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PURPOSE This study aimed to screen the entire genome for genetic markers associated with risk for Achilles tendon injury. METHODS A genome-wide association analysis was performed using data from the Kaiser Permanente Research Board and the UK Biobank. Achilles tendon injury cases were identified based on electronic health records from the Kaiser Permanente Research Board databank and the UK Biobank from individuals of European ancestry. Genome-wide association analyses from both cohorts were tested for Achilles tendon injury using a logistic regression model adjusting for sex, height, weight, and race/ethnicity using allele counts for single nucleotide polymorphisms (SNP). Previously identified genes within the literature were also tested for association with Achilles tendon injury. RESULTS There were a total of 12,354 cases of Achilles tendon injury and 483,080 controls within the two combined cohorts, with 67 SNP in three chromosomal loci demonstrating a genome-wide significant association with Achilles tendon injury. The first locus contains a single SNP (rs183364169) near the CDCP1 and TMEM158 genes on chromosome 3. The second locus contains 65 SNP in three independently segregating sets near the MPP7 gene on chromosome 10. The last locus contains a single SNP (rs4454832) near the SOX21 and GPR180 genes on chromosome 13. The current data were used to test 14 candidate genes previously reported to show an association with Achilles tendon injury, but none showed a significant association (all P > 0.05). CONCLUSION Three loci were identified as potential risk factors for Achilles tendon injury and deserve further validation and investigation of molecular mechanisms.

PURPOSE This study aimed to screen the entire genome for genetic markers associated with risk for concussion. METHODS A genome-wide association analyses was performed using data from the Kaiser Permanente Research Bank and the UK Biobank. Concussion cases were identified based on electronic health records from the Kaiser Permanente Research Bank and the UK Biobank from individuals of European ancestry. Genome-wide association analyses from both cohorts were tested for concussion using a logistic regression model adjusting for sex, height, weight, and race/ethnicity using allele counts for single nucleotide polymorphisms. Previously identified genes within the literature were also tested for association with concussion. RESULTS There were a total of 4064 cases of concussion and 291,472 controls within the databases, with two single nucleotide polymorphisms demonstrating a genome-wide significant association with concussion. The first polymorphism, rs144663795 (P = 9.7 × 10-11; OR = 2.91 per allele copy), is located within the intron of SPATA5. Strong, deleterious mutations in SPATA5 cause intellectual disability, hearing loss, and vision loss. The second polymorphism, rs117985931 (P = 3.97 × 10-9; OR = 3.59 per allele copy), is located within PLXNA4. PLXNA4 plays a key role is axon outgrowth during neural development, and DNA variants in PLXNA4 are associated with risk for Alzheimer's disease. Previous investigations have identified five candidate genes that may be associated with concussion, but none showed a significant association in the current model (P < 0.05). CONCLUSION Two genetic markers were identified as potential risk factors for concussion and deserve further validation and investigation of molecular mechanisms.

Shoulder dislocations are common shoulder injuries associated with athletic activity in contact sports, such as football, rugby, wrestling, and hockey. Identifying genetic loci associated with shoulder dislocation could shed light on underlying mechanisms for injury and identify predictive genetic markers. To identify DNA polymorphisms associated with shoulder dislocation, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 662 cases of shoulder dislocation and 82 602 controls from the European ancestry group. rs12913965 showed an association with shoulder dislocation at genome-wide significance (p=9.7×10−9; odds ratio=1.6) from the European ancestry group. Individuals carrying one copy of the risk allele (T) at rs12913965 showed a 69% increased risk for shoulder dislocation in our cohort. rs12913965 is located within an intron of the TICRR gene, which encodes TOPBP1 interacting checkpoint and replication regulator involved in the cell cycle. rs12913965 is also associated with changes in expression of the ISG20 gene, which encodes an antiviral nuclease induced by interferons. This genetic marker may one day be used to identify athletes with a higher genetic risk for shoulder dislocation. It will be important to replicate this finding in future studies.

De Quervain’s tenosynovitis is a repetitive strain injury involving synovial inflammation of the tendons of the first extensor compartment of the wrist. It is relatively common in the general population, and is the most common radial-sided tendinopathy seen in athletes. Identifying a genetic marker associated with de Quervain’s tenosynovitis could provide a useful tool to help identify those individuals with an increased risk for injury. A genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health (RPGEH) including 4,129 cases and 98,374 controls. rs35360670 on chromosome 8 showed an association with de Quervain’s tenosynovitis at genome-wide significance (p=1.9×10−8; OR=1.46; 95% CI=1.38–1.59). This study is the first genome-wide screen for de Quervain's tenosynovitis and provides insights regarding its genetic etiology as well as a DNA marker with the potential to inform athletes and other high-risk individuals about their relative risk for injury.

Medial collateral ligament (MCL) injuries are a common knee injury, especially in competitive athletes. Identifying genetic loci associated with MCL injury could shed light on its etiology. A genome-wide association screen was performed using data from the Research Program in Genes, Environment and Health (RPGEH) including 1 572 cases of MCL injury and 100 931 controls. 2 SNPs (rs80351309 and rs6083471) showed an association with MCL injury at genome-wide significance (p

Background: Faster treatment with tPA in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California (KPNC) redesigned its acute stroke workflow across all 21 KPNC stroke centers to have all stroke alerts actively managed by a core group of vascular neurologists via telemedicine. We examined the effect of KPNC’s Stroke EXPRESS (EXpediting the PRrocess of Evaluating and Stopping Stroke) program on door-to-needle (DTN) time and symptomatic intracranial hemorrhage (sICH) rates. Methods: The Stroke EXPRESS program was rolled out across KPNC in a staggered fashion from 9/2015 to 1/2016 with the goals of expediting the evaluation and determination for tPA and speeding up the assessment for large vessel occlusion to allow for timely transfer for thrombectomy. We compared DTN times for 6 months before implementation to the same 6-month calendar period after implementation. Results: After implementation, tPA administrations increased from 38/month at baseline to 80/month (P Conclusions: Implementation of the Stroke EXPRESS regional telemedicine program in KPNC was associated with an increase in tPA administrations, markedly shorter DTN times, and no change in the rate of sICH.

37 Background: In 2012, the USPSTF gave a “D” grade to PSA-based prostate cancer screening stating “the benefits of PSA-based screening for prostate cancer do not outweigh the harms”. The impact on prostate cancer screening, detection and presentation are unknown. Methods: A retrospective cohort design encompassing the years 2010 to 2015. In screen-eligible, KPNC members (African American men ages 45-69 and all other men ages 50-69), the annual rates of PSA testing, prostate biopsy and the grade and stage of all prostate cancers at presentation were compared between the pre-guideline period, 2010/2011; and the post-guideline period , 2014/2015. Results: The rate of screening declined substantially from the pre-guideline period to the post-guideline period, from a rate of 42.7% of eligible men screened per year during 2010/2011 to a rate of 32.5% of eligible men screened per year during 2014/2015; the relative rate and 95% confidence interval (CI) was 0.762 (0.759-0.765). Comparing the same time periods, the rates of prostate biopsy and overall prostate cancer detection declined even more sharply, with relative rates of 0.391 (95%CI 0.375-0.407) and 0.455 (95%CI 0.436-0.475) respectively. There was a modest increase in the rate of metastatic disease between these two time periods, with a relative rate of 1.29 (95%CI 1.11-1.48). Conclusions: Following the 2012 USPSTF statement, significant declines in PSA testing, prostate biopsy and overall cancer detection rates were seen along with a significant increase in the rate of patients presenting with metastatic disease. [Table: see text]

Im Unterschied zu jungeren wird bei alteren Patienten mit Ruckenschmerzen oft schon beim ersten Arztbesuch eine bildgebende Diagnostik empfohlen, da bei diesen die Wahrscheinlichkeit fur einen ernsten Hintergrund der Beschwerden hoher ist. Aber ergibt sich wirklich ein statistischer Vorteil durch eine fruhe Bildgebung?

Background/Aims Migraine, a common neurological disorder, is among the top 20 causes of disability worldwide. One-year prevalence of migraine in the US is estimated to range from 8–15%, with women affected at approximately three times the rate of men. Current methods for migraine ascertainment from headache clinics and surveys are costly, affected by clinic-ascertainment bias, and do not work in situations where patient contact is not feasible. With the growing use of electronic medical records (EMR), new methods must be developed for identifying and tracking migraine prevalence over time. We sought to develop an EMR algorithm, to identify migraine, and to characterize its prevalence in Kaiser Permanente Northern California (KPNC).