Background The Fistula Risk Score (FRS) is a clinical tool developed from single-institutional data using primarily intraoperative factors to characterize the risk of clinically relevant pancreatic ...fistula (CR-POPF) after pancreaticoduodenectomy. We developed a modified FRS based on objective, nationally accrued data that is more readily determined before resection. Study Design The 2012 NSQIP Pancreatic Demonstration Project (PDP) was used to identify 1,731 pancreaticoduodenectomy resections over 14 months (2011 to 2012). A randomly generated 70% cohort was used for model development, and the remaining 30% for internal validation. Univariate analysis was used to identify predictors of CR-POPF. Variables with a value of p < 0.1 were included in multivariable modeling. Results Five significant predictors of CR-POPF were identified and assigned points based on odds ratios: sex, BMI, preoperative total bilirubin, pancreatic ductal diameter, and gland texture. The 10-point model was further applied to the 2014 PDP for external validation. In the testing group, risk scores of 0 to 2 (negligible risk), 3 to 6 (low risk), 7 to 8 (intermediate risk), and 9 to 10 (high risk) were associated with CR-POPF rates of 0%, 6.7%, 16.4%, and 33.7%, respectively. Similar values were seen using the internal validation cohort: 0%, 6.3%, 13.5%, and 31.0%, respectively. The external validation values were 2.9%, 10.2%, 16.4%, and 25.8%, respectively. Conclusions This modified FRS allows for estimation of CR-POPF risk using preoperative and easily determined intraoperative factors, and will allow comparison of performance data for individual surgeons to national norms, improved perioperative counseling, and potential for scrutinizing and/or implementing interventions designed to decrease CR-POPF rates.
The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) ...in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE.
The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE.
In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted.
The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy.
The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE. Serefoglu EC, McMahon CG, Waldinger MD, Althof SE, Shindel A, Adaikan G, Becher EF, Dean J, Giuliano F, Hellstrom WJG, Giraldi A, Glina S, Incrocci L, Jannini E, McCabe M, Parish S, Rowland D, Segraves RT, Sharlip I, and Torres LO. An evidence-based unified definition of lifelong and acquired premature ejaculation: Report of the second International Society for Sexual Medicine Ad Hoc Committee for the Definition of Premature Ejaculation. Sex Med 2014;2:41–59.
Summary Every year, more than 2 million women worldwide are diagnosed with breast or cervical cancer, yet where a woman lives, her socioeconomic status, and agency largely determines whether she will ...develop one of these cancers and will ultimately survive. In regions with scarce resources, fragile or fragmented health systems, cancer contributes to the cycle of poverty. Proven and cost-effective interventions are available for both these common cancers, yet for so many women access to these is beyond reach. These inequities highlight the urgent need in low-income and middle-income countries for sustainable investments in the entire continuum of cancer control, from prevention to palliative care, and in the development of high-quality population-based cancer registries. In this first paper of the Series on health, equity, and women’s cancers, we describe the burden of breast and cervical cancer, with an emphasis on global and regional trends in incidence, mortality, and survival, and the consequences, especially in socioeconomically disadvantaged women in different settings.
Single-qubit rotations and two-qubit CNOT operations are crucial ingredients for universal quantum computing. Although high-fidelity single-qubit operations have been achieved using the electron spin ...degree of freedom, realizing a robust CNOT gate has been challenging because of rapid nuclear spin dephasing and charge noise. We demonstrate an efficient resonantly driven CNOT gate for electron spins in silicon. Our platform achieves single-qubit rotations with fidelities greater than 99%, as verified by randomized benchmarking. Gate control of the exchange coupling allows a quantum CNOT gate to be implemented with resonant driving in ~200 nanoseconds. We used the CNOT gate to generate a Bell state with 78% fidelity (corrected for errors in state preparation and measurement). Our quantum dot device architecture enables multi-qubit algorithms in silicon.
Summary Background Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We ...aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas. Methods In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5–50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov , number NCT01578499. Findings Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4–26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1–58·4; p<0·0001). Grade 3–4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group. Interpretation Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene. Funding Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.
Orthostatic changes in systolic blood pressure (SBP) impact cardiovascular outcomes. In this study, we aimed to determine the pattern of orthostatic systolic pressure changes in participants enrolled ...in the SBP Intervention Trial (SPRINT) at their baseline visit before randomization and sought to understand clinical factors predictive of these changes. Of the 9323 participants enrolled in SPRINT, 8662 had complete data for these analyses. The SBP after 1 minute of standing was subtracted from the mean value of the three preceding seated SBP values. At the baseline visit, medical history, medications, anthropometric measures, and standard laboratory testing were undertaken. The mean age of SPRINT participants was 68 years, two-thirds were male, with 30% black, 11% Hispanic, and 55% Caucasian. The spectrum of SBP changes on standing demonstrated that increases in SBP were as common as declines, and about 5% of participants had an increase, and 5% had a decrease of >20 mm Hg in SBP upon standing. Female sex, taller height, more advanced kidney disease, current smoking, and several drug classes were associated with larger declines in BP upon standing, while black race, higher blood levels of glucose and sodium, and heavier weight were associated with more positive values of the change in BP upon standing. Our cross-sectional results show a significant spectrum of orthostatic SBP changes, reflecting known (eg, age) and less well-known (eg, kidney function) relationships that may be important considerations in determining the optimal target blood pressure in long-term outcomes of older hypertensive patients.
Abstract Background Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction in women, but the role of rehabilitation after SCAD is unclear. Methods We designed a ...dedicated SCAD cardiac rehabilitation (SCAD-CR) program for our SCAD survivors at Vancouver General Hospital. This program encompasses a multidisciplinary approach including exercise rehabilitation, psychosocial counselling, dietary and cardiovascular disease education, and peer group support. Exercise and educational classes were scheduled weekly with a targeted participation of 6 months. Psychosocial counselling, mindful living sessions, social worker and psychiatry evaluations, and peer-group support were offered. Results We report our first consecutive cohort of 70 SCAD women who joined SCAD-CR from November 2011 to April 2015. The average age was 52.3 ± 8.4 years. Mean participation duration was 12.4 ± 10.5 weeks; 28 completed 6 months, 48 completed ≥ 1 month. At entry, 44 (62.9%) had recurrent chest pains and average metabolic equivalents on exercise treadmill test was 10.1 ± 3.3. At program exit, the proportion with recurrent chest pains was lower (37.1%) and average metabolic equivalents was higher 11.5 ± 3.5 (both P < 0.001). There was a significant improvement in the STOP-D depression questionnaire, with mean scores of 13.0 ± 1.4 before and 8.0 ± 1.7 after the SCAD-CR ( P = 0.046). Twenty (28.6%) social worker referrals and 19 (27.1%) psychiatry referrals were made. Mean follow-up was 3.8 ± 2.9 years from the presenting SCAD event, and the major cardiac adverse event rate was 4.3%, lower than our non-SCAD-CR cohort (n = 145; 26.2%; P < 0.001). Conclusions This is the first dedicated SCAD-CR program to address the unique exercise and psychosocial needs of SCAD survivors. Our program appears safe and beneficial in improving chest pain, exercise capacity, psychosocial well-being and cardiovascular events.
Abstract Objectives The aim of this study was to identify a unifying cardiac pathophysiology that explains the cardiac pathological features in sickle cell disease (SCD). Background Cardiopulmonary ...complications, the leading cause of adult death in SCD, are associated with heart chamber dilation, diastolic dysfunction, elevated tricuspid regurgitant jet velocity (TRV), and pulmonary hypertension. However, no unifying cardiac pathophysiology has been identified to explain these findings. Methods In a 2-part study, we first examined patients with SCD who underwent screening echocardiography during steady state at our institution. We then conducted a meta-analysis of cardiac studies in SCD. Results In the 134 patients with SCD studied (median age 11 years), significant enlargement of the left atrial volume was present ( z -score 3.1, p = 0.002), shortening fraction was normal (37.6 ± 4.7%), and lateral and septal ratios of mitral velocity to early diastolic velocity of the mitral annulus (E/e′) were severely abnormal in 8% and 14% of patients, respectively, indicating impaired diastolic function. Both TRV and lateral E/e′ correlated with enlarged left atrial volume in SCD (p = 0.003 and p = 0.006, respectively). Meta-analysis of 68 studies confirmed significant left atrial diameter enlargement in patients with SCD compared with controls, evidence of diastolic dysfunction and enlarged left ventricular end-diastolic dimension with normal shortening fraction. The majority of patients with catheter-confirmed pulmonary hypertension had mild pulmonary venous hypertension consistent with restrictive cardiac physiology. Conclusions Patients with SCD have a unique form of cardiomyopathy with restrictive physiology that is superimposed on hyperdynamic physiology and is characterized by diastolic dysfunction, left atrial dilation, and normal systolic function. This combination results in mild, secondary, pulmonary venous hypertension and elevated TRV. Sudden death is common in other forms of restrictive cardiomyopathy. Our finding of this unique restrictive cardiomyopathy may explain the increased mortality rates and sudden death seen in patients with SCD with mildly elevated TRV.
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