The increasing prevalence of infections due to multidrug-resistant (MDR) gram-negative bacteria constitutes a serious threat to global public health due to the limited treatment options available and ...the historically slow pace of development of new antimicrobial agents. Infections due to MDR strains are associated with increased morbidity and mortality and prolonged hospitalization, which translates to a significant burden on healthcare systems. In particular, MDR strains of Enterobacteriaceae (especially Klebsiella pneumoniae and Escherichia coli), Pseudomonas aeruginosa, and Acinetobacter baumannii have emerged as particularly serious concerns. In the United States, MDR strains of these organisms have been reported from hospitals throughout the country and are not limited to a small subset of hospitals. Factors that have contributed to the persistence and spread of MDR gram-negative bacteria include the following: overuse of existing antimicrobial agents, which has led to the development of adaptive resistance mechanisms by bacteria; a lack of good antimicrobial stewardship such that use of multiple broad-spectrum agents has helped perpetuate the cycle of increasing resistance; and a lack of good infection control practices. The rising prevalence of infections due to MDR gram-negative bacteria presents a significant dilemma in selecting empiric antimicrobial therapy in seriously ill hospitalized patients. A prudent initial strategy is to initiate treatment with a broad-spectrum regimen pending the availability of microbiological results allowing for targeted or narrowing of therapy. Empiric therapy with newer agents that exhibit good activity against MDR gram-negative bacterial strains such as tigecycline, ceftolozane-tazobactam, ceftazidime-avibactam, and others in the development pipeline offer promising alternatives to existing agents.
Background Maintenance hemodialysis is typically prescribed thrice weekly irrespective of a patient’s residual kidney function (RKF). We hypothesized that a less frequent schedule at hemodialysis ...therapy initiation is associated with greater preservation of RKF without compromising survival among patients with substantial RKF. Study Design A longitudinal cohort. Setting & Participants 23,645 patients who initiated maintenance hemodialysis therapy in a large dialysis organization in the United States (January 2007 to December 2010), had available RKF data during the first 91 days (or quarter) of dialysis, and survived the first year. Predictor Incremental (routine twice weekly for >6 continuous weeks during the first 91 days upon transition to dialysis) versus conventional (thrice weekly) hemodialysis regimens during the same time. Outcomes Changes in renal urea clearance and urine volume during 1 year after the first quarter and survival after the first year. Results Among 23,645 included patients, 51% had substantial renal urea clearance (≥3.0 mL/min/1.73 m2 ) at baseline. Compared with 8,068 patients with conventional hemodialysis regimens matched based on baseline renal urea clearance, urine volume, age, sex, diabetes, and central venous catheter use, 351 patients with incremental regimens exhibited 16% (95% CI, 5%-28%) and 15% (95% CI, 2%-30%) more preserved renal urea clearance and urine volume at the second quarter, respectively, which persisted across the following quarters. Incremental regimens showed higher mortality risk in patients with inadequate baseline renal urea clearance (≤3.0 mL/min/1.73 m2 ; HR, 1.61; 95% CI, 1.07-2.44), but not in those with higher baseline renal urea clearance (HR, 0.99; 95% CI, 0.76-1.28). Results were similar in a subgroup defined by baseline urine volume of 600 mL/d. Limitations Potential selection bias and wide CIs. Conclusions Among incident hemodialysis patients with substantial RKF, incremental hemodialysis may be a safe treatment regimen and is associated with greater preservation of RKF, whereas higher mortality is observed after the first year of dialysis in those with the lowest RKF. Clinical trials are needed to examine the safety and effectiveness of twice-weekly hemodialysis.
Background COVID-19's pulmonary manifestations are broad, ranging from pneumonia with no supplemental oxygen requirements to acute respiratory distress syndrome (ARDS) with acute respiratory failure ...(ARF). In response, new oxygenation strategies and therapeutics have been developed, but their large-scale effects on outcomes in severe COVID-19 patients remain unknown. Therefore, we aimed to examine the trends in mortality, mechanical ventilation, and cost over the first six months of the pandemic for adult COVID-19 patients in the US who developed ARDS or ARF. Methods and findings The Vizient Clinical Data Base, a national database comprised of administrative, clinical, and financial data from academic medical centers, was queried for patients greater than or equal to 18-years-old with COVID-19 and either ARDS or ARF admitted between 3/2020-8/2020. Demographics, mechanical ventilation, length of stay, total cost, mortality, and discharge status were collected. Mann-Kendall tests were used to assess for significant monotonic trends in total cost, mechanical ventilation, and mortality over time. Chi-square tests were used to compare mortality rates between March-May and June-August. 110,223 adult patients with COVID-19 ARDS or ARF were identified. Mean length of stay was 12.1±13.3 days and mean total cost was $35,991±32,496. Mechanical ventilation rates were 34.1% and in-hospital mortality was 22.5%. Mean cost trended downward over time (p = 0.02) from $55,275 (March) to $18,211 (August). Mechanical ventilation rates trended down (p<0.01) from 53.8% (March) to 20.3% (August). Overall mortality rates also decreased (p<0.01) from 28.4% (March) to 13.7% (August). Mortality rates in mechanically ventilated patients were similar over time (p = 0.45), but mortality in patients not requiring mechanical ventilation decreased from March-May compared to June-July (13.5% vs 4.6%, p<0.01). Conclusions This study describes the outcomes of a large cohort with COVID-19 ARDS or ARF and the subsequent decrease in cost, mechanical ventilation, and mortality over the first 6 months of the pandemic in the US.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Limiting in-person contact was a key strategy for controlling the spread of the highly infectious novel coronavirus (COVID-19). To protect patients and staff from the risk of infection while ...providing continued access to necessary health care services, we implemented a new electronic consultation (e-consult) service that allowed referring providers to receive subspecialty consultations for patients who are hospitalized and do not require in-person evaluation by the specialist.
We aimed to assess the impact of implementing e-consults in the inpatient setting to reduce avoidable face-to-face referrals during the COVID-19 pandemic.
This quality improvement study evaluated all inpatient e-consults ordered from July 2020 to December 2022 at the University of California Irvine Medical Center. The impact of e-consults was assessed by evaluating use (eg, number of e-consults ordered), e-consult response times, and outcome of the e-consult requests (eg, resolved electronically or converted to the in-person evaluation of patient).
There were 1543 inpatient e-consults ordered across 11 participating specialties. A total of 53.5% (n=826) of requests were addressed electronically, without the need for a formal in-person evaluation of the patient. The median time between ordering an e-consult and a specialist documenting recommendations in an e-consult note was 3.7 (IQR 1.3-8.2) hours across all specialties, contrasted with 7.3 (IQR 3.6-22.0) hours when converted to an in-person consult (P<.001). The monthly volume of e-consult requests increased, coinciding with surges of COVID-19 cases in California. After the peaks of the COVID-19 crisis subsided, the use of inpatient e-consults persisted at a rate well above the precrisis levels.
An inpatient e-consult service was successfully implemented, resulting in fewer unnecessary face-to-face consultations and significant reductions in the response times for consults requested on patients who are hospitalized and do not require an in-person evaluation. Thus, e-consults provided timely, efficient delivery of inpatient consultation services for appropriate problems while minimizing the risk of direct transmission of the COVID-19 virus between health care providers and patients. The service also demonstrated its value as a tool for effective inpatient care coordination beyond the peaks of the pandemic leading to the sustainability of service and value.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are ...concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing.
The rapid spread of coronavirus disease 2019 (COVID-19) revealed significant constraints in critical care capacity. In anticipation of subsequent waves, reliable prediction of disease severity is ...essential for critical care capacity management and may enable earlier targeted interventions to improve patient outcomes. The purpose of this study is to develop and externally validate a prognostic model/clinical tool for predicting COVID-19 critical disease at presentation to medical care.
This is a retrospective study of a prognostic model for the prediction of COVID-19 critical disease where critical disease was defined as ICU admission, ventilation, and/or death. The derivation cohort was used to develop a multivariable logistic regression model. Covariates included patient comorbidities, presenting vital signs, and laboratory values. Model performance was assessed on the validation cohort by concordance statistics. The model was developed with consecutive patients with COVID-19 who presented to University of California Irvine Medical Center in Orange County, California. External validation was performed with a random sample of patients with COVID-19 at Emory Healthcare in Atlanta, Georgia.
Of a total 3208 patients tested in the derivation cohort, 9% (299/3028) were positive for COVID-19. Clinical data including past medical history and presenting laboratory values were available for 29% (87/299) of patients (median age, 48 years range, 21-88 years; 64% 36/55 male). The most common comorbidities included obesity (37%, 31/87), hypertension (37%, 32/87), and diabetes (24%, 24/87). Critical disease was present in 24% (21/87). After backward stepwise selection, the following factors were associated with greatest increased risk of critical disease: number of comorbidities, body mass index, respiratory rate, white blood cell count, % lymphocytes, serum creatinine, lactate dehydrogenase, high sensitivity troponin I, ferritin, procalcitonin, and C-reactive protein. Of a total of 40 patients in the validation cohort (median age, 60 years range, 27-88 years; 55% 22/40 male), critical disease was present in 65% (26/40). Model discrimination in the validation cohort was high (concordance statistic: 0.94, 95% confidence interval 0.87-1.01). A web-based tool was developed to enable clinicians to input patient data and view likelihood of critical disease.
We present a model which accurately predicted COVID-19 critical disease risk using comorbidities and presenting vital signs and laboratory values, on derivation and validation cohorts from two different institutions. If further validated on additional cohorts of patients, this model/clinical tool may provide useful prognostication of critical care needs.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcomes in the ...geriatric population, but in an opposite direction. Some degrees of elevated BMI, serum cholesterols, and BP are reportedly associated with lower, instead of higher, risk of death among the elderly. This phenomenon is termed "reverse epidemiology" or "risk factor paradox" (such as obesity paradox) and is also observed in a variety of chronic disease states such as end-stage renal disease requiring dialysis, chronic heart failure, rheumatoid arthritis, and AIDS. Several possible causes are hypothesized to explain this risk factor reversal: competing short-term and long-term killers, improved hemodynamic stability in the obese, adipokine protection against tumor necrosis factor-α, lipoprotein protection against endotoxins, and lipophilic toxin sequestration by the adipose tissue. It is possible that the current thresholds for intervention and goal levels for such traditional risk factors as BMI, serum cholesterol, and BP derived based on younger populations do not apply to the elderly, and that new levels for such risk factors should be developed for the elderly population. Reverse epidemiology of conventional cardiovascular risk factors may have a bearing on the management of the geriatric population, thus it deserves further attention.
Obesity, a risk factor for
chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular ...risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in the elderly. These are populations in whom protein-energy wasting and inflammation are strong predictors of early death. Both larger muscle mass and higher body fat provide longevity in these patients, whereas thinner body habitus and weight loss are associated with higher mortality. Muscle mass appears to be superior to body fat in conferring an even greater survival. The obesity paradox may be the result of a time discrepancy between competing risk factors, i.e., overnutrition as the long-term killer versus undernutrition as the short-term killer. Hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may play important roles. Despite claims that obesity paradox is a statistical fallacy and a result of residual confounding, the consistency of data and other causality clues suggest a high biologic plausibility. Examining the causes and consequences of the obesity paradox may help discover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A consistent association between low serum sodium measured at a single-point-in-time (baseline sodium) and higher mortality has been observed in hemodialysis patients. We hypothesized that both low ...and high time-varying sodium levels (sodium levels updated at quarterly intervals as a proxy of short-term exposure) are independently associated with higher death risk in hemodialysis patients.
We examined the association of baseline and time-varying pre-dialysis serum sodium levels with all-cause mortality among adult incident hemodialysis patients receiving care from a large national dialysis organization during January 2007-December 2011. Hazard ratios were estimated using multivariable Cox models accounting for case-mix+laboratory covariates and incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose.
Among 27 180 patients, a total of 7562 deaths were observed during 46 194 patient-years of follow-up. Median (IQR) at-risk time was 1.4 (0.6, 2.5) years. In baseline analyses adjusted for case-mix+laboratory results, sodium levels <138 mEq/L were associated with incrementally higher mortality risk, while the association of sodium levels ≥140 mEq/L with lower mortality reached statistical significance only for the highest level of pre-dialysis sodium (reference: 138-<140 mEq/L). In time-varying analyses, we observed a U-shaped association between sodium and mortality such that sodium levels <138 and ≥144 mEq/L were associated with higher mortality risk. Similar patterns were observed in models incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose.
We observed a U-shaped association of time-varying pre-dialysis serum sodium and all-cause mortality in hemodialysis patients, suggesting that both hypo- and hypernatremia carry short-term risk in this population.
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