OBJECTIVE:To estimate the burden of encephalitis-associated hospitalizations in the United States for 1998–2010.
METHODS:Using the Nationwide Inpatient Sample, a nationally representative database of ...hospitalizations, estimated numbers and rates of encephalitis-associated hospitalizations for 1998–2010 were calculated. Etiology and outcome of encephalitis-associated hospitalizations were examined, as well as accompanying diagnoses listed along with encephalitis on the discharge records. Total hospital charges (in 2010 US dollars) were assessed.
RESULTS:An estimated 263,352 (standard error3,017) encephalitis-associated hospitalizations occurred in the United States during 1998–2010, which corresponds to an average of 20,258 (standard error232) encephalitis-associated hospitalizations per year. A fatal outcome occurred in 5.8% (95% confidence interval CI5.6%–6.0%) of all encephalitis-associated hospitalizations and in 10.1% (95% CI9.2%–11.2%) and 17.1% (95% CI14.6%–20.0%) of encephalitis-associated hospitalizations in which a code for HIV or a tissue or organ transplant was listed, respectively. The proportion of encephalitis-associated hospitalizations in which an etiology for encephalitis was specified was 50.3% (95% CI49.6%–51.0%) and that for which the etiology was unspecified was 49.7% (95% CI49.0%–50.4%). Total charges for encephalitis-associated hospitalizations in 2010 were an estimated $2.0 billion.
CONCLUSIONS:Encephalitis remains a major public health concern in the United States. Among the large number of encephalitis-associated hospitalizations for which an etiology is not reported may be novel infectious and noninfectious forms of encephalitis. Associated conditions such as HIV or transplantation increase the risk of a fatal outcome from an encephalitis-associated hospitalization and should be monitored.
Background.Infectious diseases (IDs) cause widespread morbidity and mortality. We describe the epidemiology of ID hospitalizations in the United States with use of a nationally representative ...database. Methods.First-listed ID hospitalizations in the United States were analyzed using the Nationwide Inpatient Sample for 1998–2006. Hospitalization rates were calculated overall for IDs and for specific ID groups. Results.An estimated 40,085,978 (standard error, 255,418) hospitalizations with a first-listed ID occurred during 1998–2006, for an age-adjusted hospitalization rate of 154.4 (95% confidence interval, 153.3–155.5) hospitalizations per 10,000 persons. The rate increased slightly over the study period (152.5 95% confidence interval, 149.6–155.4 in 1998 vs 162.2 95% confidence interval, 158.7–165.5 in 2006); an increase was seen for both sexes, for older patients, and for Hispanic patients. Among those aged 5–39 years, female patients had a significantly higher hospitalization rate than did male patients; male patients had higher rates among the youngest children and adults aged ⩾40 years. Approximately 4.5 million hospital days and $865 billion in hospital charges were associated with primary ID hospitalizations over the study period. Lower respiratory tract infections were the most commonly listed ID (34.4%), followed by kidney, urinary tract, and bladder infections; cellulitis; and abdominal and rectal infections. Conclusions.The ID hospitalization rate increased during 1998–2006, reflecting an increase in ID hospitalizations among adults aged ⩾30 years, particularly older adults. Differences in trends and patterns of ID hospitalizations were noted by sex, age group, and race. Lower respiratory tract infections accounted for the largest proportion of ID hospitalizations. Future efforts should focus on preventive measures and improving early interventions for IDs.
BackgroundIn April 2003, an outbreak of monkeypox occurred in the United States following the importation of monkeypox virus (MPXV)–infected animals in a consignment of exotic pets from West Africa. ...Transmission of the virus to non-African captive species, including prairie dogs, preceded human disease MethodsWe evaluated the influence of the route of infection on clinical illness for persons with confirmed and probable cases of human monkeypox. Exposures were categorized as being “noninvasive” (e.g., the person touched an infected animal, cleaned an infected animal’s cage, and/or stood within 6 feet of an infected animal) or “complex” (e.g., invasive bite or scratch from an ill prairie dog plus potential noninvasive exposure), and associations between exposure, illness manifestation, and illness progression (i.e., elapsed time from first exposure to an ill prairie dog through various benchmarks of illness) were assessed ResultsPatients with complex exposures were more likely than patients with noninvasive exposures to have experienced pronounced signs of systemic illness (49.1% vs. 16.7%; P=.041) and to have been hospitalized during illness (68.8% vs. 10.3%; P<.001). Complex exposures were also associated with shorter incubation periods (9 days for complex exposures vs. 13 days for noninvasive exposures) and the absence of a distinct febrile prodrome ConclusionsThe findings of this study indicate that route of infection can influence monkeypox illness manifestations
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve cardiovascular and renal outcomes in patients with type 2 diabetes through distinct ...mechanisms. However, evidence on clinical outcomes in patients treated with both GLP-1 RA and SGLT2i is lacking. We aim to provide insight into the effects of open-label SGLT2i use in parallel with or shortly after once-weekly GLP-1 RA exenatide (EQW) on cardiorenal outcomes.
In the EXSCEL cardiovascular outcomes trial EQW arm, SGLT2i drop-in occurred in 8.7% of participants. These EQW+SGLT2i users were propensity-matched to: (1) placebo-arm participants not taking SGLT2i (n = 572 per group); and to (2) EQW-arm participants not taking SGLT2i (n = 575), based on their last measured characteristics before SGLT2i initiation, and equivalent study visit in comparator groups. Time-to-first major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR slopes were quantified using mixed model repeated measurement analyses.
In adjusted analyses, the risk for MACE with combination EQW+SGLT2i use was numerically lower compared with both placebo (adjusted hazard ratio 0.68, 95% CI 0.39-1.17) and EQW alone (0.85, 0.48-1.49). Risk of ACM was nominally significantly reduced compared with placebo (0.38, 0.16-0.90) and compared with EQW (0.41, 0.17-0.95). Combination EQW+SGLT2i use also nominally significantly improved estimated eGFR slope compared with placebo (+ 1.94, 95% CI 0.94-2.94 mL/min/1.73 m
/year) and EQW alone (+ 2.38, 1.40-3.35 mL/min/1.73 m
/year).
This post hoc analysis supports the hypothesis that combinatorial EQW and SGLT2i therapy may provide benefit on cardiovascular outcomes and mortality. Trial registration Clinicaltrials.gov, Identifying number: NCT01144338, Date of registration: June 15, 2010.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND:The present study describes the rate and trends of childhood hospitalizations with Kawasaki syndrome (KS) in the United States.
METHODS:Retrospective analysis of hospitalizations with KS ...among children <18 years of age in the United States using the Kidsʼ Inpatient Database (1997, 2000, 2003, and 2006) and the Nationwide Inpatient Sample (1998–2007).
RESULTS:The KS-associated hospitalization rate for children <5 years of age was 20.8 (95% CI18.5–23.1) per 100,000 children in 2006. Annual rates remained constant during the study period, except for a peak in 2005. In 2006, 76.8% (SE = 0.9%) of an estimated 5523 (SE = 289) KS-associated hospitalizations among children <18 years of age were <5 years of age. The mean age for all children at hospitalization was 3.0 years (SE <0.1); 25.7 months (SE = 0.3) for children <5 years of age, and 24.8 months (SE = 0.4) and 27.1 months (SE = 0.5) for boys and girls, respectively. The rate for boys was higher than that for girls (24.2 95% CI21.3–27.1 and 16.8 95% CI14.7–18.9, respectively). The rate for Asian/Pacific Islander children (30.3 95% CI20.2–40.4) was the highest among the racial groups.
CONCLUSIONS:The national KS-associated annual hospitalization rate for children <5 years of age from 1997 to 2007 was relatively stable and was similar to previously published rates, except for an increase in 2005. Most hospitalizations were in children <3 years of age with few hospitalizations during the first 2 months of age. Children of Asian/Pacific Islander descent had the highest hospitalization rate.
Background. Each year, Bordetella pertussis infection causes an estimated 294,000 deaths worldwide, primarily among young, nonvaccinated children. Approximately 90% of all deaths due to pertussis in ...the Unites States occur in young infants. These children often develop intractable pulmonary hypertension; however, the pathophysiologic mechanism responsible for this complication has not been well characterized, and there have been no detailed descriptions of the pathology of this disease since the 1940s. Methods. Respiratory tissue samples obtained at autopsy from 15 infants aged ⩽4 months who had polymerase chain reaction- or culture-confirmed B. pertussis pneumonia were evaluated by multiple histochemical stains, immunohistochemical evaluation, and electron microscopic examination. Results. The pulmonary histopathologic examination of the samples revealed a descending infection dominated by necrotizing bronchiolitis, intra-alveolar hemorrhage, and fibrinous edema. All samples had marked leukocytosis, and most showed luminal aggregates of abundant leukocytes in small pulmonary arteries, veins, and lymphatics. A novel immunohistochemical stain for B. pertussis revealed abundant extracellular bordetellae in cilia of the trachea, bronchi, and bronchioles, as well as intracellular bacteria and antigens in alveolar macrophages and ciliated epithelium. Conclusions. Pertussis should be suspected in any infant death associated with marked leukocytosis, bronchopneumonia, or refractory pulmonary hypertension, particularly in children aged ⩽4 months. The pathologic findings identified in the respiratory tracts of these children, in addition to recognized physiologic responses of the infant lung to hypoxia, suggest that B. pertussis pneumonia triggers a cascade of events that includes acute pulmonary vasoconstriction and pertussis toxin-mediated increases in circulating leukocyte mass. These responses ultimately compromise pulmonary blood flow, exacerbate hypoxemia, and create a vicious cycle of refractory pulmonary hypertension.
The sodium-glucose cotransporter 2 inhibitors (SGLT2i) empagliflozin and canagliflozin reduce the incidence of major adverse cardiovascular events (MACE), all-cause mortality (ACM), and renal events ...in cardiovascular outcomes trials, with observational real-world evidence suggesting class effect benefits that include dapagliflozin. We examined the placebo arm of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) to determine whether the effects of drop-in open-label dapagliflozin on MACE, ACM, and estimated glomerular filtration rate (eGFR) were consistent with the SGLT2i class as a whole.
SGLT2i drop-in therapy occurred in 10.6% of EXSCEL participants, with 5.2% taking dapagliflozin. Propensity-matched cohorts of SGLT2i users and nonusers (
= 709 per group) were generated on the basis of their characteristics before open-label SGLT2i drop-in or at baseline for participants taking SGLT2i at enrollment and an equivalent study visit for non-SGLT2i users. Time to first adjudicated MACE and ACM was analyzed using Cox regression. eGFR slopes were compared between matched cohorts using a mixed-model repeated-measures analysis.
In adjusted analyses, SGLT2i users (compared with nonusers) had a numerically lower risk of MACE (adjusted hazard ratio 0.79 95% CI 0.49-1.28), as did dapagliflozin users (0.55 0.26-1.15). SGLT2i users had a significantly lower ACM risk (0.51 0.27-0.95; dapagliflozin: 0.66 0.25-1.72). Compared with nonusers, eGFR slope was significantly better for SGLT2i users overall (+1.78 95% CI 0.87-2.69 mL/min/1.73 m
per year) and for dapagliflozin users (+2.28 1.01-3.54 mL/min/1.73 m
per year).
This post hoc analysis of the placebo arm of EXSCEL supports a beneficial class effect for all SGLT2i, including dapagliflozin, for reduced ACM and less eGFR decline.
Background. Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and ...epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses. Methods. Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by ⩾1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri. Results. During 1998–2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluores-cence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever. Conclusions. Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever. An unnamed, apparently new rickettsia has been repeatedly isolated at the Rocky Mountain Laboratory during the past nine years from specimens of Amblyomma maculatum, a tick of wide distribution in the Southern States…the presumptive evidence from animal experimentation suggests that human infection might be confusingly similar to spotted fever. Parker Ralph R. 1948 1, p. 146
The effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on renal outcomes in patients with type 2 diabetes at high cardiovascular risk are modest or neutral. However, GLP‐1RAs may confer ...clinical benefits in those at high risk of progressive renal function loss. We examined the effects of once‐weekly exenatide (EQW) on estimated glomerular filtration rate (eGFR) slope and urinary albumin:creatinine ratio (UACR) as a function of baseline UACR in 3503 EXSCEL participants (23.7%) with eGFR data available and 2828 participants (19.2%) with UACR change data available. EQW improved eGFR slope assessed via mixed model repeated measures, compared with placebo, in participants with baseline UACR >100 mg/g (0.79 mL/min/1.73 m2/year 95% confidence interval {CI} 0.24–1.34) and UACR >200 mg/g (1.32 mL/min/1.73 m2/year 95% CI 0.57–2.06), but not at lower UACR thresholds. EQW reduced UACR, compared with placebo, assessed via analysis of covariance, consistently across subgroups with baseline UACR >30 mg/g (28.2% reduction), baseline UACR >100 mg (22.5% reduction) and baseline UACR >200 mg (34.5% reduction). This post hoc EXSCEL analysis suggests that EQW reduces UACR, with improvement in eGFR slope specifically in participants with elevated baseline UACR.
About one-third of the ~1200 transiting planet candidates detected in the first four months of Kepler data are members of multiple candidate systems. There are 115 target stars with two candidate ...transiting planets, 45 with three, 8 with four, and 1 each with five and six. We characterize the dynamical properties of these candidate multi-planet systems. The distribution of observed period ratios shows that the vast majority of candidate pairs are neither in nor near low-order mean-motion resonances. Nonetheless, there are small but statistically significant excesses of candidate pairs both in resonance and spaced slightly too far apart to be in resonance, particularly near the 2:1 resonance. We find that virtually all candidate systems are stable, as tested by numerical integrations that assume a nominal mass-radius relationship. Several considerations strongly suggest that the vast majority of these multi-candidate systems are true planetary systems. Using the observed multiplicity frequencies, we find that a single population of planetary systems that matches the higher multiplicities underpredicts the number of singly transiting systems. We provide constraints on the true multiplicity and mutual inclination distribution of the multi-candidate systems, revealing a population of systems with multiple super-Earth-size and Neptune-size planets with low to moderate mutual inclinations.
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