Healthcare system variability and inpatient maternal mortality in the United States.

OBJECTIVE: To examine the association of inpatient maternal mortality with variability in healthcare services delivery such as hospital size, urban/rural designation, teaching/non-teaching status, regional location, and insurance coverage. METHODS: This is a pooled, cross-sectional analysis of the National Inpatient Sample (2012-2014). Information on maternal demographics, clinical conditions, and birth outcomes were identified using respective ICD9-CM codes. Bivariate and multivariate analysis using logistic regression models were used to describe maternal characteristics and to calculate the risk of mortality with each independent variable. RESULTS: The weighted sample included 12,409,939 hospital records (82.6% are 18-34-year-old and 49.5% are Caucasians). Maternal death during hospitalization occurred in 1310 cases (12/100,000 live birth). Women with cardiovascular disorders, hemorrhage or sepsis were 33.6, 4.7, and 5.4 times more likely to suffer inpatient maternal mortality. Compared to small-sized hospitals, delivery at medium or large size hospitals is associated with higher mortality, adjusted odds ratios (aOR) 1.8 (1.4-2.3), and 2.2 (1.8-2.8), respectively. Adjusted OR for inpatient maternal mortality in urban non-teaching or urban teaching compared to rural hospitals were 2.2 (1.7-3.0) and 2.9 (2.2-3.9), respectively. Women in the South have higher maternal mortality compared to Northeast, aOR 1.7 (1.5-2.1). Women coved with public insurance experience higher inpatient maternal mortality compared to those with private insurance, aOR: 2.6 (2.1-3.2) and 1.9 (1.6-2.1), respectively. CONCLUSION: Factors related to variability in healthcare delivery may play a role in inpatient maternal mortality. Some could be explained by the case mix and the clinical conditions affecting birthing outcomes. A qualitative analysis is needed to explore how these factors relate to increased maternal mortality in certain hospital settings.

Cerebral tissue oxygen desaturations and increased fractional oxygen extraction events vary by gestational age in preterm infants.

BACKGROUND AND OBJECTIVES: Cerebral tissue oxygen saturation (SctO2) and cerebral fractional tissue oxygen extraction (cFTOE) changes with GA in preterm infants. This study examines changes in frequency, duration, and severity of SctO2 desaturation and increased cFTOE with GA. STUDY DESIGN: The lower limit of normal SctO2, the event threshold, was calculated using a tolerance interval method with 95% confidence interval (CI) and 90% probability. Cerebral desaturation events were defined as: 1) a drop below event threshold for at least 30 s (s), 2) preceded by a period above the event threshold for at least 30s, and 3) followed by a period above the threshold for at least 60s. RESULTS: 86% of infants <28 wk experienced one or more SctO2 desaturation event compared to 57% in >28 wk, odds ratios (OR) 4.5 (CI:1.3-15.3, p = 0.016). The severity of SctO2 desaturation events decreases at a rate of 77.9 units per wk increase in GA (p < 0.001). 39.3% of infants <28 wk experienced one or more increased cFTOE events compared to 28.6% in >28 wk, OR 1.6 (CI:0.6-4.4, p = 0.35). The severity of increasing cFTOE events decreased by 69.7 units per wk increase in GA (p < 0.001). CONCLUSION: Cerebral tissue oxygen desaturation events decrease in frequency and severity with increasing GA. The severity of increased cFTOE episodes decrease with GA.

TTLL12 is required for primary ciliary axoneme formation in polarized epithelial cells.

The primary cilium is a critical sensory organelle that is built of axonemal microtubules ensheathed by a ciliary membrane. In polarized epithelial cells, primary cilia reside on the apical surface and must extend these microtubules directly into the extracellular space and remain a stable structure. However, the factors regulating cross-talk between ciliation and cell polarization, as well as, axonemal microtubule growth and stabilization in polarized epithelia are not fully understood. In this study, we find TTLL12, a previously uncharacterized member of the Tubulin Tyrosine Ligase-Like (TTLL) family, localizes to the base of primary cilia and is required for cilia formation in polarized renal epithelial cells. We also show that TTLL12 directly binds to the α/ß-tubulin heterodimer in vitro and regulates microtubule dynamics, stability, and post-translational modifications (PTMs). While all other TTLLs catalyze the addition of glutamate or glycine to microtubule C-terminal tails, TTLL12 uniquely affects tubulin PTMs by promoting both microtubule lysine acetylation and arginine methylation. Together, this work identifies a novel microtubule regulator and provides insight into the requirements for apical extracellular axoneme formation.

Distal Transradial Access for Diagnostic Cerebral Angiography and Neurointervention: Systematic Review and Meta-analysis.

BACKGROUND: Radial artery access for cerebral angiography is traditionally performed in the wrist. Distal transradial access in the anatomic snuffbox is an alternative with several advantages. PURPOSE: Our aim was to review the safety and efficacy of distal transradial access for diagnostic cerebral angiography and neurointerventions. DATA SOURCES: We performed a comprehensive search of the literature using PubMed, Scopus, and EMBASE. STUDY SELECTION: The study included all case series of at least 10 patients describing outcomes associated with distal transradial access for diagnostic cerebral angiography or a neurointervention. DATA ANALYSIS: Random-effects models were used to obtain pooled rates of procedural success and complications. DATA SYNTHESIS: A total of 7 studies comprising 348 (75.8%) diagnostic cerebral angiograms and 111 (24.2%) interventions met the inclusion criteria. The pooled success rate was 95% (95% CI, 91%-98%; I2 = 74.33). The pooled minor complication rate was 2% (95% CI, 1%-4%; I2 = 0. No major complications were reported. For diagnostic procedures, the combined mean fluoroscopy time was 13.53 [SD, 8.82] minutes and the mean contrast dose was 74.9 [SD, 35.6] mL. LIMITATIONS: A small number of studies met the inclusion criteria, all of them were retrospective, and none compared outcomes with proximal transradial or femoral access. CONCLUSIONS: Early experience with distal transradial access suggests that it is a safe and effective alternative to proximal radial and femoral access for performing diagnostic cerebral angiography and interventions. Additional studies are needed to establish its efficacy and compare it with other access sites.

Clinical and Molecular Phenotypes of Low-Penetrance Variants of NLRP3: Diagnostic and Therapeutic Challenges.

OBJECTIVE: Cryopyrin-associated periodic syndromes (CAPS) result from gain-of-function mutations in the NLRP3 gene, which causes excessive release of interleukin-1ß (IL-1ß) and systemic inflammation. While pathogenetic NLRP3 variant phenotypes are well-characterized, low-penetrance NLRP3 variants represent a significant clinical challenge. The aims of this study were to determine the clinical phenotype, the in vitro biologic phenotype, and the effect of anti-IL-1 treatment in patients with low-penetrance NLRP3 variants. METHODS: A multicenter study of consecutive symptomatic patients with low-penetrance NLRP3 variants recruited from 7 centers between May 2012 and May 2013 was performed. The observed findings were transferred into a study database, from which they were extracted for analysis. Controls were patients with a known pathogenetic NLRP3 variant. Clinical presentation and CAPS markers of inflammation were captured. Functional assays of inflammasome activation, including caspase 1 activity, NF-κB release, cell death, and IL-1ß release, were performed. Treatment effects of IL-1 were determined. Comparisons between low-penetrance and pathogenetic NLRP3 variants were performed. RESULTS: The study included 45 patients, 21 of which were female (47%); 26 of the patients (58%) were children. NLRP3 low-penetrance variants identified in the patients were Q703K (n = 19), R488K (n = 6), and V198M (n = 20). In the controls, 28 had pathogenetic NLRP3 variants. Patients with low-penetrance NLRP3 variants had significantly more fever (76%) and gastrointestinal symptoms (73%); eye disease, hearing loss, and renal involvement were less common. Functional inflammasome testing identified an intermediate phenotype in low-penetrance NLRP3 variants as compared to wild-type and pathogenetic NLRP3 variants. All treated patients responded to IL-1 inhibition, with complete response documented in 50% of patients. CONCLUSION: Patients with low-penetrance NLRP3 variants display a distinct clinical phenotype and an intermediate biologic phenotype, including IL-1ß and non-IL-1ß-mediated inflammatory pathway activation.

Hydroconductive and silver-impregnated foam dressings: a comparison.

OBJECTIVE: As the number of commercially available wound dressings is increasing rapidly, it is important for clinicians to understand the strengths and limitations of each and to recognise relationships between wound type and dressing properties to obtain optimal healing results. Our aim is to test the antimicrobial activity of two dressings. METHOD: A hydroconductive (HC) dressing and a silver-impregnated foam (SIF) dressing were compared for their potential to reduce the levels meticillin-resistant Staphylococcus aureus (MRSA). We also assessed MRSA-derived biologically active components in liquid or agar matrices, simplified models for heavily exuding or dry wounds respectively, and in an in vivo animal model with MRSA infected wounds. RESULTS: In the agar model (dry wounds) both dressings showed a strong reduction in MRSA activities within 24 hours post-application. The antibacterial effects of the SIF dressing were more pronounced in the liquid model, however, at an increasing cytotoxic cost. In agreement with these in vitro results, assessment of dressings using an MRSA-infected wound in an rat model showed a decrease in MRSA which was significant 7 days post-burn and inoculation, with more compromised viability of MRSA. Dressings showed a similar capability to reduced and eliminate toxic shock syndrome toxin (TSST-1) at day 7 post-burn in the animal model but not at day 4, where the SIF dressing was more potent Conclusion: These results confirm the advantages of using silver in reducing bacterial load in wound treatment, except for conditions of highly exuding wounds where the cytotoxic properties of silver may offset these advantages and HC dressing use is more suitable.

Evaluation of OMNIgene®â€¢SPUTUM-stabilised sputum for long-term transport and Xpert® MTB/RIF testing in Nepal.

SETTING: German Nepal TB Project, National Tuberculosis Reference Laboratory, Kathmandu, Nepal. OBJECTIVE: To evaluate whether transporting samples in OMNIgene®â€¢SPUTUM (OM-S) reagent from a peripheral collection site to a central laboratory in Nepal can improve tuberculosis (TB) detection and increase the sensitivity of Xpert® MTB/RIF testing. DESIGN: One hundred sputum samples were split manually. Each portion was assigned to the OM-S group (OM-S added at collection, airline-couriered without cold chain, no other processing required) or the standard-of-care (SOC) group (samples airline-couriered on ice, sodium hydroxide + N-acetyl-L-cysteine processing required at the laboratory). Smear microscopy and Xpert testing were performed. RESULTS: Transport time was 2-13 days. Overall smear results were comparable (respectively 58% and 56% smear-negative results in the OM-S and SOC groups). The rate of smear-positive, Mycobacterium tuberculosis-positive (MTB+) sample detection was identical for both treatment groups, at 95%. More smear-negative MTB+ samples were detected in the OM-S group (17% vs. 13%, P = 0.0655). CONCLUSION: Sputum samples treated with OM-S can undergo multiday ambient-temperature transport and yield comparable smear and Xpert results to those of SOC samples. Further investigation with larger sample sizes is required to assess whether treating sputum samples with OM-S could increase the sensitivity of Xpert testing in smear-negative samples.

Crystallographic Studies of Telomerase.

Telomeres are nucleoprotein complexes that maintain the ends of our chromosomes thus providing genomic stability. Telomerase is a ribonucleoprotein reverse transcriptase that replicates the short tandem repeats of DNA known as telomeres. The telomeric DNA is specifically associated with two major complexes, the shelterin and CST complexes both of which are involved in telomere length regulation and maintenance along with telomerase. Obtaining structural information on these nucleoprotein complexes has been a major bottleneck in fully understanding the mechanism of action of telomeric nucleoproteins for over two decades. The recent advances in molecular and structural biology have enabled us to obtain atomic resolution structures of telomeric proteins alone and in complex with their nucleic acid substrates transforming the field and our understanding and interpretation of this unique biological pathway. Here we report our approach to obtain the structure of the Triobolium castaneum catalytic subunit of telomerase TERT (tcTERT) in its apo- and substrate-bound states.

Fall frequency and associated factors among men and women with or at risk for HIV infection.

OBJECTIVES: Falls and fall-related injuries are a major public health concern. HIV-infected adults have been shown to have a high incidence of falls. Identification of major risk factors for falls that are unique to HIV infection or similar to those in the general population will inform development of future interventions for fall prevention. METHODS: HIV-infected and uninfected men and women participating in the Hearing and Balance Substudy of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study were asked about balance symptoms and falls during the prior 12 months. Falls were categorized as 0, 1, or ≥ 2; proportional odds logistic regression models were used to investigate relationships between falls and demographic and clinical variables and multivariable models were created. RESULTS: Twenty-four per cent of 303 HIV-infected participants reported at least one fall compared with 18% of 233 HIV-uninfected participants (P = 0.27). HIV-infected participants were demographically different from HIV-uninfected participants, and were more likely to report clinical imbalance symptoms (P ≤ 0.035). In univariate analyses, more falls were associated with hepatitis C, female sex, obesity, smoking, and clinical imbalance symptoms, but not age, HIV serostatus or other comorbidities. In multivariable analyses, female sex and imbalance symptoms were independently associated with more falls. Among HIV-infected participants, smoking, a higher number of medications, and imbalance symptoms remained independent fall predictors, while current protease inhibitor use was protective. CONCLUSIONS: Similar rates of falls among HIV-infected and uninfected participants were largely explained by a high prevalence of imbalance symptoms. Routine assessment of falls and dizziness/imbalance symptoms should be considered, with interventions targeted at reducing symptomatology.

Newborn Hearing Screenings in Human Immunodeficiency Virus-Exposed Uninfected Infants.

Perinatal HIV infection and congenital cytomegalovirus (CMV) infection may increase the risk for hearing loss. We examined 1,435 infants enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) network, a prospective study of the safety of in utero antiretroviral (ARV) exposures. We determined the proportion of perinatally HIV-exposed uninfected (HEU) newborns who were referred for additional hearing testing, and evaluated the association between in utero ARV exposures and newborn hearing screening results. Using a nested case-control design, we also examined congenital CMV infection in infants with and without screening referral. Congenital CMV infection was determined based on CMV DNA detection using a nested PCR assay in peripheral blood mononuclear cells obtained within 14 days of birth. Among the 1,435 infants (70% black, 31% Hispanic, 51% male), 45 (3.1%) did not pass the hearing screen and were referred for further hearing testing. Based on exact logistic regression models controlling for maternal use of tobacco and ototoxic medications, first trimester exposure to Tenofovir was associated with lower odds of a newborn hearing screening referral [adjusted odds ratio (aOR) = 0.41, 95% confidence interval (CI): 0.14-1.00]. Exposure to Atazanavir was linked to higher odds of newborn screening referral, although not attaining significance [aOR = 1.84, 95% CI: 0.92-3.56]. Maternal ARV use may have varying effects on newborn hearing screenings. These results highlight the importance for audiologists to be knowledgeable of in utero ARV exposures in HEU children because of the possibility of higher referrals in these children.

Value of sialendoscopy-assisted transoral sublingual gland resection for a plunging ranula: case report and review.

OBJECTIVE: To highlight the value of sialendoscopy during transoral resection of the sublingual gland for a plunging ranula to prevent iatrogenic injury to the submandibular duct. METHOD AND RESULTS: The clinical course of a 20-year-old male with a plunging ranula was analysed. The patient underwent transoral resection of the affected sublingual gland and pseudocyst. Sialendoscopy was used to confirm patency of the submandibular duct with placement of a Marchal dilator to aid in preservation of the duct during sublingual gland dissection. The sublingual gland was successfully removed, with no injury to the submandibular duct or lingual nerve. During follow up, the patient had slight numbness to the tip of the tongue, which resolved after 2-3 days. Post-operative examination showed the submandibular duct to be intact and there was no swelling of the submandibular area. CONCLUSION: Sialendoscopy-assisted transoral sublingual gland resection for a plunging ranula is a safe and effective technique. Sialendoscopy aids in skeletonisation and preservation of the submandibular duct.

Recommendations for the allergy management in the primary care.

The majority of patients seeking medical advice for allergic diseases are first seen in a primary care setting. Correct diagnosis with identification of all offending allergens is an absolute prerequisite for appropriate management of allergic disease by the general practitioner. Allergy diagnostic tests recommended for use in primary care are critically reviewed in accordance with the significant workload in a primary care setting. Simplified pathways for recognition and diagnosis of allergic diseases are proposed, that should be further adapted to local (national) conditions.

EEG and neuroimaging correlations in children with lissencephaly.

PURPOSE: To study the usefulness of EEG in the diagnosis of lissencephaly, a rare cortical developmental disorder associated with abnormal cellular proliferation. Currently, the clinical emphasis is placed on the radiological and genetic aspects for the diagnosis of lissencephaly. METHODS: This is a retrospective review of consecutive EEG recordings and imaging data from 14 children, with the diagnosis of lissencephaly, who were admitted from January 1998 to January 2010. All EEG recordings were performed with the 10-20 system of electrode placement, in both awake and sleep states. All EEG recordings were reviewed using anterior-posterior bipolar and transverse montages and then they were interpreted blindly, with respect to the imaging and genetic investigations for each patient. RESULTS: All children showed one of the three characteristic EEG patterns reported in the literature of lissencephaly. The EEG pattern I, showed an anterior posterior gradient that corresponded to the severity of the imaging study abnormality. All patients were on two or more AEDs and reported to continue having active epilepsy. CONCLUSION: In a child with clinical characteristics of lissencephaly, one of these three reported EEG patterns can prove useful in making the diagnosis very probable, preceding imaging and genetic testing.

Guidelines for the genetic diagnosis of hereditary recurrent fevers.

Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing. Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.

Comparison of Airtraq optical laryngoscope and Storz video laryngoscope in a cadaver model / 世界急诊医学杂志（英文）

BACKGROUND: Airway management in the emergency department is a critical intervention that requires both standard techniques and rescue techniques to ensure a high rate of success. Recently, video laryngoscope (VL) systems have become increasingly common in many large urban Eds, but these systems may exceed the budgets of smaller rural Eds and EMS services and the Airtraq optical laryngoscope (OL) may provide an effective, low-cost alternative. We hypothesized that laryngeal view and time to endothracheal tube placement for OL and VL intubations would not be significantly different. METHODS: This was a prospective, crossover trial. Setting: University-based emergency medicine residency program procedure laboratory utilizing lightly embalmed cadavers. Subjects:PGY1-3 emergency medicine residents. The study subjects performed timed endotracheal intubations alternately using the OL and VL. The subjects then rated the Cormack-Lehane laryngeal view for each device. Statistical analysis: Mean time to intubation and the mean laryngeal view score were calculated with 95％ confidence intervals and statistical significance was determined by Student's t test. RESULTS: Fourteen subjects completed the study. The average laryngeal view achieved with the OL vs. the VL was not significantly different, with Cormack-Lehane grade of 1.14 vs. 1.07, respectively. Time to endotracheal intubation, however, was significantly different (P<0.001) with the average time to intubation for the OL 25.49 seconds (95％ CI: 17.95-33.03) and the VL 13.41 seconds (10.27-16.55). CONCLUSION: The Airtraq OL and the Storz VL yielded similar laryngeal views in the lightly embalmed cadaver model. Time to endotracheal tube placement, however, was less for the VL.

Resolution of remodeling in eosinophilic esophagitis correlates with epithelial response to topical corticosteroids.

BACKGROUND: Esophageal remodeling occurs in eosinophilic esophagitis (EE) patients but whether the components of remodeling in the subepithelium are reversible by administration of topical oral corticosteroids is unknown. METHODS: We quantitated the degree of lamina propria remodeling in esophageal biopsies obtained before and after at least 3 months of therapy with budesonide in 16 pediatric EE subjects. In addition, we investigated whether corticosteroid therapy modulated vascular activation (expression of VCAM-1; level of interstitial edema), TGFbeta(1) activation (levels of TGFbeta(1), phosphorylated Smad2/3), and performed a pilot analysis of a polymorphism in the TGFbeta(1) promoter in relation to EE subjects who had reduced remodeling with budesonide therapy. RESULTS: EE subjects were stratified based on the presence (n = 9) or absence (n = 7) of decreased epithelial eosinophilia following budesonide. Patients with residual eosinophil counts of

Role of radiotherapy in adenoid cystic carcinoma of the head and neck.

This study retrospectively reviewed 183 cases of adenoid cystic carcinoma treated over 40 years. The local recurrence free survival rate was 68.2 per cent at five years and 40.8 per cent at 10 years. At 10 years, local recurrence free survival was significantly worse following radiotherapy alone (0 per cent), compared with surgery alone (41.8 per cent, p = 0.004) or combined with post-operative radiotherapy (43.5 per cent, p = 0.001). Neither tumour stage three or four, perineural invasion, solid subtype nor involved margins predicted local recurrence. Treatment with radiotherapy alone resulted in worse survival than surgery alone (p = 0.002) or combined with post-operative radiotherapy (p = 0.001). Survival rates following local recurrence (n = 34) were higher following surgery (p = 0.006) but not significantly improved following radiotherapy (p = 0.139). Chemotherapy for distant metastases did not prolong survival (p = 0.747) but did result in improved eating and aesthetics scores, while decreasing overall physical health. These results indicate that surgery is preferable for primary and recurrent adenoid cystic carcinoma of the head and neck. The incidence of local recurrence following surgery and postoperative radiotherapy was similar to surgery alone cases although the latter had less adverse prognostic features. Contemporary chemotherapy may benefit quality of life but not survival in patients with distant metastases due to adenoid cystic carcinoma of the head and neck.

Initial description of the human NLRP3 promoter.

Mutations in NLRP3 (CIAS1) are identified in a continuum of related inflammatory disorders, known as cryopyrinopathies since NLRP3 codes for the protein cryopyrin. Approximately 40% of patients with classic presentation lack mutations in the coding region of NLRP3 suggesting heterogeneity or epigenetic factors. Cryopyrin is a key regulator of proinflammatory cytokine release. Therefore, variations in the NLRP3 promoter sequence may have effects on disease state in patients with cryopyrinopathies and other inflammatory diseases. In this report, we confirmed three 5'-untranslated region splice forms with two separate transcriptional start sites, and identified potential promoter regions and six new DNA promoter variants. One variant is unique to a mutation negative cryopyrinopathy patient and increases in vitro gene expression. Additional studies can now be performed to further characterize the NLRP3 promoter and sequence variants, which will lead to better understanding of the regulation of NLRP3 expression and its role in disease.