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Marian Karafa, Anna Karafova Faculty of Physical Education, Gdansk University of Physical Education and Sport, Gdansk, PolandCorrespondence: Marian KarafaGdansk University of Physical Education and Sport, Department of Physiotherapy, Kazimierza Górskiego 1, Gdansk 80-336, PolandTel +48 883641324Email marian.karafa@awf.gda.plAbstract: The effectiveness of compression therapy in the treatment of venous leg ulcers has been confirmed in many scientific studies. The healing process depends on many of its parameters, such as the type of compression bandages, their elastic properties and sub-bandage pressure. However, there is no standard protocol that would ensure success for all patients. A pressure of about 83 mmHg provides complete compression for both superficial and deep veins; however, applying compression bandages under such high pressure is a difficult task, even for experienced therapists. Here, we present the case of a 61-year-old woman with approximately 2.5-year-old venous ulcer in her left leg due to chronic venous insufficiency (CVI). Our study aimed to show that routine pressure control at each bandage renewal using the Kikuhime device, as well as their twice daily application in the first week of therapy reduced the healing time of a venous leg ulcer with an area of about 20 cm2 to four weeks.Keywords: venous ulcers, compression therapy, sub-bandage pressure, Kikuhime device

This study evaluated how different levels of pressure under inelastic multi-layer bandages affect the reduction of secondary arm lymphedema and patient comfort throughout therapy. Ninety-six women with lymphedema after breast cancer treatment were randomized into three groups of 32 patients depending on level of applied pressure in compression therapy: group I (control) at 21-30 mmHg; study groups II A at 31-40 mmHg and group II B at 41-60 mmHg. All patients were treated with complex decongestive therapy (CDT) and intermittent pneumatic compression (IPC) before compression. Fixed points of bilateral arms were measured at the start (first visit), after 24 h, 7 days, and 14 days of therapy. Edema severity was measured by summary calculation. Results were presented as a relative metric coefficient of arm lymphedema (RMCAL) which is the difference between sums of circumferences of the edematous arm and the contralateral side expressed in percents. In order to evaluate the patient comfort after finishing a two-week therapy all patients assessed the level of accompanying pain using the numeric pain rating scale (NRS). At the start of therapy median arm circumference difference (RMCAL) was 18.60%, 18.51%, and 19.05% in groups I-II B, respectively. After 24 h the median RMCAL was reduced to 14.49%, 12.13%, and 12.64%. This was further reduced to 10.77%, 6.98%, and 8.48% at one week and 10.28%, 5.75%, and 7.20% in each group, respectively. There was no statistically significant difference between RMCAL values in group II A and II B throughout the therapy. In group II A (NRS = 2), applied bandages were better tolerated than in both II B (NRS = 5) and control groups (NRS = 8). These results demonstrate that inelastic multi-layer bandages applied in groups II A and II B (41-60 mmHg) led to the same reduction of swollen arm circumference with group II being better tolerated. The lowest compression (control at 21-30 mmHg) produced the smallest reduction. In addition, since the greatest reduction was seen in the first week of therapy while the second week served to maintain the reduction, compression garments may be able to be ordered after one week of therapy for more efficient patient care. [ABSTRACT FROM AUTHOR]

Background: Sensitive and specific biomarkers for use in progressive multiple sclerosis (MS) have not been established. We investigate neurofilament light (NfL) as a treatment response biomarker in progressive MS., Objective: To evaluate whether ibudilast 100 mg/day alters serum and cerebrospinal fluid (CSF) levels of NfL in progressive MS., Methods: In a protocol-defined exploratory analysis from a 2-year, phase 2 clinical trial of ibudilast in progressive MS (NCT01982942), serum samples were collected from 239 subjects and a subset contributed CSF and assayed using single-molecule assay (SIMOA) immunoassay. A mixed model for repeated measurements yielded log(NfL) as the response variable., Results: The geometric mean baseline serum NfL was 31.9 and 28.8 pg/mL in placebo and ibudilast groups, respectively. The geometric mean baseline CSF NfL was 1150.8 and 1290.3 pg/mL in placebo and ibudilast groups, respectively. Serum and CSF NfL correlations were r  = 0.52 and r  = 0.78 at weeks 48 and 96, respectively. Over 96 weeks, there was no between-group difference in NfL in either serum ( p  = 0.76) or CSF ( p  = 0.46). After controlling for factors that may affect NfL, no effect of ibudilast on NfL in either serum or CSF was observed., Conclusion: Ibudilast treatment was not associated with a change in either serum or CSF NfL.

Objective: The authors examine the associations of generational affiliation on empathy and burnout in a sample of millennial (born between 1982 and 2000) and Generation X (born between 1965 and 1981) residents and fellows., Methods: At a single large institution during the 2013-2014 academic year, residents and fellows were asked to complete the Jefferson Scale of Physician Empathy and Maslach Burnout Inventory (MBI). Responses were combined with GME database content. Multivariable regression analysis included generation affiliation, race, gender, and post-graduate year (PGY) as covariates., Results: The study sample included 388 millennial (mean age = 29.3) and 200 Generation X trainees (mean age = 34.6), with the response rate being 96.5%. Groups were statistically different by gender (p < 0.001) and PGY level (p < 0.001). After adjustment for gender, race, and PGY level, no statistically significant differences were found between millennial and Generation X groups in mean scores of empathy or burnout. Empathy was associated with PGY level (p = 0.0008) and race (p < 0.0001), with decreased empathy in advanced training levels and increased empathy in Hispanic/Latino race. Burnout rate was associated with PGY level (p = 0.001) but not generational affiliation (p = 0.6). The MBI depersonalization subscale was associated with PGY level (p < 0.001) and race (p = 0.0034), with decreased depersonalization in advanced training levels and Hispanic/Latino race. The emotional exhaustion and personal accomplishment MBI subscales did not demonstrate any significant associations in the multivariable regression model., Conclusions: In a compared sample of millennial and Generation X residents and fellows, PGY level and Hispanic/Latino race (though not generation affiliation) were significantly associated with both empathy and MBI depersonalization subscale scores, while only PGY level was significantly associated with burnout rate. This study presents further evidence of de-escalating burnout and declining empathy over the course of medical residency.

Objective: Primary lymphoedema is rare and in most cases develops in the lower extremities. In some cases, conservative treatment is insufficient and can be supported by surgical procedure. The aim of this case study was to show the difference in the effectiveness of a compression wrap device and compression stockings in the treatment of primary lymphoedema., Method: Before and after liposuction the patient was treated on an outpatient basis every day for three weeks. This consisted of complex decongestive therapy (CDT) including manual lymph drainage, tailored exercises, skin and nail care, compression therapy and intermittent pneumatic compression. After CDT, the patient was provided with a flat-knit compression garment. Measurements were taken at one week and at three months of wearing the compression garment. The oedema severity was measured by summary calculation method. For both healthy and swollen limbs, the sum of circumferences taken at nine fixed measuring points was determined. The difference between these sums expressed in percents was presented as a relative metric coefficient of leg lymphoedema (RMCL)., Results: At the start of therapy, the difference in circumference between the healthy and swollen limb was 21.85%. After CDT (RMCL: 13.46%), the patient was provided with a flat-knit compression stocking (class 3). After one week, the RMCL was 15.92%, while after three months RCML was 20.84%. Because fluid retention was observed the patient was again treated with CDT (RMCL: 13.89%). The patient was provided with compression stocking (class 4). After one week of wearing, the RMCL was 15.77%, while after three months RMCL was 20.26%. As the results proved unsatisfactory, the patient was treated with CDT (RMCL: 13.60%) and a combination of two class 4 compression stockings was used. After one week, RMCL was 14.91%, while after three months RMCL was 19.25%. As the effects of oedema reduction were insufficient, the patient was treated again with CDT (RMCL: 13.89%) and advised to replace one of the stockings with a CirAid device (adjustable compression wrap). After one week, RMCL was 14.18% and after three months RMCL was 14.76%. The patient then qualified for liposuction (RMCL: 7.81%). At three months after surgery, the compression stocking was replaced by an adjustable compression wrap, to reduce the difference in circumference between healthy and swollen limbs (from 21.85 % to 8.68%)., Conclusion: This case study shows that in primary oedema one class of compression garment is not always sufficient, nor is the combination of two garments with varying degrees of compression. In some cases, the situation requires the use of non-elastic leg binders such as a CircAid device which, thanks to its greater stiffness, helps improve clinical outcomes.

Background: Consultation psychiatrists are often asked to assess factitious disorder (FD), yet this is challenging as confirmation depends on rarely achieved direct evidence of illness-inducing behaviors. Diagnosis is thus based on other variables, such as atypical features of the medical presentation and certain patient behaviors. This study sought to assess a cohort of patients with FD for demographic and clinical variables, but also psychological and behavioral ones unexamined in previous studies., Methods: 49 previously-identified FD patients at a single site were reviewed retrospectively and variables collected included demographic, medical, psychiatric, social, behavioral, and treatment-related. Descriptive statistical analysis was used., Results: Patients were mostly: 1) under age 40 (82%), 2) female (90%), 3) with past psychiatric (92%), family psychiatric (78%), and traumatic (69%) histories; 4) direct intravenous access (67%); and 7) some exposure to healthcare training (67%). All (100%) subjects had an identifiable family dynamic issue, including household abuse, parental divorce, parental influence/enmeshment, grief, and/or significant other conflict. Financial, emotional, or social incentives were common, and most patients (88%) exhibited at least 4 FD-related behaviors., Conclusion: FD represents a complex disorder of abnormal illness behaviors with predisposing developmental and perpetuating sociobehavioral variables previously unexplored. Future investigational, educational, and quality improvement directions are considered., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: In this study, clinical nurses' documentation of incontinence-associated dermatitis (IAD) were compared with wound expert documentation before and after implementing a valid, reliable severity index (SI) instrument., Methods: A prospective, non-equivalent, two group comparative design within three hospital medical units. Pre- and post-implementation skin condition documentation were compared by clinician type, and post-implementation IADSI scores were assessed for agreement using standard and weighted Kappa., Results: Of 89 patients (pre-, n=48 and post-, n=38), mean (standard deviation) age was 72.4±13.7 years and 57.3% had IAD. Mean IADSI score was 13.2 (standard deviation: 10.5; range: 0-52), reflecting pink intact skin. Post-implementation, skin documentation between clinicians was more likely to match, from 35.4 to 84.2%, p<0.001. Post-implementation, after controlling for age, gender and race, the odds ration (OR) of matched documentation between clinicians was 5.80 ([95% confidence interval: 1.8, 18.6], p=0.003) compared with pre-implementation. In the post-implementation period, standard Kappas for agreement in clinical nurse-wound expert documentation in the lower back/buttocks/upper thigh areas ranged from 0.82 to 1.0, reflecting very good agreement. Weighted kappas ranged from 0.76 to 1.0, also reflecting good to very good agreement., Conclusion: Implementation of an IADSI assessment instrument improved accuracy of IAD documentation.

Background: Associations between the crude capture of polyallergy-also known as multiple chemical sensitivity or multiple drug intolerance syndrome-and mental health/functional somatic syndrome disorders, healthcare utilization, or other clinical phenomenon have not been examined extensively., Methods: An IRB-approved retrospective chart review of all patients between age 18 and 70 who had a clinical encounter at a large medical center between 2009 and 2014. Patients were stratified into 4 categories based on the absolute number of chart-documented allergies: (1) no allergies; (2) normal allergy (1-4 allergies); (3) polyallergy (5-9 allergies); and (4) "ultrapolyallergy," (≥10 allergies), which were corroborated through a sensitivity analysis. Demographics, comorbidities, and medications were clustered per allergy grouping. Analysis of variance, chi-square, and multivariable logistic regression analyses were employed to test for associations., Results: 2,007,434 patients were examined ("no allergy" group, n = 1,423,631, 70.9%; "normal allergy" group: n = 549,927, 27.4%; "polyallergy" group n = 29,453, 1.5%; "ultrapolyallergy" group, n = 4,423, 0.22%). Proportion of females increased from 51% in the "no allergy" group to 89.6% in the "ultrapolyallergy" group (p < 0.001). Rates of mental health and functional somatic syndrome disorder diagnoses increased significantly across allergy groups (p < 0.001). All psychotropic medication classes were increased significantly across allergy groups (p < 0.001). Healthcare utilization was also significantly elevated across allergy cohorts (p <0.001)., Conclusions: This study demonstrates that polyallergy/multiple chemical sensitivity may serve as a crude yet meaningful indicator of comorbid psychopathology. Drug intolerance mechanisms are reviewed, and both clinical and investigational implications are examined., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the outcomes, safety, and response to subsequent therapies of patients with metastatic urothelial carcinoma (mUC) treated with atezolizumab outside clinical trials., Objectives: The objectives of the study include to report the clinical efficacy and safety of atezolizumab, and the response to future therapies in clinical practice outside clinical trials., Patient and Methods: This is a retrospective, single-center study including consecutive patients with confirmed mUC who received at least one dose of atezolizumab 1200 mg every 3 weeks between May 2016 and April 2017., Results: Seventy-nine patients, median age 72 years (range 29-93), 71% men and 76% ECOG PS 0-1, were identified. Most patients (79%) had primary cancer in the bladder, 62% had prior surgery, and 75% received at least one prior line of treatment (34 patients had prior cisplatin-based chemotherapy). Best response included 18% partial response, 29% stable disease, and 53% progressive disease. Patients were on atezolizumab for a median of 2.7 months (95%CI, 1.8-3.6) and median PFS was 3.2 months (95%CI, 1.6-4.8). A total of 33 (42%) patients had significant (any cause) AEs, including grade 4 hyperbilirubinemia in two patients; no toxic deaths were reported. At time of data analysis, only 18% of patients received at least one subsequent line of treatment for a median of 1.8 months (95%CI, 0.0-5.0) while 42% were referred to palliative care/hospice or died., Conclusions: Patients with mUC who progressed on atezolizumab were unlikely to receive subsequent systemic treatments and the benefit of those treatments appeared limited in our cohort. The findings may impact timing and designs of clinical trials in mUC.

Introduction: Enteral access through the jejunum is indicated when patients cannot tolerate oral intake or gastric feeding. While multiple approaches for feeding jejunal access exist, few studies have compared the efficacy of these techniques. The purpose of this study was to investigate the long-term durability, re-intervention rates, and nutritional outcomes following percutaneous endoscopic gastrostomy tubes with jejunal extension tubes (PEG-JET) versus laparoscopic jejunostomy tubes (j-tubes)., Methods: Retrospective chart review was performed on all patients who underwent PEG-JET or laparoscopic jejunostomy tube placement from January 2005 through December 2015 at our institution. Thirty-day and long-term outcomes were compared between the two groups., Results: A total of 105 patients underwent PEG-JET and 307 patients underwent laparoscopic j-tube placement during the defined study period. In terms of 30-day outcomes, patients who underwent PEG-JET placement were significantly more likely to experience a tube dislodgement event (p = 0.005) and undergo a re-intervention (p < 0.001). Patients who had a laparoscopic j-tube placed were significantly more likely to meet their enteral feeding goals (p = 0.002) and less likely to require nutritional supplementation with total parenteral nutrition (TPN) (p < 0.001). With regard to long-term outcomes, patients who underwent PEG-JET placement were significantly more likely to experience tube occlusion (p < 0.001) and require an endoscopic or surgical tube re-intervention (p < 0.001). Patients who underwent laparoscopic j-tube placement were significantly more likely to experience a tube site leak (p = 0.015) but were less likely to require nutritional supplementation with TPN (p = 0.001)., Conclusion: Laparoscopic jejunostomy tubes provide more durable long-term enteral access compared to PEG-JET. Consideration should be given to laparoscopic jejunostomy tube placement in eligible patients who cannot tolerate oral intake or gastric enteral feeding.

Background: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest., Objective: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS., Methods: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0-6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1-2 × 10 6 MSCs/kg were thawed and administered IV., Results: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1-3 passages) was 1.9 × 10 6 MSCs/kg (range, 1.5-2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation., Conclusion: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

Background: Psychosocial and ethical variables influence physicians in requesting decision-making capacity (DMC) evaluations. Previous authors have classified certain DMC evaluation requests as "unwarranted" when there is no explicit suspicion or evidence that the patient might lack DMC., Objective: To explore psychosocial and ethical reasons motivating both "warranted" and "unwarranted" DMC evaluation requests by physicians in the medical setting., Methods: A retrospective electronic health record review was approved by the institutional review board. All psychiatric consultation requests identified as DMC evaluation requests between January 1, 2012 and December 31, 2012 were assessed independently by 2 reviewers. Each reviewer identified each DMC evaluation request as "warranted" vs "unwarranted." Unwarranted DMC evaluation requests were defined as those lacking explicit suspicion that the patient might lack DMC or those with explicit evidence of a patient with blatantly impaired DMC. We hypothesized that most (over half) DMC evaluation requests would be deemed unwarranted. Descriptive statistics, chi-square/Fisher exact tests, and t-test/ANOVA were used., Results: A total of 146 DMC evaluations were reviewed, and 83 (56.8%) of these were deemed unwarranted. Of these, most were likely driven by a previous neuropsychiatric disturbance (p < 0.001). Various other psychosocial and ethical patterns were identified (i.e., the practice of defensive medicine and guardianship concerns)., Conclusion: Over half of DMC evaluation requests in a general medical setting were unwarranted. Many such requests were motivated by unarticulated psychosocial and ethical factors. DMC evaluation requests appear to serve as a means for indirectly resolving various psychosocial and ethical dilemmas beyond assessing DMC itself. Implications and future directions are discussed., (Copyright © 2017 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: A majority of academic medical centers (AMCs) have now adopted conflict of interest policies (COI) to address relationships with pharmaceutical and device industries that can increase the risk of bias in patient care, education and research. However, AMCs may have little information on the impact of their policies. This paper provides a new method, which is a free, publicly-available survey, to fill this information gap and improve COI programs at AMCs., Methods & Findings: The survey, piloted in three AMCs and designed in collaboration with national conflicts of interest policy experts, covers a range of universal compliance-related concerns, which allows institutions to tailor questions to align with their own policies and culture. The survey was low-burden, and provided important data for these AMCs to evaluate their policies. A descriptive analysis of the pooled pilot site data (n = 1578) was performed, which found that a majority of respondents did not have financial ties with industry and a majority was satisfied with specific COI policies at their institutions. The analysis also showed that the survey is sensitive to differences that AMCs will find meaningful. For instance, individuals with industry ties were significantly more likely than individuals without ties to think that COI policies unnecessarily hindered interactions with industry (p = .004), were ineffective at reducing harm to patients (p < .001), and were ineffective in reducing bias in medical education (p>.001)., Conclusion: The survey is now free and publicly available for use by any institution. AMCs can use the results to update and refine policies, and to provide ongoing education regarding existing policies.

Purpose: The purpose of this study was to validate a 10-factor model of risk factors for hospital-acquired pressure injury (HAPI) risk in patients with vascular disease., Subjects and Setting: Medical reviews identified 800 patients from a 1063 admissions to a 1400 bed quarternary care hospital in the midwestern United States., Design: Retrospective review of medical records., Methods: Medical records of consecutive patients treated during an 18-month period on a medical-surgical vascular progressive care unit were reviewed. Ten previously identified risk factors for HAPI-(1) lower right ankle-brachial index, (2) low Braden Scale for Pressure Sore Risk score, (3) cared for in intensive care unit, (4) low serum hematocrit values, (4) elevated serum hematocrit levels (5) female gender, (6) nonwhite individual, (7) atherosclerosis, (8) diabetes mellitus, (9) elevated blood urea nitrogen levels, and (10) high body mass index-were compared to determine their ability to predict development of HAPI. Logistic regression model was used to validate the model., Results: One hundred forty-six (16.1%) out of 800 patients developed an HAPI. The 10-factor risk model produced a concordance index of predicted to actual risk of 0.851, and the likelihood of developing an HAPI based on the model was significant (P < .001)., Conclusions: A 10-factor model of HAPI risk was developed for patients with vascular disease. Routine assessment of risk factors is crucial in planning individualized interventions to diminish the risk of HAPI occurrences.

Background: Skilled physician communication is a key component of patient experience. Large-scale studies of exposure to communication skills training and its impact on patient satisfaction have not been conducted., Objective: We aimed to examine the impact of experiential relationship-centered physician communication skills training on patient satisfaction and physician experience., Design: This was an observational study., Setting: The study was conducted at a large, multispecialty academic medical center., Participants: Participants included 1537 attending physicians who participated in, and 1951 physicians who did not participate in, communication skills training between 1 August 2013 and 30 April 2014., Intervention: An 8-h block of interactive didactics, live or video skill demonstrations, and small group and large group skills practice sessions using a relationship-centered model., Main Measures: Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS), Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CGCAHPS), Jefferson Scale of Empathy (JSE), Maslach Burnout Inventory (MBI), self-efficacy, and post course satisfaction., Key Results: Following the course, adjusted overall CGCAHPS scores for physician communication were higher for intervention physicians than for controls (92.09 vs. 91.09, p < 0.03). No significant interactions were noted between physician specialty or baseline CGCAHPS and improvement following the course. Significant improvement in the post-course HCAHPS Respect domain adjusted mean was seen in intervention versus control groups (91.08 vs. 88.79, p = 0.02) and smaller, non-statistically significant improvements were also seen for adjusted HCAHPS communication scores (83.95 vs. 82.73, p = 0.22). Physicians reported high course satisfaction and showed significant improvement in empathy (116.4 ± 12.7 vs. 124 ± 11.9, p < 0.001) and burnout, including all measures of emotional exhaustion, depersonalization, and personal accomplishment. Less depersonalization and greater personal accomplishment were sustained for at least 3 months., Conclusions: System-wide relationship-centered communication skills training improved patient satisfaction scores, improved physician empathy, self-efficacy, and reduced physician burnout. Further research is necessary to examine longer-term sustainability of such interventions.

Background: The aim of the present study was to assess the risk of overall mortality, coronary artery disease (CAD), and congestive heart failure (CHF) in patients with type 2 diabetes mellitus (T2DM) treated with metformin (MF) and an additional antidiabetic agent., Methods: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 13,185 adult patients (>18 years) with T2DM from January 2008 to June 2013 and received a prescription for MF in combination with a sulfonylurea (SU; n = 9419), thiazolidinedione (TZD; n = 1846), dipeptidyl peptidase-4 inhibitor (DPP-4i; n = 1487), or a glucagon-like peptide-1 receptor agonist (GLP-1a; n = 433). Multivariate Cox models with propensity analysis were used to compare cohorts, with MF+SU serving as the comparator group., Results: The mean (±SD) age was 60.6 ± 12.6 years, with 54.6% male and 75.8% Caucasians. The median follow-up was 4 years. There were 1077 deaths, 1733 CAD events, and 528 CHF events in 55,100 person-years of follow-up. A higher risk of CHF was observed with MF+DPP-4i use (hazard ratio [HR] 1.104; 95% confidence interval [CI] 1.04-1.17; P = 0.001). A trend towards improved overall survival for users of MF+TZD (HR 0.86; 95% CI 0.74-1.0; P = 0.05) and MF+GLP-1a (HR 0.569; 95% CI 0.30-1.07; P = 0.08) was observed. No significant differences in the risk of CAD were identified., Conclusions: Consistent with recent studies, our results raise concern for an increased risk of CHF with use of DPP-4i., (© 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Purpose: Low serum 25-hydroxyvitamin D [25(OH)D] levels have been linked to both cancer incidence and poor prognosis. The frequency of 25(OH)D tests and clinical factors associated with low levels in cancer patients are unknown., Patients and Methods: Electronic medical records from 2006 to 2007 of 39,252 adult solid tumor patients were reviewed. Data included demographics, cancer sites (primary and metastatic), and first serum 25(OH)D level during the study period. Laboratory data, comorbidities, selected medications, and anticancer treatment within the prior 2 months were recorded. Data were compared between (1) those tested and not tested and (2) 25(OH)D levels≤10 ng/ml (deficient), 11-30 ng/ml (insufficient), and ≥31 ng/ml (sufficient). Stepwise logistic regression identified independent predictors of low serum 25(OH)D levels., Results: The cohort was 86% Caucasian and 48% female with a mean age of 63±14 years (mean±SD). The most prevalent cancer was breast (19%). In total, 2,098 (5%) had a 25(OH)D test. Of those tested, 133 (6%) had levels≤10 ng/ml and 1,311 (62%) 11-30 ng/ml. Tests were more frequent in females and in those with breast, skin, and thyroid cancers (P<0.001). Low 25(OH)D levels were associated (in univariable analyses) with male gender, non-Caucasian race, gastrointestinal tumor primary sites, metastatic disease, benign liver disease, low serum albumin, and elevated liver enzymes. Significant factors in multivariable models for 25(OH)D levels≤10 and ≤30 ng/ml included non-Caucasian race, primary cancer site, and test calendar month. Vitamin D supplements and recent antineoplastic medication were associated with sufficient levels., Conclusions: Low (deficient or insufficient) 25(OH)D serum levels were highly prevalent in people with solid tumors. Vitamin D tests were infrequent and paradoxically less often done in high-risk groups. Tests were more frequent in females and in those with breast, skin, and thyroid cancers. Further research should examine role of routine 25(OH)D tests, the clinical consequences of low levels, and therapeutic supplementation in people with cancer.

Background: Although pressure ulcer (PU) risk factors are well known in the general population, little research is available in hospitalized surgical patients admitted with vascular diseases., Methods: Using a retrospective medical records review, characteristics of hospitalized surgical patients with vascular diseases were assessed. Variables were based on literature review of PUs and availability of medical records and administrative data. Trained registered nurses collected data. Analyses included descriptive and comparative statistics, and multivariable modeling was used to determine predictors of PU., Results: In 849 adult admissions, 18.9% had a PU; 11.8% were hospital-acquired PU (HAPU). Patients were more likely to be elderly, male (n = 575; 67.7%), and Caucasian (n = 704; 83.3%). Common diagnoses were aneurysms/embolisms (43.2%) and atherosclerosis (31.2%). Patients with HAPU were more likely to be discharged to a skilled nursing or other facility compared with home (P < .001). In univariate analyses, 12 patient characteristics were associated with HAPU presence: Female gender, non-married status, current smoker, non-Caucasian race, non-intensive care unit (ICU) stay, primary diagnosis of atherosclerosis, higher analgesic use, higher right ankle brachial index (ABI), lower Braden score, higher blood urea nitrogen (BUN) higher serum creatinine and higher total protein levels. In multivariate analyses, nine factors predicted HAPU: Lower right ABI and Braden score, an ICU stay, low and high hematocrit values, female gender, non-White race, atherosclerosis history, and higher BUN and body mass index (BMI). The concordance index for the nine-item model was 0.854., Conclusion: The rate of HAPU in hospitalized surgical patients with vascular diseases was greater than expected. Assessment of important HAPU factors and implementation of interventions are needed to decrease risk and improve clinical outcomes., (Published by Mosby, Inc.)

An emerging, cost-effective method to examine prevalent and future health risks of persons with disabilities is electronic health record (EHR) analysis. As an example, a case-control EHR analysis of adults with autism spectrum disorder receiving primary care through the Cleveland Clinic from 2005 to 2008 identified 108 adults with autism spectrum disorder. In this cohort, rates of chronic disease included 34.9% for obesity, 31.5% for hyperlipidemia, and 19.4% for hypertension. Compared with a control cohort of patients from the same health system matched for age, sex, race, and health insurance status, adults with autism spectrum disorder were more likely to be diagnosed with hyperlipidemia (odds ratio  =  2.0, confidence interval  =  1.2-3.4, p  =  .012). Without intervention, adults with autism spectrum disorder appear to be at significant risk for developing diabetes, coronary heart disease, and cancer by midlife.

Background and Aims: Adults with intellectual and other developmental disabilities (IDD) are at risk for sub-optimal primary health care. Electronic Health Record (EHR) analyses are an under-utilized resource for studying the health and primary care of this population., Methods: This was a case-control EHR analysis of adults with IDD provided primary care through the Cleveland Clinic between 2005 and 2008. The IDD cohort was identified by relevant ICD-9 codes in problem list and encounter diagnoses. A comparison cohort matched by age, sex, race, and insurance was also specified. Demographic, health and health service characteristics of the two cohorts were compared., Findings: The IDD cohort consisted of 1267 individuals, mean age 39 years, 54% male, 78% Caucasian. Age, sex, racial, and health insurance characteristics were similar in the 2534 individuals in the comparison cohort. Individuals with IDD were significantly more likely to carry diagnoses of epilepsy, constipation, osteoporosis, obesity, and hyperlipidemia; but were significantly less likely to bear diagnoses of hypertension, diabetes, osteoarthritis, heart failure, coronary heart disease, and COPD. Despite a lower mean BMI, individuals with IDD were more likely to be labeled obese. Only genetic consultation rates were higher in the IDD cohort., Discussion: Health services research related to persons with IDD is becoming more feasible as large health systems adopt EHRs. Further analyses from this dataset will investigate whether variations in disease rates in adults with IDD represent true differences in disease prevalence versus disparities in health care.

Context: Anorexia is a common symptom in cancer and is usually assessed by multiple questions and multidimensional questionnaires. A simplified questionnaire would be less burdensome to patients and abbreviate the process., Objectives: We compared the reliability at one point in time, sensitivity to change over time, and prognostic accuracy of a two-item questionnaire with the Functional Assessment of Anorexia and Cachexia Therapy shortened 12-question version (A/CS-12)., Methods: Individuals with cancer, who were cognitively intact and verbally agreed to participate, completed a two-item questionnaire and A/CS-12 in random order and again seven days later. We compared the direction of response to the summated two-item questionnaire to the validated A/CS-12 score at a single point in time, then intra-patient changes over a seven-day period of time. Scores of both questionnaires were divided into poor, moderate and good appetite and compared to survival using Kaplan-Meyer curves. Bootstrapping was used to construct confidence intervals for estimated probability agreement. Survival analysis also used hazard ratios from a Cox Proportional Hazards model., Results: One hundred seventeen individuals from a single institution participated, who were either admitted to an inpatient palliative unit or seen in an outpatient/palliative medicine unit. Median age was 58.8 (range 10.7-87.1 years). Agreement at one point in time was 0.64 (95% confidence interval [CI] 0.63 - 0.66). Agreement over time was 0.53 (CI 0.41 - 0.64). The A/CS-12 predicted survival based on scores on Days 1 and 7 (P<0.001), (P=0.003) (HR 0.97 day 1, HR 0.95 day 7), whereas the simplified questionnaire failed to predict survival., Conclusions: A simplified questionnaire has moderate correlation with the A/CS-12 at one point in time but loses sensitivity over time, and lacks the ability to predict survival. A change in the questionnaire may improve reliability. Changing question 2 of the simplified questionnaire to a neutral form (better, same or worse appetite) may improve sensitivity and prognostic capability.

Background: Vascular access is a critical skill for emergency physicians. However, it can be unpredictably challenging in some patients. While ultrasound-guided vascular access has been encouraged in emergency departments, there have been few studies evaluating echo-enhanced needles and their usefulness in performing vascular access., Aims: Our purpose was to determine if the use of an echo-enhanced needle tip results in faster vascular access times, with fewer needle sticks, fewer redirections, and improved needle visualization in ultrasound-guided vascular access with the vessel in the short axis., Methods: This is a prospective, randomized, observational study of ultrasound-guided vascular access on a vascular phantom comparing an echo-enhanced needle with a standard needle. Each participant viewed a teaching video demonstrating typical ultrasound-guided vascular access and then attempted ultrasound-guided vascular access using both a standard and an echo-enhanced needle with the vessel in the short axis. The numbers of needle sticks, redirections, and time to dye flash were measured., Results: The 69 participants attempted 69 short-axis ultrasound-guided vascular cannulations with no difference in time to dye flash between needle types: the median time from needle stick to flash was 17.56 s [interquartile range (IQR): 12.37-33.15] for the standard needle and 19.22 s (IQR: 10.19-31.10) for the echo-enhanced needle. There was no difference between needle types for number of needle sticks or redirects., Conclusion: Echo-enhanced needles did not provide objective performance improvement compared to standard needles during ultrasound-guided vascular access with a vascular access model in the short axis.

Prior studies of myeloma treated with conventional chemotherapy or autologous stem cell transplantation have shown immunohistochemistry for cyclin D1, fibroblast growth factor receptor 3, and p53 to be prognostically significant. The clinical significance of these phenotypic abnormalities in thalidomide-based regimens is currently unknown. We examined the clinical significance of immunohistochemistry for cyclin D1, fibroblast growth factor receptor 3, p53, and cyclin D3 in 94 patients treated with pegylated doxorubicin, vincristine, dexamethasone, and thalidomide, including 49 newly diagnosed and 45 relapsed/refractory patients. The incidence of positivity for cyclin D1, fibroblast growth factor receptor 3, p53, and cyclin D3 was similar in newly diagnosed versus relapsed/refractory groups (37%, 8%, 4%, and 2% versus 42%, 7%, 11%, and 2%, respectively). In contrast to prior studies of other therapeutic regimens, cyclin D1 negativity or fibroblast growth factor receptor 3 positivity did not convey an adverse progression-free or overall survival. p53 positivity, although uncommon, was associated with shorter progression-free and overall survival in newly diagnosed cases. The findings suggest that a thalidomide-based regimen may overcome the poor prognosis associated with a cyclin D1-negative or fibroblast growth factor receptor 3-positive phenotype.

The relationship between multiple sclerosis (MS) disease activity and myelin protein-induced cytokine responses over time is not elucidated. We addressed this relationship by examining longitudinal cytokine responses to myelin proteins every three months for one year, in the context of gadolinium (gad)-enhancing brain lesions and of clinical relapses. The ELISPOT assay was used to determine the ex vivo cytokine production in response to nine amino acid long peptides spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP) molecules in relapsing-remitting (RR) MS patients and matched healthy controls. We identified three longitudinal levels of myelin-induced cytokine secretion by adding up the positive responses for all PLP or MBP peptides obtained for five timepoints, at three-month intervals: low reactivity (< 200 cumulative cytokine-secreting cells), isolated peptide reactivity (201-450 cumulative cytokine-secreting cells) and recurrent protein-wide bursts of cytokine reactivity (> 451 cumulative cytokine-secreting cells). The majority of MS patients showed recurrent bursts to PLP and MBP. In contrast, controls showed a more even distribution between all levels of cytokine reactivity. The majority of patients with gad-enhancing lesions showed PLP/IFN gamma and MBP/IFN gamma recurrent burst responses. This is the first longitudinal study on MS patients in which nine amino acid long myelin peptides are used to reveal the broad range of PLP- and MBP-peptide cytokine reactivity across the whole molecule of these two major myelin proteins. This study also reveals the extremely dynamic nature of the immune reactivity to numerous regions of myelin, which can fluctuate dramatically over time. Such fluctuation could hamper the efficacy of antigen-based therapies for MS.

Objective: This study evaluates the use of high-frequency ultrasound in the measurement of the material nature of the pediatric craniofacial skeleton., Study Design and Setting: Three desiccated human skulls, aged 1 year, 5 years, and adult, underwent ultrasonic evaluation at 6 sites on each hemicranium., Results: The overall mean signal reflection coefficients for the infant, child, and adult skulls are 98.8 mV (13.75 mV SD), 172 mV (24.5 mV SD), and 230 mV (23.5 mV SD), respectively. The mean signal reflection coefficient is positively correlated with increasing chronological age. Comparison of intrasubject signal patterns suggests bone density fields, which vary as a function of growth., Conclusion: High-frequency ultrasound provides accurate measurements of the osseous impedance of the craniofacial skeleton. Pattern analysis suggests increases in skull density with greater growth and age., Significance: Although further testing must be performed in vivo, high-frequency ultrasound may accurately measure the osseous impedance of the pediatric craniofacial skeleton., Ebm Rating: C.

Hormone replacement therapy has been associated with venous thromboembolism. Controversy exists regarding the appropriate management of hormone replacement in the perioperative setting and in other situations--such as acute illness--predisposing to acute venous thromboembolism. We performed a case-control study to determine whether perioperative hormone replacement is associated with venous thromboembolism following hip and knee arthroplasty. 108 patients with postoperative venous thrombosis were matched by age, date and type of surgery, and surgeon with 210 controls without thrombosis. Perioperative hormone replacement use was no more prevalent in patients with postoperative thrombosis than those without. Eighteen (16.7%) women with post-operative thrombosis had taken perioperative hormone replacement compared to 49 (23.3%) of controls: odds ratio = 0.66; (95% CI 0.35-1.18; p=0.17). After multivariate analysis, the adjusted odds ratios were similar. Variables predicting post-operative thrombosis included: prior venous thromboembolism (OR = 2.3; p = 0.02), rheumatologic disease (OR = 2.2; p = 0.03), and absence of pharmacologic antithrombotic prophylaxis (OR = 13.4; p = 0.005). Cases and controls were otherwise similar. Users of hormone replacement were similar to non-users except that they were less likely to have coronary disease (OR 0.34; p = 0.03) or prior thrombosis (OR = 0.28; p = 0.04), and were younger (median age 67 versus 74 years; p <0.0001). We found no association between perioperative hormone replacement and post-operative thrombosis in patients undergoing major orthopaedic surgery. Routine discontinuation of these medications preoperatively--and possibly in other situations predisposing to thrombosis, such as acute medical illness--may be unnecessary in patients receiving appropriate pharmacologic antithrombotic prophylaxis.

Unlabelled: In this randomized, prospective, double-blinded clinical trial, we sought to investigate whether diaspirin-crosslinked hemoglobin (DCLHb) can reduce the perioperative use of allogeneic blood transfusion. One-hundred-eighty-one elective surgical patients were enrolled at 19 clinical sites from 1996 to 1998. Selection criteria included anticipated transfusion of 2-4 blood units, aortic repair, and major joint or abdomino-pelvic surgery. Once a decision to transfuse had been made, patients received initially up to 3 250-mL infusions of 10% DCLHb (n = 92) or 3 U of packed red blood cells (PRBCs) (n = 89). DCLHb was infused during a 36-h perioperative window. On the day of surgery, 58 of 92 (64%; confidence interval [CI], 54%-74%) DCLHb-treated patients received no allogeneic PRBC transfusions. On Day 1, this number was 44 of 92 (48%; CI, 37%-58%) and decreased further until Day 7, when it was 21 of 92 (23%; CI, 15%-33%). During the 7-day period, 2 (1-4) units of PRBC per patient were used in the DCLHb group compared with 3 (2-4) units in the control patients (P = 0.002; medians and 25th and 75th percentiles). Mortality (4% and 3%, respectively) and incidence of suffering at least one serious adverse event (21% and 15%, respectively) were similar in DCLHb and PRBC groups. The incidence of jaundice, urinary side effects, and pancreatitis were more frequent in DCLHb patients. The study was terminated early because of safety concerns. Whereas the side-effect profile of modified hemoglobin solutions needs to be improved, our data show that hemoglobin solutions can be effective at reducing exposure to allogeneic blood for elective surgery., Implications: In a randomized, double-blinded red blood cell controlled, multicenter trial, diaspirin-crosslinked hemoglobin spared allogeneic transfusion in 23% of patients undergoing elective noncardiac surgery. The observed side-effect profile indicates a need for improvement in hemoglobin development.

Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid-eye-movement (REM) sleep, slow-wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep., Methods: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow-up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test., Results: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP-treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects., Conclusions: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption.

The inability to measure borders and variation in the number of 1-mm cross sections acquired from an identical length of vessel in serial intravascular ultrasound (IVUS) pullbacks represents potential errors in calculating volumes by IVUS. In a clinical IVUS trial, the percentage of nonmeasurable lumen and external elastic membrane borders, and the percent variation in the number of 1-mm cross sections acquired from an identical vessel length at 2 separate time points, were determined. A statistical model that simulated the effect of varying the percentage of the total number of cross sections in a pullback (i.e., sample fraction) was developed using SAS software. Mean and maximum errors for calculation of atheroma volume for each sample fraction were determined. The mean percentage of nonmeasurable lumen and external elastic membrane borders in an individual patient was 8.4 +/- 8.4% and 17.4 +/- 18.4%, respectively. Mean variation in the number of 1-mm cross sections acquired in serial studies was 5.6 +/- 6.2%. A decrease in sample fraction from 95% to 50% was associated with a linear increase in the mean and maximum errors in atheroma volume, from 2.0 +/- 0.9% and 5.9 +/- 3.0%, to 7.1 +/- 2.8% and 23.4 +/- 10.3%, respectively. Thus, nonmeasurable borders and variation in the number of 1-mm cross sections acquired from an identical length of vessel in serial studies are real considerations in clinical IVUS trials. However, given the reported incidence of these considerations in this clinical trial, our statistical model suggests that the impact of each of these considerations on atheroma volume calculation is small.

Objective: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes., Methods: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997., Results: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization., Conclusions: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

Background: The results of in-hospital resuscitations may depend on a variety of factors related to the patient, the environment, and the extent of resuscitation efforts. We studied these factors in a large tertiary referral hospital with a dedicated certified resuscitation team responding to all cardiac arrests., Methods: Statistical analysis of 445 prospectively recorded resuscitation records of patients who experienced cardiac arrest and received advanced cardiac life support resuscitation. We also report the outcomes of an additional 37 patients who received limited resuscitation efforts because of advance directives prohibiting tracheal intubation, chest compressions, or both., Main Outcome Measures: Survival immediately after resuscitation, at 24 hours, at 48 hours, and until hospital discharge., Results: Overall, 104 (23%) of 445 patients who received full advanced cardiac life support survived to hospital discharge. Survival was highest for patients with primary cardiac disease (30%), followed by those with infectious diseases (15%), with only 8% of patients with end-stage diseases surviving to hospital discharge. Neither sex nor age affected survival. Longer resuscitations, increased epinephrine and atropine administration, multiple defibrillations, and multiple arrhythmias were all associated with poor survival. Patients who experienced arrests on a nursing unit or intensive care unit had better survival rates than those in other hospital locations. Survival for witnessed arrests (25%) was significantly better than for nonwitnessed arrests (7%) (P =.005). There was a disproportionately high incidence of nonwitnessed arrests during the night (12 AM to 6 AM) in unmonitored beds, resulting in uniformly poor survival to hospital discharge (0%). None of the patients whose advance directives limited resuscitation survived., Conclusions: Very ill patients in unmonitored beds are at increased risk for a nonwitnessed cardiac arrest and poor resuscitation outcome during the night. Closer vigilance of these patients at night is warranted. The outcome of limited resuscitation efforts is very poor.

Purpose: This study was undertaken to determine the safety and efficacy of reoperations for recurrent carotid stenosis (REDOCEA) at the Cleveland Clinic., Materials and Methods: From 1989 to 1999, 206 consecutive REDOCEAs were performed in 199 patients (131 men, 68 women) with a mean age of 68 years (median, 69 years; range, 47-86 years). A total of 119 procedures (57%) were performed for severe asymptomatic stenosis, 55 (27%) for hemispheric transient ischemic attacks or amaurosis fugax, 26 (13%) for prior stroke, and 6 (3%) for vertebrobasilar symptoms. Eleven REDOCEAs (5%) were combined with myocardial revascularization, and another 19 (9%) represented multiple carotid reoperations (17 second reoperations and 2 third reoperations). Three REDOCEAs (1%) were closed primarily, and nine (4%) required interposition grafts, whereas the remaining 194 (95%) were repaired with either vein patch angioplasty (139 [68%]) or synthetic patches (55 [27%]). Three patients (2%) were lost to follow-up, but late information was available for 196 patients (203 operations) at a mean interval of 4.3 years (median, 3.9 years; maximum, 10.2 years)., Results: Considering all 206 procedures, there were 7 early (< 30 days) postoperative neurologic events (3.4%), including 6 perioperative strokes (2.9%) and 1 occipital hemorrhage (0.5%) on the 12th postoperative day. Seventeen additional neurologic events occurred during the late follow-up period, consisting of eight strokes (3.9%) and nine transient ischemic attacks (4.4 %). With the Kaplan-Meier method, the estimated 5-year freedom from stroke was 92% (95% CI, 88%-96%). There were two early postoperative deaths (1%), both from cardiac complications after REDOCEAs combined with myocardial revascularization procedures. With the Kaplan-Meier method, the estimated 5-year survival was 81% (range, 75%-88%). A univariate Cox regression model yielded the presence of coronary artery disease as the only variable that was significantly associated with survival (P =.024). The presence of pulmonary disease (P =.036), diabetes (P =.01), and advancing age (P =.006) was found to be significantly associated with stroke after REDOCEA. Causes of 53 late deaths were cardiovascular problems in 25 patients (47%), unknown in 14 (26%), renal failure in 4 (8%), stroke in 3 (6%), and miscellaneous in 7 (13%)., Conclusions: We conclude that REDOCEA may be safely performed in selected patients with recurrent carotid stenosis and that most of these patients enjoy long-term freedom from stroke.

Objective: Practice guidelines call for the careful titration of sedatives and analgesics during endoscopy, with time taken between incremental doses to assess effect. This approach is time-consuming and has never been validated in a prospective trial. The aim of this study was to compare the safety and efficacy of titration, as outlined in practice guidelines, with a single, rapid bolus of sedatives before colonoscopy., Methods: Consecutive colonoscopy outpatients were randomized to a single, rapid bolus of meperidine and midazolam or to a titration of doses every 3 min until predefined levels of somnolence were achieved. The colonoscopist was not present during sedation and remained blinded as to which technique was used. Supplemental O2 was given for SaO2 <90% on three or more occasions. Total physician time was calculated from the first injection of sedatives to the removal of the colonoscope. Patient assessments of pain and tolerance were obtained at the time of discharge using visual analog scales of 100 mm (0 = excellent and 100 = unbearable)., Results: A total of 101 patients were randomized (49 bolus, 52 titration). Demographic features were similar for both groups. Titration required more physician time than did bolus (32.2 min vs 20.1 min, p < 0.001) and was associated with an increased need for supplemental O2 (44% vs 14%, p = 0.002). Mean tolerance scores were similar (titration 16.3 vs bolus 15.3, p = 0.72)., Conclusions: Rapid bolus sedation for colonoscopy saves significant endoscopist time, is associated with less O2 desaturation, and provides equivalent levels of patient comfort. A revision of the guidelines for sedation and analgesia during endoscopy should be considered.