Congenital infections as contributors to the onset of diabetes in children: A longitudinal study in the United States, 2001‐2017

BackgroundMaternal infections during pregnancy, particularly with rubella virus, were reported to increase the risk of diabetes in children. Widespread vaccination has decreased the number of infants with congenital rubella syndrome in the United States, although it remains a problem in developing countries. Because vaccine hesitancy has recently increased, we investigated the association between congenital infections with subsequent diabetes risk in children in the United States.MethodsUsing data from a nationwide private health insurer for years 2001‐2017, 1 475 587 infants were followed for an average of 3.9 years (maximum 16.5 years). Information was obtained regarding congenital infections (rubella, cytomegalovirus, other congenital infections) and perinatal infections, as well as for the development of diabetes mellitus and diabetic ketoacidosis.ResultsThere were 781 infants with congenital infections and 73 974 with perinatal infections. Diabetes developed in 3334 children. The odds of developing diabetes for infants with congenital rubella infection were 12‐fold greater (P = .013) and, for infants with congenital cytomegalovirus infection, were 4‐fold greater (P = .011) than infants without congenital or perinatal infection. Infants with other congenital infections had 3‐fold greater odds of developing diabetes (P = .044). Results were similar for diabetes ketoacidosis. Infants with other perinatal infections had 49% greater odds of developing diabetes during the follow‐up period (P < .001).ConclusionCongenital and other perinatal infections are associated with elevated risks of developing diabetes mellitus during childhood. Vaccination for rubella remains an important preventive action to reduce the incidence of diabetes in children.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154971/1/pedi12957.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154971/2/pedi12957_am.pd

Increased Risk of Infection and Mortality in Women after Cardiac Surgery Related to Allogeneic Blood Transfusion

Background: Infection and mortality rates are greater in women than in men after cardiac surgery. This study was conducted to assess whether allogeneic blood transfusion could partially account for this gender difference, as transfusion has been associated with immunomodulation. Methods: A cohort study was conducted in 380 patients at the University of Rochester Medical Center. Subjects were adult patients who underwent primary coronary artery bypass graft (CABG) surgery, primary valve replacement surgery, or both. Information was collected about blood components transfused, as well as postoperative infection, pulmonary dysfunction, and in-hospital mortality. Results: Women were more likely to receive allogeneic red blood cells (RBCs) or platelets than men (odds ratio [OR] 21.6, 95% CI 3.8, 124.2) and a greater quantity of blood than men. Patients who received allogeneic blood were 4.4 times more likely to develop an infection than those who did not (95% CI 1.5, 13.2). There was a positive linear correlation between number of units of blood received and number of days with fever (p < 0.001) and hospital length of stay (p < 0.001). This was particularly evident in patients who received four or more units of nonleukoreduced blood components. Women had a greater risk of infection (p = 0.005), pulmonary dysfunction (p = 0.005), and mortality (p = 0.007) than men during hospitalization. Conclusions: One reason for the greater mortality in women after cardiac surgery may be the increased likelihood of receiving nonleukoreduced allogeneic RBCs and platelets. Transfusion increased the risk of infection; infection, then, increased the likelihood of pulmonary dysfunction and mortality.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63383/1/jwh.2007.0397.pd

Meta-analysis: insulin sensitizers for the treatment of non-alcoholic steatohepatitis

Aliment Pharmacol Ther 2010; 32: 1211–1221Non-alcoholic fatty liver disease generally has a benign course; however, patients with non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma. Currently, there is a lack of consensus about optimal NASH treatment.To assess the efficacy of insulin-sensitizing agents on histological and biochemical outcomes in randomized control trials of biopsy-proven NASH.Multiple online databases and conference abstracts were searched. Random effects meta-analyses were performed, with assessment for heterogeneity and publication bias.Nine trials were included; five trials using thiazolidinediones (glitazones), three using metformin and one trial using both drugs. There was no publication bias. Compared with controls, glitazones resulted in improved steatosis (WMD = 0.57, 95% CI 0.36–0.77, P  = <0.001), hepatocyte ballooning (WMD = 0.36, 95% CI 0.24–0.49, P  < 0.001) and ALT (WMD = 16.4, 95% CI 7.7–25.0, P  < 0.001), but not inflammation ( P  = 0.09) or fibrosis ( P  = 0.11). In patients without diabetes, glitazones significantly improved all histological and biochemical outcomes, most importantly including fibrosis (WMD = 0.29, 95% CI 0.078–0.51, P  = 0.008). Metformin failed to improve any pooled outcome.Treatment of NASH with glitazones, but not metformin, demonstrates a significant histological and biochemical benefit, especially in patients without diabetes. Additional studies are needed to investigate long-term outcomes of glitazone therapy in patients without diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79251/1/j.1365-2036.2010.04467.x.pd

Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions

Abstract Background Colorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Although individuals diagnosed early have a greater than 90 % chance of survival, more than one-third of individuals do not adhere to screening recommendations partly because the standard diagnostics, colonoscopy and sigmoidoscopy, are expensive and invasive. Thus, there is a great need to improve the sensitivity of non-invasive tests to detect early stage cancers and adenomas. Numerous studies have identified shifts in the composition of the gut microbiota associated with the progression of CRC, suggesting that the gut microbiota may represent a reservoir of biomarkers that would complement existing non-invasive methods such as the widely used fecal immunochemical test (FIT). Methods We sequenced the 16S rRNA genes from the stool samples of 490 patients. We used the relative abundances of the bacterial populations within each sample to develop a random forest classification model that detects colonic lesions using the relative abundance of gut microbiota and the concentration of hemoglobin in stool. Results The microbiota-based random forest model detected 91.7 % of cancers and 45.5 % of adenomas while FIT alone detected 75.0 % and 15.7 %, respectively. Of the colonic lesions missed by FIT, the model detected 70.0 % of cancers and 37.7 % of adenomas. We confirmed known associations of Porphyromonas assaccharolytica, Peptostreptococcus stomatis, Parvimonas micra, and Fusobacterium nucleatum with CRC. Yet, we found that the loss of potentially beneficial organisms, such as members of the Lachnospiraceae, was more predictive for identifying patients with adenomas when used in combination with FIT. Conclusions These findings demonstrate the potential for microbiota analysis to complement existing screening methods to improve detection of colonic lesions.http://deepblue.lib.umich.edu/bitstream/2027.42/134551/1/13073_2016_Article_290.pd

DNA from fecal immunochemical test can replace stool for detection of colonic lesions using a microbiota-based model

Abstract Background There is a significant demand for colorectal cancer (CRC) screening methods that are noninvasive, inexpensive, and capable of accurately detecting early stage tumors. It has been shown that models based on the gut microbiota can complement the fecal occult blood test and fecal immunochemical test (FIT). However, a barrier to microbiota-based screening is the need to collect and store a patient’s stool sample. Results Using stool samples collected from 404 patients, we tested whether the residual buffer containing resuspended feces in FIT cartridges could be used in place of intact stool samples. We found that the bacterial DNA isolated from FIT cartridges largely recapitulated the community structure and membership of patients’ stool microbiota and that the abundance of bacteria associated with CRC were conserved. We also found that models for detecting CRC that were generated using bacterial abundances from FIT cartridges were equally predictive as models generated using bacterial abundances from stool. Conclusions These findings demonstrate the potential for using residual buffer from FIT cartridges in place of stool for microbiota-based screening for CRC. This may reduce the need to collect and process separate stool samples and may facilitate combining FIT and microbiota-based biomarkers into a single test. Additionally, FIT cartridges could constitute a novel data source for studying the role of the microbiome in cancer and other diseases.http://deepblue.lib.umich.edu/bitstream/2027.42/134673/1/40168_2016_Article_205.pd

Depression, antidepressant medications, and risk of Clostridium difficile infection

Abstract Background An ancillary finding in previous research has suggested that the use of antidepressant medications increases the risk of developing Clostridium difficile infection (CDI). Our objective was to evaluate whether depression or the use of anti-depressants altered the risk of developing CDI, using two distinct datasets and study designs. Methods In Study 1, we conducted a longitudinal investigation of a nationally representative sample of older Americans (n = 16,781), linking data from biennial interviews to physician and emergency department visits, stays in hospital and skilled nursing facilities, home health visits, and other outpatient visits. In Study 2, we completed a clinical investigation of hospitalized adults who were tested for C. difficile (n = 4047), with cases testing positive and controls testing negative. Antidepressant medication use prior to testing was ascertained. Results The population-based rate of CDI in older Americans was 282.9/100,000 person-years (95% confidence interval (CI)) 226.3 to 339.5) for individuals with depression and 197.1/100,000 person-years for those without depression (95% CI 168.0 to 226.1). The odds of CDI were 36% greater in persons with major depression (95% CI 1.06 to 1.74), 35% greater in individuals with depressive disorders (95% CI 1.05 to 1.73), 54% greater in those who were widowed (95% CI 1.21 to 1.95), and 25% lower in adults who did not live alone (95% CI 0.62 to 0.92). Self-reports of feeling sad or having emotional, nervous or psychiatric problems at baseline were also associated with the later development of CDI. Use of certain antidepressant medications during hospitalization was associated with altered risk of CDI. Conclusions Adults with depression and who take specific anti-depressants seem to be more likely to develop CDI. Older adults who are widowed or who live alone are also at greater risk of CDI.http://deepblue.lib.umich.edu/bitstream/2027.42/112859/1/12916_2012_Article_763.pd

Under Pressure: Financial Effect of the Hospital‐Acquired Conditions Initiative–A Statewide Analysis of Pressure Ulcer Development and Payment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112254/1/jgs13475.pd

Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study

Abstract Background While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (0–19 years) to that of adults (20–64 years). Methods In this longitudinal study, the Clinformatics® Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 2001–2015). Incidence rates and exact Poisson 95% confidence intervals were calculated by age group, sex, census division, and year of diagnosis. Changes in rates over time were assessed by negative binomial regression. Results Overall, there were 32,476 individuals who developed type 1 diabetes in the cohort. The incidence rate was greatest in youth aged 10–14 years (45.5 cases/100,000 person-years); however, because adulthood spans over a longer period than childhood, there was a greater number of new cases in adults than in youth (n = 19,174 adults; n = 13,302 youth). Predominance in males was evident by age 10 and persisted throughout adulthood. The male to female incidence rate ratio was 1.32 (95% CI 1.30–1.35). The incidence rate of type 1 diabetes in youth increased by 1.9% annually from 2001 to 2015 (95% CI 1.1–2.7%; P < 0.001), but there was variation across regions. The greatest increases were in the East South Central (3.8%/year; 95% CI 2.0–5.6%; P < 0.001) and Mountain divisions (3.1%/year; 95% CI 1.6–4.6%; P < 0.001). There were also increases in the East North Central (2.7%/year; P = 0.010), South Atlantic (2.4%/year; P < 0.001), and West North Central divisions (2.4%/year; P < 0.001). In adults, however, the incidence decreased from 2001 to 2015 (−1.3%/year; 95% CI −2.3% to −0.4%; P = 0.007). Greater percentages of cases were diagnosed in January, July, and August for both youth and adults. The number of new cases of type 1 diabetes (ages 0–64 years) in the United States is estimated at 64,000 annually (27,000 cases in youth and 37,000 cases in adults). Conclusions There are more new cases of type 1 diabetes occurring annually in the United States than previously recognized. The increase in incidence rates in youth, but not adults, suggests that the precipitating factors of youth-onset disease may differ from those of adult-onset disease.https://deepblue.lib.umich.edu/bitstream/2027.42/139053/1/12916_2017_Article_958.pd

Observation of playa salts as nuclei in orographic wave clouds

During the Ice in Clouds Experiment-Layer Clouds (ICE-L), dry lakebed, or playa, salts from the Great Basin region of the United States were observed as cloud nuclei in orographic wave clouds over Wyoming. Using a counterflow virtual impactor in series with a single-particle mass spectrometer, sodium-potassium-magnesium-calcium-chloride salts were identified as residues of cloud droplets. Importantly, these salts produced similar mass spectral signatures to playa salts with elevated cloud condensation nuclei (CCN) efficiencies close to sea salt. Using a suite of chemical characterization instrumentation, the playa salts were observed to be internally mixed with oxidized organics, presumably produced by cloud processing, as well as carbonate. These salt particles were enriched as residues of large droplets (>19 μm) compared to smaller droplets (>7 μm). In addition, a small fraction of silicate-containing playa salts were hypothesized to be important in the observed heterogeneous ice nucleation processes. While the high CCN activity of sea salt has been demonstrated to play an important role in cloud formation in marine environments, this study provides direct evidence of the importance of playa salts in cloud formation in continental North America has not been shown previously. Studies are needed to model and quantify the impact of playas on climate globally, particularly because of the abundance of playas and expected increases in the frequency and intensity of dust storms in the future due to climate and land use changes

Caring for Individuals with Dementia and Cognitive Impairment, Not Dementia: Findings from the Aging, Demographics, and Memory Study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106975/1/j.1532-5415.2010.03304.x.pd