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Communication errors during shift-to-shift handoffs are a leading cause of preventable adverse events. Nevertheless, handoff skills are variably taught at medical schools. The authors administered questionnaires on handoffs to interns during orientation. Questions focused on medical school handoff education, experiences, and perceptions. The majority (546/718) reported having some form of education on handoffs during medical school, with 48% indicating this was 1 hour or less. Most respondents (98%) reported that they believe patients experience adverse events because of inadequate handoffs, and more than one third had witnessed a patient safety issue. Results show that medical school graduates are not receiving adequate handoff training. Yet graduates are expected to conduct safe patient handoffs at the start of residency. Given that ineffective handoffs pose a significant patient safety risk, medical school graduates should have a baseline competency in handoff skills. This will require medical schools to develop, implement, and study handoff education. [ABSTRACT FROM AUTHOR]

Objective Our aims were to evaluate whether there is an inverse association between body mass index (BMI) and umbilical artery pH and to investigate the contribution of intraoperative hypotension on the umbilical artery pH. Study Design We conducted a retrospective cohort study of all women with a nonanomalous singleton at 37 to 41 weeks who underwent a scheduled cesarean delivery under spinal anesthesia at our facility from January 2006 to March 2012. The primary outcome was the proportion of patients in each BMI category with arterial cord pH < 7.10. Intraoperative blood pressure data were compared across BMI categories. Results In total, 717 mother--infant pairs met enrollment criteria. Mean arterial pH was significantly lower in women with elevated BMI (p = 0.014), notably with BMI ≥ 40 kg/m². Baseline blood pressure increased linearly with increasing BMI (p < 0.001), however, so did the maximum drop in all blood pressure parameters (p < 0.001). After adjusting for potential confounders, including blood pressure, there was no longer an association between cord pH and BMI (p = 0.72). Conclusion For women undergoing a scheduled cesarean delivery under spinal anesthesia, umbilical artery pH is lower in women with BMI ≥40 kg/m². Relative hypotension after spinal anesthesia is more pronounced with increasing BMI and may explain this effect. [ABSTRACT FROM AUTHOR]

Background: Black individuals are at greater risk of stroke and vitamin D deficiency than white individuals. Epidemiologic studies have shown that low 25-hydroxyvitamin D concentrations are associated with increased risk of stroke, but these studies had limited representation of black individuals. Methods: We examined the association of 25-hydroxyvitamin D with incident stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a cohort of black and white adults ≥45 years of age. Using a case- cohort study design, plasma 25-hydroxyvitamin D was measured in 610 participants who developed incident stroke (cases) and in 937 stroke-free individuals from a stratified cohort random sample of REGARDS participants (comparison cohort). Results: In multivariable models adjusted for socio-demographic factors, co-morbidities and laboratory values including parathyroid hormone, lower 25-hydroxyvitamin D concentrations were associated with higher risk of stroke (25-hydroxyvitamin D >30 ng/mL reference; 25-hydroxyvitamin D concentrations 20-30 ng/mL, hazard ratio 1.33, 95% confidence interval (95% CI) 0.89,1.96; 25-hydroxyvitamin D <20 ng/mL, hazard ratio 1.85, 95% CI 1.17, 2.93). There were no statistically significant differences in the association of lower 25-hydroxyvitamin D with higher risk of stroke in black vs. white participants in fully adjusted models (hazard ratio comparing lowest vs. highest 25-hydroxyvitamin D category 2.62, 95% CI 1.18, 5.83 in blacks vs. 1.64, 95% CI 0.83, 3.24 in whites, Pinteraction=0.82). The associations were qualitatively unchanged when restricted to ischemic or hemorrhagic stroke subtypes or when using racespecific cut-offs for 25-hydroxyvitamin D categories. [ABSTRACT FROM AUTHOR]

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 59 and 39 half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3-6 days before symptom onset and 14-17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized. [ABSTRACT FROM AUTHOR]

Multiple sclerosis typically has onset in young adults and new disease activity diminishes with age. Most clinical trials of disease-modifying therapies for multiple sclerosis have not enrolled individuals older than 55 years. Observational studies suggest that risk of return of disease activity after discontinuation of a disease-modifying therapies is greatest in younger patients with recent relapses or MRI activity. We aimed to determine whether risk of disease recurrence in older patients with no recent disease activity who discontinue disease-modifying therapy is increased compared to those who remain on disease-modifying therapy. DISCOMS was a multicentre, randomised, controlled, rater-blinded, phase 4, non-inferiority trial. Individuals with multiple sclerosis of any subtype, 55 years or older, with no relapse within the past 5 years or new MRI lesion in the past 3 years while continuously taking an approved disease-modifying therapy were enrolled at 19 multiple sclerosis centres in the USA. Participants were randomly assigned (1:1 by site) with an interactive response technology system to either continue or discontinue disease-modifying therapy. Relapse assessors and MRI readers were masked to patient assignment; patients and treating investigators were not masked. The primary outcome was percentage of individuals with a new disease event, defined as a multiple sclerosis relapse or a new or expanding T2 brain MRI lesion, over 2 years. We assessed whether discontinuation of disease-modifying therapy was non-inferior to continuation using a non-inferiority, intention-to-treat analysis of all randomly assigned patients, with a predefined non-inferiority margin of 8%. This trial is registered at ClinicalTrials.gov , NCT03073603 , and is completed. 259 participants were enrolled between May 22, 2017, and Feb 3, 2020; 128 (49%) were assigned to the continue group and 131 (51%) to the discontinue group. Five participants were lost to follow-up (continue n=1, discontinue n=4). Six (4·7%) of 128 participants in the continue group and 16 (12·2%) of 131 in the discontinue group had a relapse or a new or expanding brain MRI lesion within 2 years. The difference in event rates was 7·5 percentage points (95% CI 0·6–15·0). Similar numbers of participants had adverse events (109 [85%] of 128 vs 104 [79%] of 131) and serious adverse events (20 [16%] vs 18 [14%]), but more adverse events (422 vs 347) and serious adverse events (40 vs 30) occurred in the discontinue group. The most common adverse events were upper respiratory infections (20 events in 19 [15%] participants in the continue group and 37 events in 30 [23%] participants in the discontinue group). Three participants in the continue group and four in the discontinue group had treatment-related adverse events, of which one in each group was a serious adverse event (multiple sclerosis relapse requiring admission to hospital). One participant in the continue group and two in the discontinue group died; no deaths were deemed to be related to treatment. We were unable to reject the null hypothesis and could not conclude whether disease-modifying therapy discontinuation is non-inferior to continuation in patients older than 55 years with multiple sclerosis and no recent relapse or new MRI activity. Discontinuation of disease-modifying therapy might be a reasonable option in patients older than 55 years who have stable multiple sclerosis, but might be associated with a small increased risk of new MRI activity. Patient-Centered Outcomes Research Institute and the National Multiple Sclerosis Society. [ABSTRACT FROM AUTHOR]

The pericapsular nerve group (PENG) block is a novel regional anaesthesia technique that has been proposed as an effective motor-sparing block for total hip arthroplasty. Recent randomised studies show conflicting results regarding the analgesic efficacy of the PENG block for total hip arthroplasty. We conducted a randomised controlled observer-blinded single-centre superiority trial comparing the efficacy of the PENG block with no block for patients undergoing primary total hip arthroplasty under spinal anaesthesia. All subjects received multimodal analgesia consisting of paracetamol and celecoxib. The primary outcome was quality of recovery (QoR) at 24 h as measured by the QoR-15 questionnaire. A total of 112 participants (56 in each group) were included in the analysis. The median (inter-quartile range [IQR]) 24-h QoR-15 scores were higher in subjects who received a PENG block (132 [116–138]) compared with subjects who did not (103 [97–112]) with a median difference of 26 (95% confidence interval, 18–31; P <0.001). Similarly, QoR-15 at 48 h was higher in the PENG group, and opioid use at 24 and 48 h postoperatively was significantly lower in the PENG group. However, we did not find significant differences in pain score, distance to ambulation, or anti-emetic use at any time point. We did not observe any PENG block-related complications. Adding a PENG block to a multimodal analgesia regimen that includes paracetamol and celecoxib improves the quality of recovery and reduces opioid requirements for patients undergoing primary total hip arthroplasty under spinal anaesthesia. NCT04591353. [ABSTRACT FROM AUTHOR]

Background: New hypertension and heart failure guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with preserved ejection fraction (HFpEF) and hypertension be lowered to <130 mm Hg.Methods: Of the 6778 hospitalized patients with HFpEF and a history of hypertension in the Medicare-linked OPTIMIZE-HF registry, 3111 had a discharge SBP <130 mm Hg. Using propensity scores for SBP <130 mm Hg, we assembled a matched cohort of 1979 pairs with SBP <130 versus ≥130 mm Hg, balanced on 66 baseline characteristics (mean age, 79 years; 69% women; 12% African American). We then assembled a second matched cohort of 1326 pairs with SBP <120 versus ≥130 mm Hg. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with SBP <130 and <120 mm Hg were separately estimated in the matched cohorts using SBP ≥130 mm Hg as the reference.Results: HRs (95% CIs) for 30-day, 12-month, and 6-year all-cause mortality associated with SBP <130 mm Hg were 1.20 (0.91-1.59; P = 0.200), 1.11 (0.99-1.26; P = 0.080), and 1.05 (0.98-1.14; P = 0.186), respectively. Respective HRs (95% CIs) associated with SBP <120 mm Hg were 1.68 (1.21-2.34; P = 0.002), 1.28 (1.11-1.48; P = 0.001), and 1.11 (1.02-1.22; P = 0.022). There was no association with readmission.Conclusions: Among older patients with HFpEF and hypertension, compared with SBP ≥130 mm Hg, the new target SBP <130 mm Hg had no association with outcomes but SBP <120 mm Hg was associated with a higher risk of death but not of readmission. Future prospective studies need to evaluate optimal SBP treatment goals in these patients. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes.Objectives: The purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF.Methods: Of the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort.Results: Matched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up.Conclusions: Hospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF. [ABSTRACT FROM AUTHOR]

Background: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis.Methods and Findings: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence.Conclusions: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis.Trial Registration: Clinicaltrials.gov, NCT02319525. [ABSTRACT FROM AUTHOR]

Background: The efficacy of mineralocorticoid receptor antagonists or aldosterone antagonists in heart failure with reduced ejection fraction (HFrEF) is well known. Less is known about their effectiveness in real-world older patients with HFrEF.Methods: Of the 8206 patients with heart failure and ejection fraction ≤35% without prior spironolactone use in the Medicare-linked OPTIMIZE-HF registry, 6986 were eligible for spironolactone therapy based on serum creatinine criteria (men ≤2.5 mg/dL, women ≤2.0 mg/dL) and 865 received a discharge prescription for spironolactone. Using propensity scores for spironolactone use, we assembled a matched cohort of 1724 (862 pairs) patients receiving and not receiving spironolactone, balanced on 58 baseline characteristics (Creatinine Cohort: mean age, 75 years, 42% women, 17% African American). We repeated the above process to assemble a secondary matched cohort of 1638 (819 pairs) patients with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 (eGFR Cohort: mean age, 75 years, 42% women, 17% African American).Results: In the matched Creatinine Cohort, spironolactone-associated hazard ratios (95% confidence intervals) for all-cause mortality, heart failure readmission, and combined endpoint of heart failure readmission or all-cause mortality were 0.92 (0.81-1.03), 0.87 (0.77-0.99), and 0.87 (0.79-0.97), respectively. Respective hazard ratios (95% confidence intervals) in the matched eGFR Cohort were 0.87 (0.77-0.98), 0.92 (0.80-1.05), and 0.91 (0.82-1.02).Conclusions: These findings provide evidence of consistent, albeit modest, clinical effectiveness of spironolactone in older patients with HFrEF regardless of renal eligibility criteria used. Additional strategies are needed to improve the effectiveness of aldosterone antagonists in clinical practice. [ABSTRACT FROM AUTHOR]

Background: National heart failure guidelines recommend quadruple therapy with renin-angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium-glucose cotransporter 2 inhibitors for patients with heart failure with reduced ejection fraction (HFrEF), most of whom also receive loop diuretics. However, the guidelines are less clear about the safe approaches to discontinuing older drugs whose decreasing or residual benefit is less well understood. The objective of this study was to examine whether digoxin can be safely discontinued in patients with HFrEF receiving beta-blockers., Methods: In OPTIMIZE-HF, of 2,477 patients with HFrEF (EF ≤45%) receiving beta-blockers and digoxin, digoxin was discontinued in 450 patients. We assembled a propensity score-matched cohort of 433 pairs of patients in which digoxin continuation vs. discontinuation groups were balanced on 51 baseline characteristics. Using the same approach, from 992 patients not on beta-blockers, we assembled a matched cohort of 198 pairs of patients also balanced on 51 baseline characteristics. Hazard ratios (HRs) and 95% CIs for one-year outcomes were estimated., Results: Among patients receiving beta-blockers, digoxin discontinuation had no association with the combined endpoint of heart failure readmission or death (HR, 1.01; 95% CI, 0.85-1.19), heart failure readmission (HR, 1.03; 95% CI, 0.85-1.25) or death (HR, 0.91; 95% CI, 0.72-1.14). Respective HRs (95% CIs) among patients not receiving beta-blockers were 1.60 (1.25-2.04), 1.62 (1.18-2.22) and 1.43 (1.08-1.89)., Conclusions: Digoxin can be discontinued without increasing the risk of adverse outcomes in patients with HFrEF receiving beta-blockers. Future studies need to examine the residual benefit of older heart failure drugs to ensure their safe discontinuation in patients with HFrEF receiving newer guideline-directed medical therapy., (Copyright © 2024. Published by Elsevier Inc.)

Our goal was to survey people with epilepsy (PWE) about their interest in and factors that may influence willingness and ability to participate in an exercise randomized controlled trial (RCT). A brief survey was administered to 100 PWE asking if they would take part in a hypothetical 6-week exercise intervention RCT. Follow-up questions queried reasons for and against participation and why participation would be difficult. Sixty-nine percent of respondents indicated willingness to participate. The top reason for participation was "to improve overall health with exercise" (n = 49). The top reason for why participation would be difficult was they "do not have a reliable source of transportation" (n = 27). The top reason for not participating was "not interested in research participation" (n = 19). Preliminary results were used to budget for transportation in a prospective RCT (NCT04959019). Of the first 27 PWE enrolled (63 % female; 44 % African American/Black), six (50 % female; 50 % African American/Black) have used the transportation service. The majority of PWE surveyed were interested in participating in an exercise RCT, but some indicated barriers. Accommodating transportation in an ongoing RCT has facilitated recruitment of PWE who would otherwise not be able to participate. Barriers to participation should be accounted for when designing studies., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JPS is the Editor-in-Chief of Epilepsy & Behavior Reports, associate editor of Journal of Epileptology, editorial board member for Epilepsy & Behavior, Journal of Medical Science, and Folia Medica Copernicana, and receives royalties from Elsevier; receives funding from NIH, NSF, DoD, Shor Foundation for Epilepsy Research, UCB Biosciences, NeuroPace Inc., SAGE Therapeutics Inc., Serina Therapeutics Inc., LivaNova Inc., Greenwich Biosciences Inc., Biogen Inc., Eisai Inc., State of AL; is on consulting /advisory boards for PureTech Health, Biopharmaceutical Research Company, LivaNova Inc., UCB Pharma, AdCel Pharma, iFovea Inc.; has served on the Alabama State Medical Cannabis Study Commission (nominated by Gov. Ivey); serves on the Alabama Medical Cannabis Commission (2021–2025; nominated by Dr. Scott Harris, State Health Officer). JBA is associate editor of Epilepsy & Behavior Reports; receives funding from NIH, McKnight Brain Institute, DoD, LivaNova Inc.; has served as a consultant for LivaNova, Inc.; has received honoraria from Cleveland Clinic and University of Auckland and travel funds from the International League Against Epilepsy; serves on a Data Safety Monitoring Board (University of Alabama at Birmingham/University of Colorado Anschutz Medical Campus); serves on the American Epilepsy Society Scientific Program Committee. The rest of the authors have no disclosures to declare., (© 2023 The Authors. Published by Elsevier Inc.)

Sugammadex produces recovery from neuromuscular blockade more rapidly and reliably than neostigmine. We sought to determine if sugammadex is associated with improved perioperative efficiency when compared to traditional neuromuscular blockade reversal with neostigmine, potentially offsetting the higher medication cost. This retrospective analysis involved patients receiving either neostigmine or sugammadex for reversal of neuromuscular blockade at a single academic tertiary care hospital. The final propensity-matched groups consisted of 4060 in each group (neostigmine or sugammadex). The primary outcome measured was total time in the operating room. Secondary outcomes included specific measures of perioperative efficiency as well as postoperative pulmonary failure. The average operating room time for patients was 169.59 [1.27] minutes for neostigmine and 157.06 [1.33] minutes for sugammadex ( P  < 0.001). The difference was primarily accounted for by shorter surgical times (121.45 [1.18] vs 109.62 [1.22] minutes, P  < 0.011). Sugammadex was also associated with a shorter post-anesthesia care unit length of stay (102.47 [1.04] vs 98.67 [1.02] minutes, P  < 0.001). For 8120 patients, sugammadex use was associated with shorter operating room and surgical durations as well as shorter post-anesthesia care unit stay. The favorable pharmacodynamic profile of sugammadex may improve surgical and perioperative efficiency and offset higher medication cost., (Copyright © 2022 Baylor University Medical Center.)

Objective: Epidural anesthesia for the parturient is often provided in a clinical context where rapid onset of segmental analgesia is important; however, little is published on the ideal local anesthetic to safely achieve this onset. To fi ll this gap in knowledge, we studied bupivacaine and lidocaine, two local anesthetics (LA) commonly used for labor epidural activation, either as a single drug or in combination to determine the onset of epidural analgesia., Methods: In this double-blinded study, seventy-five patients were randomized into three groups (n = 25 each) for labor epidural activation: 10 mL of 0.25% bupivacaine, 10 mL of 1% lidocaine, or 5 mL of 0.25% bupivacaine plus 5 mL of 1% lidocaine. Patients were assessed for the fi rst 20 min after drug administration at 5-min intervals. Data collected included sensory level to pinprick, maternal blood pressure, vasopressor administration, and peak motor blockade., Results: Data were analyzed on 71 of 75 patients. Time to loss of sensation to pinprick at the T10 dermatome in the bupivacaine group was signifi cantly longer than the lidocaine group (p = 0.006), but the time to loss of sensation to pinprick at the T10 dermatome did not signifi cantly differ in the bupivacaine plus lidocaine group when compared to both the bupivacaine (p = 0.114) as well as the lidocaine (p = 0.203) groups. Phenylephrine usage did not signifi cantly differ amongst the three groups (p = 0.062)., Conclusion: Lidocaine provides statistically signifi cant faster onset of epidural analgesia when compared to bupivacaine only. Combining the two LA did not signifi cantly affect onset.

Background: Clinical intuition suggests that a sharp increase in the number of enhancing lesions should signal an increased risk of relapse. The 'rule of five' recommends that subjects exhibiting at least five lesions over the baseline level be referred for closer monitoring. This rule has been used as an informal safety criterion with limited formal evaluation., Objective: The purpose of this study was to determine the best threshold for the rule and to demonstrate its predictive validity for risk of subsequent relapses for multiple sclerosis (MS) trials., Methods: We used logistic regression modeling to apply the rule to patient data from a phase II clinical trial. Predictive validity was ascertained using rate ratios and receiver operating characteristic (ROC) curves., Results: We found that, for these data, a threshold of five lesions over the baseline constituted the best definition of a threshold. Overall, 35% of subjects broke the rule at least once. Breaking the rule increased the odds of imminent relapse by a factor of 3.2 (95% confidence interval (CI): 1.8-5.5)., Conclusion: Breaking the rule of five was found to be a significant predictor of an imminent relapse. Length of follow-up and the number of lesions discovered via magnetic resonance imaging (MRI) were also significant predictors of relapse.