Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial.

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin.

Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction.

BACKGROUND AND OBJECTIVES: Tranexamic acid (TXA) has been shown to decrease perioperative blood loss, transfusions, and cost in patients undergoing resection of aggressive bone tumors and endoprosthetic reconstruction. This study explored the effect of TXA administration on postoperative mobilization in these patients. METHODS: This study included 126 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction; 61 patients in the TXA cohort and 65 patients in the non-TXA cohort. Postoperative physical therapy (PT) and occupational therapy notes were reviewed; patient ambulation distance and duration of therapies were recorded. RESULTS: Patients in the TXA cohort ambulated further on all postoperative days, which was significant on postoperative Day 1 (POD1) (p = 0.002) and postoperative Day 2 (POD2) (p < 0.001). The TXA cohort ambulated 85% further per PT session 87.7 versus 47.4 ft (p < 0.001) and participated 14% longer, 36.1 versus 31.7 min (p < 0.001). Multivariate analysis identified a significant inverse association between postoperative hospitalization length and POD1, POD2, postoperative Day 3, and total ambulation (p < 0.001). Blood transfusion was independently associated with a 1.5 day increase in postoperative hospitalization (95% confidence interval: 0.64-2.5; p < 0.001). CONCLUSIONS: TXA administration was associated with increased postoperative ambulation and endurance. Increased postoperative ambulation was associated with decreased length of stay and increased likelihood to discharge home.

Avoidance of injury to the posterior neurovascular bundle during total ankle arthroplasty - A simple technical tip.

Iatrogenic nerve injury to the tibial nerve is a serious but avoidable complication of total ankle replacements and may be under-reported as it may go unrecognised or thought to be due to tarsal tunnel syndrome. The tibial nerve is particularly vulnerable during the saw cuts at the posteromedial corner without appropriate protection. Prior to drilling the tibial and talar pins of the adjustment block for the Infinity ankle replacement we perform a 2 cm incision behind the medial malleolus. The tibialis posterior tendon sheath is identified and incised. A periosteal elevator is used to develop a plane between the back of the tibia and the tibialis posterior tendon and then exchanged for a mini Hohmann retractor protecting the neurovascular bundle. This allows us to drill the pins and saw cuts safely. The Hohmann retractor can be felt at the tip of the saw blade providing reassurance that the blade is not too deep. Our technique has not previously been reported in the literature. It acts as a simple reproducible way of avoiding injury to structures at the back of the ankle joint.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial.

BACKGROUND: The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. METHODS: We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. FINDINGS: Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). INTERPRETATION: These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. FUNDING: Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.

Timing of procedural stroke and death in asymptomatic patients undergoing carotid endarterectomy: individual patient analysis from four RCTs.

BACKGROUND: The effectiveness of carotid endarterectomy (CEA) for stroke prevention depends on low procedural risks. The aim of this study was to assess the frequency and timing of procedural complications after CEA, which may clarify underlying mechanisms and help inform safe discharge policies. METHODS: Individual-patient data were obtained from four large carotid intervention trials (VACS, ACAS, ACST-1 and GALA; 1983-2007). Patients undergoing CEA for asymptomatic carotid artery stenosis directly after randomization were used for the present analysis. Timing of procedural death and stroke was divided into intraoperative day 0, postoperative day 0, days 1-3 and days 4-30. RESULTS: Some 3694 patients were included in the analysis. A total of 103 patients (2·8 per cent) had serious procedural complications (18 fatal strokes, 68 non-fatal strokes, 11 fatal myocardial infarctions and 6 deaths from other causes) [Correction added on 20 April, after first online publication: the percentage value has been corrected to 2·8]. Of the 86 strokes, 67 (78 per cent) were ipsilateral, 17 (20 per cent) were contralateral and two (2 per cent) were vertebrobasilar. Forty-five strokes (52 per cent) were ischaemic, nine (10 per cent) haemorrhagic, and stroke subtype was not determined in 32 patients (37 per cent). Half of the strokes happened on the day of CEA. Of all serious complications recorded, 44 (42·7 per cent) occurred on day 0 (20 intraoperative, 17 postoperative, 7 with unclear timing), 23 (22·3 per cent) on days 1-3 and 36 (35·0 per cent) on days 4-30. CONCLUSION: At least half of the procedural strokes in this study were ischaemic and ipsilateral to the treated artery. Half of all procedural complications occurred on the day of surgery, but one-third after day 3 when many patients had been discharged.

ANTECEDENTES: La efectividad de la endarterectomía carotídea (carotid endarterectomy, CEA) en la prevención de un accidente cerebrovascular depende de que este procedimiento tenga pocos riesgos. El objetivo de este estudio fue evaluar la frecuencia y el momento de aparición de las complicaciones tras una CEA, lo que podría clarificar los mecanismos subyacentes y ayudar a establecer una política de altas hospitalarias segura. MÉTODOS: Se utilizaron los datos de los pacientes incluidos en cuatro grandes ensayos de intervención carotídea (VACS, ACAS, ACST-1 y GALA; 1983-2007). Para el presente análisis se utilizaron los datos de pacientes sometidos a CEA por estenosis de la arteria carótida asintomática recogidos inmediatamente tras la aleatorización. Se consideraron diferentes intervalos entre el procedimiento, la muerte o el accidente cerebrovascular: intraoperatorio día 0, postoperatorio día 0, postoperatorio días 1-3 y postoperatorio días 4-30. RESULTADOS: En el análisis se incluyeron 3.694 pacientes. Se detectaron complicaciones graves relacionadas con el procedimiento en 103 (2,8%) pacientes (18 accidentes cerebrovasculares fatales, 68 accidentes cerebrovasculares no fatales, 11 infartos de miocardio fatales y 6 muertes por otras causas). De los 86 accidentes cerebrovasculares, 67 (78%) fueron ipsilaterales, 17 (20%) contralaterales y dos (2%) vertebrobasilares. Los accidentes cerebrovasculares fueron isquémicos en 45 (52%) casos, hemorrágicos en 9 (10%) y no se pudo determinar el subtipo de ictus en 32 (37%). La mitad de los accidentes cerebrovasculares ocurrieron el día de la CEA. De todas las complicaciones graves registradas, 44 (43%) ocurrieron en el día 0 (20 intraoperatorias, 17 postoperatorias y 7 en períodos poco definidos), 23 (22%) entre los días 1-3 y 36 (35%) entre los días 4-30. CONCLUSIÓN: En este estudio, al menos la mitad de los accidentes cerebrovasculares relacionados con la CEA fueron isquémicos e ipsilaterales respecto a la arteria tratada. La mitad de todas las complicaciones de la CEA ocurrieron el día de la cirugía, pero un tercio de los casos se presentaron después del día 3, cuando muchos pacientes ya habían sido dados de alta.

Changes in Nuclear Shape and Gene Expression in Response to Simulated Microgravity Are LINC Complex-Dependent.

Microgravity is known to affect the organization of the cytoskeleton, cell and nuclear morphology and to elicit differential expression of genes associated with the cytoskeleton, focal adhesions and the extracellular matrix. Although the nucleus is mechanically connected to the cytoskeleton through the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, the role of this group of proteins in these responses to microgravity has yet to be defined. In our study, we used a simulated microgravity device, a 3-D clinostat (Gravite), to investigate whether the LINC complex mediates cellular responses to the simulated microgravity environment. We show that nuclear shape and differential gene expression are both responsive to simulated microgravity in a LINC-dependent manner and that this response changes with the duration of exposure to simulated microgravity. These LINC-dependent genes likely represent elements normally regulated by the mechanical forces imposed by gravity on Earth.

Cultural revitalization as a restorative process to combat racial and cultural trauma and promote living well.

OBJECTIVES: This article explores the impact of a decade of cultural education and revitalization with the Miami Tribe of Oklahoma, as they strive to recover from years of historical trauma and cultural oppression. The recovery or resilience is measured through behaviors (defined as living well") seen in tribal youth and community engagement. This study has 4 research questions focused on academic attainment, physical and mental health, community engagement, and national/tribal growth. METHOD: A series of studies using both qualitative (ethnographic-observation and interview) and quantitative measures (survey) examined language use, educational attainment, and tribal event engagement. The samples consisted of 32 Myaamia college students (59% female, 41% male) who matriculated at Miami University between 2013 and 2017 and about 800 community members in attendance at various community events from 2012 to 2017 upon which observational data were collected. RESULTS: Ethnographic content analysis of interviews and descriptive and regression analyses suggest an increase in graduation rates among the college sample who took culture courses, a stronger sense of belonging, an increase in language use and tribal event attendance among tribal members, and increases in scores on Snowshoe's (2015) Cultural Connectedness Scale for the college sample taking culture courses signaling shifts in identity. CONCLUSIONS: This study suggests that reclaiming one's culture and language has an impact on restoring wellness among this tribal nation. Cultural rejuvenation of the Myaamiaki may represent a shift in the way healthy living can be conceptualized within tribal communities. The authors stress the importance of using community knowledge in conjunction with global knowledge to develop community-specific and community-implemented interventions for health promotion. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

PTEN loss and activation of K-RAS and ß-catenin cooperate to accelerate prostate tumourigenesis.

Aberrant phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) and WNT signalling are emerging as key events in the multistep nature of prostate tumourigenesis and progression. Here, we report a compound prostate cancer murine model in which these signalling pathways cooperate to produce a more aggressive prostate cancer phenotype. Using Cre-LoxP technology and the probasin promoter, we combined the loss of Pten (Ptenfl/fl ), to activate the PI3K signalling pathway, with either dominant stabilized ß-catenin [Catnb+/lox(ex3) ] or activated K-RAS (K-Ras+/V12 ) to aberrantly activate WNT and MAPK signalling, respectively. Synchronous activation of all three pathways (triple mutants) significantly reduced survival (median 96 days) as compared with double mutants [median: 140 days for Catnb+/lox(ex3) Ptenfl/fl ; 182 days for Catnb+/lox(ex3) K-Ras+/V12 ; 238 days for Ptenfl/fl K-Ras+/V12 ], and single mutants [median: 383 days for Catnb+/lox(ex3) ; 407 days for Ptenfl/fl ], reflecting the accelerated tumourigenesis. Tumours followed a stepwise progression from mouse prostate intraepithelial neoplasia to invasive adenocarcinoma, similar to that seen in human disease. There was significantly elevated cellular proliferation, tumour growth and percentage of invasive adenocarcinoma in triple mutants as compared with double mutants and single mutants. Triple mutants showed not only activated AKT, extracellular-signal regulated kinase 1/2, and nuclear ß-catenin, but also significantly elevated signalling through mechanistic target of rapamycin complex 1 (mTORC1). In summary, we show that combined deregulation of the PI3K, MAPK and WNT signalling pathways drives rapid progression of prostate tumourigenesis, and that deregulation of all three pathways results in tumours showing aberrant mTORC1 signalling. As mTORC1 signalling is emerging as a key driver of androgen deprivation therapy resistance, our findings are important for understanding the biology of therapy-resistant prostate cancer and identifying potential approaches to overcome this. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

An Improved Variant of Soybean Type 1 Diacylglycerol Acyltransferase Increases the Oil Content and Decreases the Soluble Carbohydrate Content of Soybeans.

Kinetically improved diacylglycerol acyltransferase (DGAT) variants were created to favorably alter carbon partitioning in soybean (Glycine max) seeds. Initially, variants of a type 1 DGAT from a high-oil, high-oleic acid plant seed, Corylus americana, were screened for high oil content in Saccharomyces cerevisiae Nearly all DGAT variants examined from high-oil strains had increased affinity for oleoyl-CoA, with S0.5 values decreased as much as 4.7-fold compared with the wild-type value of 0.94 µm Improved soybean DGAT variants were then designed to include amino acid substitutions observed in promising C. americana DGAT variants. The expression of soybean and C. americana DGAT variants in soybean somatic embryos resulted in oil contents as high as 10% and 12%, respectively, compared with only 5% and 7.6% oil achieved by overexpressing the corresponding wild-type DGATs. The affinity for oleoyl-CoA correlated strongly with oil content. The soybean DGAT variant that gave the greatest oil increase contained 14 amino acid substitutions out of a total of 504 (97% sequence identity with native). Seed-preferred expression of this soybean DGAT1 variant increased oil content of soybean seeds by an average of 3% (16% relative increase) in highly replicated, single-location field trials. The DGAT transgenes significantly reduced the soluble carbohydrate content of mature seeds and increased the seed protein content of some events. This study demonstrated that engineering of the native DGAT enzyme is an effective strategy to improve the oil content and value of soybeans.

Quality-of-life outcomes from the Prostate Adenocarcinoma: TransCutaneous Hormones (PATCH) trial evaluating luteinising hormone-releasing hormone agonists versus transdermal oestradiol for androgen suppression in advanced prostate cancer.

OBJECTIVES: To compare quality-of-life (QoL) outcomes at 6 months between men with advanced prostate cancer receiving either transdermal oestradiol (tE2) or luteinising hormone-releasing hormone agonists (LHRHa) for androgen-deprivation therapy (ADT). PATIENTS AND METHODS: Men with locally advanced or metastatic prostate cancer participating in an ongoing randomised, multicentre UK trial comparing tE2 versus LHRHa for ADT were enrolled into a QoL sub-study. tE2 was delivered via three or four transcutaneous patches containing oestradiol 100 µg/24 h. LHRHa was administered as per local practice. Patients completed questionnaires based on the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core (EORTC QLQ-C30) with prostate-specific module QLQ PR25. The primary outcome measure was global QoL score at 6 months, compared between randomised arms. RESULTS: In all, 727 men were enrolled between August 2007 and October 2015 (412 tE2, 315 LHRHa) with QoL questionnaires completed at both baseline and 6 months. Baseline clinical characteristics were similar between arms: median (interquartile range) age of 74 (68-79) years and PSA level of 44 (19-119) ng/mL, and 40% (294/727) had metastatic disease. At 6 months, patients on tE2 reported higher global QoL than those on LHRHa (mean difference +4.2, 95% confidence interval 1.2-7.1; P = 0.006), less fatigue, and improved physical function. Men in the tE2 arm were less likely to experience hot flushes (8% vs 46%), and report a lack of sexual interest (59% vs 74%) and sexual activity, but had higher rates of significant gynaecomastia (37% vs 5%). The higher incidence of hot flushes among LHRHa patients appear to account for both the reduced global QoL and increased fatigue in the LHRHa arm compared to the tE2 arm. CONCLUSION: Patients receiving tE2 for ADT had better 6-month self-reported QoL outcomes compared to those on LHRHa, but increased likelihood of gynaecomastia. The ongoing trial will evaluate clinical efficacy and longer term QoL. These findings are also potentially relevant for short-term neoadjuvant ADT.

A uniquely Canadian military moment: Sam Hughes and the No. 7 General Hospital, 1915-1916.

SUMMARY: Universities across Canada actively supported the call to arms in 1914, and Queen's University in Kingston, Ontario, was no different. Though a myriad of units composed of Queen's faculty and students were created, the university perceived the military hospital raised by the school's medical faculty to be among its most vital contributions to the First World War. This commentary describes the engagement of the No. 7 General Hospital with the Minister of Militia, Sam Hughes, which has become an almost unknown footnote to its illustrious story. This commentary has an Appendix, available at canjsurg.ca.

Laparoendoscopic single-site donor nephrectomy (LESS-DN) versus standard laparoscopic donor nephrectomy.

BACKGROUND: Advances in minimally invasive surgery for live kidney donors have led to the development of laparoendoscopic single site donor nephrectomy (LESS-DN). At present, laparoscopic donor nephrectomy is the technique of choice for donor nephrectomy globally. Compared with open surgical approaches, laparoscopic donor nephrectomy is associated with decreased morbidity, faster recovery times and return to normal activity, and shorter hospital stays. LESS-DN differs from standard laparoscopic donor nephrectomy; LESS-DN requires a single incision through which the procedure is performed and donor kidney is removed. Previous studies have hypothesised that LESS-DN may provide additional benefits for kidney donors and stimulate increased donor rates. OBJECTIVES: This review looked at the benefits and harms of LESS-DN compared with standard laparoscopic nephrectomy for live kidney donors. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 28 January 2016 through contact with the Information Specialist using search terms relevant to this review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared LESS-DN with laparoscopic donor nephrectomy in adults. DATA COLLECTION AND ANALYSIS: Three authors independently assessed studies for eligibility and conducted risk of bias evaluation. Summary estimates of effect were obtained using a random-effects model and results were expressed as risk ratios (RR) or risk difference (RD) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. MAIN RESULTS: We included three studies (179 participants) comparing LESS-DN with laparoscopic donor nephrectomy. There were no significant differences between LESS-DN and laparoscopic donor nephrectomy for mean operative time (2 studies, 79 participants: MD 6.36 min, 95% CI -11.85 to 24.57), intra-operative blood loss (2 studies, 79 participants: MD -8.31 mL, 95% CI -23.70 to 7.09), or complication rates (3 studies, 179 participants: RD 0.05, 95% CI -0.04 to 0.14). Pain scores at discharge were significantly less in the LESS-DN group (2 studies, 79 participants: MD -1.19, 95% CI -2.17 to -0.21). For all other outcomes (length of hospital stay; length of time to return to normal activities; blood transfusions; conversion to another form of surgery; warm ischaemia time; total analgesic requirement; graft loss) there were no significant differences observed.Although risk of bias was assessed as low overall, one study was assessed at high risk of attrition bias. AUTHORS' CONCLUSIONS: Given the small number and size of included studies it is uncertain whether LESS-DN is better than laparoscopic donor nephrectomy. Well designed and adequately powered RCTs are needed to better define the role of LESS-DN as a minimally invasive option for kidney donor surgery.

Assessing the economic burden of Alzheimer's disease patients first diagnosed by specialists.

BACKGROUND: It is not known if there is a differential impact on Alzheimer's disease (AD) diagnosis and outcomes if/when patients are diagnosed with cognitive decline by specialists versus non-specialists. This study examined the cost trajectories of Medicare beneficiaries initially diagnosed by specialists compared to similar patients who received their diagnosis in primary care settings. METHODS: Patients with ≥2 claims for AD were selected from de-identified administrative claims data for US Medicare beneficiaries (5 % random sample). The earliest observed diagnosis of cognitive decline served as the index date. Patients were required to have continuous Medicare coverage for ≥12 months pre-index (baseline) and ≥12 months following the first AD diagnosis, allowing for up to 3 years from index to AD diagnosis. Time from index date to AD diagnosis was compared between those diagnosed by specialists (i.e., neurologist, psychiatrist, or geriatrician) versus non-specialists using Kaplan-Meier analyses with log-rank tests. Patient demographics, Charlson Comorbidity Index (CCI) during baseline, and annual all-cause medical costs (reimbursed by Medicare) in baseline and follow-up periods were compared across propensity-score matched cohorts. RESULTS: Patients first diagnosed with cognitive decline by specialists (n = 2593) were younger (78.8 versus 80.8 years old), more likely to be male (40 % versus 34 %), and had higher CCI scores and higher medical costs at baseline than those diagnosed by non-specialists (n = 13,961). However, patients diagnosed by specialists had a significantly shorter time to AD diagnosis, both before and after matching (mean [after matching]: 3.5 versus 4.6 months, p < 0.0001). In addition, patients diagnosed by specialists had significantly lower average total all-cause medical costs in the first 12 months after their index date, a finding that persisted after matching ($19,824 versus $25,863, p < 0.0001). Total per-patient annual medical costs were similar for the two groups starting in the second year post-index. CONCLUSIONS: Before and after matching, patients diagnosed by a specialist had a shorter time to AD diagnosis and incurred lower costs in the year following the initial cognitive decline diagnosis. Differences in costs converged during subsequent years. This suggests that seeking care from specialists may yield more timely diagnosis, appropriate care and reduced costs among those with cognitive decline.

Robotic-Assisted Gynecologic Surgery and Perioperative Morbidity in Elderly Women.

STUDY OBJECTIVE: To assess perioperative complications, conversions, and operative times in patients age ≥75 years undergoing robotic-assisted gynecologic surgery. DESIGN: Retrospective cohort study (Canadian Task Force classification II-2). SETTING: High-volume, 2-physician gynecologic oncology practice. PATIENTS: A total of 705 women who underwent any robot-assisted gynecologic procedure for benign (n = 380) or malignant (n = 325) conditions between July 2008 and May 2014. Fifty patients age ≥75 years (elderly group) were compared with 655 patients age <75 years (younger group). INTERVENTIONS: Operative data were gathered prospectively for all robotic-assisted procedures. Demographic and perioperative outcomes were analyzed retrospectively for this study. MEASUREMENTS AND MAIN RESULTS: The mean age was 81.3 ± 4.2 years (range, 75.0-90.5 years) in the elderly group and 52.8 ± 11.5 years (range, 22.9-74.6 years) in the younger group. The elderly group had higher rates of surgery for malignancy (90.0% vs 43.2%; p < .01) and lymphadenectomy (44.0% vs 23.4%; p < .01), and was more likely to have cardiovascular disease (88.0% vs 37.6%; p < .01). There were no between-group differences in body mass index or history of chronic obstructive pulmonary disease, diabetes mellitus, or more than 1 previous abdominal surgical procedure. The elderly group was more likely to have a length of stay greater than postoperative day one (30.0% vs 14.8%; p = .01) and had a higher incidence of postoperative cardiac arrhythmia (8.0% vs 1.2%; p < .01). The elderly group also had a smaller median uterine size (83.0 ± 49.1 g vs 126.0 ± 189.5 g; p < .01), but total operative time, rate of conversion (6.0% vs 1.8%) and rate of blood transfusion (2.0% vs 1.5%) were not significantly different between the 2 groups. Rates of bowel and genitourinary injury were <1% in both groups, and there was no between-group difference in postoperative infectious morbidity, vaginal cuff complications, or reoperation. CONCLUSION: The perioperative complication rates of robotic-assisted surgery are comparable in elderly women and younger women, despite a longer hospital length of stay and greater likelihood of postoperative arrhythmia in elderly women.

Impact of a Telehealth and Care Management Program on All-Cause Mortality and Healthcare Utilization in Patients with Heart Failure.

BACKGROUND: Telehealth has the potential to improve chronic disease management and outcomes, but data regarding direct benefit of telehealth in patients with heart failure (HF) have been mixed. The objective of this study was to determine whether the Health Buddy Program (HBP) (Bosch Healthcare, Palo Alto, CA), a content-driven telehealth system coupled with care management, is associated with improved outcomes in Medicare beneficiaries with HF. MATERIALS AND METHODS: This was a retrospective cohort study of 623 Medicare beneficiaries with HF offered HBP enrollment compared with a propensity score-matched control group of Medicare beneficiaries with HF from the Medicare 5% sample. Associations between availability of the HBP and all-cause mortality, hospitalization, hospital days, and emergency department visits were evaluated. RESULTS: Beneficiaries offered enrollment in the HBP had 24.9% lower risk-adjusted all-cause mortality over 3 years of follow-up (hazard ratio [HR] = 0.75; 95% confidence interval [CI], 0.63-0.89; p = 0.001). Patients who used the HBP at least once (36.9%) had 57.2% lower mortality compared with matched controls (HR = 0.43; 95% CI, 0.31-0.60; p < 0.001), whereas patients who did not use the HBP had no significant difference in survival (HR = 0.96; 95% CI, 0.78-1.19; p = 0.69). Patients offered the HBP also had fewer hospital admissions following enrollment (Δ = -0.05 admissions/quarter; p = 0.011), which was primarily observed in patients who used the HBP at least once (Δ = -0.10 admissions/quarter; p < 0.001). CONCLUSIONS: The HBP, a content-driven telehealth system coupled with care management, was associated with significantly better survival and reduced hospitalization in Medicare beneficiaries with HF. Prospective study is warranted to determine the mechanism of this association and opportunities for optimization.

Misuse of "Power" and Other Mechanical Terms in Sport and Exercise Science Research.

Despite the Système International d'Unitès (SI) that was published in 1960, there continues to be widespread misuse of the terms and nomenclature of mechanics in descriptions of exercise performance. Misuse applies principally to failure to distinguish between mass and weight, velocity and speed, and especially the terms "work" and "power." These terms are incorrectly applied across the spectrum from high-intensity short-duration to long-duration endurance exercise. This review identifies these misapplications and proposes solutions. Solutions include adoption of the term "intensity" in descriptions and categorizations of challenge imposed on an individual as they perform exercise, followed by correct use of SI terms and units appropriate to the specific kind of exercise performed. Such adoption must occur by authors and reviewers of sport and exercise research reports to satisfy the principles and practices of science and for the field to advance.

The Burden of Undiagnosed Opioid Abuse Among Commercially Insured Individuals.

OBJECTIVES: Estimate the prevalence and healthcare costs of undiagnosed opioid abuse among commercially insured individuals. STUDY DESIGN: Retrospective analysis of de-identified pharmacy and medical claims data and publicly-available survey data (no IRB approval required). METHODS: This study focused on commercially insured individuals. Rates of prescription pain-reliever abuse/dependence ("abuse") among individuals ages ≥12 were calculated using National Survey on Drug Use and Health (NSDUH) public-use data for 2006-2011 and assumed to capture both diagnosed and undiagnosed opioid abuse. Rates of undiagnosed opioid abuse were calculated as the difference between NSDUH rates and published rates of diagnosed opioid abuse. OptumHealth Reporting and Insights claims data were used to estimate the healthcare costs of undiagnosed abuse. Diagnosed abusers ages 12-64 were identified using ICD-9-CM diagnosis codes for opioid abuse/dependence. Pre-diagnosis costs were assumed to be a proxy for undiagnosed opioid abuse costs. The ratio of undiagnosed to diagnosed abuse costs was calculated as the ratio of annual per-patient healthcare costs between pre-diagnosis and post-diagnosis periods. RESULTS: While rates of diagnosed opioid abuse among commercially insured individuals increased from 0.07% in 2006 to 0.19% in 2011, rates of undiagnosed abuse decreased from 0.42% to 0.38% over the same time period. Annual per-patient healthcare costs of undiagnosed abusers were 69.2% of those of diagnosed abusers. CONCLUSIONS: Per-patient healthcare costs of undiagnosed abusers among the commercially insured are estimated to be lower than those of diagnosed abusers. However, the higher prevalence of undiagnosed opioid abuse implies that undiagnosed abuse represents a substantial burden to commercial payers.

Healthcare professional requirements for the care of adult diabetes patients managed with insulin pumps in Australia.

BACKGROUND: Healthcare professional (HCP) time supporting insulin pump therapy (IPT) has not been documented, yet it is important in planning and allocating resources for effective care. AIM: This study aims to determine HCP time spent in IPT patient care to inform resource planning for optimal IPT delivery. METHODS: Twenty-four Australian adult IPT-experienced institutions (14 government funded, seven private, three both) collected data between April 2012 and January 2013 prospectively, including: patient demographics, HCP classification, purpose of HCP-patient interaction, interaction mode and HCP time with the patient. A subset of patients was tracked from pre-pump education until stable on IPT. RESULTS: Data on 2577 HCP-adult patient interactions (62% face-to-face, 29% remote, 9% administrative) were collected over 12.2 ± 6.4 weeks for 895 patients; age 35.4 ± 14.2 years; 67% female; 99% type 1 diabetes, representing 25% of all IPT patients of the institutions. Time (hours) spent on IPT interactions per centre per week were: nurses 5.4 ± 2.8, dietitians 0.4 ± 0.2 and doctors 1.0 ± 0.5. IPT starts accounted for 48% of IPT interaction time. The percentage of available diabetes clinic time spent on outpatient IPT interactions was 20.4%, 4.6% and 2.7% for nurses, dietitians and doctors respectively. Fifteen patients tracked from pre-pump to stabilisation over 11.8 ± 4.5 weeks, required a median (range) of 9.2 (3.0-20.9), 2.4 (0.5-6.0) and 1.8 (0.5-5.4) hours per patient from nurses, dietitians and doctors respectively. CONCLUSIONS: IPT patient care represents a substantial investment in HCP time, particularly for nurses. Funding models for IPT care need urgent review to ensure this now mainstream therapy integrates well into healthcare resources.

Medical costs of Alzheimer's disease misdiagnosis among US Medicare beneficiaries.

INTRODUCTION: Recent developments in diagnostic technology can support earlier, more accurate diagnosis of non-Alzheimer's disease (AD) dementias. METHODS: To evaluate potential economic benefits of early rule-out of AD, annual medical resource use and costs for Medicare beneficiaries potentially misdiagnosed with AD prior to their diagnosis of vascular dementia (VD) or Parkinson's disease (PD) were compared with that of similar patients never diagnosed with AD. RESULTS: Patients with prior AD diagnosis used substantially more medical services every year until their VD/PD diagnosis, resulting in incremental annual medical costs of approximately $9,500-$14,000. However, following their corrected diagnosis, medical costs converged with those of patients never diagnosed with AD. DISCUSSION: The observed correlation between timing of correct diagnosis and subsequent reversal in excess costs is strongly suggestive of the role of misdiagnosis of AD - rather than AD comorbidity - in this patient population. Our findings suggest potential benefits from earlier, accurate diagnosis.

The generalization of visuomotor learning to untrained movements and movement sequences based on movement vector and goal location remapping.

The planning of goal-directed movements is highly adaptable; however, the basic mechanisms underlying this adaptability are not well understood. Even the features of movement that drive adaptation are hotly debated, with some studies suggesting remapping of goal locations and others suggesting remapping of the movement vectors leading to goal locations. However, several previous motor learning studies and the multiplicity of the neural coding underlying visually guided reaching movements stand in contrast to this either/or debate on the modes of motor planning and adaptation. Here we hypothesize that, during visuomotor learning, the target location and movement vector of trained movements are separately remapped, and we propose a novel computational model for how motor plans based on these remappings are combined during the control of visually guided reaching in humans. To test this hypothesis, we designed a set of experimental manipulations that effectively dissociated the effects of remapping goal location and movement vector by examining the transfer of visuomotor adaptation to untrained movements and movement sequences throughout the workspace. The results reveal that (1) motor adaptation differentially remaps goal locations and movement vectors, and (2) separate motor plans based on these features are effectively averaged during motor execution. We then show that, without any free parameters, the computational model we developed for combining movement-vector-based and goal-location-based planning predicts nearly 90% of the variance in novel movement sequences, even when multiple attributes are simultaneously adapted, demonstrating for the first time the ability to predict how motor adaptation affects movement sequence planning.