women were identified in antenatal clinic after meeting predefined low-risk criteria. 27.3% of women (n=131/479) delivering by ELCS entered the FTP. 76.2% of women on the FTP were discharged on day 1. Mean LoS fell to 1.31 days. 94.2% of women who established breast feeding at day 1 were still breast feeding at 7 days. Overall satisfaction at day 7 was 4.71 on a 5-point Likert scale. 73.1% of women reported good pain control. Additional financial savings are estimated at £99 886 annually. There were no related cases of readmission. Day 1 discharge after ELCS is safe and acceptable in carefully selected, low-risk women and has high satisfaction. There may be resultant financial savings and improved flow through a maternity unit with no detected adverse effect on breast feeding, maternal morbidity or postnatal readmissions.

Comparison of keyboard colonization before and after use in an inpatient setting and the effect of keyboard covers.

Computer keyboards may contribute to patient infections. We cultured new keyboards, with/without keyboard covers, before placing them in adult inpatient rooms and recultured after 6 months. Nonpathogenic bacteria were present initially but potentially pathogenic bacteria were cultured only after use. Coagulase negative Staphylococcus colonization increased after use (P < .001). Keyboards with a cover had more potentially pathogenic bacteria (22% vs 16%), which although not significant statistically (P = .72), likely due to sample size, trended against covers offering protection.

Surveillance of carbapenem-resistant Klebsiella pneumoniae: tracking molecular epidemiology and outcomes through a regional network.

Carbapenem resistance in Gram-negative bacteria is on the rise in the United States. A regional network was established to study microbiological and genetic determinants of clinical outcomes in hospitalized patients with carbapenem-resistant (CR) Klebsiella pneumoniae in a prospective, multicenter, observational study. To this end, predefined clinical characteristics and outcomes were recorded and K. pneumoniae isolates were analyzed for strain typing and resistance mechanism determination. In a 14-month period, 251 patients were included. While most of the patients were admitted from long-term care settings, 28% of them were admitted from home. Hospitalizations were prolonged and complicated. Nonsusceptibility to colistin and tigecycline occurred in isolates from 7 and 45% of the patients, respectively. Most of the CR K. pneumoniae isolates belonged to repetitive extragenic palindromic PCR (rep-PCR) types A and B (both sequence type 258) and carried either blaKPC-2 (48%) or blaKPC-3 (51%). One isolate tested positive for blaNDM-1, a sentinel discovery in this region. Important differences between strain types were noted; rep-PCR type B strains were associated with blaKPC-3 (odds ratio [OR], 294; 95% confidence interval [CI], 58 to 2,552; P < 0.001), gentamicin nonsusceptibility (OR, 24; 95% CI, 8.39 to 79.38; P < 0.001), amikacin susceptibility (OR, 11.0; 95% CI, 3.21 to 42.42; P < 0.001), tigecycline nonsusceptibility (OR, 5.34; 95% CI, 1.30 to 36.41; P = 0.018), a shorter length of stay (OR, 0.98; 95% CI, 0.95 to 1.00; P = 0.043), and admission from a skilled-nursing facility (OR, 3.09; 95% CI, 1.26 to 8.08; P = 0.013). Our analysis shows that (i) CR K. pneumoniae is seen primarily in the elderly long-term care population and that (ii) regional monitoring of CR K. pneumoniae reveals insights into molecular characteristics. This work highlights the crucial role of ongoing surveillance of carbapenem resistance determinants.

Recent developments in septic bursitis.

Septic bursitis is a disease that can be difficult to distinguish from aseptic bursitis. There are no definitive treatment guidelines. The optimal duration of antibiotic therapy is not defined. Most of the cases are due to infection with Staphylococcus aureus, although many other pathogens can also cause this infection. The optimal management includes early recognition and prompt initiation of appropriate antibiotic therapy. Surgical management may be necessary, and complications can arise from open procedures. Endoscopic bursectomy may be considered for patients requiring surgical debridement. This approach may lead to decreased morbidity in those requiring surgical intervention.

Inhibition of vancomycin-resistant enterococcus by continuous-flow cultures of human stool microflora with and without anaerobic gas supplementation.

A continuous-flow competitive exclusion (CFCE) culture model of human stool microflora was used to examine whether supplemental anaerobic gas is necessary for maintenance of anaerobes and inhibition of vancomycin-resistant Enterococcus (VRE). CFCE cultures of human stool microflora were maintained with supplemental nitrogen, without supplemental nitrogen, or with percolated room air. Cultures with or without supplemental nitrogen maintained >9 log(10) CFU mL(-1) of obligate anaerobes and eliminated 10(6) CFU mL(-1) of VRE. When room air was percolated into the culture, anaerobes were detected at < or =2 log(10) CFU mL(-1), and the same VRE inoculum was not eliminated ( P < 0.001). These data demonstrate that human stool CFCE cultures maintain high levels of obligate anaerobes and inhibit VRE without the addition of supplemental anaerobic gas.