bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and Thirty‐day Outcomes of Emergency Department Patients With Elevated Creatine Kinase
Authors: Grunau Brian E. , Pourvali Reza , Wiens Matthew O. , Levin Adeera , Li Jennifer , Grafstein Eric , Joo Dan , Scheuermeyer Frank Xavier
Published: July 2014

Objectives

Rhabdomyolysis, as defined by an elevation in creatine kinase (CK), may lead to hemodialysis and death in emergency department (ED) patients, but the patient characteristics, associated conditions, and 30‐day outcomes of patients with CK values over 1,000 U/L have not been described.

Methods

All consecutive ED patients with serum CK values over 1,000 U/L between January 1, 2006, and December 31, 2008, were retrospectively identified from two urban hospitals. Patient characteristics, ED treatment, and ED discharge diagnoses were determined by medical record review. Provincial databases were linked to identify patients who died or were treated with hemodialysis within 30 days. The primary outcome was the combined occurrence of death or need for hemodialysis within 30 days. Secondary outcomes included the incidence of acute kidney injury (AKI) and the proportion of patients with initial estimated glomerular filtration rates (eGFR) > 60 mL/min/1.73 m2 who died or required hemodialysis.

Results

Four‐hundred patients were identified, the median age was 50 years (interquartile range [IQR] = 35 to 69 years), and 77% were male, with 35% of patients discharged home from the ED. The most common ED discharge diagnoses were related to recreational drug use, infections, and traumatic or musculoskeletal complaints. Within 30 days, 32 (8.0%, 95% confidence interval [CI] = 5.3% to 11%) experienced primary outcomes, with 18 (4.5%, 95% CI = 2.55% to 6.5%) requiring hemodialysis and 21 deaths (5.3%, 95% CI = 3.1% to 7.4%). AKI occurred in 151 patients (38%, 95% CI = 33% to 43%). Of the 257 patients (64%) with initial eGFRs > 60 mL/min/1.73 m2, none required hemodialysis.

Conclusions

In ED patients with initial CK > 1,000 U/L, the incidence of death or hemodialysis was 8% within 30 days. Patients with initial eGFRs > 60 mL/min/1.73 m2 appear to be at a low risk of these outcomes from rhabdomyolysis.
A Comparison of Cosmetic Outcomes of Lacerations on the Extremities and Trunk Using Absorbable Versus Nonabsorbable Sutures
Authors: Tejani Cena , Sivitz Adam B. , Rosen Micheal D. , Nakanishi Albert K. , Flood Robert G. , Clott Mathew A. , Saccone Paul G. , Luck Raemma P.
Published: July 2014

Objectives

The primary objective was to compare the cosmetic outcomes of traumatic trunk and extremity lacerations repaired using absorbable versus nonabsorbable sutures. The secondary objective was to compare complication rates between the two groups.

Methods

This was a randomized controlled trial comparing wounds repaired with Vicryl Rapide and Prolene sutures. Pediatric and adult patients with lacerations were enrolled in the study. At a 10‐day follow‐up, the wounds were evaluated for infection and dehiscence. After 3 months, patients returned to have the wounds photographed. Two plastic surgeons blinded to the method of closure rated the cosmetic outcome of each wound using a 100‐mm visual analog scale (VAS). Using a noninferiority design, a VAS score of 13 mm or greater was considered to be a clinically significant difference. We used a Student's t‐test to compare differences between mean VAS scores and odds ratios (ORs) to compare differences in complication rates between the two groups.

Results

Of the 115 patients enrolled, 73 completed the study including 35 in the Vicryl Rapide group and 38 in the Prolene group. The mean (±SD) age of patients who completed the study was 22.1 (±15.5) years, and 39 were male. We found no significant differences in the age, race, sex, length of wound, number of sutures, or layers of repair in the two groups. The observer's mean VAS for the Vicryl Rapide group was 54.1 mm (95% confidence interval [CI] = 44.5 to 67.0 mm) and for the Prolene group was 54.5 mm (95% CI = 45.7 to 66.3 mm). The resulting mean difference was 0.5 mm (95% CI = –12.1 to 17.2 mm; p = 0.9); thus noninferiority was established. Statistical testing showed no differences in the rates of complications between the two groups, but a higher percentage of the Vicryl Rapide wounds developed complications.

Conclusions

The use of absorbable sutures for the repair of simple lacerations on the trunk and extremities should be considered as an alternative to nonabsorbable suture repair.
“Rewarding and Challenging at the Same Time”: Emergency Medicine Residents' Experiences Caring for Patients Who Are Homeless
Authors: Doran Kelly M. , Curry Leslie A. , Vashi Anita A. , Platis Stephanie , Rowe Michael , Gang Maureen , Vaca Federico E.
Published: July 2014

Objectives

The objectives were to examine how emergency medicine (EM) residents learn to care for patients in the emergency department (ED) who are homeless and how providing care for patients who are homeless influences residents' education and professional development as emergency physicians.

Methods

We conducted in‐depth, one‐on‐one interviews with EM residents from two programs. A random sample of residents stratified by training year was selected from each site. Interviews were digitally recorded and professionally transcribed. A team of researchers with diverse content‐relevant expertise reviewed transcripts independently and applied codes to text segments using a grounded theory approach. The team met regularly to reconcile differences in code interpretations. Data collection and analysis occurred iteratively, and interviews continued until theoretical saturation was achieved.

Results

Three recurring themes emerged from 23 resident interviews. First, residents learn unique aspects of EM by caring for patients who are homeless. This learning encompasses both specific knowledge and skills (e.g., disease processes infrequently seen in other populations) and professional development as an emergency physician (e.g., the core value of service in EM). Second, residents learn how to care for patients who are homeless through experience and informal teaching rather than through a formal curriculum. Residents noted little formal curricular time dedicated to homelessness and instead learned during clinical shifts through personal experience and by observing more senior physicians. One unique method of learning was through stories of “misses,” in which patients who were homeless had bad outcomes. Third, caring for patients who are homeless affects residents emotionally in complex, multifaceted ways. Emotions were dominated by feelings of frustration. This frustration was often related to feelings of futility in truly helping homeless patients, particularly for patients who were frequent visitors to the ED and who had concomitant alcohol dependence.

Conclusions

Caring for ED patients who are homeless is an important part of EM residency training. Our findings suggest the need for increased formal curricular time dedicated to the unique medical and social challenges inherent in treating patients who are homeless, as well as enhanced support and resources to improve the ability of residents to care for this vulnerable population. Future research is needed to determine if such interventions improve EM resident education and, ultimately, result in improved care for ED patients who are homeless.
Critical Drug Shortages: Implications for Emergency Medicine
Authors: Mazer‐Amirshahi Maryann , Pourmand Ali , Singer Steven , Pines Jesse M. , van den Anker John
Published: July 2014

Prescription drug shortages have become increasingly common and more severe over the past decade. In addition, reported shortages are longer in duration and have had a greater effect on patient care. Some of the causes of current drug shortages are multifactorial, including the consolidation of drug manufacturers, quality problems at production plants that restrict the supply of drugs, and a lack of financial incentives for manufacturers to produce certain products, particularly generic medications. Generic injectable medications are most commonly affected by shortages because the production process is complex and costly for these drugs, and profit margins are often smaller than for branded medications. Many commonly used emergency department (ED) generic injectables have been affected by shortages, including multiple resuscitation and critical care drugs. Several reports have shown that shortages can potentially have major effects on the quality of medical care, including medication errors, treatment delays, adverse outcomes, and increased health care costs. Currently, no published data exist outside of case reports that directly link ED‐based drug shortages to overall patient safety events; however, there are several examples in the ED where first‐line therapies for life‐saving medications have been in short supply, and alternatives have higher rates of adverse events, narrower therapeutic indexes, or both. Aside from increasing notification about shortages, the U.S. Food and Drug Administration has little power to coerce manufacturers to produce medications during a shortage. Therefore, ED providers must learn to mitigate the effects of shortages locally, through active communication with pharmacy staff to identify safe and effective alternatives for commonly used medications when possible. Particularly given the effect on critical care medications, therapeutic alternatives should be clearly communicated to all staff so that providers have easy access to this information during resuscitations. This review focuses on the etiology of drug shortages, their effect on the ED, and potential solutions and mitigation strategies.
Assessment of Dyspnea Early in Acute Heart Failure: Patient Characteristics and Response Differences Between Likert and Visual Analog Scales
Authors: Pang Peter S. , Collins Sean P. , Sauser Kori , Andrei Adin‐Cristian , Storrow Alan B. , Hollander Judd E. , Tavares Miguel , Spinar Jindrich , Macarie Cezar , Raev Dimitar , Nowak Richard , Gheorghiade Mihai , Mebazaa Alexandre
Published: July 2014

Background

Dyspnea is the most common symptom in acute heart failure (AHF), yet how to best measure it has not been well defined. Prior studies demonstrate differences in dyspnea improvement across various measurement scales, yet these studies typically enroll patients well after the emergency department (ED) phase of management.

Objectives

The aim of this study was to determine predictors of early dyspnea improvement for three different, commonly used dyspnea scales (i.e., five‐point absolute Likert scale, 10‐cm visual analog scale [VAS], or seven‐point relative Likert scale).

Methods

This was a post hoc analysis of URGENT Dyspnea, an observational study of 776 patients in 17 countries enrolled within 1 hour of first physician encounter. Inclusion criteria were broad to reflect real‐world clinical practice. Prior literature informed the a priori definition of clinically significant dyspnea improvement. Resampling‐based multivariable models were created to determine patient characteristics significantly associated with dyspnea improvement.

Results

Of the 524 AHF patients, approximately 40% of patients did not report substantial dyspnea improvement within the first 6 hours. Baseline characteristics were similar between those who did or did not improve, although there were differences in history of heart failure, coronary artery disease, and initial systolic blood pressure. For those who did improve, patient characteristics differed across all three scales, with the exception of baseline dyspnea severity for the VAS and five‐point Likert scale (c‐index ranged from 0.708 to 0.831 for each scale).

Conclusions

Predictors of early dyspnea improvement differ from scale to scale, with the exception of baseline dyspnea. Attempts to use one scale to capture the entirety of the dyspnea symptom may be insufficient.
Delaying the American Board of Emergency Medicine Qualifying Examination Is Associated With Poorer Performance
Authors: Marco Catherine A. , Counselman Francis L. , Korte Robert C. , Purosky Robert G. , Whitley Cameron Thomas , Reisdorff Earl J.
Published: July 2014

Objectives

The initial step in certification by the American Board of Emergency Medicine (ABEM) requires passing a multiple‐choice‐question qualifying examination. The qualifying examination is typically taken in the first year after residency training. This study was undertaken to determine if a delay in taking the qualifying examination is associated with poorer performance. The authors also examined the relationship between in‐training examination scores and qualifying examination scores.

Methods

This was a pooled time‐series cross‐section study. Primary measurements were initial qualifying examination scores, the timing of the qualifying examination, and in‐training examination scores. The three groups, based on qualifying examination timing, were immediate, 1‐year delay, and ≥2‐year delay. In‐training examination scores were analyzed to determine the relationship between intrinsic ability, examination timing, and qualifying examination scores. For analysis, a generic pooled ordinary least‐squares dummy variable model with robust standard errors was used. A pre hoc level of significance was determined to be α < 0.01.

Results

There were 16,353 qualifying examination test administrations between 2000 and 2012. In‐training examination scores were positively correlated with qualifying examination scores (p < 0.001). The group pass rates were 98.9% immediate, 95.6% 1‐year delay, and 86.6% ≥2‐year delay. After controlling for in‐training examination scores, delay taking the qualifying examination of 1 year was associated with a decrease in score of –0.6 (p = 0.003). A delay in taking the qualifying examination ≥2 years was associated with a decrease in score of –2.5 points (p < 0.001).

Conclusions

After accounting for innate ability using in‐training examination scores, delay taking the qualifying examination was associated with poorer performance. This effect was more pronounced if the delay was ≥2 years.
Programmatic Assessment of Level 1 Milestones in Incoming Interns
Authors: Hauff Samantha R. , Hopson Laura R. , Losman Eve , Perry Marcia A. , Lypson Monica L. , Fischer Jonathan , Santen Sally A.
Published: July 2014

Objectives

With the Accreditation Council for Graduate Medical Education (ACGME) Next Accreditation System, emergency medicine (EM) residency programs will be required to report residents' progress through the EM milestones. The milestones include five progressively advancing skill levels, with Level 1 defining the skill set of a medical school graduate and Level 5, that of an attending physician. The ACGME stresses that multiple forms of assessment should be used to ensure capture of the multifaceted competencies. The objective of this study was to determine the feasibility and results of programmatic assessment of Level 1 milestones using multisource assessments for incoming EM interns in July.

Methods

The study population was interns starting in 2012 and 2013. Interns' Level 1 milestone assessment was done with four distinct methods: 1) the postgraduate orientation assessment (POA) by the Graduate Medical Education Office for all incoming interns (this multistation examination covers nine of the EM milestones and includes standardized patient cases, task completion, and computer‐based stations); 2) direct observation of patient encounters by core faculty using a milestones‐based clinical skills competency checklist; 3) the global monthly assessment at the end of the intern orientation month that was updated to reflect the EM milestones; and 4) faculty assessment during procedural labs. These occurred during the July orientation month that included the POA, clinical shifts, didactic sessions, and procedure labs.

Results

In the POA, interns were competent in 48% to 93% of the milestones assessed. Overall, competency was 70% to 80%, with low scores noted in aseptic technique (patient care Milestone 13 [PC13]) and written and verbal hand‐off (interpersonal communications skills [ICS]2). In overall communication, 70% of interns demonstrated competency. In excess of 80% demonstrated competency in critical values interpretation (PC3), informed consent (PC9), pain assessment (PC11), and geriatric functional assessment (PC3). On direct observation, almost all Level 1 milestones were achieved (93% to 100%); however, only 78% of interns achieved competency in pharmacotherapy (PC5). On global monthly evaluations, all interns met Level 1 milestones.

Conclusions

A multisource assessment of EM milestones is feasible and useful to determine Level 1 milestones achievement for incoming interns. A structured assessment program, used in conjunction with more traditional forms of evaluation such as global monthly evaluations and direct observation, is useful for identifying deficits in new trainees and may be able inform the creation of early intervention programs.
Prevalence of Nonmedical Problems Among Older Adults Presenting to the Emergency Department
Authors: Stevens Tarshona B. , Richmond Natalie L. , Pereira Gregory F. , Shenvi Christina L. , Platts‐Mills Timothy F.
Published: July 2014

Objectives

Health outcomes among older emergency department (ED) patients may be influenced by physical, economic, and psychological problems not routinely identified during the ED visit. The objective of this study was to characterize such problems among older adults presenting to the ED.

Methods

This was a prevalence study with enrollment during 4‐hour periods randomly selected between 9 a.m. and 9 p.m. on random days of the week over a period of 8 weeks at an academic ED in the southeast United States. Participants were noninstitutionalized, cognitively intact adults aged 65 years or older without life‐threatening illness or injury. Consenting patients were asked about the frequency of 10 prespecified problems during the past year.

Results

Patients (N = 138) were non‐Hispanic white (69%) and female (57%) and almost all had primary providers (95%) and health insurance (98%). Forty percent reported their overall health as fair (21%) or poor (19%). Hazardous drinking habits were reported by 10% of patients. The prevalence of problems occurring either “sometimes” or “often” in the past year were pain (60%), difficulty walking (47%), lack of money (32%), isolation and loneliness (14%), lack of transportation (12%), difficulty scheduling a doctor's appointment (4%), difficulty getting prescriptions filled (4%), and lack of dental care (6%). Nine patients (7%) reported experiencing physical or psychological abuse at some point in the past year. Females, minorities, and individuals living in urban areas reported higher rates of most problems.

Conclusions

Nonmedical problems are common among cognitively intact, independent living, non–critically ill older patients presenting to an ED in the southeast United States.
Diagnostic Yields, Charges, and Radiation Dose of Chest Imaging in Blunt Trauma Evaluations
Authors: Rodriguez Robert M. , Baumann Brigitte M. , Raja Ali S. , Langdorf Mark I. , Anglin Deirdre , Bradley Richard N. , Medak Anthony J. , Mower William R. , Hendey Gregory W.
Published: July 2014

Background

Chest radiography (CXR) is the most common imaging in adult blunt trauma patient evaluation. Knowledge of the yields, attendant costs, and radiation doses delivered may guide effective chest imaging utilization.

Objectives

The objectives were to determine the diagnostic yields of blunt trauma chest imaging (CXR and chest computed tomography [CT]), to estimate charges and radiation exposure per injury identified, and to delineate assessment points in blunt trauma evaluation at which decision instruments for selective chest imaging would have the greatest effect.

Methods

From December 2009 to January 2012, we enrolled patients older than 14 years who received CXR during blunt trauma evaluations at nine U.S. Level I trauma centers in this prospective, observational study. Thoracic injury seen on chest imaging and clinical significance of the injury were defined by a trauma expert panel. Yields of imaging were calculated, as well as mean charges and effective radiation dose (ERD) per injury.

Results

Of 9,905 enrolled patients, 55.4% had CXR alone, 42.0% had both CXR and CT, and 2.6% had CT alone. The yields for detecting thoracic injury were CXR 8.4% (95% confidence intervals [CIs]) = 7.8% to 8.9%), chest CT 28.8% (95% CI = 27.5% to 30.2%), and chest CT after normal CXR 15.0% (95% CI = 13.9% to 16.2%). The mean charges and ERD (millisievert [mSv]) per injury diagnosis of CXR, chest CT, and chest CT after normal CXR were $3,845 (0.24 mSv), $10,597 (30.9 mSv), and $20,347 (59.3 mSv), respectively. The mean charges and ERD per clinically major thoracic injury diagnosis on chest CT after normal CXR were $203,467 and 593 mSv.

Conclusions

Despite greater diagnostic yield, chest CT entails substantially higher charges and radiation dose per injury diagnosed, especially when performed after a normal CXR. Selective chest imaging decision instruments should identify patients who require no chest imaging and patients who may benefit from chest CT after a normal CXR.
A systematic review and meta‐analysis of the i‐gel® vs laryngeal mask airway in adults
Authors: de Montblanc J. , Ruscio L. , Mazoit J. X. , Benhamou D.
Published: July 2014

We systematically reviewed 31 adult randomised clinical trials of the i‐gel® vs laryngeal mask airway. The mean (95% CI) leak pressure difference and relative risk (95% CI) of insertion on the first attempt were similar: 0.40 (−1.23 to 2.02) cmH2O and 0.98 (0.95–1.01), respectively. The mean (95% CI) insertion time and the relative risk (95% CI) of sore throat were less with the i‐gel: by 1.46 (0.33–2.60) s, p = 0.01, and 0.59 (0.38–0.90), p = 0.02, respectively. The relative risk of poor fibreoptic view through the i‐gel was 0.29 (0.16–0.54), p < 0.0001. All outcomes displayed substantial heterogeneity, I2 ≥ 75%. Subgroup analyses did not decrease heterogeneity, but suggested that insertion of the i‐gel was faster than for first‐generation laryngeal mask airways and that the i‐gel leak pressure was higher than first generation, but lower than second‐generation, laryngeal mask airways. A less frequent sore throat was the main clinical advantage of the i‐gel.
Risk factors of symptomatic NSAID‐induced small intestinal injury and diaphragm disease
Authors: Ishihara M. , Ohmiya N. , Nakamura M. , Funasaka K. , Miyahara R. , Ohno E. , Kawashima H. , Itoh A. , Hirooka Y. , Watanabe O. , Ando T. , Goto H.
Published: July 2014

Background

The aetiology for nonsteroidal anti‐inflammatory drug (NSAID)‐induced small intestinal injuries has not been well characterised.

Aim

To determine the risk factors of symptomatic NSAID‐induced small intestinal injuries, including diaphragm disease.

Methods

Of the 1262 symptomatic patients who underwent videocapsule endoscopy and/or double‐balloon enteroscopy, 156 consecutive patients were verified as having taken NSAIDs. Their CYP2C9*2, *3 and *13 single nucleotide polymorphisms (SNPs) were determined by allelic discrimination with Taqman 5’‐nuclease assays.

Results

Of the 156 NSAIDs users, 31 patients (20%) were diagnosed with NSAID‐induced small intestinal injury. Multivariate analysis indicated that the presence of comorbidities and the use of oxicams (meloxicam, ampiroxicam and lornoxicam) or diclofenac were associated with an increased risk of NSAID‐induced small intestinal injury (adjusted OR: 2.97, 95% CI: 1.05–8.41, P = 0.041 and adjusted OR: 7.05, 95% CI: 2.04–24.40, P = 0.002, respectively). The combination of aspirin and non‐aspirin NSAID was more damaging than aspirin alone. Age, sex, concomitant use of proton pump inhibitors, indications for NSAIDs use, duration of NSAIDs use and CYP2C9*2, *3 and *13SNPs were unrelated. The use of meloxicam and CYP2C9*3SNPs were significantly associated with an increased risk for diaphragm disease (adjusted OR: 183.75, 95% CI: 21.34–1582.38; P < 0.0001 and adjusted OR: 12.94, 95% CI: 1.55–108.36, P = 0.018, respectively).

Conclusion

The use of specific NSAIDs and the factors interfering with NSAIDs metabolism might associate with small intestinal injury, especially with diaphragm disease.
Systematic review: the association between eosinophilic oesophagitis and coeliac disease
Authors: Lucendo A. J. , Arias Á. , Tenias J. M.
Published: July 2014

Background

The relationship between eosinophilic oesophagitis (EoE) and coeliac disease (CD) remains controversial, with studies yielding varied results.

Aim

To systematically review the evidence of a possible association between both diseases.

Methods

Electronic searches were performed with keywords relating to EoE and CD in the MEDLINE, EMBASE and SCOPUS databases. Summary estimates were calculated. A random‐effects model was used depending on heterogeneity (I2). Publication bias was assessed with the aid of funnel plot analysis, along with the Begg–Mazumdar, Harbord and Egger tests.

Results

The search yielded 197 references; 30 were included in the quantitative summary, with most of these presenting methodological inconsistencies. Significant publication bias in favour of short studies reporting positive associations between both diseases was documented. The prevalence of EoE in CD ranged from 0% to 10.7% (I2 = 78.9%). Prevalence of CD in EoE varied between 0.16% and 57.1% (I2 = 89%). One high‐quality, prospective, randomly selected, population‐based study documented a 1.1% prevalence of CD, with no patients presenting EoE. Clinical and methodological heterogeneity hindered the performance of quantitative summaries for prevalence data. A gluten‐free diet was effective in achieving histological remission of EoE in 32.1% of coeliac patients (95% confidence interval, 14.9–52.2%; I2 = 52.2%), which was similar to that expected for wheat elimination in EoE patients.

Conclusions

While a lack of valid studies prevents us from completely ruling out a true association between EoE and CD, currently available evidence does not support this hypothesis. Indeed, the only epidemiological study with sufficient validity points to the independence of both diseases.
Emotion regulation strategies in preschool children
Authors: Sala Maria Nives , Pons Francisco , Molina Paola
Published: July 2014

This study investigated the development of emotion regulation strategies as reflected in the narratives of children between the ages of 3 and 6 years. An experimental procedure based on story completion tasks was devised to elicit the emotion‐related narratives of 69 preschool children. Coding of the narratives led to the observation of different emotion regulation strategies: Behavioural strategies, social support, and cognitive reappraisal. Several significant gender and age differences were identified in the use of these strategies. In addition, verbal skills, non‐verbal intelligence, and emotion comprehension were found to be associated with use of the observed emotion regulation strategies, although only at specific ages.
Influenza A infection enhances antigen‐induced airway inflammation and hyperresponsiveness in young but not aged mice
Authors: Birmingham J. M. , Gillespie V. L. , Srivastava K. , Li X‐M. , Busse P. J.
Published: July 2014

Background

Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established.

Objective

To investigate age‐related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen‐specific IgE production, antigen‐induced airway inflammation and airway hyperresponsiveness in mice.

Methods

To accomplish this objective, the following model system was used. Young (6 week) and aged (18 months) BALB/c mice were first infected with a non‐lethal dose of influenza virus A (H/HKx31). Mice were then ovalbumin (OVA)‐sensitized during the acute infection (3‐days post inoculation) and then chronically underwent challenge to the airways with OVA. Forty‐eight hours after the final OVA challenge, airway hyperresponsiveness (AHR), bronchoalveolar fluid (BALF) cellular and cytokine profile, antigen‐specific IgE and IgG1, and lung tissue inflammation were measured.

Results

Age‐specific differences were noted on the effect of a viral infection, allergic sensitization, airway inflammation and airway hyperresponsiveness. Serum OVA‐specific IgE was significantly increased in only the aged mice infected with influenza virus. Despite greater morbidity (e.g. weight loss and sickness scores) during the acute infection in the 18‐month old mice that were OVA‐sensitized, there was little effect on the AHR and BALF cellular differential. In contrast, BALF neutrophils and AHR increased, but eosinophils decreased in 6‐week mice that were OVA‐sensitized during an acute influenza infection.

Conclusion

With increased age in a mouse model, viral infection prior to antigen sensitization affects the airway and systemic allergic response differently. These differences may reflect distinct phenotypic features of allergic inflammation in older patients with asthma.
Hypertension and hypertensive cardiomyopathy in patients with a relapse‐free history of phaeochromocytoma
Authors: Weismann Dirk , Liu Dan , Bergen Till , Peitzsch Mirko , Raida Anna , Wagner Martin , Fassnacht Martin , Weidemann Frank , Allolio Bruno
Published: July 2014

Background

In patients with a relapse‐free history of phaeochromocytoma/paraganglioma (PCC/PGL), persistent hypertension has been reported, but has not been well characterized.

Methods

In 28 patients [mean age 54·5 (26–81) years] with a relapse‐free history of PCC/PGLs, we prospectively analysed resting, supine blood pressure (BP), ambulatory BP, echocardiography, exercise testing, metabolic parameters and retrospectively collected data from the time of diagnosis (baseline). Echocardiographic measures were compared to healthy (n = 28) and hypertensive controls (n = 15).

Results

Median follow‐up was 6 [1–16] years. Three patients had normal office and ambulatory BP and three patients had only increased office BP. Fifty‐four per cent of patients had a blunted circadian rhythm. Comparing normal, hypertensive and PCC/PGL patients, we found significant differences in end‐diastolic septal thickness (8·8 ± 0·2, 13·8 ± 0·4, 10·0 ± 0·3 mm, P < 0·05), septal basal thickness (9·0 ± 0·3, 15·9 ± 0·5, 11·2 ± 0·4 mm, P < 0·05) and left ventricular mass (143 ± 8, 255 ± 19, 169 ± 9 g, P < 0·05). In five patients, seven major cardiovascular events were observed. Compared to baseline, no significant difference was found in systolic (140 ± 35 vs 137 ± 18 mmHg) and diastolic (85 ± 18 vs 83 ± 10 mmHg) BP. An increase or a decrease in BP (>10 mmHg) was found in 36% and 39% of patients, respectively. The number of antihypertensive drugs had not changed [1 (0–3) vs 1 (0–4)]. Fewer patients received insulin (1 vs 3) or oral antiglycaemic drugs (2 vs 7).

Conclusion

Our data indicate that hypertension persists after removal of PCG/PGL in a substantial proportion of patients. Hypertensive heart disease is common, and cardiovascular events are frequent in patients with a history of PCC/PGL.
Maturity onset diabetes of the young in India – a distinctive mutation pattern identified through targeted next‐generation sequencing
Authors: Chapla Aaron , Mruthyunjaya Mahesh Doddabelavangala , Asha Hesarghatta Shyamasunder , Varghese Denny , Varshney Manika , Vasan Senthil K. , Venkatesan Padmanaban , Nair Veena , Mathai Sarah , Paul Thomas Vizhalil , Thomas Nihal
Published: July 2014

Objective

To establish and utilize a Next‐Generation Sequencing (NGS)‐based strategy to screen for maturity onset diabetes of the young (MODY) gene mutations in subjects with early‐onset diabetes.

Patients and Methods

Maturity onset diabetes of the young (MODY) genetic testing was carried out in 80 subjects of Asian Indian origin with young onset diabetes to identify mutations in a comprehensive panel of ten MODY genes. A novel multiplex polymerase chain reaction (PCR)‐based target enrichment was established, followed by NGS on the Ion Torrent Personal Genome Machine (PGM). All the mutations and rare variants were confirmed by Sanger sequencing.

Results

We identified mutations in 11 (19%) of the 56 clinically diagnosed MODY subjects and seven of these mutations were novel. The identified mutations include p.H241Q, p.E59Q, c.‐162G>A 5′ UTR in NEUROD1, p.V169I cosegregating with c.493‐4G>A and c.493‐20C>T, p.E271K in HNF4A, p.A501S in HNF1A, p.E440X in GCK, p.V177M in PDX1, p.L92F in HNF1B and p.R31L in PAX4 genes. Interestingly, two patients with NEUROD1 mutation were also positive for the p.E224K mutation in PDX1 gene. These patients with coexisting NEUROD1–PDX1 mutations showed a marked reduction in glucose‐induced insulin secretion. All 24 subjects who had not met the clinical criteria of MODY were negative for the mutations. To the best of our knowledge, this is the first report of PDX1, HNF1B, NEUROD1 and PAX4 mutations from India.

Conclusions

Multiplex PCR coupled with NGS provides a rapid, cost‐effective and accurate method for comprehensive parallelized genetic testing of MODY. When compared to earlier reports, we have identified a higher frequency and a novel digenic mutation pattern involving NEUROD1 and PDX1 genes.
Chemotherapy with cyclophosphamide, vincristine and dacarbazine for malignant paraganglioma and pheochromocytoma: systematic review and meta‐analysis
Authors: Niemeijer N.D. , Alblas G. , van Hulsteijn L.T. , Dekkers O.M. , Corssmit E.P.M.
Published: July 2014

Background

Chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) can be used for palliative treatment of malignant pheochromocytoma and paraganglioma. However, the precise effect of this chemotherapeutic regimen on tumour volume is unclear. The main objective of this study was to perform a systematic review and meta‐analysis assessing the effect of chemotherapy with CVD on tumour volume in patients with malignant paraganglioma/pheochromocytoma.

Methods

A literature search was performed in October 2013 to identify potentially relevant studies. Main outcomes were the pooled percentages of complete response, partial response and stable disease after chemotherapy with CVD. A meta‐analysis was performed with an exact likelihood approach using a logistic regression. Pooled percentages with 95% confidence intervals (CI) were reported.

Results

Four studies concerning a total of 50 patients with malignant paraganglioma/pheochromocytoma reported on treatment with a combination of CVD chemotherapy. A meta‐analysis of the effect of chemotherapy on tumour volume showed pooled percentages of complete response, partial response and stable disease of, respectively, 4% (95% CI: 1%–15%), 37%(95% CI: 25%–51%) and 14% (95% CI: 7%–27%). Only two studies concerning a total of 35 patients assessed the response on catecholamine excess; pooled percentages for complete, partial and stable hormonal response were 14% (95% CI: 6%–30%), 40% (95% CI: 25%–57%) and 20% (95% CI: 10%–36%), respectively. Duration of response was also reported in only two studies with a median duration of response of 20 months and 40 months.

Conclusions

Data on the effects of a combination of CVD chemotherapy on malignant paraganglioma/pheochromocytoma suggest that a partial response concerning tumour volume can be achieved in about 37% of patients and a partial response on catecholamine excess in about 40% of patients. However, in the included studies, the protocol when to initiate treatment was not well described. Therefore, it cannot be excluded that the reported effect of chemotherapy on tumour volume reflects the natural course of the disease, at least partially.
Information Processing and Dynamics in Minimally Cognitive Agents
Authors: Beer Randall D. , Williams Paul L.
Published: July 2014

There has been considerable debate in the literature about the relative merits of information processing versus dynamical approaches to understanding cognitive processes. In this article, we explore the relationship between these two styles of explanation using a model agent evolved to solve a relational categorization task. Specifically, we separately analyze the operation of this agent using the mathematical tools of information theory and dynamical systems theory. Information‐theoretic analysis reveals how task‐relevant information flows through the system to be combined into a categorization decision. Dynamical analysis reveals the key geometrical and temporal interrelationships underlying the categorization decision. Finally, we propose a framework for directly relating these two different styles of explanation and discuss the possible implications of our analysis for some of the ongoing debates in cognitive science.
Aortic Valve Stenosis Planimetry by Means of Three‐Dimensional Transesophageal Echocardiography in the Real Clinical Setting: Feasibility, Reliability and Systematic Deviations
Authors: Saura Daniel , de la Morena Gonzalo , Flores‐Blanco Pedro J. , Oliva María J. , Caballero Luis , González‐Carrillo Josefa , Espinosa María D. , López‐Ruiz María , García‐Navarro Miguel , Valdés Mariano
Published: July 2014

Aims

To assess the feasibility and reliability of aortic valve area (AVA) planimetry by means of three‐dimensional transesophageal echocardiography (3DTEE) as compared with the transthoracic echocardiogram (TTE) calculation of AVA, to determine the systematic deviations between measurements, and to describe the distribution of mean systolic in relation with 3DTEE anatomical AVA.

Methods and Results

Three hundred seven patients with aortic valve stenosis (AVS) underwent both TTE and 3DTEE for AVA measurement by means of the continuity equation and direct anatomical planimetry, respectively. AVA planimetry was achieved in 282 (91.9%) of patients. Severity of the aortic valve calcification was independently associated with a poorer performance of planimetry. Intraclass correlation coefficient yielded a 0.848 (95% CI: 0.807–0.879) value. 3DTEE rendered a mild constant underestimation of AVA in comparison with TTE. Severe aortic stenosis according to the area criterion (<1 cm2) despite mean systolic gradient below 40 mm Hg was detected in 37.6% of the study population, and in 33.7% of the subset of patients with preserved left ventricular ejection fraction.

Conclusions

Reliability of AVA planimetry by 3DTEE in comparison with the calculation by TTE is good, but 3DTEE underestimates slightly the measurement. Feasibility of the technique is good but independently affected by valvular calcification. Inconsistent classification of AVS severity as graded by AVA or mean systolic gradient is observed in the overall population and in patients with preserved systolic function.
Left Atrial Deformation Predicts Pulmonary Capillary Wedge Pressure in Pediatric Heart Transplant Recipients
Authors: Yeh Jay , Aiyagari Ranjit , Gajarski Robert J. , Zamberlan Mary C. , Lu Jimmy C.
Published: July 2014

Background

Pulmonary capillary wedge pressure (PCWP) is an important indicator in pediatric heart transplant patients, but commonly used noninvasive surrogates, such as ratio of early diastolic mitral inflow velocity to annular velocity (E/E'), have limitations in this population. This study aimed to evaluate the relation of left atrial (LA) peak systolic strain and distensibility with PCWP in pediatric heart transplant recipients.

Methods

Consecutive pediatric heart transplant patients were enrolled at time of cardiac catheterization, with echocardiogram immediately afterward. E/E' ratio at the lateral and medial mitral annulus, peak LA systolic longitudinal strain by speckle tracking, and LA distensibility were measured from echocardiograms and compared to invasively measured PCWP.

Results

In 38 patients (11.1 ± 5.8 years old), PCWP correlated with peak LA systolic strain (r = ‐0.44, P = 0.01) and LA distensibility (r= −0.43, P = 0.02), but not with E/E'. On receiver operating characteristics analysis, LA strain had a higher area under the curve than LA distensibility (0.846 vs. 0.606). LA strain <18.9% had sensitivity 62% and specificity 95%, with likelihood ratio 12.3 for PCWP ≥12. However, LA strain had lower intra‐observer and inter‐observer reproducibility than distensibility (intra‐class correlation coefficients 0.89 and 0.75 vs. 0.93 and 0.90).

Conclusions

Peak LA systolic strain and LA distensibility may be more useful surrogates of left ventricular filling pressure than E/E' in the pediatric heart transplant population, with greater reproducibility of LA distensibility. Longitudinal studies are needed to evaluate which parameters track changes in PCWP and clinical outcome.
Prevalence and Long‐Term Prognosis of Patients with Complete Bundle Branch Block (Right or Left Bundle Branch) with Normal Left Ventricular Ejection Fraction Referred for Stress Echocardiography
Authors: Supariwala Azhar A. , Po Jose Ricardo F. , Mohareb Sameh , Aslam Farhan , Kaddaha Firas , Mian Zainab I. , Chaudhry Farhan , Otokiti Ahmed , Chaudhry Farooq A.
Published: July 2014

Background

The prognostic value of stress echocardiography (SE) in patients with complete bundle branch blocks (BBB) with normal left ventricular ejection fraction (LVEF) has not been well described. We sought to determine the prognostic value of SE in patients with BBB and normal LVEF.

Methods

We analyzed 7214 patients (58 ± 14 years; 57% female) with a mean follow‐up time of 9 ± 4 years. Dobutamine SE was performed in 51% of patients and exercise SE was performed in 49%. All‐cause mortality data were obtained from the Social Security Death Index.

Results

There were 222 (3%) patients with right bundle branch block (RBBB) and 50 (0.7%) patients with left bundle branch block (LBBB). Patients with LBBB were 3 times more likely to have an abnormal stress test after adjusting for age, gender, mode of stress test, and coronary artery disease risk factors (OR = 3.3; 95% CI: 1.86–5.92; P < 0.001). The mortality rates were 4.5%/year for patients with LBBB, 2.5%/year for patients with RBBB, and 1.9%/year for patients without BBB (P < 0.001). Among patients with a normal SE, those with LBBB had similar mortality to those without LBBB (HR = 0.9; 95% CI: 0.4–2.2; P = 0.8). Patients with LBBB and abnormal SE had more than 2 times greater risk of all‐cause mortality (HR = 2.4; 95% CI: 1.4–4.2; P = 0.002).

Conclusion

A normal stress echocardiogram in LBBB is associated with benign prognosis while those with LBBB and abnormal SE have the worst outcomes.
Normal Pediatric Data for Isovolumic Acceleration at the Lateral Tricuspid Valve Annulus—A Heart Rate – Dependent Measure of Right Ventricular Contractility
Authors: Weismann Constance G. , Bamdad Michaela C. , Abraham Sharon , Ghiroli Stephen , Dziura James , Hellenbrand William E.
Published: July 2014

Background

Quantitative assessment of right ventricular (RV) function is important for the management of patients with congenital heart disease. Tissue Doppler (TDI)‐derived myocardial acceleration during isovolumic contraction (IVA) is an echocardiographic measure of contractility that is independent of loading conditions. The aim of this study was to establish normative data for IVA at the lateral tricuspid valve annulus (RV IVA).

Methods

This is a retrospective study of 340 children who had normal echocardiograms. We analyzed RV IVA in relation to age, body surface area (BSA), gender, heart rate (HR), tricuspid annular plane systolic excursion (TAPSE), and TDI‐derived S′ (RV S′).

Results

RV IVA showed a positive correlation with HR (r = 0.58, P<0.001) and a negative correlation with age and BSA (r = −0.44, P<0.001, for both). RV IVA ranged from 2.3 m/sec2 (±2 SD: 1–3.7 m/sec2) at a HR of <60 beats per minute (bpm) to 4.9 m/sec2 (±2 SD: 3.5–6.4 m/sec2) at a HR of >160 bpm. When RV IVA was corrected for HR (RV IVAc), it became independent of HR, age, BSA, and gender. The mean RV IVAc was 2.3 m/sec1.5 (±2 SD: 1.1–3.6 m/sec1.5). There was a correlation of normalized RV IVAc with normalized TAPSE and RV S′.

Conclusion

RV IVA, a marker of RV contractility, shows a strong dependence on HR. HR corrected RV IVA (RV IVAc) is independent of age, BSA, gender, and HR. We suggest measuring RV IVAc routinely in patients at risk for RV dysfunction.
Role of Three‐Dimensional Echocardiography in Management of Acquired Intracardiac Shunts
Authors: Taskesen Tuncay , Goldberg Steven L. , Gill Edward Allen
Published: July 2014

Gerbode defect and sinus of Valsalva aneurysm fistula are congenital and acquired forms of intracardiac shunt. The increasing prevalence of invasive, recurrent cardiovascular procedures cause tissue damage and has led to more iatrogenic and acquired cases of predominantly congenital shunt over time. We report 2 cases of acquired intracardiac fistula precisely defined by Real time three‐dimensional transesophageal echocardiography (3DTEE). The first case is a 70‐year‐old male with Gerbode defect after second aortic valve replacement surgery due to prosthetic valve endocarditis and the other case is a 41‐year‐old male with sinus of Valsalva aneurysm fistula between aorta and right atrium post subclinical infective endocarditis. Advanced cardiac imaging techniques such as cardiac computerized tomography, MRI and Real time three‐dimensional (3D) echocardiography help to precisely detect intracardiac fistula and provide detailed anatomic and physiologic information. The relatively low cost, lack of radiation exposure, portability and guiding characteristic make real time 3DTEE an imaging technique with arguably the most advantages. Surgical repair is the usual treatment for intracardiac shunt, and percutaneous catheter‐based closure is a less invasive alternative.
The effect of large‐scale privatization on public sector pay gap in a transition economy
Authors: Nikolic Jelena
Published: July 2014

Estimating the public–private sector earnings differentials in Serbia from 1995 until 2008 this paper finds significant changes at the mean and across the earnings distribution. The results show that the average public sector pay gap was negative at early stages of economic transition but grew to be positive during large‐scale privatizations. The paper uses different sources of data and adopts a number of statistical procedures, including a novel instrument to infer the likelihood of changes in the individual public sector status due to privatization.
Flowers for bees, autumn colours for whom? An experimental test with autumn colouration in mountain birches (Betula pubescens ssp. czerepanovii) as a signal against the moth Epirrita autumnata
Authors: Isaksen Trond , Folstad Ivar
Published: July 2014

In 2001, Hamilton and Brown proposed a controversial hypothesis of handicap signalling to potential insect parasites as an adaptive explanation for autumn leaf colouration. In subsequent studies there has been little attention to the costs and benefits of early autumnal colour change. Yet, in an observational study by Hagen et al. (2003) it was demonstrated that birch trees [Betula pubescens ssp. czerepanovii Ehrhart (Betulaceae)] turning yellow early in autumn had less damage from insects chewing on leaves the subsequent summer. Here, two experiments are presented which test the mechanisms in this model. The first addresses the proposed defence of leaves of B. pubescens ssp. czerepanovii by letting caterpillars of Epirrita autumnata Borkhausen (Lepidoptera: Geometridae), the birches’ most common insect parasites, choose between leaves from trees that either turned yellow late or early the foregoing autumn. The second experiment addresses whether adult female E. autumnata choose between early or late senescent (i.e., yellow or green) ‘twigs’ when ovipositing in autumn. We could not find evidence of preferences in either larvae or females, suggesting that timing of colour change in B. pubescens ssp. czerepanovii is not a warning signal that elicits a response in E. autumnata.