Mary V. Baker

We describe two extended haplotypes that cover the human tau gene. In a total of approximately 200 unrelated caucasian individuals there is complete disequilibrium between polymorphisms which span the gene (which covers approximately 100 kb of DNA). This suggests that the establishment of the two haplotypes was an ancient event and either that recombination is suppressed in this region, or that recombinant genes are selected against. Furthermore, we show that the more common haplotype (H1) is significantly over-represented in patients with progressive supranuclear palsy (PSP), extending earlier reports of an association between an intronic dinucleotide polymorphism and PSP.

OBJECTIVE: To analyze the association of polymorphisms in the tau gene with pathologically confirmed corticobasal degeneration (CBD). BACKGROUND: The authors previously described an extended tau haplotype (H1) that covers the human tau gene and is associated with the development of progressive supranuclear palsy (PSP). The authors now extend this analysis to CBD, a neurodegenerative condition with clinical and neuropathologic similarities to PSP. Like PSP, CBD is associated with accumulation of aggregates containing the 4-repeat isoforms of tau. Because of difficulty in diagnosis of CBD, the authors only analyzed cases with pathologically confirmed CBD. METHODS: The authors collected 57 unrelated, neuropathologically confirmed cases of CBD. Tau sequencing in these cases failed to show the presence of pathogenic mutations. Polymorphisms that spanned the tau gene were analyzed in all CBD cases and controls. RESULTS: Analyzing tau polymorphisms in CBD cases showed that the frequency of H1 and H1/H1 was significantly increased when analyzing all cases and when separating by country of origin. H1 frequency in all CBD cases was 0.921, compared with a control frequency of 0.766 (X(2) = 9.1, p = 0.00255 [1df], OR 3.56 [8.43 > CI 95% > 1.53]). The H1/H1 frequency was also significantly higher at 0.842 compared with 0.596 in age-matched controls (X(2) = 17.42, p = 0.00016, 2df), OR 3.61 [7.05 > CI 95% > 1.85]). CONCLUSIONS: The CBD tau association described here suggests that PSP and CBD share a similar cause, although the pathogenic mechanism behind the two diseases leads to a different clinical and pathologic phenotype.

OBJECTIVE: To evaluate the rate of vaginal hysterectomy and outcomes after initiation of a prospective decision-tree algorithm to determine the optimal surgical route of hysterectomy. METHODS: A prospective algorithm to determine optimal route of hysterectomy was developed, which uses the following factors: history of laparotomy, uterine size, and vaginal access. The algorithm was implemented at our institution from November 24, 2015, to December 31, 2017, for patients requiring hysterectomy for benign indications. Expected route of hysterectomy was assigned by the algorithm and was compared with the actual route performed to identify compliance compared with deviation. Surgical outcomes were analyzed. RESULTS: Of 365 patients who met inclusion criteria, 202 (55.3%) were expected to have a total vaginal hysterectomy, 57 (15.6%) were expected to have an examination under anesthesia followed by total vaginal hysterectomy, 52 (14.2%) were expected to have an examination under anesthesia followed by robotic-assisted total laparoscopic hysterectomy, and 54 (14.8%) were expected to have an abdominal or robotic-laparoscopic route of hysterectomy. Forty-six procedures (12.6%) deviated from the algorithm to a more invasive route (44 robotic, two abdominal). Seven patients had total vaginal hysterectomy when robotic-assisted total laparoscopic hysterectomy or abdominal hysterectomy was expected by the algorithm. Overall, 71% of patients were expected to have a vaginal route of hysterectomy per the algorithm, of whom 81.5% had a total vaginal hysterectomy performed; more than 99% of the total vaginal hysterectomies attempted were successfully completed. CONCLUSION: Vaginal surgery is feasible, carries a low complication rate with excellent outcomes, and should have a place in gynecologic surgery. National use of this prospective algorithm may increase the rate of total vaginal hysterectomy and decrease health care costs.

INTRODUCTION: We calculate the financial margins for delivery of routine antenatal care as reimbursed by Medicaid. Prenatal care cost varies with overhead, health care provider type, and number of office visits. Antenatal care is only one component of the global maternity bundle, which also includes intrapartum and postpartum care. METHODS: Time for provision of low-risk antenatal care was determined prospectively from a study of 133 low-risk pregnant patients. Health care provider time cost was estimated using mean wages for obstetricians and midwives. Margins were estimated by subtracting cost of provider services and overhead for the antenatal component of maternity care from total Medicaid reimbursement for the pregnancy global package (CPT 59400) using 2015 dollars. The maternity bundle elements of routine prenatal laboratory tests, ultrasounds, intrapartum care, and postpartum care were not included in our analysis of cost components. RESULTS: Patients received an average of 215 minutes of direct provider time per pregnancy. At the 50th percentile for physician payment and assuming overhead is 53.4% of revenue, practice margins varied by state from -$1067 to +$675, with a median of -$357. Median margins for midwifery care were +$15, with a range of -$579 to +$885. Margins were negative if overhead costs exceeded 33% of revenue for physician care and 55% of revenue for midwifery care. DISCUSSION: In many states, Medicaid reimbursement for the global maternity package is less than the actual cost of antenatal care alone. Improving reimbursement or decreasing costs is necessary to make maternity care more cost-effective.