A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.

Melanoma information on the Internet: often incomplete--a public health opportunity?

PURPOSE: To assess the accuracy and completeness of information regarding melanoma on the Internet, retrieved by use of search engines. METHODS: The first 30 uniform/universal resource locators (URLs) from each of eight search engines using the search term "melanoma" were retrieved for evaluation of accuracy and completeness using a 35-point checklist rating system instrument. Four reviewers independently rated each of 35 sites, and one reviewer rated all 74 assessable sites. Kappa statistics were used to evaluate interrater variability. RESULTS: A total of 74 assessable Web sites were evaluated. The remainder were inaccessible, link pages only, or duplicates. Thirty-five Web sites were each independently rated by four reviewers. The remaining 39 Web sites were each rated by one reviewer. The mean kappa statistic for all variables and all rater pairs for which a kappa could be calculated was 0.824, indicating excellent overall inter-rater reliability. The majority of Web sites failed to include complete information on general information, risk factors, diagnosis, treatment, prevention, and prognosis. Ten Web sites (14%) contained a total of 13 inaccuracies, most relatively minor. CONCLUSION: Medical information retrieved with the search term melanoma was likely to lack complete basic melanoma information and contained inaccuracies in 14% of sites. Health care providers can help patients by recommending comprehensive and accurate Web sites for patient review, by working to create accurate and thorough Web-based health information material, and by educating patients and the public about the variability in completeness and accuracy.

Women in surgical residency training programs.

BACKGROUND: Increasing numbers of women are entering surgical fields. The purpose of this study was to assess whether orthopaedic surgery is significantly different from other surgical fields in the recruitment of women to training programs. METHODS: We analyzed data from the American Association of Medical Colleges as reported in annual issues on medical education in the Journal of the American Medical Association for the years 1970 to 2001, excluding 1975. Using linear regression models, we analyzed two factors: changes in the percentage of women within orthopaedic residencies (i.e., the ratio of men to women) and changes in the percentage of all female residents who choose to enter orthopaedics compared with other types of surgical residencies. RESULTS: The percentage of women in the entering classes of medical school has increased from 11.1% in 1970 to 47.8% in 2001, while the percentage of women in orthopaedics has increased from 0.6% in 1970 to 9.0% in 2001. Orthopaedic residencies have the lowest percentage of women compared with all other primary surgical specialties. Only thoracic surgery, a field entered secondarily after the completion of general surgical training, has a lower percentage. The increases in the percentage of women in orthopaedics over the past thirty years have been significantly lower than those in every other primary surgical field (including general surgery, obstetrics and gynecology, ophthalmology, otolaryngology, and urology), except neurosurgery, and are markedly different from the percentages of women in the entering classes of medical school. The percentage of all female residents who choose an orthopaedic residency is 0.6%, a number that has not changed over the past twenty years. CONCLUSIONS: Orthopaedic surgery has not had the same success in recruiting female trainees that other surgical fields have had. Furthermore, there appears to be a leveling of the recruitment rate over the past two decades, indicating that the higher numbers of women entering medicine will not be sufficient to improve gender representation in orthopaedic surgery training.

The thermal effects of intramedullary reaming.

OBJECTIVE: To study the effect of tourniquet control on intramedullary reaming. DESIGN: An experimental prospective nonsurvival animal study was performed using 5 mongrel dogs. A pneumatic tourniquet was randomized to either the right or left hind limb. Tibial intramedullary reaming was performed with progressively larger reamers. Cortical temperatures were measured using thermocouples inserted into the tibial diaphyseal cortex. Thermocouples were connected to an analog to digital converter that output continuous data that was collected on a computer. Upon completion of the procedure, the animals were killed. RESULTS: The peak and low temperatures for each thermocouple with each reamer passage were recorded. Reamer sizes larger than the internal diameter of the intramedullary canal produced higher peak temperatures. The mean delta t (peak temperature minus low temperature) was calculated for each reamer passage. This measurement represents the overall amount of heat generated during each reamer passage. There were no significant differences between the 2 conditions (P = 0.8, paired t test). Temperatures decreased in between reamer exchange but did not return to baseline levels. CONCLUSIONS: Because similar temperatures were measured both with and without a tourniquet, the risk of thermal necrosis appears to be related more to the process of intramedullary reaming than to the tourniquet. Higher temperatures were measured with reamer sizes larger than the internal diameter of the intramedullary canal. Increasing the time interval between the passage of successive reamers may allow heat to dissipate and decrease the risk of thermal necrosis. The clinical practice of limited reaming ("ream-to-fit") should minimize the occurrence of this complication.

Internet use by patients in orthopaedic surgery.

This study evaluated Internet use among orthopaedic patients in a private practice general orthopaedic setting. Of 201 participants, 45% had used the Internet either personally or thru a surrogate to search for information about their orthopaedic condition. Utilization of the Internet was significantly higher than that reported for a community orthopaedic practice surveyed in 1998, suggesting that utilization by orthopaedic patient populations mirrors the increasing societal use for health information. Most users in this study employed multiple search strategies, including using search engines and sites recommended by others. The majority of users found medical information on Internet sites to be useful and accurate. The number one choice for reconciling conflicting information was to ask a physician or a nurse. Most users and non-users reported that they would recommend the Internet to others as a source for medical information. We recommend several strategies for orthopaedic surgeons to stay abreast of these changes and to utilize Internet Patient education resources to their own advantage.

Outcome study of children, adolescents, and adults with sacral agenesis.

Musculoskeletal functional outcome was assessed in children and adults with sacral agenesis and no myelomeningocele. General health, musculoskeletal function, and psychosocial adjustment were assessed in 16 sacral agenesis patients (10 males, 6 females; mean age, 14 +/- 5 years) using previously validated patient and parent self-report questionnaires. Radiographs were reviewed to classify each patient by Renshaw type. Most patients were happy with their looks, and all felt that their general health was good to excellent. Patients reported being limited in function by their low back and distal lower extremities. Half were limited by pain. They reported problems functioning in physically demanding situations, although most were able to participate in low-demand physical activities. No relationship was found between pain and Renshaw type nor between overall satisfaction and Renshaw type.

Ultrasound of the navicular during the simulated Ponseti maneuver.

Nonoperative treatment of the equinovarus foot has had a recent resurgence because of popularization of the Ponseti casting method. This method is based in part on reducing the talonavicular joint by moving the navicular laterally and the head of the talus medially. This study dynamically demonstrates the effect of a simulated Ponseti manipulation on the navicular.

Curve progression in scoliosis associated with Chiari I malformation following suboccipital decompression.

Nine children with scoliosis and Chiari I malformations were followed 1-11 years after suboccipital decompression. Eight also had syringomyelia. Despite initial curve stabilization, at final follow-up eight curves were of the magnitude to require spinal fusion. Neither bracing nor secondary neurosurgical procedures arrested progressive curves.

Bladder cancer facts: accuracy of information on the Internet.

PURPOSE: Patients continually seek information regarding the etiology, diagnosis, management and treatment of bladder cancer. The Internet has a growing number of health web sites and it is a tremendous resource for medical information. We examined the accuracy and completeness of bladder cancer sites on the World Wide Web. MATERIALS AND METHODS: Internet searching was performed by retrieving the first 30 universal resource locators from 8 popular search engines using the search term bladder cancer. A total of 38 independent web sites were evaluated. Other sites were inaccessible, duplicates or only contained linked pages. Two reviewers evaluated the accuracy and completeness of information using a predetermined 41-point checklist rating instrument that evaluated essential information related to bladder cancer. The kappa statistic was used to evaluate interrater variability. RESULTS: The mean kappa statistic for evaluable variables was 0.70. Most nonevaluable variables had excellent agreement, indicating good overall interrater reliability. No rating factor was present on 100% of sites. Eight factors were present and accurate on 80% to 90% of web pages and related to signs/symptoms, risk factors, diagnostic tests and treatment of early stage disease. Six factors were inaccurate on 32% of sites, including incidence (7), staging (3), recurrence (1), and treatment of early invasive (1) and metastatic (1) disease. CONCLUSIONS: Bladder cancer information retrieved from the majority of medical web sites was incomplete. However, general information relating to presentation, diagnosis, staging and treatment of low stage disease was present and accurate on most sites. Although inaccurate information was detected on 32% of the sites, it tended to be related to outdated information. It is reasonable to refer patients to select comprehensive web sites to obtain pertinent information about bladder cancer.

Glenoid inclination is associated with full-thickness rotator cuff tears.

Anatomic factors, such as a hooked acromion, have been associated with rotator cuff disorders. Orientation of the glenoid relative to the scapula has been implicated in shoulder instability, but it has not been linked to rotator cuff disorders. The purpose of the current study was to test the hypothesis that superior inclination of the glenoid is associated with full-thickness rotator cuff tears. Glenoid inclination angles were measured from 16 shoulder radiographs of a convenience sample of eight cadavers in which one shoulder had an intact rotator cuff and the other shoulder had a full-thickness rotator cuff tear. Glenoid inclination angles for shoulders with rotator cuff tears were compared with contralateral normal shoulders using nonparametric statistical analysis. The glenoid inclination angle was greater in cadaver shoulders having full-thickness rotator cuff tears (98.6 degrees ) than in shoulders without tears (91.0 degrees ). A second experiment was done to assess the reliability of using 34 Grashey view radiographs from a clinical population to measure glenoid inclination angle. A method to measure the glenoid inclination on Grashey views was tested and was found to correlate with the inclination angles measured on cadaveric scapulae. Intrarater reliability of measurements from clinical Grashey views was 0.93, and interrater reliability was at least 0.88.