Background Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen ...sensitization, or to inhaled corticosteroid treatment. Objectives We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. Methods Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2–related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. Results The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus , Neisseria , Fusobacterium , and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2–high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Conclusion Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention.
OBJECTIVE To assess the prevalence, clinical presentations, and neuroimaging abnormalities in a series of patients treated for eclampsia at Mayo Clinic in Rochester, MN. PATIENTS AND METHODS We ...reviewed the records of all pregnant patients diagnosed as having eclampsia at Mayo Clinic in Rochester, MN, between January 1, 2001, and December 31, 2008. All patients who underwent neuroimaging were identified, and all studies were reviewed by an independent neuroradiologist. Comparisons were made between groups who did and did not undergo imaging to identify differentiating clinical or laboratory variables. RESULTS Thirteen cases of eclampsia were found, with neuroimaging studies available for 7: magnetic resonance imaging (n=6) and computed tomography (n=1). All 7 patients developed eclamptic seizures, and 2 of 7 patients had severe hypertension, with recorded systolic blood pressures exceeding 180 mm Hg. Neuroimaging showed characteristic changes of posterior reversible encephalopathy syndrome (PRES) in all patients. Follow-up imaging showed resolution in 2 of 3 patients; 1 patient had residual neuroimaging abnormalities. CONCLUSION Our results suggest that the clinical syndrome of eclampsia is associated with an anatomical substrate that is recognizable by neuroimaging as PRES. The levels of blood pressure elevation are lower than those reported in cases of PRES because of hypertensive encephalopathy. Further studies are needed to determine whether more aggressive blood pressure control and early neuroimaging may have a role in the management of these patients.
Preeclampsia and cognitive impairment later in life Fields, Julie A., PhD; Garovic, Vesna D., MD; Mielke, Michelle M., PhD ...
American journal of obstetrics and gynecology,
07/2017, Letnik:
217, Številka:
1
Journal Article
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Background Hypertension is a risk factor for cerebrovascular disease and cognitive impairment. Women with hypertensive episodes during pregnancy report variable neurocognitive changes within the ...first decade following the affected pregnancy. However, long-term follow-up of these women into their postmenopausal years has not been conducted. Objective The aim of this study was to examine whether women with a history of preeclampsia were at increased risk of cognitive decline 35-40 years after the affected pregnancy. Study Design Women were identified and recruited through the medical linkage, population-based Rochester Epidemiologic Project. Forty women with a history of preeclampsia were age- and parity-matched to 40 women with a history of normotensive pregnancy. All women underwent comprehensive neuropsychological assessment and completed self-report inventories measuring mood, ie, depression, anxiety, and other symptoms related to emotional state. Scores were compared between groups. In addition, individual cognitive scores were examined by neuropsychologists and a neurologist blinded to pregnancy status, and a clinical consensus diagnosis of normal, mild cognitive impairment, or dementia for each participant was conferred. Results Age at time of consent did not differ between preeclampsia (59.2 range 50.9-71.5 years) and normotensive (59.6 range 52.1-72.2 years) groups, nor did time from index pregnancy (34.9 range 32.0-47.2 vs 34.5 range 32.0-46.4 years, respectively). There were no statistically significant differences in raw scores on tests of cognition and mood between women with histories of preeclampsia compared to women with histories of normotensive pregnancy. However, a consensus diagnosis of mild cognitive impairment or dementia trended toward greater frequency in women with histories of preeclampsia compared to those with normotensive pregnancies (20% vs 8%, P = .10) and affected more domains among the preeclampsia group ( P = .03), most strongly related to executive dysfunction ( d = 1.96) and verbal list learning impairment ( d = 1.93). Conclusion These findings suggest a trend for women with a history of preeclampsia to exhibit more cognitive impairment later in life than those with a history of normotensive pregnancy. Furthermore, the pattern of cognitive changes is consistent with that observed with vascular disease/white matter pathology.
Abstract Background Familial involvement is common in dilated cardiomyopathy (DCM) and >40 genes have been implicated in causing disease. However, the role of genetic testing in clinical practice is ...not well defined. We examined the experience of clinical genetic testing in a diverse DCM population to characterize the prevalence and predictors of gene mutations. Methods and Results We studied 264 unrelated adult and pediatric DCM index patients referred to 1 reference lab for clinical genetic testing. Up to 10 genes were analyzed ( MYH7 , TNNT2 , TNNI3 , TPM1 , MYBPC3 , ACTC , LMNA , PLN , TAZ , and LDB3 ), and 70% of patients were tested for all genes. The mean age was 26.6 ± 21.3 years, and 52% had a family history of DCM. Rigorous criteria were used to classify DNA variants as clinically relevant (mutations), variants of unknown clinical significance (VUS), or presumed benign. Mutations were found in 17.4% of patients, commonly involving MYH7 , LMNA , or TNNT2 (78%). An additional 10.6% of patients had VUS. Genetic testing was rarely positive in older patients without a family history of DCM. Conversely in pediatric patients, family history did not increase the sensitivity of genetic testing. Conclusions Using rigorous criteria for classifying DNA variants, mutations were identified in 17% of a diverse group of DCM index patients referred for clinical genetic testing. The low sensitivity of genetic testing in DCM reflects limitations in both current methodology and knowledge of DCM-associated genes. However, if mutations are identified, genetic testing can help guide family management.
Background A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood. ...Objective The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia. Study Design Women without prior cardiovascular events (40 with and 40 without histories of preeclampsia, matched for parity and age at index birth) were recruited from a large population-based cohort of women who were residents of Olmsted County, Minnesota, and who delivered from 1976 through 1982. Computed tomography was performed to measure CAC in Agatston units. All pregnancy histories and covariates were confirmed by review of the medical records. Current clinical variables were assessed at the time of imaging. Differences between women with and without histories of preeclampsia were examined using χ2 tests and tests; CAC, in particular, was compared as a categorical and ordinal variable, with a χ2 test and with Wilcoxon 2-sample tests and ordinal logistic regression, as appropriate. Results Mean age (SD) at imaging was 59.5 (±4.6) years. Systolic and diastolic blood pressures, hyperlipidemia, and current diabetes status did not differ between women with and without histories of preeclampsia. However, the frequencies of having a current clinical diagnosis of hypertension (60% vs 20%, P < .001) and higher body mass index in kg/m2 (29.8; interquartile range, 25.9-33.7 vs 25.3; interquartile range, 23.1-32.0, median 25th-75th percentile, P = .023) were both greater in the women with histories of preeclampsia compared to those without. The frequency of a CAC score >50 Agatston units was also greater in the preeclampsia group (23% vs 0%, P = .001). Compared to women without preeclampsia, the odds of having a higher CAC score was 3.54 (confidence interval CI, 1.39–9.02) times greater in women with prior preeclampsia without adjustment, and 2.61 (CI, 0.95–7.14) times greater after adjustment for current hypertension. After adjustment for body mass index alone, the odds of having a higher CAC based on a history of preeclampsia remained significant at 3.20 (CI, 1.21–8.49). Conclusion In this first prospective cohort study with confirmation of preeclampsia by medical record review, a history of preeclampsia is associated with an increased risk of CAC >30 years after affected pregnancies, even after controlling individually for traditional risk factors. A history of preeclampsia should be considered in risk assessment when initiating primary prevention strategies to reduce cardiovascular disease in women. Among women with histories of preeclampsia, the presence of CAC may be able to identify those at a particularly high cardiovascular risk, and should be the subject of future studies.
ABSTRACT Purpose Although barriers to shared decision making in intensive care units are well documented, there are currently no easily scaled interventions to overcome these problems. We sought to ...assess stakeholders’ perceptions of the acceptability, usefulness, and design suggestions for a tablet-based tool to support communication and shared decision making in ICUs. Methods We conducted in-depth semi-structured interviews with 58 key stakeholders (30 surrogates and 28 ICU care providers). Interviews explored stakeholders’ perceptions about the acceptability of a tablet-based tool to support communication and shared decision making, including the usefulness of modules focused on orienting families to the ICU, educating them about the surrogate’s role, completing a question prompt list, eliciting patient values, educating about treatment options, eliciting perceptions about prognosis, and providing psychosocial support resources. The interviewer also elicited stakeholders’ design suggestions for such a tool. We used constant comparative methods to identify key themes that arose during the interviews Results Overall, 95% (55/58) of participants perceived the proposed tool to be acceptable, with 98% (57/58) of interviewees finding six or more of the seven content domains acceptable. Stakeholders identified several potential benefits of the tool including that it would help families prepare for the surrogate role and for family meetings as well as give surrogates time and a framework to think about the patient’s values and treatment options. Key design suggestions included: conceptualize the tool as a supplement to rather than a substitute for surrogate-clinician communication; make the tool flexible with respect to how, where, and when surrogates can access the tool; incorporate interactive exercises; use video and narration to minimize the cognitive load of the intervention; and build an extremely simple user interface to maximize usefulness for individuals with low computer literacy. Conclusion There is broad support among stakeholders for the use of a tablet-based tool to improve communication and shared decision making in ICUs. Eliciting the perspectives of key stakeholders early in the design process yielded important insights to create a tool tailored to the needs of surrogates and care providers in ICUs.
Preeclampsia and ESRD: The Role of Shared Risk Factors Kattah, Andrea G., MD; Scantlebury, Dawn C., MBBS; Agarwal, Sanket, MBBS ...
American journal of kidney diseases,
04/2017, Letnik:
69, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk ...factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors. Study Design Population-based nested case-control study. Setting & Participants The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or ≥4). Predictor Preeclamptic pregnancy, confirmed by medical record review. Outcome ESRD. Measurements Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension. Results There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37). Limitations The limited number of ESRD cases and missing data for prepregnancy kidney function. Conclusions Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.
Abstract Introduction Pre-incision operating room(OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. ...Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency and decreasing cost. Methods Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/minute (m) of OR time was $54. Patients classified as in the OR ≤10m prior to attending arrival or >10m prior to attending arrival. Results 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 months. 128 patients were in the OR ≤10m prior to attending arrival and 99 patients were >10m (3m±3 vs. 35m±14, p<0.01). ≤10m procedures started sooner after patient arrival in OR (40m±11 vs. 63m±19, p<0.01)which equated to $1,202 of savings before incision. While attending time in the OR prior to incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the ≤10m groups, saving $2,416±477 and $1,458±244, respectively (p<0.01). Attending time in OR prior to thyroidectomy was 13 minutes longer in ≤10m than >10m (p<0.01), but incisions were made 20 minutes sooner (p<0.01) equating to $1076±120 in savings. Conclusion Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings.
Background Interferon-alfa (IFN-α) has been implicated in the pathogenesis of psoriasis. Objective To evaluate the safety profile of MEDI-545, a fully human anti–IFN-α monoclonal antibody and to ...explore its effect on the involvement of type I IFN-α activity in the maintenance of established plaque psoriasis. Methods We conducted an 18-week, randomized, double-blind, placebo-controlled, dose-escalating study in 36 subjects with chronic plaque psoriasis. Subjects received one intravenous dose of MEDI-545 (0.3-30.0 mg/kg) or placebo. Study outcomes were safety profile, pharmacokinetics, immunogenicity, and clinical effects. Results There was no difference in adverse events between MEDI-545 and placebo. Two serious adverse events were reported; one drug-related hypotensive infusion reaction occurred in one subject in the 30.0 mg/kg MEDI-545 dose group, causing discontinuation of study drug in that subject and study dismissal of the other subjects in the same cohort; and a myocardial infarction occurred in one subject in the 10 mg/kg MEDI-545 dose group, which was considered to be unrelated to treatment. MEDI-545 was nonimmunogenic, had a half-life of 21 days, showed no significant inhibition of the type I IFN gene signature, and had no clinical activity. Limitations The study addressed only IFN-α and chronic psoriatic lesions. Conclusion The safety profile of MEDI-545 supports further clinical development. IFN-α does not appear to be significantly involved in the maintenance of established plaque psoriasis.
Objective Hyperhomocysteinemia is associated with an elevated cardiovascular disease risk. We examined whether women with a history of hypertension in pregnancy are more likely to have a high level ...of serum homocysteine decades after pregnancy. Study Design Serum homocysteine was measured at a mean age of 60 years in nulliparous women (n = 216), and women with a history of normotensive (n = 1825) or hypertensive (n = 401) pregnancies who participated in the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Relationships between homocysteine and pregnancy history were examined by linear and logistic regression, controlling for multiple covariates including personal and family history of hypertension, diabetes, obesity, tobacco use, and demographics. Results A history of hypertension in pregnancy, when compared with normotensive pregnancy, was associated with a 4.5% higher serum homocysteine level ( P = .015) and 1.60-fold increased odds of having an elevated homocysteine (95% confidence interval, 1.15–2.21; P = .005) after adjusting for potentially confounding covariates. In contrast, a history of normotensive pregnancy, as compared with nulliparity, was associated with a 6.1% lower serum homocysteine level ( P = .005) and a 0.49-fold reduced odds of elevated homocysteine levels (95% confidence interval, 0.32–0.74; P < .001). Conclusion Homocysteine levels decades after pregnancy are higher in women with a history of pregnancy hypertension, even after controlling for potential confounders. Thus, pregnancy history may prompt homocysteine assessment and risk modification in an attempt at primary prevention of cardiovascular disease.
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