The Patientʼs Perception of Eosinophilic Esophagitis Related Symptoms: a Qualitative Content Analysis

Background and Aims: The international EEsAI study group is currently developing an activity index for Eosinophilic Esophagitis (EoE). A potential discrepancy between patient and physician reported EoE symptoms has not been assessed yet. Therefore, we aimed to evaluate patient reported items describing their EoE activity and to compare these with the physicianʼs perception. Methods: A questionnaire was sent to 100 EoE patients in Switzerland. EoE-related symptoms dependent and independent of food intake were reported by patients. Results were analyzed using a qualitative content analysis and compared with symptoms reported by international EoE experts in Delphi rounds. Results: The questionnaire response rate was 64/100. The following items were developed by combining categories based on patients answers: food-consistency related dysphagia, frequency and severity of dysphagia, food impaction, strategies to avoid food impaction, food allergy, drinking-related retrosternal pain. The following food categories associated with dysphagia were identified: meat, rice, dry bread, French fries, raw, fibrous foods, others. Sports and psychological stress were identified as triggers for non-food intake related EoE symptoms. A good correlation was found between patient and physicianʼs reported EoE related symptoms. Conclusions: There is a good correlation between patient reported symptoms and the physicianʼs perception of clinical items as reported by international EoE experts. These patient reported outcomes will now be incorporated into the EEsAI questionnaire that measures EoE activity.

Errors in palliative care: kinds, causes, and consequences: a pilot survey of experiences and attitudes of palliative care professionals.

Abstract Background: Medical errors have recently been recognized as a relevant concern in public health, and increasing research efforts have been made to find ways of improving patient safety. In palliative care, however, studies on errors are scant. Objective: Our aim was to gather pilot data concerning experiences and attitudes of palliative care professionals on this topic. Methods: We developed a questionnaire, which consists of questions on relevance, estimated frequency, kinds and severity of errors, their causes and consequences, and the way palliative care professionals handle them. The questionnaire was sent to all specialist palliative care institutions in the region of Bavaria, Germany (n=168; inhabitants 12.5 million) reaching a response rate of 42% (n=70). Results: Errors in palliative care were regarded as a highly relevant problem (median 8 on a 10-point numeric rating scale). Most respondents experienced a moderate frequency of errors (1-10 per 100 patients). Errors in communication were estimated to be more common than those in symptom control. The causes most often mentioned were deficits in communication or organization. Moral and psychological problems for the person committing the error were seen as more frequent than consequences for the patient. Ninety percent of respondents declared that they disclose errors to the harmed patient. For 78% of the professionals, the issue was not a part of their professional training. Conclusion: Professionals acknowledge errors-in particular errors in communication-to be a common and relevant problem in palliative care, one that has, however, been neglected in training and research.

Prise en charge du traumatisme cranio-cérébral sévère [Update on the management of severe traumatic brain injury]

Prognosis after severe traumatic brain injury (TBI) is determined by the severity of initial injury and secondary cerebral damage. The main determinants of secondary cerebral damage are brain ischemia and oedema. Traumatic brain injury is a heterogeneous disease. Head CT-scan is essential in evaluating initial type of injury and severity of brain oedema. A standardised approach based on prevention and treatment of secondary cerebral damage is the only effective therapeutic strategy of severe TBI. We review the classification, pathophysiology and treatment of secondary cerebral damage after severe TBI and discuss the management of intracranial hypertension, cerebral perfusion pressure and brain ischemia.

Influence of the morphology of the dural sac on surgical decision making in lumbar spinal stenosis

Introduction: Surgical decision making in lumbar spinal stenosis (LSS) takes into account primarily clinical symptoms as well as concordant radiological findings. We hypothesized that a wide variation of operative threshold would be found in particular as far as judgment of severity of radiological stenosis is concerned. Patients and methods: The number of surgeons who would proceed to decompression was studied relative to the perceived severity of radiological stenosis based either on measurements of dural sac cross sectional area (DSCA) or on the recently described morphological grading as seen on axial T2 MRI images. A link to an electronic survey page with a set of ten axial T2 MRI images taken from ten patients with either low back pain or LSS were sent to members of three national or international spine societies. Those 10 images were randomly presented initially and re-shuffled on a second page including this time DSCA measurements in mm2, ranging from 14 to 226 mm2, giving a total of 20 images to appraise. Morphological grades were ranging from grade A to D. Surgeons were asked if they would consider decompression given the radiological appearance of stenosis and that symptoms of neurological claudication were severe in patients who were otherwise fit for surgery. Fisher's exact test was performed following dichotomization of data when appropriate. Results: A total of 142 spine surgeons (113 orthopedic spine surgeons, 29 neurosurgeons) responded from 25 countries. A substantial agreement was observed in operating patients with severe (grade C) or extreme (grade D) stenosis as defined by the morphological grade compared to lesser stenosis (A&B) grades (p<0.0001). Decision to operate was not dependent on number of years in practice, medical density in practicing country or specialty although more neurosurgeons would operate on grade C stenosis (p<0.005). Disclosing the DSCA measurement did not alter the decision to operate. Although 20 surgeons only had prior knowledge of the description of the morphological grading, their responses showed no statistically significant difference with those of the remaining 122 physicians. Conclusions: This study showed that surgeons across borders are less influenced by DSCA in their decision making than by the morphological appearance of the dural sac. Classifying LSS according to morphology rather than surface measurements appears to be consistent with current clinical practice.

Prise en charge de l'asthme en médecine de premier recours [Management of asthma in primary care medicine].

The international recommendations issued by GINA (Global Initiative for Asthma) have undergone considerable adaptations over the last years. This article proposes the local adaptation of those guidelines bearing on the practical aspects of the treatment for the general practitioner's use. One of the fundamental changes in these new guidelines on good practice relates to the permanent adaptation of the treatment on the basis of symptom control rather than on the severity of the asthma. Another change from the old recommendations concerns the manner in which the asthma is categorised into different phases.

Prise en charge initiate du sepsis sévère et du choc septique [Management of severe sepsis and septic shock].

Severe sepsis and septic shock are systemic manifestations of the host response to infection. Mortality remains high despite advances in pathophysiological knowledge. Hemodynamic and respiratory management is largely supportive, while early antibiotics administration and source of infection's control are crucial for patient outcome. We review the principles guiding the initial management of these patients in emergency situation.

A homozygous missense mutation in SCNN1A is responsible for a transient neonatal form of pseudohypoaldosteronism type 1.

Pseudohypoaldosteronism type 1 (PHA1) is a monogenic disorder of mineralocorticoid resistance characterized by salt wasting, hyperkalemia, high aldosterone levels, and failure to thrive. An autosomal recessive form (AR-PHA1) is caused by mutations in the epithelial sodium channel ENaC with usually severe and persisting multiorgan symptoms. The autosomal dominant form of PHA1 (AD-PHA1) is due to mutations in the mineralocorticoid receptor causing milder and transient symptoms restricted to the kidney. We identified a homozygous missense mutation in the SCNN1A gene (c.727T>C/p.Ser(243)Pro), encoding α-subunit of ENaC (α-ENaC) in a prematurely born boy with a severe salt-losing syndrome. The patient improved rapidly under treatment, and dietary salt supplementation could be stopped after 6 mo. Interestingly, the patient's sibling born at term and harboring the same homozygous Ser(243)Pro mutation showed no symptom of salt-losing nephropathy. In vitro expression of the αSer(243)Pro ENaC mutant revealed a slight but significant decrease in ENaC activity that is exacerbated in the presence of high Na(+) load. Our study provides the first evidence that ENaC activity is critical for the maintenance of salt balance in the immature kidney of preterm babies. Together with previous studies, it shows that, when the kidney is fully mature, the severity of the symptoms of AR-PHA1 is related to the degree of the ENaC loss of function. Finally, this study identifies a novel functional domain in the extracellular loop of ENaC.

Use of lights and siren: is there room for improvement?

OBJECTIVE: The objective of this study was to analyse the use of lights and siren (L&S) during transport to the hospital by the prehospital severity status of the patient and the time saved by the time of day of the mission. METHODS: We searched the Public Health Services data of a Swiss state from 1 January 2010 to 31 December 2010. All primary patient transports within the state were included (24 718). The data collected were on the use of L&S, patient demographics, the time and duration of transport, the type of mission (trauma vs. nontrauma) and the severity of the condition according to the National Advisory Committee for Aeronautics (NACA) score assigned by the paramedics and/or emergency physician. We excluded 212 transports because of missing data. RESULTS: A total of 24 506 ambulance transports met the inclusion criteria. L&S were used 4066 times, or in 16.6% of all missions. Of these, 40% were graded NACA less than 4. Overall, the mean total transport time to return to the hospital was 11.09 min (confidence interval 10.84-11.34) with L&S and 12.84 min (confidence interval 12.72-12.96) without. The difference was 1.75 min (105 s; P<0.001). For night-time runs alone, the mean time saved using L&S was 0.17 min (10.2 s; P=0.27). CONCLUSION: At present, the use of L&S seems questionable given the severity status or NACA score of transported patients. Our results should prompt the implementation of more specific regulations for L&S use during transport to the hospital, taking into consideration certain physiological criteria of the victim as well as time of day of transport.

The fibrinogen- and fibronectin-binding domains of Staphylococcus aureus fibronectin-binding protein A synergistically promote endothelial invasion and experimental endocarditis.

Staphylococcus aureus experimental endocarditis relies on sequential fibrinogen binding (for valve colonization) and fibronectin binding (for endothelial invasion) conferred by peptidoglycan-attached adhesins. Fibronectin-binding protein A (FnBPA) reconciles these two properties--as well as elastin binding--and promotes experimental endocarditis by itself. Here we attempted to delineate the minimal subdomain of FnBPA responsible for fibrinogen and fibronectin binding, cell invasion, and in vivo endocarditis. A large library of truncated constructs of FnBPA was expressed in Lactococcus lactis and tested in vitro and in animals. A 127-amino-acid subdomain spanning the hinge of the FnBPA fibrinogen-binding and fibronectin-binding regions appeared necessary and sufficient to confer the sum of these properties. Competition with synthetic peptides could not delineate specific fibrinogen- and fibronectin-binding sites, suggesting that dual binding arose from protein folding, irrespective of clearly defined binding domains. Moreover, coexpressing the 127-amino-acid subdomain with remote domains of FnBPA further increased fibrinogen binding by &gt; or =10 times, confirming the importance of domain interactions for binding efficacy. In animals, fibrinogen binding (but not fibronectin binding) was significantly associated with endocarditis induction, whereas both fibrinogen binding and fibronectin binding were associated with disease severity. Moreover, fibrinogen binding also combined with fibronectin binding to synergize the invasion of cultured cell lines significantly, a feature correlating with endocarditis severity. Thus, while fibrinogen binding and fibronectin binding were believed to act sequentially in colonization and invasion, they appeared unexpectedly intertwined in terms of both functional anatomy and pathogenicity (in endocarditis). This unforeseen FnBPA subtlety might bear importance for the development of antiadhesin strategies.

Early apoptosis of rod photoreceptors in Rpe65(-/-) mice is associated with the upregulated expression of lysosomal-mediated autophagic genes.

RPE65-related Leber's congenital amaurosis (LCA) is a rod-cone dystrophy whose clinical outcome is mainly attributed to the loss of rod photoreceptors followed by cone degeneration. Pathogenesis in Rpe65(-/-) mice is characterized by a slow and progressive degeneration of rods dependent on the constitutive activation of unliganded opsin. We previously reported that this opsin-mediated apoptosis of rods was dependent on Bcl-2-apoptotic pathway and Bax-induced pro-death activity. In this study, we report early initial apoptosis in the newly differentiated retina of Rpe65(-/-) mice. Apoptotic photoreceptors were identified as rods and resulted from pathological phototransduction signaling. This wave of early apoptosis triggered Bcl-2-related pathway and Bax apoptotic activity, while activation of the caspases was not induced. Following cellular stress, multiple signaling pathways are initiated which either commit cells to death or trigger pro-survival responses including autophagy. We report that Bcl-2-related early rod apoptosis was associated with the upregulation of autophagy markers including chaperone-mediated autophagy (CMA) substrate receptor LAMP-2 and lysosomal hydrolases Cathepsin S and Lysozyme. This suggests that lysosomal-mediated autophagy may be triggered in response to early rod apoptosis in Rpe65-LCA disease. These results highlight that Rpe65-related primary stress induces early signaling events, which trigger Bax-induced-apoptotic pathway and autophagy-mediated cellular response. These events may determine retinal cell fate, progression and severity of the disease.

Somewhere between illusion of control and powerlessness : trying to situate the pathological gambler's locus of control

It has been suggested that pathological gamblers develop illusory perceptions of control regarding the outcome of the games and should express higher Internal and Chance locus of control. A sample of 48 outpatients diagnosed with pathological gambling disorder who participated in this ex post facto study, completed the Internality, Powerful Others, and Chance scale, the South Oaks Gambling Screen questionnaire, and the Beck Depression Inventory. Results for the locus of control measure were compared with a reference group. Pathological gamblers scored higher than the reference group on the Chance locus of control, which increased with the severity of cases. Moreover, Internal locus of control did show a curvilinear relationship with the severity of cases. Pathological gamblers have specific locus of control scores that vary in function of the severity, in a linear fashion or a non-linear fashion according to the scale. This effect might be caused by competition between "illusion of control" and the tendency to attribute adverse consequence of gambling to external causes.

Therapy of mild to moderate luminal Crohn's disease.

The management of luminal Crohn's disease, the most common form of initial presentation of the disease, depends on the location and the severity of the lesions. Mild to moderate disease represents a relatively large proportion of patients with a first flare of luminal disease, which may also be associated with perianal disease. As quality of life of these patients correlates with disease activity, adequate therapy is a central goal of the overall patient management. Treatment options include mainly sulfasalazine, budesonide and systemic steroids, while the role of mesalazine and antibiotics remains controversial. The role of biological therapies in mild to moderate disease has not been thoroughly evaluated and will not be discussed here.

The scarf osteotomy for the treatment of hallux valgus deformity: a review of 84 cases.

This study reviewed the subjective, clinical and radiological outcome of 71 patients (84 feet) treated by scarf osteotomy for hallux valgus deformity at our institution from 1995 to 1998 with an average follow-up time of 22 months (range, 17 to 48 months). At the time of follow-up, 39% of the patients were very satisfied, 50% were satisfied and 11% were not satisfied. The mean AOFAS score raised significantly from 43 points (14-68) preoperatively to 82 points (39 to 100) at follow-up (p &lt; 0.001). The radiological angles including M1-M2, M1-P1, M1-M5 and DMAA improved significantly (p &lt; 0.001). Among the 16 complications recorded, seven (8%) were minor and nine (11%) required an additional procedure. The scarf osteotomy of the first metatarsal coupled with a lateral soft-tissue release and, in three-quarters of our cases, with a basal closing wedge varisation osteotomy of the first phalanx, resulted in overall high satisfaction rate as well as significant clinical and radiological improvements in our series. Nevertheless, the range of motion of the first MP joint remained low: 30 degrees to 74 degrees in 52 patients (62%) and &lt;30 degrees in four patients (5%). Furthermore, the mobility of the first ray as well as the consequences of the procedure in the sagittal plane need to be assessed more accurately, and this may be achieved by incorporating measurement of the plantar pressures in the forefoot area into the global rating system.

Ruling out coronary artery disease in primary care: development and validation of a simple prediction rule.

BACKGROUND: Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. METHODS: We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain (n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). RESULTS: The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83-0.91) for the derivation cohort and 0.90 (95% CI 0.87-0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3-5 points; negative result <or= 2 points), which had a sensitivity of 87.1% (95% CI 79.9%-94.2%) and a specificity of 80.8% (77.6%-83.9%). INTERPRETATION: The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.

Preoperative assessment of neurovesical function in children with anorectal malformation: association with vertebral and spinal malformations.

PURPOSE: We preoperatively assessed neurovesical function and spinal cord function in children with anorectal malformations. In cases of neurovesical dysfunction we looked for an association with vertebral malformation or myelodysplasia. MATERIALS AND METHODS: We prospectively evaluated 80 children with anorectal malformations via preoperative urodynamics and magnetic resonance imaging of the spine. Bladder compliance and volume, detrusor activity and vesicosphincteric synergy during voiding allowed urodynamic evaluation. Results were reported according to Wingspread and Krickenbeck classifications of anorectal malformations. RESULTS: Urodynamic findings were pathological in 14 children (18%). Pathological evaluations did not seem related to type of fistula or level of anorectal malformation. Vertebral anomalies were seen in 34 patients (43%) and myelodysplasia in 16 (20%). Neither vertebral anomaly nor myelodysplasia seemed associated with type of fistula or severity of anorectal malformation. Of 14 children with pathological urodynamics no vertebral anomaly or myelodysplasia was found in 7. Of 66 children with normal urodynamics 40 presented with vertebral or spinal malformation. CONCLUSIONS: Lower urinary tract dysfunction is common in patients with anorectal malformations. Normal spine or spinal cord does not exclude neurovesical dysfunction. Myelodysplasia or vertebral anomaly does not determine lower urinary tract dysfunction. Thus, we recommend preoperative urodynamic assessment of the bladder and magnetic resonance imaging of the spine in children with anorectal malformations.