The IC3D classification of the corneal dystrophies.

BACKGROUND: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis. PURPOSE: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis. METHODS: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature. RESULTS: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available. CONCLUSIONS: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d.

Appropriateness of respiratory care: development of evidence-based guidelines in an acute care hospital

Background: Respiratory care is universally recognised as useful, but its indications and practice vary markedly. In order to improve appropriateness of respiratory care in our hospital, we developed evidence-based local guidelines in a collaborative effort involving physiotherapists, physicians, and health services researchers. Methods: Recommendations were developed using the standardised RAND appropriateness method. A literature search was performed for the period between 1995 and 2008 based on terms associated with guidelines and with respiratory care. Publications were assessed according to the Oxford classification of quality of evidence. A working group prepared proposals for recommendations which were then independently rated by a multidisciplinary expert panel. All recommendations were then discussed in common and indications for procedures were rated confidentially a second time by the experts. Each indication for respiratory care was classified as appropriate, uncertain, or inappropriate, based on the panel median rating and the degree of intra-panel agreement. Results: Recommendations were formulated for the following procedures: non-invasive ventilation, continuous positive airway pressure, intermittent positive pressure breathing, intrapulmonary percussive ventilation, mechanical insufflation-exsufflation, incentive spirometry, positive expiratory pressure, nasotracheal suctioning, noninstrumental airway clearance techniques. Each recommendation referred to a particular medical condition, and was assigned to a hierarchical category based on the quality of evidence from literature supporting the recommendation and on the consensus of experts. Conclusion: Despite a marked heterogeneity of scientific evidence, the method used allowed us to develop commonly agreed local guidelines for respiratory care. In addition, this work fostered a closer relationship between physiotherapists and physicians in our institution.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. LEVEL OF EVIDENCE: II.

Validation of the instability shoulder index score in a multicenter reliability study in 114 consecutive cases.

BACKGROUND: Anterior shoulder stabilization surgery with the arthroscopic Bankart procedure can have a high recurrence rate in certain patients. Identifying these patients to modify outcomes has become a focal point of research. PURPOSE: The Instability Shoulder Index Score (ISIS) was developed to predict the success of arthroscopic Bankart repair. Scores range from 0 to 10, with higher scores predicting a higher risk of recurrence after stabilization. The interobserver reliability of the score is not known. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: This is a prospective multicenter (North America and Europe) study of patients suffering from shoulder instability and waiting for stabilization surgery. Five pairs of independent evaluators were asked to score patient instability severity with the ISIS. Patients also completed functional scores (Western Ontario Shoulder Instability Index [WOSI], Disabilities of the Arm, Shoulder and Hand-short version [QuickDASH], and Walch-Duplay test). Data on age, sex, number of dislocations, and type of surgery were collected. The test-retest method and intraclass correlation coefficient (ICC: >0.75 = good, >0.85 = very good, and >0.9 = excellent) were used for analysis. RESULTS: A total of 114 patients with anterior shoulder instability were included, of whom 89 (78%) were men. The mean age was 28 years. The ISIS was very reliable, with an ICC of 0.933. The mean number of dislocations per patient was higher in patients who had an ISIS of ≥6 (25 vs 14; P = .05). Patients who underwent more complex arthroscopic procedures such as Hill-Sachs remplissage or open Latarjet had higher preoperative ISIS outcomes, with a mean score of 4.8 versus 3.4, respectively (P = .002). There was no correlation between the ISIS and the quality-of-life questionnaires, with Pearson correlations all >0.05 (WOSI = 0.39; QuickDASH = 0.97; Walch-Duplay = 0.08). CONCLUSION: Our results show that the ISIS is reliable when used in a multicenter study with anterior traumatic instability populations. There was no correlation between the ISIS and the quality-of-life questionnaires, but surgical decisions reflected its increased use.

Improving the implementation of evidence-based knowledge in healthcare

The pace of development of new healthcare technologies and related knowledge is very fast. Implementation of high quality evidence-based knowledge is thus mandatory to warrant an effective healthcare system and patient safety. However, even though only a small fraction of the approximate 2500 scientific publication indexed daily in Medline is actually useful to clinical practice, the amountof the new information is much too large to allow busy healthcare professionals to stay aware of possibly important evidence-based information.

Feasibility and clinical outcomes when using practice guidelines for evaluation of fever in returning travelers and migrants : a validation study.

BACKGROUND: Practice guidelines for examining febrile patients presenting upon returning from the tropics were developed to assist primary care physicians in decision making. Because of the low level of evidence available in this field, there was a need to validate them and assess their feasibility in the context they have been designed for. OBJECTIVES: The objectives of the study were to (1) evaluate physicians' adherence to recommendations; (2) investigate reasons for non-adherence; and (3) ensure good clinical outcome of patients, the ultimate goal being to improve the quality of the guidelines, in particular to tailor them for the needs of the target audience and population. METHODS: Physicians consulting the guidelines on the Internet (www.fevertravel.ch) were invited to participate in the study. Navigation through the decision chart was automatically recorded, including diagnostic tests performed, initial and final diagnoses, and clinical outcomes. The reasons for non-adherence were investigated and qualitative feedback was collected. RESULTS: A total of 539 physician/patient pairs were included in this study. Full adherence to guidelines was observed in 29% of the cases. Figure-specific adherence rate was 54.8%. The main reasons for non-adherence were as follows: no repetition of malaria tests (111/352) and no presumptive antibiotic treatment for febrile diarrhea (64/153) or abdominal pain without leukocytosis (46/101). Overall, 20% of diversions from guidelines were considered reasonable because there was an alternative presumptive diagnosis or the symptoms were mild, which means that the corrected adherence rate per case was 40.6% and corrected adherence per figure was 61.7%. No death was recorded and all complications could be attributed to the underlying illness rather than to adherence to guidelines. CONCLUSIONS: These guidelines proved to be feasible, useful, and leading to good clinical outcomes. Almost one third of physicians strictly adhered to the guidelines. Other physicians used the guidelines not to forget specific diagnoses but finally diverged from the proposed attitudes. These diversions should be scrutinized for further refinement of the guidelines to better fit to physician and patient needs.

Do antibody responses to malaria vaccine candidates influenced by the level of malaria transmission protect from malaria?

OBJECTIVES: To examine whether the humoural response to malaria vaccine candidate antigens, Plasmodium falciparum [circumsporozoite repetitive sequence (NANP)(5) GLURP fragments (R0 and R2) and MSP3] varies with the level of malaria transmission and to determine whether the antibodies (IgG) present at the beginning of the malaria transmission season protect against clinical malaria. METHODS: Cross-sectional surveys were conducted to measure antibody response before, at the peak and at the end of the transmission season in children aged 6 months to 10 years in two villages with different levels of malaria transmission. A cohort study was performed to estimate the incidence of clinical malaria. RESULTS: Antibodies to these antigens showed different seasonal patterns. IgG concentrations to any of the four antigens were higher in the village with high entomological inoculation rate. Multivariate analysis of combined data from the two villages indicated that children who were classified as responders to the selected antigens were at lower risk of clinical malaria than children classified as non-responders [(NANP)(5) (incidence rate ratio (IRR) = 0.65, 95% CI: 0.46-0.92; P = 0.016), R0 (IRR = 0.69, 95% CI: 0.48-0.97; P = 0.032), R2 (IRR = 0.73, 95% CI: 0.50-1.06; P = 0.09), MSP3 (IRR = 0.52, 95% CI: 0.32-0.85; P = 0.009)]. Fitting a model with all four antibody responses showed that MSP3 looked the best malaria vaccine candidate (IRR = 0.63; 95% CI: 0.38-1.05; P = 0.08). CONCLUSION: Antibody levels to the four antigens are affected by the intensity of malaria transmission and associated with protection against clinical malaria. It is worthwhile investing in the development of these antigens as potential malaria vaccine candidates.

Double-bundle transtibial posterior cruciate ligament reconstruction with a tendon-patellar bone-semitendinosus tendon autograft: clinical results with a minimum of 2 years' follow-up.

PURPOSE: The purpose of this study was to evaluate the clinical and subjective outcomes after arthroscopic-assisted double-bundle posterior cruciate ligament (PCL) reconstruction. METHODS: A series of 15 patients with grade III isolated chronic PCL tears underwent double-bundle PCL reconstruction. Of these patients, 8 (53%) had simultaneous fractures. The mean time from accident to surgery was 10.8 months (range, 8 to 15 months). The mean age at the time of surgery was 28.2 years (range, 17 to 43 years). All of the patients reported knee insecurity during activities of daily living or light sporting activities, with associated anterior knee pain in 5 patients. Preoperatively, posterolateral or posteromedial corner injuries were ruled out through accurate clinical examination. The knees were assessed before surgery and at a mean follow-up of 3.2 years (range, 2 to 5 years) with a physical examination, 4 different rating scales, and stress radiographs obtained with a Telos device (Telos, Marburg, Germany). RESULTS: Postoperative physical examination revealed a reduction of the posterior drawer and tibial step-off in all cases, although the posterior laxity was not completely normalized. Nevertheless, the patients were subjectively better after surgery. The subjective International Knee Documentation Committee score was significantly ameliorated. With regard to the objective International Knee Documentation Committee score, 6 knees (40%) were graded as abnormal because of posterior displacement of 6 mm or greater on follow-up stress radiographs with the Telos device. On the Lysholm knee scoring scale, the score was excellent in 13% of patients and good in 87%. The mean score on the Hospital for Special Surgery knee ligament rating scale was 85.8. The Tegner activity score showed an amelioration after surgery, but no patient resumed his or her preinjury level of activities. The postoperative stress radiographs revealed an improvement in posterior instability of 50% or more in all but 3 knees (20%). CONCLUSIONS: Our technique of double-bundle PCL reconstruction produced a significant reduction in knee symptoms and allowed the patients to return to moderate or strenuous activity, although the posterior tibial translation was not completely normalized and our results appear to be no better than the results of single-bundle PCL reconstruction. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Complications of shoulder arthroplasty for osteoarthritis with posterior glenoid wear.

BACKGROUND: Anatomical total shoulder arthroplasty (TSA) for glenohumeral osteoarthritis (OA) and severe posterior glenoid wear may entail early postoperative complications (recurrence of posterior subluxation, glenoid loosening). To avoid these mechanical problems, reverse shoulder arthroplasty (RSA) has recently been proposed, mainly for its intrinsic stability. Our purpose was to present the results of TSA and RSA in glenohumeral OA with posterior glenoid wear of at least 20°. HYPOTHESIS: By virtue of its constrained design, RSA could prevent recurrence of posterior subluxation and limit the occurrence of mechanical complications. MATERIALS AND METHODS: A consecutive series of 23 patients (27 shoulders) were treated for glenohumeral OA with total shoulder prostheses: 19 TSAs and 8 RSAs. Mean age was 70years (range, 47-85years), mean retroversion angle 28° (20°-50°) and mean subluxation index 74% (57-89%). Constant Score, Subjective Shoulder Value (SSV), QuickDASH and Simple Shoulder Test (SST) were measured, and radiological examinations were performed at a mean follow-up of 52months (24-95months). RESULTS: TSA and RSA patients respectively displayed Constant Scores of 65 and 65, SSV of 79% and 74%, QuickDASH of 16 and 27, and SST of 88 and 78. Two patients underwent surgical revision of TSA because of glenoid loosening; 52% of TSA patients presented complete radiolucent lines and 11% recurrence of posterior subluxation. CONCLUSION: Complications are frequently observed after shoulder arthroplasty for OA with severe glenoid retroversion. RSA could be an alternative to TSA for selected patients, independently of rotator cuff status. Studies on RSA in this specific indication with longer follow-up are now needed. LEVEL OF EVIDENCE: Level IV; retrospective case series.

Development of appropriateness criteria for the surgical treatment of symptomatic lumbar degenerative spondylolisthesis (LDS).

PURPOSE: Spine surgery rates are increasing worldwide. Treatment failures are often attributed to poor patient selection and inappropriate treatment, but for many spinal disorders there is little consensus on the precise indications for surgery. With an aging population, more patients with lumbar degenerative spondylolisthesis (LDS) will present for surgery. The aim of this study was to develop criteria for the appropriateness of surgery in symptomatic LDS. METHODS: A systematic review was carried out to summarize the current level of evidence for the treatment of LDS. Clinical scenarios were generated comprising combinations of signs and symptoms in LDS and other relevant variables. Based on the systematic review and their own clinical experience, twelve multidisciplinary international experts rated each scenario on a 9-point scale (1 highly inappropriate, 9 highly appropriate) with respect to performing decompression only, fusion, and instrumented fusion. Surgery for each theoretical scenario was classified as appropriate, inappropriate, or uncertain based on the median ratings and disagreement in the ratings. RESULTS: 744 hypothetical scenarios were generated; overall, surgery (of some type) was rated appropriate in 27 %, uncertain in 41 % and inappropriate in 31 %. Frank panel disagreement was low (7 % scenarios). Face validity was shown by the logical relationship between each variable's subcategories and the appropriateness ratings, e.g., no/mild disability had a mean appropriateness rating of 2.3 ± 1.5, whereas the rating for moderate disability was 5.0 ± 1.6 and for severe disability, 6.6 ± 1.6. Similarly, the average rating for no/minimal neurological abnormality was 2.3 ± 1.5, increasing to 4.3 ± 2.4 for moderate and 5.9 ± 1.7 for severe abnormality. The three variables most likely (p < 0.0001) to be components of scenarios rated "appropriate" were: severe disability, no yellow flags, and severe neurological deficit. CONCLUSION: This is the first study to report criteria for determining candidacy for surgery in LDS developed by a multidisciplinary international panel using a validated method (RAM). The panel ratings followed logical clinical rationale, indicating good face validity. The work refines clinical classification and the phenotype of degenerative spondylolisthesis. The predictive validity of the criteria should be evaluated prospectively to examine whether patients treated "appropriately" have better clinical outcomes.

Genetic team composition and level of selection in the evolution of cooperation

In cooperative multiagent systems, agents interac to solve tasks. Global dynamics of multiagent teams result from local agent interactions, and are complex and difficult to predict. Evolutionary computation has proven a promising approach to the design of such teams. The majority of current studies use teams composed of agents with identical control rules ("geneti- cally homogeneous teams") and select behavior at the team level ("team-level selection"). Here we extend current approaches to include four combinations of genetic team composition and level of selection. We compare the performance of genetically homo- geneous teams evolved with individual-level selection, genetically homogeneous teams evolved with team-level selection, genetically heterogeneous teams evolved with individual-level selection, and genetically heterogeneous teams evolved with team-level selection. We use a simulated foraging task to show that the optimal combination depends on the amount of cooperation required by the task. Accordingly, we distinguish between three types of cooperative tasks and suggest guidelines for the optimal choice of genetic team composition and level of selection