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Cryptococcal meningitis (CM) causes significant morbidity and mortality globally; however, recent national trends have not been described. Incidence and trends for CM-associated hospitalizations in 18 states were estimated using the Agency for Healthcare and Research Quality (AHRQ) State Inpatient Databases (SID) datasets for 1997 through 2009. We identified 30,840 hospitalizations coded for CM, of which 21.6% were among HIV-uninfected patients. CM in-hospital mortality was significant (12.4% for women and 10.8% for men) with a total of 3,440 deaths over the study period. Co-morbidities of CM coded at increased frequency in HIV-uninfected CM hospitalized populations included hydrocephalus and acute/chronic renal failure as well as possible predispositions including transplantation, combined T and B cell defects, Cushing's syndrome, liver disease and hypogammaglobulinemia. Median hospitalization costs were significant for CM and higher for HIV-uninfected patients (16,803.01 vs. 15,708.07; p<0.0001). Cryptococcal meningitis remains a disease with significant morbidity and mortality in the U.S. and the relative burden among persons without HIV infection is increasing.

The importance of bacterial infections following respiratory syncytial virus (RSV) remains unclear. We evaluated whether variations in RSV epidemic timing and magnitude are associated with variations in pneumococcal disease epidemics and whether changes in pneumococcal disease following the introduction of seven-valent pneumococcal conjugate vaccine (PCV7) were associated with changes in the rate of hospitalizations coded as RSV. We used data from the State Inpatient Databases (Agency for Healthcare Research and Quality), including >700,000 RSV hospitalizations and >16,000 pneumococcal pneumonia hospitalizations in 36 states (1992/1993-2008/2009). Harmonic regression was used to estimate the timing of the average seasonal peak of RSV, pneumococcal pneumonia, and pneumococcal septicemia. We then estimated the association between the incidence of pneumococcal disease in children and the activity of RSV and influenza (where there is a well-established association) using Poisson regression models that controlled for shared seasonal variations. Finally, we estimated changes in the rate of hospitalizations coded as RSV following the introduction of PCV7. RSV and pneumococcal pneumonia shared a distinctive spatiotemporal pattern (correlation of peak timing: ρ = 0.70, 95% CI: 0.45, 0.84). RSV was associated with a significant increase in the incidence of pneumococcal pneumonia in children aged <1 y (attributable percent [AP]: 20.3%, 95% CI: 17.4%, 25.1%) and among children aged 1-2 y (AP: 10.1%, 95% CI: 7.6%, 13.9%). Influenza was also associated with an increase in pneumococcal pneumonia among children aged 1-2 y (AP: 3.2%, 95% CI: 1.7%, 4.7%). Finally, we observed a significant decline in RSV-coded hospitalizations in children aged <1 y following PCV7 introduction (-18.0%, 95% CI: -22.6%, -13.1%, for 2004/2005-2008/2009 versus 1997/1998-1999/2000). This study used aggregated hospitalization data, and studies with individual-level, laboratory-confirmed data could help to confirm these findings. These analyses provide evidence for an interaction between RSV and pneumococcal pneumonia. Future work should evaluate whether treatment for secondary bacterial infections could be considered for pneumonia cases even if a child tests positive for RSV. Please see later in the article for the Editors' Summary.

Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime in temperate countries including the United States, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV. In the United States, RSV activity is highly spatially structured, with seasonal peaks beginning in Florida in November through December and ending in the upper Midwest in February-March, and prolonged disease activity in the southeastern US. Using data on both age-specific hospitalizations and laboratory reports of RSV in the US, and employing a combination of statistical and mechanistic epidemic modeling, we examined the association between environmental variables and state-specific measures of RSV seasonality. Temperature, vapor pressure, precipitation, and potential evapotranspiration (PET) were significantly associated with the timing of RSV activity across states in univariate exploratory analyses. The amplitude and timing of seasonality in the transmission rate was significantly correlated with seasonal fluctuations in PET, and negatively correlated with mean vapor pressure, minimum temperature, and precipitation. States with low mean vapor pressure and the largest seasonal variation in PET tended to experience biennial patterns of RSV activity, with alternating years of \"early-big\" and \"late-small\" epidemics. Our model for the transmission dynamics of RSV was able to replicate these biennial transitions at higher amplitudes of seasonality in the transmission rate. This successfully connects environmental drivers to the epidemic dynamics of RSV; however, it does not fully explain why RSV activity begins in Florida, one of the warmest states, when RSV is a winter-seasonal pathogen. Understanding and predicting the seasonality of RSV is essential in determining the optimal timing of immunoprophylaxis.

Background. In 2006, RotaTeq (RV5) was recommended for routine vaccination of United States (US) infants. We compared hospitalization rates for acute gastroenteritis among US children aged <5 years during pre-RV5 rotavirus seasons from 2000 through 2006 with those during the post-RV5 2007 and 2008 seasons. Methods. Using 100% hospital discharge data from 18 states, accounting for 49% of the US population, we calculated acute gastroenteritis hospitalization rates for children aged <5 years by rotavirus season, 8 age groups (0–2, 3–5, 6–11, 12–17, 18–23, 24–35, 36–47, and 48–59 months), and state. Results. Compared with the median rate for the 2000–2006 rotavirus seasons (101.1 hospitalizations per 10,000 children), the rates for 2007 and 2008 (85.5 and 55.5 hospitalizations per 10,000 children) were 16% and 45% lower, respectively. Children aged 0–2 months had a 28% reduction, those aged 6–23 months had a reduction of 50%, and children aged 3–5 months and 24–59 months had reductions ranging between 42% and 45% during the 2008 rotavirus season, compared with the median rate for 2000–2006 rotavirus seasons. Conclusions. The introduction of the RV5 vaccine was associated with a dramatic reduction in hospitalizations for acute gastroenteritis among US children during the 2008 rotavirus season.

Background Missed colonoscopy appointments delay screening and treatment for gastrointestinal disorders. Prior nonadherence with other care components may be associated with missed colonoscopy appointments. Objective To assess variability in prior adherence behaviors and their association with missed colonoscopy appointments. Design Retrospective cohort study. Participants Patients scheduled for colonoscopy in an integrated healthcare system between January 2016 and December 2018. Main Measures Prior adherence behaviors included: any missed outpatient appointment in the previous year; any missed gastroenterology clinic or colonoscopy appointment in the previous 2 years; and not obtaining a bowel preparation kit pre-colonoscopy. Other sociodemographic, clinical, and system characteristics were included in a multivariable model to identify independent associations between prior adherence behaviors and missed colonoscopy appointments. Key Results The median age of the 57,590 participants was 61 years; 52.8% were female and 73.4% were white. Of 77,684 colonoscopy appointments, 3,237 (4.2%) were missed. Individuals who missed colonoscopy appointments were more likely to have missed a previous primary care appointment (62.5% vs. 38.4%), a prior gastroenterology appointment (18.4% vs. 4.7%) or not to have picked up a bowel preparation kit (42.4% vs. 17.2%), all p < 0.001. Correlations between the three adherence measures were weak (phi < 0.26). The rate of missed colonoscopy appointments increased from 1.8/100 among individuals who were adherent with all three prior care components to 24.6/100 among those who were nonadherent with all three care components. All adherence variables remained independently associated with nonadherence with colonoscopy in a multivariable model that included other covariates; adjusted odds ratios (with 95% confidence intervals) were 1.6 (1.5–1.8) for outpatient appointments, 1.9 (1.7–2.1) for gastroenterology appointments, and 3.1 (2.9–3.4) for adherence with bowel preparation kits, respectively. Conclusions Three prior adherence behaviors were independently associated with missed colonoscopy appointments. Studies to predict adherence should use multiple, complementary measures of prior adherence when available.

Retention in hypertension care, medication adherence, and blood pressure (BP) may have been affected by the COVID‐19 pandemic. In a retrospective cohort study of 64 766 individuals with treated hypertension from an integrated health care system, we compared hypertension care during the year pre‐COVID‐19 (March 2019–February 2020) and the first year of COVID‐19 (March 2020–February 2021). Retention in hypertension care was defined as receiving clinical BP measurements during COVID‐19. Medication adherence was measured using prescription refills. Clinical care was assessed by in‐person and virtual visits and changes in systolic and diastolic BP. The cohort had a mean age of 67.8 (12.2) years, 51.2% were women, and 73.5% were White. In 60 757 individuals with BP measurements pre‐COVID‐19, 16618 (27.4%) had no BP measurements during COVID‐19. Medication adherence declined from 86.0% to 80.8% (p < .001). In‐person primary care visits decreased from 2.7 (2.7) to 1.4 (1.9) per year, while virtual contacts increased from 9.5 (12.2) to 11.2 (14.2) per year (both p < .001). Among individuals with BP measurements, mean (SD) systolic BP was 126.5 mm Hg (11.8) pre‐COVID‐19 and 127.3 mm Hg (12.6) during COVID‐19 (p = .14). Mean diastolic BP was 73.5 mm Hg (8.5) pre‐COVID‐19 and 73.5 mm Hg (8.7) during COVID‐19 (p = .77). Even in this integrated health care system, many individuals did not receive clinical BP monitoring during COVID‐19. Most individuals who remained in care maintained pre‐COVID BP. Targeted outreach may be necessary to restore care continuity and hypertension control at the population level.

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.

We used the State Inpatient Databases from the United States Agency for Healthcare Research and Quality to provide state-specific age-adjusted blastomycosis-associated hospitalization incidence throughout the entire United States. Among the 46 states studied, states within the Mississippi and Ohio River valleys had the highest age-adjusted hospitalization incidence. Specifically, Wisconsin had the highest age-adjusted hospitalization incidence (2.9 hospitalizations per 100,000 person-years). Trends were studied in the five highest hospitalization incidence states. From 2000 to 2011, blastomycosis-associated hospitalizations increased significantly in Illinois and Kentucky with an average annual increase of 4.4% and 8.4%, respectively. Trends varied significantly by state. Overall, 64% of blastomycosis-associated hospitalizations were among men and the median age at hospitalization was 53 years. This analysis provides a complete epidemiologic description of blastomycosis-associated hospitalizations throughout the endemic area in the United States.

The drivers of invasive pneumococcal disease seasonality are unknown. We found that pediatric cases with a pneumonia diagnosis peaked in winter and were associated with respiratory syncytial virus (RSV), whereas nonpneumonia cases peaked in autumn and were associated with variations in bacterial carriage. Background.  Winter-seasonal epidemics of pneumococcal disease provide an opportunity to understand the drivers of incidence. We sought to determine whether seasonality of invasive pneumococcal disease is caused by increased nasopharyngeal transmission of the bacteria or increased susceptibility to invasive infections driven by cocirculating winter respiratory viruses. Methods.  We analyzed pneumococcal carriage and invasive disease data collected from children <7 years old in the Navajo/White Mountain Apache populations between 1996 and 2012. Regression models were used to quantify seasonal variations in carriage prevalence, carriage density, and disease incidence. We also fit a multivariate model to determine the contribution of carriage prevalence and RSV activity to pneumococcal disease incidence while controlling for shared seasonal factors. Results.  The seasonal patterns of invasive pneumococcal disease epidemics varied significantly by clinical presentation: bacteremic pneumococcal pneumonia incidence peaked in late winter, whereas invasive nonpneumonia pneumococcal incidence peaked in autumn. Pneumococcal carriage prevalence and density also varied seasonally, with peak prevalence occurring in late autumn. In a multivariate model, RSV activity was associated with significant increases in bacteremic pneumonia cases (attributable percentage, 15.5%; 95% confidence interval [CI], 1.8%–26.1%) but was not associated with invasive nonpneumonia infections (8.0%; 95% CI, −4.8% to 19.3%). In contrast, seasonal variations in carriage prevalence were associated with significant increases in invasive nonpneumonia infections (31.4%; 95% CI, 8.8%–51.4%) but not with bacteremic pneumonia. Conclusions.  The seasonality of invasive pneumococcal pneumonia could be due to increased susceptibility to invasive infection triggered by viral pathogens, whereas seasonality of other invasive pneumococcal infections might be primarily driven by increased nasopharyngeal transmission of the bacteria.

Background Rates of sepsis/septicemia hospitalization in the US have risen significantly during recent years. Antibiotic resistance and use may contribute to those rates through various mechanisms, including lack of clearance of resistant infections following antibiotic treatment, with some of those infections subsequently devolving into sepsis. At the same time, there is limited information on the effect of prescribing of certain antibiotics vs. others on the rates of septicemia and sepsis-related hospitalizations and mortality. Methods We used multivariable linear regression to relate state-specific rates of outpatient prescribing overall for oral fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011 and 2012 to state-specific rates of septicemia hospitalization (ICD-9 codes 038.xx present anywhere on a discharge diagnosis) in each of the following age groups of adults: (18-49y, 50-64y, 65-74y, 75-84y, 85 + y) reported to the Healthcare Cost and Utilization Project (HCUP) between 2011 and 2012, adjusting for additional covariates, and random effects associated with the ten US Health and Human Services (HHS) regions. Results Increase in the rate of prescribing of oral penicillins by 1 annual dose per 1000 state residents was associated with increases in annual septicemia hospitalization rates of 0.19 (95% CI (0.02,0.37)) per 10,000 persons aged 50-64y, of 0.48(0.12,0.84) per 10,000 persons aged 65-74y, and of 0.81(0.17,1.40) per 10,000 persons aged 74-84y. Increase by 1 in the percent of African Americans among state residents in a given age group was associated with increases in annual septicemia hospitalization rates of 2.3(0.32,4.2) per 10,000 persons aged 75-84y, and of 5.3(1.1,9.5) per 10,000 persons aged over 85y. Average minimal daily temperature was positively associated with septicemia hospitalization rates in persons aged 18-49y, 50-64y, 75-84y and over 85y. Conclusions Our results suggest positive associations between the rates of prescribing for penicillins and the rates of hospitalization with septicemia in US adults aged 50-84y. Further studies are needed to better understand the potential effect of antibiotic replacement in the treatment of various syndromes, including the potential impact of the recent US FDA guidelines on restriction of fluoroquinolone use, as well as the potential effect of changes in the practices for prescribing of penicillins on the rates of sepsis-related hospitalization and mortality.