Patterns of medication use and imaging following initial diagnosis of sarcoidosis.

INTRODUCTION: Sarcoidosis is a rare inflammatory disease with unclear natural history. Using a large, retrospective, longitudinal, population-based cohort, we sought to define its natural history in order to guide future clinical studies. METHODS: We identified 722 newly diagnosed cases of sarcoidosis within Kaiser Permanente Northwest health care records between 1995 and 2015. We investigated immunosuppressive medication use in the two years following diagnosis, analyzed demographic and clinical characteristics, and quantified chest imaging and pulmonary function testing (PFTs) across the clinical course. RESULTS: Over two years of follow-up, 41% of patients were treated with prednisone. Of those, 75% tapered off their first course within 100 days, although half of those patients required recurrent therapy. Five percent of the entire cohort remained on prednisone for longer than one year, with an average daily dose of 10-20 mg. Chest imaging was associated with early prednisone use, and chest CT was associated with changes in prednisone dose. PFTs or demographics were not associated with prednisone use. Cumulative prednisone doses were significantly higher in African Americans (1,845 mg additional) and those who had a chest CT (2,015 mg additional). Overall, PFTs were less frequently obtained than chest imaging and had no significant change over disease course. DISCUSSION: The natural history of sarcoidosis varies greatly. For those requiring therapy, corticosteroid burden is high. Chest imaging drives medication dose changes as compared to PFTs, but neither outcome fully captures the entire history of disease. Prospective cohorts are needed with purposefully collected, repeated measures that include objective clinical assessments and symptoms.

Warmer weather as a risk factor for hospitalisations due to urinary tract infections.

The incidence of urinary tract infections (UTIs) is seasonal, and this seasonality may be explained by changes in weather, specifically, temperature. Using data from the Nationwide Inpatient Sample, we identified the geographic location for 581 813 hospital admissions with the primary diagnosis of a UTI and 56 630 773 non-UTI hospitalisations in the United States. Next, we used data from the National Climatic Data Center to estimate the monthly average temperature for each location. Using a case-control design, we modelled the odds of a hospital admission having a primary diagnosis of UTI as a function of demographics, payer, location, patient severity, admission month, year and the average temperature for the admission month. We found, after controlling for patient factors and month of admission, the odds of a UTI diagnosis increased with higher temperatures in a dose-dependent manner. For example, relative to months with average temperatures of 5-7.5 °C, an admission in a month with an average temperature of 27.5-30 °C has 20% higher odds of a primary diagnosis of UTI. However, in months with extremely high average temperatures (above 30 °C), the odds of a UTI admissions decrease, perhaps due to changes in behaviour. Thus, at a population level, UTI-related hospitalisations are associated with warmer weather.

Controversies in tuberculous infection among pediatric infectious disease specialists in North America.

OBJECTIVE: To evaluate the extent to which advancements in the diagnosis and treatment of latent tuberculous infection (LTBI) have been integrated into practice by pediatric infectious disease (PID) specialists. DESIGN: We conducted an online survey of the Infectious Diseases Society of America's Emerging Infections Network (EIN) membership. RESULTS: Of the 323 members, 197 (61%) responded: 7% cared for ⩾5 children with TB disease and 34% for ⩾5 children with LTBI annually. We identified substantial variations in the use of interferon-gamma release assays (IGRAs) based upon age, immune status, and TB risk factors. In addition, tuberculin skin test (TST) use was three times more common in younger children. Variations existed in managing children with discordant TST and IGRA results. Less variation existed in LTBI treatment, with 86% preferring a 9-month course of isoniazid; few other, newer regimens were used routinely. CONCLUSION: Substantial variations exist in LTBI management; uptake of newer diagnostic tools and treatment regimens has been slow. Variations in practice and the lag time to integrating new data into practice may indicate the relative infrequency with which providers encounter LTBI. Our findings reflect the need for increased visibility of existing TB guidelines and resources for expert consultation for scenarios not covered by guidelines.

Acute myocardial infarctions, strokes and influenza: seasonal and pandemic effects.

The incidence of myocardial infarctions and influenza follow similar seasonal patterns. To determine if acute myocardial infarctions (AMIs) and ischaemic strokes are associated with influenza activity, we built time-series models using data from the Nationwide Inpatient Sample. In these models, we used influenza activity to predict the incidence of AMI and ischaemic stroke. We fitted national models as well as models based on four geographical regions and five age groups. Across all models, we found consistent significant associations between AMIs and influenza activity, but not between ischaemic strokes and influenza. Associations between influenza and AMI increased with age, were greatest in those aged >80 years, and were present in all geographical regions. In addition, the natural experiment provided by the second wave of the influenza pandemic in 2009 provided further evidence of the relationship between influenza and AMI, because both series peaked in the same non-winter month.

Communication gaps for solid organ transplant-transmitted infections among infectious disease physicians: an Emerging Infections Network survey.

Infectious disease (ID) physicians were surveyed concerning knowledge and management of potential transplant-transmitted infections (TTIs). On the basis of cumulative responses to 4 questions that assessed solid organ transplant-related clinical exposures and experience, respondents were divided into 3 groups: most, some, or little transplant experience. Rapid access to donor data was identified as the most important factor when evaluating a potential TTI. Despite varying experience in transplant infections, ID physicians are frequently asked for opinions regarding donor suitability and TTI management. Improved ID physician access to donor information and educational resources will allow more optimal management of potential TTIs.

A statewide outbreak of Cryptosporidium and its association with the distribution of public swimming pools.

In order to characterize the association between county-level risk factors and the incidence of Cryptosporidium in the 2007 Iowa outbreak, we used generalized linear mixed models with the number of Cryptosporidium cases per county as the dependent variable. We employed a spatial power covariance structure, which assumed that the correlation between the numbers of cases in any two counties decreases as the distance between them increases. County population size was included in the model to adjust for population differences. Independent variables included the number of pools in specific pool categories (large, small, spa, wading, waterslide) and pool-owner classes (apartment, camp, country club or health club, hotel, municipal, school, other) as well as the proportion of residents aged <5 years. We found that increases in the number of bigger pools, pools with more heterogeneous mixing (municipal pools vs. country club or apartment pools), and pools catering to young children (wading pools) are associated with more cases at the county level.

An analysis of seasonality of sarcoidosis in the United States veteran population: 2000-2007.

BACKGROUND: The onset of sarcoidosis is thought to be seasonal, particularly Lofgren's syndrome. However, there are conflicting data on seasonality by country and by radiographic stage. OBJECTIVE: The objective of this study was to determine if there is seasonality of the diagnosis of sarcoidosis in outpatients in the United States. METHODS AND RESULTS: Using time series methods, we performed a retrospective analysis of 3791 incident cases of sarcoidosis in the Veteran's Health Administration national outpatient claims database (2000-2007). We did not find overall seasonality in the occurrence of new sarcoidosis in United States Veterans (p = 0.9860), even after we subdivided the United States by northern (p = 0.6824) and southern regions (p = 0.4588). CONCLUSION: The lack of seasonality in this study indicates that season is not a dominant factor in complex gene-environment-host interaction that precedes presentation of new sarcoidosis cases in the United States Veteran population.

Treatment patterns of pediatric nontuberculous mycobacterial (NTM) cervical lymphadenitis as reported by nationwide surveys of pediatric otolaryngology and infectious disease societies.

OBJECTIVE: To describe physician diagnostic and therapeutic strategies for pediatric nontuberculous mycobacterial (NTM) lymphadenitis, a disease for which surgical excision is recommended. METHODS: We surveyed members of the Infectious Diseases Society of America Emerging Infections Network (EIN) and the American Society of Pediatric Otolaryngology (ASPO). We asked them to report clinical and microbiologic details of recent cases of NTM lymphadenitis seen in their practices. RESULTS: 200 physicians reported a total of 277 NTM lymphadenitis cases. Cervical lymph nodes (84%) were most frequently involved, and a majority of patients were non-Hispanic white (62%) males (54%) with median age 3.0 years. Tissue culture (61%) or polymerase chain reaction (12%) was utilized most frequently to confirm NTM etiology. In most (59%) cases, an etiologic organism was not identified. In cases, where an NTM organism isolate was identified, Mycobacterium avium complex (n=82, 72%) was the most common. Surgical excision followed by adjunctive antibiotic therapy was favored in the majority (59%) of cases where a treatment method was reported. The use of surgical excision alone or antibiotic therapy alone was reported respectively in 24% and 17% of cases. Antibiotics were prescribed without diagnostic confirmation of infectious organisms in 28% of cases. CONCLUSION: Pediatric otolaryngologists and infectious disease specialists frequently treat cervical lymphadenitis empirically as NTM disease without bacteriologic confirmation. Antibiotic therapy is frequently employed with or without surgical excision.

A spatial analysis of the spread of mumps: the importance of college students and their spring-break-associated travel.

To characterize the association between county-level risk factors and the incidence of mumps in the 2006 Iowa outbreak, we used generalized linear mixed models with the number of mumps cases per county as the dependent variable. To assess the impact of spring-break travel, we tested for differences in the proportions of mumps cases in three different age groups. In the final multivariable model, the proportion of Iowa's college students per county was positively associated (P<0.0001) with mumps cases, but the number of colleges was negatively associated with cases (P=0.0002). Thus, if the college students in a county were spread among more campuses, this was associated with fewer mumps cases. Finally, we found the proportion of mumps cases in both older and younger persons increased after 1 April (P=0.0029), suggesting that spring-break college travel was associated with the spread of mumps to other age groups.

Mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor and other newly approved biologic therapies: case finding through the Emerging Infections Network.

We present the results of a nationwide survey of infectious disease consultants to identify mycobacterial and other serious infections in patients receiving anti-tumor necrosis factor compounds and other novel targeted therapies. Nontuberculous mycobacterial infections, histoplasmosis, and invasive Staphylococcus aureus infection were all reported more frequently than was tuberculosis disease in this context.

Effect of antiretroviral therapy and hepatitis c co-infection on changes in lipid levels in HIV-Infected patients 48 weeks after initiation of therapy.

Hepatitis C virus (HCV) commonly co-infects HIV-infected individuals. Antiretroviral therapy (ART) is associated with elevated serum lipid levels, and HCV infection is associated with low serum lipid levels. Fasting lipid levels were investigated in 1,434 ART-naïve HIV-infected people participating in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) protocol who prospectively initiated ART with 3 agents. Subjects with elevated liver-associated enzymes (>5 x ULN) were excluded. Demographics, body mass index, HCV status, CD4 cell count, HIV RNA, liver enzymes, lipid levels, and glucose were assessed before and following 48 weeks of ART. HCV-positive subjects (n = 160; 11%) were older, more likely to be Black, have a history of intravenous drug use (IDU), have higher baseline liver-associated enzyme levels than the HCV-negative group (p < .001 for each), and to have diabetes at baseline (5% vs. 2%, p = .07). Lipid levels rose in both groups following ART, and the differences were not significant except that HDL levels increased significantly more in the HCV-positive group (p = .006). In summary, HCV infection did not appear to provide significant protection against ART-induced hyperlipidemia in this cohort of HIV-infected subjects prospectively enrolled in ART trials, although HDL levels rose to a greater degree.

Association of hypocholesterolaemia with hepatitis C virus infection in HIV-infected people.

OBJECTIVE: To study the impact of hepatitis C virus (HCV) status on serum cholesterol levels in HIV-infected patients. METHODS: We retrospectively analysed data from the 881 participants of the Veterans Ageing Cohort 3 Site Study. Four different models were constructed using total cholesterol, low-density lipid (LDL) cholesterol, high-density lipid (HDL) cholesterol and triglycerides as dependent variables. The relevant covariates included HCV antibody status, HIV medication class, CD4 count, HIV viral load, glucose level, lipid-lowering drug use, gender, race, age, liver function test results, ethanol use, drug use, and HIV exposure category. Variables excluded from the final model included niacin use, gender, race, age, current ethanol use, and HIV exposure category. RESULTS: Of the 881 HIV-positive patients enrolled in the study, 700 (79%) were screened for HCV antibody, with 300 (42.8%) HCV antibody positive and 400 (57.2%) HCV antibody negative. A positive HCV antibody status was independently associated with lower total cholesterol levels (P=0.001) and LDL cholesterol levels (P<0.001) but not with lower HDL cholesterol or triglyceride levels. HCV-positive patients had predicted LDL levels 19 mg/dL lower than those of HCV-negative subjects. HCV infection was also associated with a decreased use of lipid-lowering medication, and protease inhibitor use was associated with increased LDL and total cholesterol levels. CONCLUSIONS: HCV infection has been associated with lower cholesterol levels in HIV-negative individuals, and the same appears to be true with HIV-infected patients. This is an interesting finding given that HCV particles bind to LDL receptors in vitro and also because HCV-lipid interactions appear to be important in the HCV replication cycle.

Vaccines, biological warfare, and bioterrorism.

This article presents a brief history of the use of biological agents in warfare and bioterrorism. Bacillus anthracis, smallpox virus, and Yersinia pestis, historically have been and currently are considered the most likely candidates for potential use under these circumstances. This article discusses the clinical syndromes these agents cause and the role of vaccines in protection against them.