Vasodilators for primary Raynaud's phenomenon.

BACKGROUND: Numerous agents have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered to be the drugs of choice, evidence of the effects of alternative pharmacological treatments is limited. This is an update of a review first published in 2008. OBJECTIVES: To assess the effects of drugs with vasodilator effects on primary Raynaud's phenomenon as determined by frequency, severity, and duration of vasospastic attacks; quality of life; adverse events; and Raynauds Condition Score. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trial register to November 16, 2020. SELECTION CRITERIA: We included randomized controlled trials evaluating effects of oral, intravenous, and topical formulations of any drug with vasodilator effects on subjective symptoms, severity scores, and radiological outcomes in primary Raynaud's phenomenon. Treatment with calcium channel blockers was not assessed in this review, nor were these agents compared. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed studies using the Cochrane "Risk of bias" tool, and extracted study data. Outcomes of interest included frequency, severity, and duration of attacks; quality of life (QoL); adverse events (AEs); and the Raynaud Condition Score (RCS). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified seven new studies for this update. In total, we included 15 studies involving 635 participants. These studies compared different vasodilators to placebo. Individual studies used different methods and measures to report different outcomes. Angiotensin-converting enzyme (ACE) inhibitors Combining data from three studies revealed a possible small increase in the frequency of attacks per week after treatment (captopril or enalapril) compared to placebo (mean difference [MD] 0.79, 95% confidence interval [CI] 0.43 to 1.17; low-certainty evidence). There was no evidence of a difference between groups in severity of attacks (MD -0.17, 95% CI -4.66 to 4.31; 34 participants, 2 studies; low-certainty evidence); duration of attacks (MD 0.54, 95% CI -2.42 to 1.34; 14 participants, 1 study; low-certainty evidence); or AEs (risk ratio [RR] 1.35, 95% CI 0.67 to 2.73; 46 participants, 3 studies; low-certainty evidence). QoL and RCS were not reported. Alpha blockers Two studies used alpha blockers (buflomedil or moxisylyte). We were unable to combine data due to the way results were presented. Buflomedil probably reduced the frequency of attacks compared to placebo (MD -8.82, 95% CI -11.04 to -6.60; 31 participants, 1 study; moderate-certainty evidence) and may improve severity scores (MD -0.41, 95% CI -0.62 to -0.30; moderate-certainty evidence). With moxisylyte, investigators reported fewer attacks (P < 0.02), less severe symptoms (P < 0.01), and shorter duration of attacks, but the clinical relevance of these results is unclear. No evidence of a difference in AEs between buflomedil and placebo groups was noted (RR 1.41, 95% CI 0.27 to 7.28; 31 participants, 1 study; moderate-certainty evidence). More AEs were observed in participants in the moxisylyte group than in the placebo group. Prostaglandin/prostacyclin analogues One study compared beraprost versus placebo. There was no evidence of benefit for frequency (MD 2.00, 95% CI -0.35 to 4.35; 118 participants, low-certainty evidence) or severity (MD -0.06, 95% CI -0.34 to 0.22; 118 participants, low-certainty evidence) of attacks. Overall, more AEs were noted in the beraprost group (RR 1.59, 95% CI 1.05 to 2.42; 125 participants; low-certainty evidence). This study did not report on duration of attacks, QoL, or RCS. Thromboxane synthase inhibitors One study compared a thromboxane synthase inhibitor (dazoxiben) versus placebo. There was no evidence of benefit for frequency of attacks (MD 0.8, 95% CI -1.81 to 3.41; 6 participants; very low-certainty evidence). Adverse events were not reported in subgroup analyses of participants with primary Raynaud's phenomenon, and the study did not report on duration of attacks, severity of symptoms, QoL, or RCS. Selective serotonin reuptake inhibitors One study compared ketanserin with placebo. There may be a slight reduction in the number of attacks per week with ketanserin compared to placebo (MD -14.0, 95% CI -27.72 to -0.28; 41 participants; very low-certainty evidence) and reduced severity score (MD -133.00, 95% CI -162.40 to -103.60; 41 participants; very low-certainty evidence). There was no evidence that ketanserin reduced the duration of attacks (MD -4.00, 95% CI -14.82 to 6.82; 41 participants; very low-certainty evidence), or that AEs were increased in either group (RR 1.54, 95% CI 0.89 to 2.65; 41 participants; very low-certainty evidence). This study did not report on QoL or RCS. Nitrate/nitrate derivatives Four studies compared topical treatments of nitroglycerin or glyceryl trinitrate versus placebo, each reporting on limited outcomes. Meta-analysis demonstrated no evidence of effect on frequency of attacks per week (MD -1.57, 95% CI -4.31 to 1.17; 86 participants, 2 studies; very low-certainty evidence). We were unable to pool any data for the remaining outcomes. Phosphodiesterase inhibitors Three studies compared phosphodiesterase inhibitors (vardenafil, cilostazol or PF-00489791) to an equivalent placebo. Results showed no evidence of a difference in frequency of attacks (standardized MD [SMD] -0.05, 95% CI -6.71 to 6.61; 111 participants, 2 studies; low-certainty evidence), severity of attacks (MD -0.03, 95% CI -1.04 to 0.97; 111 participants, 2 studies; very low-certainty evidence), duration of attacks (MD -1.60, 95% CI -7.51 to 4.31; 73 participants, 1 study; low-certainty evidence), or RCS (SMD -0.8, 95% CI -1.74 to 0.13; 79 participants, 2 studies; low-certainty evidence). Study authors reported that 35% of participants on cilostazol complained of headaches, which were not reported in the placebo group. PF-00489791 caused 34 of 54 participants to experience AEs versus 43 of 102 participants receiving placebo (RR 1.49). Headache was most common, affecting 14 participants (PF-00489791) versus nine participants (placebo). AUTHORS' CONCLUSIONS: The included studies investigated several different vasodilators (topical and oral) for treatment of primary Raynaud's phenomenon. Small sample sizes, limited data, and variability in outcome reporting yielded evidence of very low to moderate certainty. Evidence is insufficient to support the use of vasodilators and suggests that vasodilator use may even worsen disease.

Pentosan polysulfate sodium for Ross River virus-induced arthralgia: a phase 2a, randomized, double-blind, placebo-controlled study.

BACKGROUND: Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies. METHODS: This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints. RESULTS: PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo. CONCLUSIONS: Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis. TRIAL REGISTRATION: This trial is registered at the Australian New Zealand Clinical Trials Registry # ACTRN12617000893303 .

Resident Trainees Increase Surgical Time: A Comparison of Obstetric and Gynaecologic Procedures in Academic Versus Community Hospitals.

OBJECTIVE: The impact of resident involvement in the operating room for common procedures in obstetrics and gynaecology can shed light on the resource demands of teaching. The objective of this study was to quantify the increased surgical time associated with teaching obstetrics and gynaecology resident trainees across a range of procedures known to require surgical assistance. METHODS: This population-based retrospective cohort study compared surgical duration between academic (teaching) hospitals and community (non-teaching) hospitals. The cohort was made up of adult residents of Ontario between fiscal years 2002 and 2013 who were undergoing commonly performed obstetrics and gynaecologic procedures. The most commonly billed procedures requiring surgical assistance were included: cesarean section, anterior or posterior repair, anterior and posterior repair, salpingo-oophorectomy, myomectomy, ectopic pregnancy, total or subtotal hysterectomy, vaginal hysterectomy, and laparoscopic hysterectomy. Linked administrative databases held at the Institute of Clinical Evaluative Sciences (ICES) were used to define patient-, surgeon-, institution-, and procedure-related variables to limit confounding. Surgical duration, determined by anaesthetic billing records, was analyzed using a negative binomial regression. RESULTS: The total cohort included 337 389 surgical procedures. Of these procedures, 28% (94 203 procedures) were conducted in academic settings. The mean surgical duration of the procedures of interest (excluding vaginal hysterectomy) was significantly longer in academic hospitals compared with community hospitals. With many controls for case variability, this time differential reflects the burden of teaching resident trainees and other learners in the academic environment. The operating time increased between 6% and 20% for cases completed in academic centres versus in the community. As an example, the mean surgical duration of cesarean sections was 20.6 minutes (19%) longer in academic centres. Furthermore, the data highlighted a trend of increased teaching time for laparoscopic procedures compared with open procedures. The time ratio was the greatest for salpingo-oophortectomy and surgical management of ectopic pregnancies. The additional cost of carrying out these nine procedures in academic centres during the study period was $16.3 million. CONCLUSION: The cost of teaching resident trainees is increased operative time. This increased surgical cost in a publicly funded system must be considered as funding models evolve.

Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination: Results of a randomized trial.

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

Hysterectomy in Ontario: A Population-Based Study of Outcomes and Complications in Minimally Invasive Compared with Abdominal Approaches.

OBJECTIVE: As quality-based procedures (QBPs) are being established across the province of Ontario, it is important to identify reliable quality indicators (QIs) to ensure that compensation coincides with quality. Hysterectomy is the most commonly performed gynaecologic procedure and as such is a care process for which a QBP is being developed. The aim of this study was to evaluate the technicity index (TI) as a QI for hysterectomy by defining it in the context of specific surgical outcomes and complications. METHODS: This population-based, retrospective cohort study included all women who underwent hysterectomy from April 2003 to October 2014 in the province of Ontario. Unadjusted and adjusted generalized linear models were created to assess the effect of a minimally invasive hysterectomy (MIH) approach on the primary outcome measure: all hysterectomy-associated complications (Canadian Task Force Classification II-2). RESULTS: Of the procedures meeting the study's inclusion criteria, 56.8% were performed using an abdominal hysterectomy approach, whereas 43.2% were performed using an MIH approach. Over the study period, TI improved significantly from 33.23% in 2003 to 58.47% in 2014. During this time span, the overall incidence of all hysterectomy-associated complications was 13.1%. CONCLUSION: The composite risk of all hysterectomy-associated complications was reduced by 46% with an MIH approach. The uptake of MIH improved significantly in Ontario from 2003 to 2014 and is adequately assessed by the TI. The TI is an appropriate QI for hysterectomy that can be used to track patients' outcomes and direct hysterectomy funding.

Multistate modeling and simulation of patient trajectories after allogeneic hematopoietic stem cell transplantation to inform drug development.

We present a case study for developing clinical trial scenarios in a complex progressive disease with multiple events of interest. The idea is to first capture the course of the disease in a multistate Markov model, and then to simulate clinical trials from this model, including a variety of hypothesized drug effects. This case study focuses on the prevention of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). The patient trajectory after HSCT is characterized by a complex interplay of various events of interest, and there is no established best method of measuring and/or analyzing treatment benefits. We characterized patient trajectories by means of multistate models that we fitted to a subset of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Events of interest included acute GvHD of grade III or IV, severe chronic GvHD, relapse of the underlying disease, and death. The transition probability matrix was estimated using the Aalen-Johansen estimator, and patient characteristics were identified that were associated with different transition rates. In a second step, clinical trial scenarios were simulated from the model assuming various drug effects on the background transition rates, and the operating characteristics of different endpoints and analysis strategies were compared in these scenarios. This helped devise a drug development strategy in GvHD prevention after allogeneic HSCT. More generally, multistate models provide a rich framework for exploring complex progressive diseases, and the availability of a corresponding simulation machinery provides great flexibility for clinical trial planning.

Psychometric Testing of Three Chinese Online-Related Addictive Behavior Instruments among Hong Kong University Students.

Given that there is a lack of instruments assessing internet-related addictions among Chinese population, this study aimed to validate the Chinese version of the nine-item Internet Gaming Disorder Scales- Short Form (IGDS-SF9), Bergen Social Media Addiction Scale (BSMAS), and Smartphone Application-Based Addiction Scale (SABAS) among Hong Kong university students. Participants aged between 17 and 30 years participated in the present study (n = 307; 32.4% males; mean [SD] age = 21.64 [8.11]). All the participants completed the IGDS-SF9, BSMAS, SABAS, and the Hospital Anxiety and Depression Scale (HADS). Confirmatory factor analyses (CFAs) were used to examine the factorial structures and the unidimensionality for IGDS-SF9, BSMAS, and SABAS. CFAs demonstrated that the three scales were all unidimensional with satisfactory fit indices: comparative fit index = 0.969 to 0.992. In addition, the IGDS-SF9 and BSMAS were slightly modified based on the modification index in CFA. The Chinese IGDS-SF9, BSMAS, and SABAS are valid instruments to assess the addiction levels of internet-related activities for Hong Kong university students.

The Burden of Repeat Prescribing Medications after a Related Adverse Drug Event.

The use of medications such as glyburide, neuroleptics and benzodiazepines is potentially dangerous in the elderly, as they are linked to adverse drug events such as hypoglycemia and serious falls. We used administrative data from the province of Ontario to determine how often these medications are continued after a patient experiences one of these adverse events. Over a 12-year period, we identified 31,262 patients who had a hospital presentation with hypoglycemia or a fall within three months of starting the previously listed medications. Re-dispensing of these high-risk medications occurred in 55% of patients within six months of the adverse drug event. Among patients with re-dispensed therapies, about 10% had a repeat adverse drug event. These results highlight a common problem that could potentially be addressed with better medication reconciliation and health policies directed at reducing re-dispensing of high-risk medications.

Identification of DPB1 Permissive Unrelated Donors Is Highly Likely.

HLA-DPB1 permissive matching based on T cell epitope (TCE) groups should be considered when selecting among equally matched HLA-A, -B, -C, -DRB1 unrelated hematopoietic stem cell donors to improve patient survival. Previous studies have defined 3 TCE groups based on functional assays of alloreactivity. Combinations of donor and recipient DPB1 alleles with low immunogenic potential identify permissive donors, who provide no increased risk of mortality compared with DPB1-matched donors. To determine the likelihood of identifying a DPB1 permissive-matched (includes both allele-matched and DPB1-permissive mismatched) unrelated donor for patients with high-resolution matches at 10/10 HLA-A, -B,- C, -DRB1, and -DQB1 in the Be The Match Registry, preliminary search requests from United States' transplant centers for 595 DPB1-typed patients were evaluated for existence of a DPB1 permissive-matched donor, identified either among already typed donors or by prospective DPB1 typing. The baseline DPB1 permissive match rate was 69% and improved to 80% after additional donor DPB1 typing (median, 4 donors per patient). When seeking a 10/10-matched, young (18- to 32-year-old) donor in the registry, the probability of finding a DPB1 permissive-matched donor started lower at 59% and improved to 70% after additional DPB1 testing. Our results show that most patients with a 10/10 match can find a DPB1 permissive-matched donor.

Association between day of the week of elective surgery and postoperative mortality.

BACKGROUND: In prior studies, higher mortality was observed among patients who had elective surgery on a Friday rather than earlier in the week. We investigated whether mortality after elective surgery was associated with day of the week of surgery in a Canadian population and whether the association was influenced by surgeon experience and volume. METHODS: We conducted a population-based retrospective cohort study in the province of Ontario, Canada. We included adults who underwent 1 of 12 elective daytime surgical procedures from Apr. 1, 2002, to Dec. 31, 2012. The primary outcome was 30-day mortality. We used generalized estimating equations to compare outcomes for surgeries performed on different days of the week, adjusting for patient and surgeon factors. RESULTS: A total of 402 899 procedures performed by 1691 surgeons met our inclusion criteria. The median length of hospital stay was 6 (interquartile range 5-8) days. Surgeon experience varied significantly by day of week (p < 0.001), with surgeons operating on Fridays having the least experience. Nearly all of the patients who had their procedure on a Friday had postoperative care on the weekend, as compared with 49.1% of those whose surgery was on a Monday (p < 0.001). We found no difference in the 30-day mortality between procedures performed on Fridays and those performed on Mondays (adjusted odds ratio 1.08, 95% confidence interval 0.97-1.21). INTERPRETATION: Although surgeon experience differed across days of the week, the risk of 30-day mortality after elective surgery was similar regardless of which day of the week the procedure took place.

Quick SOFA Scores Predict Mortality in Adult Emergency Department Patients With and Without Suspected Infection.

STUDY OBJECTIVE: The Quick Sequential Organ Failure Assessment (qSOFA) score (composed of respiratory rate ≥22 breaths/min, systolic blood pressure ≤100 mm Hg, and altered mental status) may identify patients with infection who are at risk of complications. We determined the association between qSOFA scores and outcomes in adult emergency department (ED) patients with and without suspected infection. METHODS: We performed a single-site, retrospective review of adult ED patients between January 2014 and March 2015. Patients triaged to fast-track, dentistry, psychiatry, and labor and delivery were excluded. qSOFA scores were calculated with simultaneous vital signs and Modified Early Warning System scores. Patients receiving intravenous antibiotics were presumed to have suspected infection. Univariate and multivariate analyses were performed to explore the association between qSOFA scores and inpatient mortality, admission, and length of stay. Receiver operating characteristics curve analysis and c statistics were also calculated for ICU admission and mortality. RESULTS: We included 22,530 patients. Mean age was 54 years (SD 21 years), 53% were women, 45% were admitted, and mortality rate was 1.6%. qSOFA scores were associated with mortality (0 [0.6%], 1 [2.8%], 2 [12.8%], and 3 [25.0%]), ICU admission (0 [5.1%], 1 [10.5%], 2 [20.8%], and 3 [27.4%]), and hospital length of stay (0 [123 hours], 1 [163 hours], 2 [225 hours], and 3 [237 hours]). Adjusted rates were also associated with qSOFA. The c statistics for mortality in patients with and without suspected infection were similarly high (0.75 [95% confidence interval 0.71 to 0.78) and 0.70 (95% confidence interval 0.65 to 0.74), respectively. CONCLUSION: qSOFA scores were associated with inpatient mortality, admission, ICU admission, and hospital length of stay in adult ED patients likely to be admitted both with and without suspected infection and may be useful in predicting outcomes.

Urinary tract infections, urologic surgery, and renal dysfunction in a contemporary cohort of traumatic spinal cord injured patients.

AIMS: The objective of this study was to measure the incidence of urinary tract infections (UTIs), urologic reconstruction/urinary diversion, and renal dysfunction after a traumatic spinal cord injury (TSCI). METHODS: Retrospective cohort study using administrative data from Ontario, Canada. All incident adult TSCI patients (2002-2013) admitted to a rehabilitation center were included. The impact of lesion level on each outcome was assessed. The rate of outcomes was further compared to an age and sex matched sample from the general population. RESULTS: A total of 2,023 incident TSCI patients were identified (median follow-up of 4.8 years). Most patients (73%) were male and median age was 50 years. Lesion level included cervical (39%), thoracolumbar (44%), and unknown (17%). The incidence of serious UTIs (requiring emergency room visit or hospital admission) was 40%. Thoracolumbar lesion TSCI patients had significantly greater risk of serious UTIs (HR 1.3, 95%CI 1.1-1.7, P < 0.01) compared to those with a cervical lesion. Urologic reconstruction/urinary diversion was carried out on 2.4% of patients. New onset renal dysfunction was identified in 4.2% (84) TSCI patients. The rate ratios for serious UTIs (10.59, 95%CI 8.71-12.89), urologic reconstruction/urinary diversion (6.48, 95%CI 3.07-13.68), and renal dysfunction (2.55, 95%CI 1.70-3.83) were significantly increased among TSCI patients compared to matched controls. CONCLUSIONS: Urologic disease is still an important source of morbidity for contemporary TSCI patients, and is more common compared to the general population. Neurourol. Urodynam. 36:640-647, 2017. © 2016 Wiley Periodicals, Inc.

Everolimus and reduced calcineurin inhibitor therapy in pediatric liver transplant recipients: Results from a multicenter, prospective study.

In a 24-month, multicenter, single-arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1-6 months post-transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment-related serious infections leading to hospitalization and premature study drug discontinuation. Subsequently, patients aged <7 years reverted to local standard-of-care immunosuppression. Mean tacrolimus concentration was above or near the upper end of the maintenance target range (2-5 ng/mL) until after month 6 post-enrollment. The primary variable, mean (SD) change in eGFR from baseline to month 12 (last observation carried forward), was +6.2 (19.5) mL/min/1.73 m2 . Two patients experienced treated biopsy-proven acute rejection. No graft losses or deaths occurred. PTLD occurred in five patients (8.9%) (3/25 [12.0%] patients <2 years, 2/31 aged 2-18 years [6.5%]). Adverse events, serious adverse events, and discontinuation due to adverse events were reported in 100.0%, 76.8%, and 44.6% of patients, respectively. In conclusion, everolimus with reduced CNI improved renal function while maintaining antirejection potency in pediatric liver transplant patients but safety outcomes suggest that patients were overimmunosuppressed.

Cardiac Surgeons after Vacation: Refreshed or Rusty?

Introduction: Many surgeons describe feeling a bit out of practice when they return from a vacation. There have been no studies assessing the impact of surgeon vacation on patient outcomes. Methods: We used administrative data from the province of Ontario to identify patients who underwent a coronary artery bypass grafting. Using a propensity score, we matched patients who underwent their procedure immediately after their surgeon returned from vacation of at least 7 days (n = 1,161) to patients who were not operated immediately before or after a vacation period (n = 2,138). Results: There was no significant difference in patient mortality (odds ratio: 1.23, p = 0.52), length of operation (relative risk [RR]: 1.00 p = 0.58), or intensive care unit/ hospital stay (RR: 0.97 p = 0.66/RR: 0.98 p = 0.54, respectively). Conclusion: There was not a significant change in risk of death, operative length, or hospital stay after a surgeon vacation.

Teaching surgery takes time: the impact of surgical education on time in the operating room.

BACKGROUND: It is generally accepted that surgical training is associated with increased surgical duration. The purpose of this study was to determine the magnitude of this increase for common surgical procedures by comparing surgery duration in teaching and nonteaching hospitals. METHODS: This retrospective population-based cohort study included all adult residents of Ontario, Canada, who underwent 1 of 14 surgical procedures between 2002 and 2012. We used several linked administrative databases to identify the study cohort in addition to patient-, surgeon- and procedure-related variables. We determined surgery duration using anesthesiology billing records. Negative binomial regression was used to model the association between teaching versus nonteaching hospital status and surgery duration. RESULTS: Of the 713 573 surgical cases included in this study, 20.8% were performed in a teaching hospital. For each procedure, the mean surgery duration was significantly longer for teaching hospitals, with differences ranging from 5 to 62 minutes across individual procedures in unadjusted analyses (all p < 0.001). In regression analysis, procedures performed in teaching hospitals were associated with an overall 22% (95% confidence interval 20%-24%) increase in surgery duration, adjusting for patient-, surgeon- and procedure-related variables as well as the clustering of patients within surgeons and hospitals. CONCLUSION: Our results show that a wide range of surgical procedures require significantly more time to perform in teaching than nonteaching hospitals. Given the magnitude of this difference, the impact of surgical training on health care costs and clinical outcomes should be a priority for future studies.

CONTEXTE: Il est généralement admis que la formation chirurgicale est associée à des interventions plus longues. L'objectif de la présente étude était de déterminer l'ampleur de cette augmentation pour les chirurgies courantes en comparant la durée des interventions dans les hôpitaux universitaires et les autres hôpitaux. MÉTHODES: Dans le cadre d'une étude de cohorte rétrospective basée sur la population, nous avons recensé tous les résidents adultes de l'Ontario (Canada) qui ont subi une intervention chirurgicale parmi une liste de 14 entre 2002 et 2012. À l'aide de plusieurs bases de données administratives reliées, nous avons constitué la cohorte de l'étude et recueilli des variables associées aux patients, aux chirurgiens et aux interventions. Nous avons déterminé la durée des opérations à partir des dossiers de facturation d'anesthésiologie. Une régression binomiale négative a été utilisée pour modéliser le lien entre le statut des hôpitaux ­ universitaires ou non ­ et la durée. RÉSULTANTS: Des 713 573 chirurgies à l'étude, 20,8 % ont eu lieu dans un hôpital universitaire. Dans tous les cas, la durée moyenne était significativement plus longue dans les hôpitaux universitaires, les écarts variant de 5 à 62 minutes pour chaque intervention dans les analyses non corrigées (p < 0,001 dans tous les cas). Selon l'analyse de régression, les chirurgies effectuées dans les hôpitaux universitaires étaient associées à une augmentation globale de la durée de 22 % (intervalle de confiance à 95 %, 20 %­24 %), après ajustement pour les variables liées aux patients, aux chirurgiens et aux interventions ainsi que pour la densité de patients pris en charge par les chirurgiens et les hôpitaux. CONCLUSION: Nos résultats montrent que de nombreuses interventions chirurgicales durent considérablement plus longtemps dans les hôpitaux universitaires que dans les autres hôpitaux. Étant donné l'ampleur de cet écart, l'étude de l'incidence de la formation chirurgicale sur les coûts des soins de santé et les résultats cliniques devrait être une priorité pour les recherches futures.

Regulatory T, natural killer T and γδ T cells in multiple sclerosis and chronic fatigue syndrome/myalgic encephalomyelitis: a comparison.

BACKGROUND: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), and Multiple Sclerosis (MS) may share some similarities in relation to reduced NK cell activity. It is likely that other cells such as regulatory T (Tregs), invariant Natural Killer T (iNKT) and gamma delta T (γδ T) cells may also be dysregulated in CFS/ME and MS. OBJECTIVE: To evaluate and compare specific immune regulatory cells of patients with CFS/ME, patients with MS and healthy controls. METHOD: Sixty three volunteers were included in this study: 24 were CFS/ME patients, 11 were MS patients and 27 were healthy controls. Blood samples were obtained from all participants for flow cytometry analysis of iNKT cells, Tregs and γδ T cell phenotypes. RESULTS: We observed a significant increase in Tregs in the CFS/ME group (p≤0.05) compared to the healthy control group. Total γδ and γδ2 T cells were significantly reduced in MS patients in comparison with the healthy control group. Conversely, CD4+iNKT percentage of iNKT, was significantly increased in the CFS/ME group compared with healthy controls and the double-negative iNKT percentage of iNKT significantly decreased compared with the healthy control group. CONCLUSIONS: This study has not identified any immunological disturbances that are common in both MS and CFS/ME patients. However, the differential expression of cell types between the conditions investigated suggests different pathways of disease. These differences need to be explored in further studies.

Off-pump or on-pump coronary-artery bypass grafting at 30 days.

BACKGROUND: The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established. METHODS: At 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization. RESULTS: There was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the off-pump group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.59) or in any of its individual components. The use of off-pump CABG, as compared with on-pump CABG, significantly reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI, 0.75 to 0.85; P<0.001), reoperation for perioperative bleeding (1.4% vs. 2.4%; relative risk, 0.61; 95% CI, 0.40 to 0.93; P=0.02), acute kidney injury (28.0% vs. 32.1%; relative risk, 0.87; 95% CI, 0.80 to 0.96; P=0.01), and respiratory complications (5.9% vs. 7.5%; relative risk, 0.79; 95% CI, 0.63 to 0.98; P=0.03) but increased the rate of early repeat revascularizations (0.7% vs. 0.2%; hazard ratio, 4.01; 95% CI, 1.34 to 12.0; P=0.01). CONCLUSIONS: There was no significant difference between off-pump and on-pump CABG with respect to the 30-day rate of death, myocardial infarction, stroke, or renal failure requiring dialysis. The use of off-pump CABG resulted in reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney injury but also resulted in an increased risk of early revascularization. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

The effect of pelvic factures on future stress incontinence and pelvic organ prolapse surgery.

INTRODUCTION AND HYPOTHESIS: Pelvic fractures in women significantly disrupt the pelvic floor, which may cause stress urinary incontinence (SUI) or pelvic organ prolapse (POP). Our objective was to assess the incidence of operative treatment for SUI and POP after pelvic fracture. METHODS: We used administrative data from Ontario, Canada, to conduct a retrospective cohort study. Female patients who underwent operative repair of a pelvic fracture between 2002 and 2010 were identified. The primary outcomes were the subsequent surgical treatment of SUI or POP. To compare the incidence with that of the general population, patients who had operative repair of a pelvic fracture were matched (1:2) to a person in the general population (with a propensity score to account for measurable potential confounders). Our primary analysis was a Cox proportional hazards model to compare hazard ratios (HR) in subjects with a pelvic facture and those without. RESULTS: We identified 390 female patients with a median age of 47 (IQR 30-67) years. Our median follow-up period was 5.9 (4.1-8.3) years. The absolute risk of SUI surgery after pelvic fracture was 3.3 % (13 out of 390) compared with 1.0 % (8 out of 769) in the matched general population sample. The HR for SUI surgery was 5.8 (95 % CI 2.2-15.1). The absolute risk of POP surgery after pelvic fracture was 1.8 % (7 out of 390) compared with 0.9 % (7 out of 769) in the matched general population. The HR for POP surgery was 2.3 (95 % CI 0.9-5.8). CONCLUSIONS: Among patients who had a pelvic fracture requiring operative repair, there appears to be a significantly increased chance of surgery for SUI, but not for POP.