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Importance: Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy.Objective: To examine whether standard cytisine treatment (25 days) was at least as effective as standard varenicline treatment (84 days) for smoking cessation.Design, Setting, and Participants: This noninferiority, open-label randomized clinical trial with allocation concealment and blinded outcome assessment was undertaken in Australia from November 2017 through May 2019; follow-up was completed in January 2020. A total of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data collection was conducted primarily by computer-assisted telephone interview, but there was an in-person visit to validate the primary outcome.Interventions: Treatments were provided in accordance with the manufacturers' recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to 1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard telephone behavioral support.Main Outcomes and Measures: The primary outcome was 6-month continuous abstinence verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin was set at 5% and the 1-sided significance threshold was set at .025.Results: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years; 742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk difference, -1.62% [1-sided 97.5% CI, -5.02% to ∞]; P = .03 for noninferiority). Self-reported adverse events occurred less frequently in the cytisine group (997 events among 482 participants) compared with the varenicline group (1206 events among 510 participants) and the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002).Conclusions and Relevance: Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation.Trial Registration: anzctr.org.au Identifier: ACTRN12616001654448. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if muscular dimensional changes with increases in torque production are influenced by age- and obesity-related increases in intramuscular fat, and its relationship to percent body fat (%BF), echo intensity (EI), strength, and maximum walking speed. Sixty-six healthy men were categorized into 3 groups based on age and body mass index status (young normal weight [YNW], older normal weight [ONW], and older obese [OB]). Participants underwent %BF assessments, resting ultrasonography to determine muscle size (cross-sectional area [CSA]) and EI of the superficial quadriceps, and a 10-m maximum walking speed assessment. Maximal and submaximal (rest-100% MVC in 10% increments) isometric leg extension strength was assessed while changes in rectus femoris (RF) CSA, width, and depth were obtained with ultrasonography. Echo intensity and %BF were different among all groups (p ≤ .007), with the YNW and OB groups exhibiting the lowest and highest %BF and EI values, respectively. The RF increased in depth and decreased in width with increases in torque intensity for all groups. The ONW group demonstrated no change (-0.08%) in RF CSA across torque intensities, whereas the YNW group (-11.5%) showed the greatest decrease in CSA, and the OB group showed a more subtle decrease (-4.6%). Among older men, a greater change in RF CSA was related to poorer EI (r = -0.355) and higher %BF (r = -0.346), while a greater decrease in RF width was associated with faster walking speeds (r = -0.431). Examining muscular dimensional changes during contraction is a unique model to investigate the influence of muscle composition on functional performance. [ABSTRACT FROM AUTHOR]

A number of different voluntary alcohol intake paradigms are available for home cage drinking studies. Traditionally, these paradigms involve single housing in order for individual intake to be measured. This study aimed at investigating the effects of pair housing on voluntary alcohol intake. Male and female Wistar rats were housed in pairs or individually for studies of voluntary alcohol intake using the modified intermittent access paradigm with alcohol access during three consecutive days per week followed by four days of water only. Individual intake of 20% alcohol solution and water was measured during 12 sessions, i.e., 4 weeks. Pair-housed animals could interact freely with their cage mate for four consecutive days each week and were then separated by an inserted mesh divider for three consecutive days each week during alcohol intake sessions. Alcohol intake and preference were compared between pair-housed and individually housed rats. The results revealed higher alcohol intake in females than in males. Pair-housed males had a higher alcohol intake and preference during the first 3 weeks, but not during the fourth week, compared to individually housed males No effect of housing condition was observed in female rats. The alcohol intake was higher on the first day of access relative to the two consecutive days in pair-housed males and higher on the first two days relative to the third day in female rats. Social rank or female estrus cycle had no effect on alcohol intake or preference. Taken together, the use of a divider during alcohol intake sessions had no impact on alcohol intake in female rats and may not exert long-term influences in male rats. Future studies are needed in order to elucidate whether the use of a divider can constitute an experimental refinement as an alternative to individual housing in studies of voluntary alcohol intake using the limited access and/or intermittent access paradigms. [ABSTRACT FROM AUTHOR]

Background: Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear.Methods: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed.Results: A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval [CI], 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out.Conclusions: Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.). [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) contains a subpopulation of cells, GBM stem cells (GSCs), that maintain the bulk tumor and represent a key therapeutic target. Norrin is a Wnt ligand that binds Frizzled class receptor 4 (FZD4) to activate canonical Wnt signaling. Although Norrin, encoded by NDP, has a well-described role in vascular development, its function in human tumorigenesis is largely unexplored. Here, we show that NDP expression is enriched in neurological cancers, including GBM, and its levels positively correlated with survival in a GBM subtype defined by low expression of ASCL1, a proneural factor. We investigated the function of Norrin and FZD4 in GSCs and found that it mediated opposing tumor-suppressive and -promoting effects on ASCL1lo and ASCL1hi GSCs. Consistent with a potential tumor-suppressive effect of Norrin suggested by the tumor outcome data, we found that Norrin signaling through FZD4 inhibited growth in ASCL1lo GSCs. In contrast, in ASCL1hi GSCs Norrin promoted Notch signaling, independently of WNT, to promote tumor progression. Forced ASCL1 expression reversed the tumor-suppressive effects of Norrin in ASCL1lo GSCs. Our results identify Norrin as a modulator of human brain cancer progression and reveal an unanticipated Notch-mediated function of Norrin in regulating cancer stem cell biology. This study identifies an unanticipated role of Norrin in human brain cancer progression. In addition, we provide preclinical evidence suggesting Norrin and canonical Wnt signaling as potential therapeutic targets for GBM subtype-restricted cancer stem cells. [ABSTRACT FROM AUTHOR]

Background: Advanced-stage ovarian cancer has a poor prognosis; surgical resection with the intent to leave no residual tumour followed by adjuvant chemotherapy is the standard treatment. Local anaesthetics (LA) have anti-inflammatory and analgesic effects. We hypothesised that intraperitoneal LA (IPLA) would lead to improved postoperative recovery, better pain relief, and earlier start of chemotherapy.Methods: This was a prospective, randomised, double-blind, placebo-controlled pilot study in 40 women undergoing open abdominal cytoreductive surgery. Patients were randomised to receive either intraperitoneal ropivacaine (Group IPLA) or saline (Group Placebo) perioperatively. Except for study drug, patients were treated similarly. Intraoperatively, ropivacaine 2 mg ml-1 or 0.9% saline was injected thrice intraperitoneally, and after operation via a catheter and analgesic pump into the peritoneal cavity for 72 h. Postoperative pain, time to recovery, home discharge, time to start of chemotherapy, and postoperative complications were recorded.Results: No complications from LA administration were recorded. Pain intensity and rescue analgesic consumption were similar between groups. Time to initiation of chemotherapy was significantly shorter in Group IPLA (median 21 [inter-quartile range 21-29] vs 29 [inter-quartile range 21-40] days; P=0.021). Other parameters including time to home readiness, home discharge and incidence, and complexity of postoperative complications were similar between the groups.Conclusions: Intraperitoneal ropivacaine during and for 72 h after operation after cytoreductive surgery for ovarian cancer is safe and reduces the time interval to initiation of chemotherapy. Larger studies are warranted to confirm these initial findings.Clinical Trial Registration: NCT02256228. [ABSTRACT FROM AUTHOR]

Objectives: To examine metabolic monitoring rates in commercially insured children and adolescents treated with a second-generation antipsychotic (SGA) during calendar years (CYs) 2016 and 2017. Methods: In this retrospective study, data were collected from a large national commercial health plan for the period covering January 1, 2016 to December 31, 2017. Commercially insured children and adolescents, aged 8-19 years with ≥2 SGA prescription claims during the CY, were identified for the CY2016 and CY2017 cohorts. The primary outcome of interest was the percentage of subjects with any glucose or lipid metabolism parameter monitoring. Other calculated metabolic testing rates included glucose, hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol (LDL-C), other cholesterol (including triglycerides), and combined glucose and lipid metabolism testing (≥1 test for blood glucose or HbA1c and ≥1 test for LDL-C or other cholesterol). Results: In CY2016 and CY2017, 1502 and 1239 subjects, respectively, were identified for this study. The most common psychiatric diagnoses in CY2016 and CY2017 were major depressive disorder (57.1%, 56.5%, respectively), anxiety disorders (42.9%, 47.5%), attention-deficit/hyperactivity disorder (41.6%, 45.8%), and bipolar disorder (24.1%, 25.9%). The rate of any metabolic testing was 53.5% in CY2016 and 51.3% in CY2017. Glucose testing (50.3%, 46.9%, respectively) was most common in both CYs, followed by LDL-C testing (31.2%, 28.5%). Rates of combined glucose and lipid metabolism testing were 30.7% in CY2016 and 26.9% in CY2017. Conclusions: Given the known potential for adverse cardiometabolic effects, rates of metabolic monitoring associated with SGA use in children and adolescents urgently need to be improved. There is a critical need for understanding barriers to routine monitoring, particularly of lipids, and developing interventions to enhance metabolic monitoring. [ABSTRACT FROM AUTHOR]

Background: Single-dose baloxavir rapidly reduces influenza virus titers and symptoms in patients with uncomplicated influenza, but viruses with reduced in vitro susceptibility due to amino acid substitutions at position 38 of polymerase acidic protein (PA/I38X) sometimes emerge.Methods: We evaluated the kinetics, risk factors, and effects on clinical and virologic outcomes of emergence of PA/I38X-substituted viruses.Results: Viruses containing PA/I38X substitutions were identified 3-9 days after baloxavir treatment in 9.7% (36/370) of patients, of whom 85.3% had transient virus titer rises. Median time to sustained cessation of infectious virus detection was 192, 48, and 96 hours in the baloxavir recipients with PA/I38X-substituted viruses, without PA/I38X-substituted viruses, and placebo recipients, respectively. The corresponding median times to alleviation of symptoms were 63.1, 51.0, and 80.2 hours, respectively. After day 5, symptom increases occurred in 11.5%, 8.0%, and 13.0%, respectively, and in 8.9% of oseltamivir recipients. Variant virus emergence was associated with lower baseline neutralizing antibody titers.Conclusions: The emergence of viruses with PA/I38X substitutions following baloxavir treatment was associated with transient rises in infectious virus titers, prolongation of virus detectability, initial delay in symptom alleviation, and uncommonly with symptom rebound. The potential transmissibility of PA/I38X-substituted viruses requires careful study.Clinical Trial Registration: NCT02954354. [ABSTRACT FROM AUTHOR]

Background: Postoperative inflammation is a common consequence of surgery and the ensuing stress response. Local anesthetics have anti-inflammatory properties. The primary aim of this study was to evaluate if LA administrated intraperitoneally perioperatively might inhibit expression of inflammatory cytokines.Methods: This was a, randomized, double blind, placebo-controlled study (ClinicalTrial.gov reg no: NCT02256228) in patients undergoing surgery for ovarian cancer. Patients were randomized to receive: intraperitoneal ropivacaine (Group IPLA) or saline (Group P) perioperatively. Except for study drug, patients were treated similarly. At the end of surgery, a multi-port catheter was inserted intraperitoneally, and ropivacaine 2 mg/mL or 0.9% saline, 10 mL was injected intermittently every other hour during 72 hours postoperatively. Systemic expression of cytokines and plasma ropivacaine were determined before and 6, 24, and 48 hours after surgery. Stress response was measured by serum glucose, cortisol, and insulin.Results: Forty patients were recruited, 20 in each group. There was no statistical significant difference in systemic cytokine between the groups at any time point. Serum cortisol was significantly lower in the IPLA group at 6 hours, median 103 nmol/L (IQR 53-250) compared to placebo, median 440 nmol/L (IQR 115-885), P = 0.023. Serum glucose and insulin were similar between the groups. Total and free serum concentrations of ropivacaine were well below toxic concentrations.Conclusion: In this small study, perioperative intraperitoneal ropivacaine did not reduce the systemic inflammatory response associated with major abdominal surgery. Total and free ropivacaine concentrations were below known toxic concentrations in humans. [ABSTRACT FROM AUTHOR]

Coccidioides is the causative agent of San Joaquin Valley fever, a fungal disease prevalent in the semiarid regions of the Americas. Efforts to develop a fungal vaccine over the last 2 decades were unsuccessful. A candidate antigen, Antigen 2 (Ag2), is notoriously difficult to express in Escherichia coli, and this study sought to accumulate the antigen at high levels in maize. Transformed maize lines accumulated recombinant Ag2 at levels >1 g/kg. Mice immunized with this antigen and challenged with live Coccidioides arthroconidia showed a reduction in the fungal load when Ag2 derived from either E. coli or maize was loaded into glucan chitin particles. A fusion of Ag2 to dendritic cell carrier peptide (DCpep) induced a T-helper type 17 response in the spleen when orally delivered, indicative of a protective immune response. The maize production platform and the glucan chitin particle adjuvant system show promise for development of a Coccidioides vaccine, but further testing is needed to fully assess the optimal method of administration. [ABSTRACT FROM AUTHOR]

Background: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.Methods: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.Results: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.Conclusions: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .). [ABSTRACT FROM AUTHOR]

Purpose: Ammonia is used as a stimulant in strength based sports to increase arousal and offset fatigue however little is known about its physiological and performance effects. The purpose of this study was twofold (1) establish the physiological response to acute ammonia inhalation (2) determine whether the timing of the physiological response corresponds with a performance enhancement, if any.Methods: Fifteen healthy males completed two trials. Trial one investigated the beat-to-beat middle cerebral artery blood flow velocity (MCAv), heart rate (HR) and mean arterial pressure (MAP) response to ammonia inhalation. During trial two, participants performed a maximal single mid-thigh pull (MTP) at various time points following ammonia inhalation in a randomised order: MTPs were conducted immediately, 15, 30 and 60 s following ammonia inhalation. A MTP with no ammonia inhalation served as the control. During this trial maximal MTP force, rate of force development (RFD) and electromyography (EMG) activity were recorded.Results: MCAvmean increased and peaked on average by 6 cm s(-1) (P < 0.001), 9.4 ± 5.5 s following ammonia inhalation. Similarly, HR was increased by 6 ± 11 beats per minute 15 s following ammonia inhalation (P < 0.001). MAP remained unchanged following inhalation (P = 0.51). The use and timing of ammonia inhalation had no effect on maximal force, RFD or EMG (all P > 0.2) compared to control.Conclusions: MCAv was elevated despite no increase in MAP occurring; this is indicative of a cerebrovascular vasodilation. Despite the marked cerebrovascular and cardiovascular response to ammonia inhalation no ergogenic effect was observed during the MTP, irrespective of the timing of administration. [ABSTRACT FROM AUTHOR]

Patient- (e.g., health literacy), provider- (e.g., clinical inertia), and system-level (e.g., under-empowered care teams) barriers have contributed to suboptimal cardiovascular disease (CVD) risk management among US Veterans.[1] Among Veterans using the Veterans Health Administration (VHA), more than 80% have at least two CVD risk factors,[2] with approximately 34% and 49% having a diagnosis of hypertension and dyslipidemia, respectively.[3] Innovative care delivery models that use patient-generated health data, integrate non-physician providers into the primary care team, and facilitate patient-provider interaction have the potential to control CVD risk factors at the individual- and population-level.[4], [5] Therefore, the objective of the Team-supported, Electronic health record (EHR)-leveraged, Active Management (TEAM) pilot study was to assess the feasibility of a multi-component CVD risk management intervention among Veterans in rural North Carolina. As the primary care infrastructure is increasingly stretched thin, this two-pronged approach may be a sustainable solution to address uncontrolled CVD risk factors for it promotes patients' awareness and management of their CVD risk and enables a single member of the primary care team to oversee a large patient panel. First, personalized CVD risk letters have the potential to educate a large population of at-risk patients and thus increase patient self-management and participation in healthcare decision-making. [Extracted from the article]

The article discusses research on the link between obesity and healthcare resource utilization (HRU) as well as medical costs. Topics include comorbidities associated with increasing body mass index (BMI) among U.S. adults, the use of drugs in relation to increasing BMI, and the connection between obesity and cardiometabolic conditions. The economic impacts of obesity are noted.

Background: Post-operative pain is common and often severe after open abdominal hysterectomy, and analgesic consumption high. This study assessed the efficacy of local infiltration analgesia (LIA) injected systematically into different tissues during surgery compared with saline on post-operative pain and analgesia.Methods: Fifty-nine patients were randomized to Group LIA (n = 29) consisting of 156 ml of a mixture of 0.2% ropivacaine + 30 mg ketorolac + 0.5 mg (5 ml) adrenaline, where the drugs were injected systematically in the operating site, around the proximal vagina, the ligaments, in the fascia and subcutaneously, or to saline and intravenous ketorolac, Group C (Control, n = 28), in a double-blind study. Post-operative pain, analgesic consumption, side-effects, and home discharge were analysed.Results: Median dose of rescue morphine given 0-24 h after surgery was significantly lower in group LIA (18 mg, IQR 5-25 mg) compared with group C (27 mg, IQR 15-43 mg, P = 0.028). Median time to first analgesic injection was significantly longer in group LIA (40 min, IQR 20-60 min) compared with group C (20 min, IQR 12-30 min, P = 0.009). NRS score was lower in the group LIA compared with group C in the direct post-operative period (0-2 h). No differences were found in post-operative side-effects or home discharge between the groups.Discussion: Systematically injected local infiltration analgesia for pain management was superior to saline in the primary endpoint, resulting in significantly lower rescue morphine requirements during 0-24 h, longer time to first analgesic request and lower early post-operative pain intensity. [ABSTRACT FROM AUTHOR]

The article focuses on experimental therapies that are used in the treatment of Ebola virus disease (EVD). Various topics discussed include mortality rate of EVD, supportive care offered to patients suffering from EVD, child's survival through these therapies and use of antiviral agents in the treatment.

Introduction: Standard treatments (STs) for smoking cessation typically combine pharmacotherapy and behavioral support but do not address the sensory and behavioral aspects of smoking which may play a role in maintaining smoking behavior. Replacing such sensations temporarily after cessation may enhance treatment efficacy. We hypothesized that denicotinized cigarettes (DNCs), which have a very low nicotine content but provide these sensory and behavioral stimuli, could help alleviate urges to smoke and tobacco withdrawal symptoms and in turn enhance the efficacy of ST.Methods: Two hundred smokers seeking treatment received nine weekly behavioral support sessions and pharmacotherapy (100 used varenicline, 100 used nicotine replacement therapy). They were randomized on the target quit day to receive 280 DNCs (used ad libitum over 2 weeks in addition to ST) or ST alone.Results: Urge-to-smoke frequency (2.61 vs. 2.96, P = .03) but not strength (2.85 vs. 3.10, P = .20) in the first week of abstinence was significantly lower in DNC users versus ST alone. There were no differences in composite withdrawal scores between groups. Abstinence was significantly higher among DNC users versus ST alone at 1 (OR = 2.07; 95% CI: 1.63% to 3.70%) and 4 weeks (OR = 1.83; 95% CI: 1.05% to 3.21%), but not at 12 weeks (OR = 1.42; 95% CI: 0.79% to 2.55%). DNC use was a significant predictor of abstinence at 1 and 4 weeks (OR = 2.63; 95% CI: 1.40% to 4.93% and OR = 2.38; 95% CI: 1.26% to 4.46%), but not at 12 weeks.Conclusions: Adding DNCs to ST has the potential to assist smokers early in their quit attempt, but research is needed to determine how best to utilize DNCs in treatment. [ABSTRACT FROM AUTHOR]

Neuroticism was incorporated into a model for predicting the well-being of family caregivers. Using data from 596 women with an adult child with a chronic disability, the model hypothesizes direct effects of neuroticism on a caregiver's perceptions of the stressor, on her wishful-escapism and problem-focused coping, and on psychological well-being. Results indicate that neuroticism exerts direct and indirect effects on negative well-being. Results also indicate that stressors have direct effects on both wishful-escapism coping and problem-focused coping. Burden had direct effects on negative psychological well-being. Diagnosis influences the model by having direct effects on stressors and wishful-escapism coping but not on problem-focused coping or burden. Inclusion of individual level variables, such as neuroticism, results in a substantial amount of explained variance in negative well-being. [ABSTRACT FROM AUTHOR]

The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to identify potential explanatory factors for racial differences in blood pressure (BP) control.Design: The design of the study was a cross-sectional studyPatients/participants: The study included 608 patients with hypertension who were either African American (50%) or white (50%) and who received primary care in Durham, NC.Measurements and Main Results: Baseline data were obtained from the Take Control of Your Blood pressure study and included clinical, demographic, and psychosocial variables potentially related to clinic BP measures. African Americans were more likely than whites to have inadequate baseline clinic BP control as defined as greater than or equal to 140/90 mmHg (49% versus 34%; unadjusted odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3-2.5). Among factors that may explain this disparity, being older, reporting hypertension medication nonadherence, reporting a hypertension diagnosis for more than 5 years, reporting high levels of stress, being worried about hypertension, and reporting an increased number of medication side effects were related to inadequate BP control. In adjusted analyses, African Americans continue to have poor BP control relative to whites; the magnitude of the association was reduced (OR = 1.5; 95% CI 1.0-2.1). Medication nonadherence, worries about hypertension, and older age (>70) continued to be related to poor BP control.Conclusions: In this sample of hypertensive patients, there were a number of factors associated with poor BP control that partially explained the observed racial disparity in hypertension control including age, medication nonadherence, and worry about BP. Medication nonadherence is of particular interest because it is a potentially modifiable factor that might be used to reduce the racial disparity in BP control. [ABSTRACT FROM AUTHOR]

Opening wedge high tibial osteotomy (OWHTO) is a recently described procedure for medial compartment arthritis of the knee in the active, younger population. Despite having a number of advantages over the traditional closing wedge high tibial osteotomy (CWHTO) a potential complication of OWHTO is a high rate of delayed- and non-union. This study reports the occurrence of delayed- and non-union following OWHTO for medial compartment arthritis of the knee. Questionnaires were sent to all current members of the Australian Knee Society (n=45), a special interest group of the Australian Orthopaedic Group. Surgeons were asked primarily to indicate how many OWHTOs they had performed, and how many of these had progressed to union, delayed-union and non-union. All 45 questionnaires were returned, with 21 surgeons (47%) performing OWHTOs. A total of 188 OWHTO cases were reported, of which 182 were complete. Of these complete cases 167 (91.8%) were classed as united, 12 (6.6%) delay-united and 3 (1.6%) non-united. The results of this study demonstrate that the rate of delayed- and non-union following OWHTO for medial compartment arthritis of the knee is relatively low and comparable to that reported for traditional CWHTO. [ABSTRACT FROM AUTHOR]

The article discusses the evolution of concepts in the asthma management landscape in the U.S. being considered as a common condition that imposes substantial patient, health care system, and socioeconomic burdens. Topics include the understanding of asthma etiology, the progress in the diagnosis of asthma, and the management of asthma in primary care. The role of primary care providers (PCPs) in teaching patients for effective self-management is also tackled.

Background: Obtaining accurate blood pressure (BP) readings is a challenge faced by health professionals. Clinical trials implement strict protocols, whereas clinical practices and studies that assess quality of care utilize a less rigorous protocol for BP measurement.Objective: To examine agreement between real-time clinic-based assessment of BP and the standard mercury assessment of BP.Design: Prospective reliability study.Patients: One hundred patients with an International Classification of Diseases-9th edition code for hypertension were enrolled.Measures: Two BP measurements were obtained with the Hawksley random-zero mercury sphygmomanometer and averaged. The clinic-based BP was extracted from the computerized medical records.Results: Agreement between the mercury and clinic-based systolic blood pressure (SBP) was good, intraclass correlation coefficient (ICC)=0.91 (95% confidence interval (CI): 0.83 to 0.94); the agreement for the mercury and clinic-based diastolic blood pressure (DBP) was satisfactory, ICC=0.77 (95% CI: 0.62 to 0.86). Overall, clinic-based readings overestimated the mercury readings, with a mean overestimation of 8.3 mmHg for SBP and 7.1 mmHg for DBP. Based on the clinic-based measure, 21% of patients were misdiagnosed with uncontrolled hypertension.Conclusions: Health professionals should be aware of this potential difference when utilizing clinic-based BP values for making treatment decisions and/or assessing quality of care. [ABSTRACT FROM AUTHOR]

Objective: To evaluate rural/urban disparities in 30-day all-cause hospital admission after cystectomy.Materials and Methods: We used the SEER-Medicare database to identify all Medicare beneficiaries who underwent radical cystectomy (ICD-9 codes 57.7, 57.71, 57.79, and 68.8) between the years 1991 and 2009, yielding a total sample size of 15,572. Our primary outcome was 30-day hospital readmission rate. Rural Urban Continuum Codes were used to designate county-level rural status based on patient residence. Location of surgery was not a variable considered in this analysis. A multivariable regression model was constructed with demographic and clinical variables as covariates.Results: A total of 2,003 rural and 2,904 urban patients (31.1% vs. 31.8%, P = 0.33) were readmitted within 30 days of discharge. In the multivariable model, older age, unmarried status, lower socioeconomic status, higher Charlson comorbidity score, shorter index admission hospital stay, and discharge to a skilled nursing facility were associated with higher odds of readmission. The variables for gender, race, cancer stage, tumor grade, and type of urinary diversion were not significant. The odds ratio for readmission was not significant for patients from rural counties in the final model.Conclusions: Rural Medicare residents were not at higher risk for 30-day all-cause hospital readmission after cystectomy after accounting for various demographic and clinical variables. [ABSTRACT FROM AUTHOR]

Background: Diabetes adversely impacts cognition. Lifestyle change can improve diabetes control and potentially improve cognition. We examined whether weight loss through reduced caloric intake and increased physical activity was associated with slower cognitive aging in older adults with type 2 diabetes mellitus.Methods: The Look AHEAD randomized controlled clinical trial delivered 10 years of intensive lifestyle intervention (ILI) that yielded long-term weight losses. During 5 years spanning the end of intervention and postintervention follow-up, repeated cognitive assessments were obtained in 1,091 individuals who had been assigned to ILI or a control condition of diabetes support and education (DSE). We compared the means and slopes of scores on cognitive testing over these repeated assessments.Results: Compared with DSE, assignment to ILI was associated with a -0.082 SD deficit in mean global cognitive function across repeated assessments (p = .010). However, overweight (body mass index [BMI] < 30 kg/m2) ILI participants had 0.099 (95% confidence interval [CI]: -0.006, 0.259) better mean global cognitive function compared with overweight DSE participants, while obese (BMI ≥ 30 kg/m2) ILI participants had -0.117 (-0.185, -0.049) SD worse mean composite cognitive function scores (interaction p = .014) compared to obese DSE participants. For both overweight and obese participants, cognitive decline was marginally (-0.014 SD/y overall) steeper for ILI participants (p = .068), with 95% CI for differences in slopes excluding 0 for measures of attention and memory.Conclusions: The behavioral weight loss intervention was associated with small relative deficits in cognitive function among individuals who were obese and marginally greater cognitive decline overall compared to control. ClinicalTrials.gov Identifier: NCT00017953. [ABSTRACT FROM AUTHOR]

Background: Cup malposition is a common cause of impingement, limitation of ROM, acceleration of bearing wear, liner fracture, and instability in THA. Previous studies of the safe zone based on plain radiographs have limitations inherent to measuring angles from two-dimensional projections. The current study uses CT to measure component position in stable and unstable hips to assess the presence of a safe zone for cup position in THA.Questions/purposes: (1) Does acetabular component orientation, when measured on CT, differ in stable components and those revised for recurrent instability? (2) Do CT data support historic safe zone definitions for component orientation in THA?Methods: We identified 34 hips that had undergone revision of the acetabulum for recurrent instability that also had a CT scan of the pelvis between August 2003 and February 2017. We also identified 175 patients with stable hip replacements who also had a CT study for preoperative planning and intraoperative navigation of the contralateral side. For each CT study, one observer analyzed major factors including acetabular orientation, femoral anteversion, combined anteversion (the sum of femoral and anatomic anteversion), pelvic tilt, total offset difference, head diameter, age, sex, and body mass index. These measures were then compared among stable hips, hips with cup revision for anterior instability, and hips with cup revision for posterior instability. We used a clinically relevant measurement of operative anteversion and inclination as opposed to the historic use of radiographic anteversion and inclination. The percentage of unstable hips in the historic Lewinnek safe zone was calculated, and a new safe zone was proposed based on an area with no unstable hips.Results: Anteriorly unstable hips compared with stable hips had higher operative anteversion of the cup (44° ± 12° versus 31° ± 11°, respectively; mean difference, 13°; 95% confidence interval [CI], 5°-21°; p = 0.003), tilt-adjusted operative anteversion of the cup (40° ± 6° versus 26° ± 10°, respectively; mean difference, 14°; 95% CI, 10°-18°; p < 0.001), and combined tilt-adjusted anteversion of the cup (64° ± 10° versus 54° ± 19°, respectively; mean difference, 10°; 95% CI, 1°-19°; p = 0.028). Posteriorly unstable hips compared with stable hips had lower operative anteversion of the cup (19° ± 15° versus 31° ± 11°, respectively; mean difference, -12°; 95% CI, -5° to -18°; p = 0.001), tilt-adjusted operative anteversion of the cup (19° ± 13° versus 26° ± 10°, respectively; mean difference, -8°; 95% CI, -14° to -2°; p = 0.014), pelvic tilt (0° ± 6° versus 4° ± 6°, respectively; mean difference, -4°; 95% CI, -7° to -1°; p = 0.007), and anatomic cup anteversion (25° ± 18° versus 34° ± 12°, respectively; mean difference, -9°; 95% CI, -1° to -17°; p = 0.033). Thirty-two percent of the unstable hips were located in the Lewinnek safe zone (11 of 34; 10 posterior dislocations, one anterior dislocation). In addition, a safe zone with no unstable hips was identified within 43° ± 12° of operative inclination and 31° ± 8° of tilt-adjusted operative anteversion.Conclusions: The current study supports the notion of a safe zone for acetabular component orientation based on CT. However, the results demonstrate that the historic Lewinnek safe zone is not a reliable predictor of future stability. Analysis of tilt-adjusted operative anteversion and operative inclination demonstrates a new safe zone where no hips were revised for recurrent instability that is narrower for tilt-adjusted operative anteversion than for operative inclination. Tilt-adjusted operative anteversion is significantly different between stable and unstable hips, and surgeons should therefore prioritize assessment of preoperative pelvic tilt and accurate placement in operative anteversion. With improvements in patient-specific cup orientation goals and acetabular component placement, further refinement of a safe zone with CT data may reduce the incidence of cup malposition and its associated complications.Level Of Evidence: Level III, diagnostic study. [ABSTRACT FROM AUTHOR]

Between September 2012 and January 20, 2017, the World Health Organization (WHO) received reports from 27 countries of 1879 laboratory-confirmed cases in humans of the Middle East respiratory syndrome (MERS) caused by infection with the MERS coronavirus (MERS-CoV) and at least 659 related deaths. Cases of MERS-CoV infection continue to occur, including sporadic zoonotic infections in humans across the Arabian Peninsula, occasional importations and associated clusters in other regions, and outbreaks of nonsustained human-to-human transmission in health care settings. Dromedary camels are considered to be the most likely source of animal-to-human transmission. MERS-CoV enters host cells after binding the dipeptidyl peptidase 4 (DPP-4) receptor and the carcinoembryonic antigen-related cell-adhesion molecule 5 (CEACAM5) cofactor ligand, and it replicates efficiently in the human respiratory epithelium. Illness begins after an incubation period of 2 to 14 days and frequently results in hypoxemic respiratory failure and the need for multiorgan support. However, asymptomatic and mild cases also occur. Real-time reverse-transcription-polymerase- chain-reaction (RT-PCR) testing of respiratory secretions is the mainstay for diagnosis, and samples from the lower respiratory tract have the greatest yield among seriously ill patients. There is no antiviral therapy of proven efficacy, and thus treatment remains largely supportive; potential vaccines are at an early developmental stage. There are multiple gaps in knowledge regarding the evolution and transmission of the virus, disease pathogenesis, treatment, and prospects for a vaccine. The ongoing occurrence of MERS in humans and the associated high mortality call for a continued collaborative approach toward gaining a better understanding of the infection both in humans and in animals. MERS-CoV was first identified in September 20121 in a patient from Saudi Arabia who had hypoxemic respiratory failure and multiorgan illness. Subsequent cases have included infections in humans across the Arabian Peninsula, occasional importations and associated clusters in other regions, and outbreaks of nonsustained human-tohuman transmission in health care settings (Fig. 1) [ABSTRACT FROM AUTHOR]

Pediatric surgeries are common and painful for children. Postoperative pain is commonly managed with analgesics; however, pain is often still problematic. Despite evidence for psychological interventions for procedural pain, there is currently no evidence synthesis for psychological interventions in managing postoperative pain in children. The purpose of this review was to assess the efficacy of psychological interventions for postoperative pain in youth. Psychological interventions included Preparation/education, distraction/imagery, and mixed. Four databases (PsycINFO, PubMed, EMBASE, and Certified Index to Nursing and Allied Health Literature) were searched to July 2015 for published articles and dissertations. We screened 1401 citations and included 20 studies of youth aged 2 to 18 years undergoing surgery. Two reviewers independently screened articles, extracted data, and assessed risk of bias. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated using RevMan 5.3. Fourteen studies (1096 participants) were included in meta-analyses. Primary outcome was pain intensity (0-10 metric). Results indicated that psychological interventions as a whole were effective in reducing children's self-reported pain in the short term (SMD = -0.47, 95% CI = -0.76 to -0.18). Subgroup analysis indicated that distraction/imagery interventions were effective in reducing self-reported pain in the short term (24 hours, SMD = -0.63, 95% CI = -1.04 to -0.23), whereas preparation/education interventions were not effective (SMD = -0.27, 95% CI = -0.61 to 0.08). Data on the effects of interventions on longer term pain outcomes were limited. Psychological interventions may be effective in reducing short-term postoperative pain intensity in children, as well as longer term pain and other outcomes (eg, adverse events) require further study. [ABSTRACT FROM AUTHOR]

Background: Management of osteoarthritis requires both medical and behavioral strategies, but some recommended therapies are underused.Objective: To examine the effectiveness of a combined patient and provider intervention for improving osteoarthritis outcomes.Design: Cluster randomized clinical trial with assignment to osteoarthritis intervention and usual care groups. (ClinicalTrials.gov: NCT01130740).Setting: Department of Veterans Affairs Medical Center in Durham, North Carolina.Participants: 30 providers (clusters) and 300 outpatients with symptomatic hip or knee osteoarthritis.Intervention: The telephone-based patient intervention focused on weight management, physical activity, and cognitive behavioral pain management. The provider intervention involved delivery of patient-specific osteoarthritis treatment recommendations to primary care providers through the electronic medical record.Measurements: The primary outcome was total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 12 months. Secondary outcomes were WOMAC function and pain subscale scores, physical performance (Short Physical Performance Battery), and depressive symptoms (Patient Health Questionnaire-8). Linear mixed models that were adjusted for clustering of providers assessed between-group differences in improvement in outcomes.Results: At 12 months, WOMAC scores were 4.1 points lower (indicating improvement) in the osteoarthritis intervention group versus usual care (95% CI, -7.2 to -1.1 points; P = 0.009). WOMAC function subscale scores were 3.3 points lower in the intervention group (CI, -5.7 to -1.0 points; P = 0.005). WOMAC pain subscale scores (P = 0.126), physical performance, and depressive symptoms did not differ between groups. Although more patients in the osteoarthritis intervention group received provider referral for recommended osteoarthritis treatments, the numbers who received them did not differ.Limitation: The study was conducted in a single Veterans Affairs medical center.Conclusion: The combined patient and provider intervention resulted in modest improvement in self-reported physical function in patients with hip and knee osteoarthritis.Primary Funding Source: Department of Veterans Affairs, Health Services Research and Development Service. [ABSTRACT FROM AUTHOR]

Medical Education 2012: 46: 564-574 Context Legislation and General Medical Council guidance require medical schools to make reasonable adjustments to enable students with disabilities to progress in their studies without disadvantage. Current definitions of disability have moved from the traditional 'medical' model to a 'social' model that emphasises the role of institutions in removing unnecessary barriers to learning through flexible provision. In response, two medical schools introduced a Student Support Card to empower students with disabilities and health issues to request reasonable adjustments. A study was carried out to ascertain the effectiveness of the Student Support Card from the user's perspective in both institutions. Methods A questionnaire survey of card-holders was conducted in 2009-2010. A total of 31 respondents took part, from among whom six volunteers were recruited to participate in semi-structured interviews. Thematic analysis was conducted and data independently analysed by two researchers. Results The results from the questionnaire indicated that the scheme was well received by students and brought clear benefits, and that the card's value lay in ownership, as well as in use. Further themes emerged from the interviews which suggested that students were judicious in requesting adjustments, thus reflecting their concerns over the disclosure of disability, the threat that their behaviour might be misinterpreted and their acquiring of the competencies necessary to become a doctor. Conclusions The benefits of such a scheme are that it is flexible and addresses unique student needs. Further research needs to focus upon: how educators perceive the utility of the Student Support Card; whether it should be embedded in the wider medical school culture, and, subsequently, how a working consensus can be achieved with regard to reasonable adjustments within vocational education in which there are clear requirements for competence. [ABSTRACT FROM AUTHOR]

Background: In recent years, much progress has been made in the treatment of multiple myeloma. However, a major limitation of existing chemotherapeutic drugs is the eventual emergence of resistance; hence, the development of novel agents with new mechanisms of action is pertinent. Here, we describe the activity and mechanism of action of pyrrolo-1,5-benzoxazepine-15 (PBOX-15), a novel microtubule-targeting agent, in multiple myeloma cells.Methods: The anti-myeloma activity of PBOX-15 was assessed using NCI-H929, KMS11, RPMI8226, and U266 cell lines, and primary myeloma cells. Cell cycle distribution, apoptosis, cytochrome c release, and mitochondrial inner membrane depolarisation were analysed by flow cytometry; gene expression analysis was carried out using TaqMan Low Density Arrays; and expression of caspase-8 and Bcl-2 family of proteins was assessed by western blot analysis.Results: Pyrrolo-1,5-benzoxazepine-15 induced apoptosis in ex vivo myeloma cells and in myeloma cell lines. Death receptor genes were upregulated in both NCI-H929 and U266 cell lines, which displayed the highest and lowest apoptotic responses, respectively, following treatment with PBOX-15. The largest increase was detected for the death receptor 5 (DR5) gene, and cotreatment of both cell lines with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the DR5 ligand, potentiated the apoptotic response. In NCI-H929 cells, PBOX-15-induced apoptosis was shown to be caspase-8 dependent, with independent activation of extrinsic and intrinsic apoptotic pathways. A caspase-8-dependent decrease in expression of Bim(EL) preceded downregulation of other Bcl-2 proteins (Bid, Bcl-2, Mcl-1) in PBOX-15-treated NCI-H929 cells.Conclusion: PBOX-15 induces apoptosis and potentiates TRAIL-induced cell death in multiple myeloma cells. Thus, PBOX-15 represents a promising agent, with a distinct mechanism of action, for the treatment of this malignancy. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other's downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection. [ABSTRACT FROM AUTHOR]

Rhinoviruses and coronaviruses are recognized as the major causes of the common cold syndrome. The role of these viruses in more serious respiratory illnesses resulting in hospitalization is less well defined. During a winter when influenza A infection was prevalent, 100 elderly adults hospitalized because of cardiopulmonary illnesses were evaluated for rhinovirus and coronavirus infection. Patients who tested negative for influenza or respiratory syncytial virus had nasal swab samples tested for rhinovirus, coronavirus OC43, and coronavirus 229E by reverse-transcription polymerase chain reaction and for coronaviruses by serologic testing. Twelve percent of patients had rhinovirus or coronavirus identified (rhinovirus, 4 patients; coronavirus 229E, 4 patients; coronavirus OC43, 3 patients; and mixed rhinovirus/coronavirus 229E infection, 1 patient). All patients had significant underlying diseases. Although all patients recovered, the mean length of stay was 8 days; 4 persons had pneumonia, and 1 required ventilator support. These data suggest that rhinoviruses and coronaviruses may be associated with serious respiratory illnesses in frail older adults. [ABSTRACT FROM AUTHOR]

Study Design: Individual participant data (IPD) meta-analysis.Objective: The aim of this study was to identify which participant characteristics moderate the effect of spinal manipulative therapy (SMT) on pain and functioning in chronic LBP.Summary Of Background: The effects of SMT are comparable to other interventions recommended in guidelines for chronic low back pain (LBP); however, it is unclear which patients are more likely to benefit from SMT compared to other therapies.Methods: IPD were requested from randomized controlled trials (RCTs) examining the effect of SMT in adults with chronic LBP for pain and function compared to various other therapies (stratified by comparison). Potential patient moderators (n = 23) were a priori based on their clinical relevance. We investigated each moderator using a one-stage approach with IPD and investigated this interaction with the intervention for each time point (1, 3, 6, and 12 months).Results: We received IPD from 21 of 46 RCTs (n = 4223). The majority (12 RCTs, n = 2249) compared SMT to recommended interventions. The duration of LBP, baseline pain (confirmatory), smoking, and previous exposure to SMT (exploratory) had a small moderating effect across outcomes and follow-up points; these estimates did not represent minimally relevant differences in effects; for example, patients with <1 year of LBP demonstrated more positive point estimates for SMT versus recommended therapy for the outcome pain (mean differences ranged from 4.97 (95% confidence interval, CI: -3.20 to 13.13) at 3 months, 10.76 (95% CI: 1.06 to 20.47) at 6 months to 5.26 (95% CI: -2.92 to 13.44) at 12 months in patients with over a year LBP. No other moderators demonstrated a consistent pattern across time and outcomes. Few moderator analyses were conducted for the other comparisons because of too few data.Conclusion: We did not identify any moderators that enable clinicians to identify which patients are likely to benefit more from SMT compared to other treatments.Level of Evidence: 2. [ABSTRACT FROM AUTHOR]

Objective: To determine whether naproxen, a propionic acid inhibitor of cyclooxygenase, alters the course of experimental rhinovirus colds.Design: A randomized, double-blind, controlled trial.Setting: Rhinovirus challenge model in volunteers cloistered in individual hotel rooms.Volunteers: Eighty-seven healthy young adults with serum neutralizing antibody titers of less than or equal to 1:2 to the challenge virus; 79 were evaluable.Intervention: Thirty-nine participants received naproxen (loading dose, 400 mg or 500 mg followed by 200 mg or 500 mg three times daily for 5 days). Forty participants received placebo. Treatment was started 6 hours after viral challenge.Measurements: Daily measurement of viral titers, symptoms, nasal mucus production, and nasal tissue use; incidence of infection and illness; and measurement of homotypic serum neutralizing antibody responses.Results: Viral titers and serum homotypic antibody responses were similar in the naproxen and placebo groups. Significant reductions in headache, malaise, myalgia, and cough occurred in the naproxen group. A 29% reduction was noted in the total (5-day) symptom score in the naproxen group (95% CI, 16% to 42%).Conclusion: Naproxen treatment did not alter virus shedding or serum neutralizing antibody responses in participants with experimental rhinovirus colds, but it had a beneficial effect on the symptoms of headache, malaise, myalgia, and cough. Prostaglandins may be among the inflammatory mediators that play a role in the pathogenesis of rhinovirus colds. [ABSTRACT FROM AUTHOR]

Objective: To characterize the prevalence, onset, and burden of urinary and bowel dysfunction in adult patients with adrenoleukodystrophy (ALD) and to evaluate any sex differences in symptom presentation.Methods: In this retrospective and prospective study, we performed medical record review (n = 103), analyzed the results of clinically indicated urodynamic testing (n = 11), and developed and distributed a symptom and quality of life (QOL) survey (n = 59).Results: Urinary and bowel symptoms are highly prevalent in both males (75.0%) and females (78.8%) in this population, most commonly urinary urgency, often leading to incontinence. Time to onset of first urinary or bowel symptom occurs approximately a decade earlier in males. Seventy-two percent of symptomatic patients report a limitation to QOL. Urodynamic evaluation provides evidence of three distinct mechanisms underlying lower urinary tract dysfunction: involuntary detrusor contractions (indicating uncontrolled neuronal stimulation with or without leakage), motor underactivity of the bladder, and asynergy between detrusor contraction and sphincter relaxation.Conclusions: Beyond gait and balance difficulties, urinary and bowel symptoms are common in adults with ALD and impair QOL. Males are affected at a younger age but both sexes experience a higher symptom burden with age. As this population also experiences gait and balance impairment, patients with ALD are more vulnerable to urinary urgency leading to incontinence. Urodynamic evaluation may help better elucidate the pathophysiologic mechanisms underlying neurogenic lower urinary tract dysfunction, which can allow more targeted treatment. [ABSTRACT FROM AUTHOR]

Background: Up to 75% of women diagnosed with breast cancer report chemotherapy-related cognitive changes (CRCC) during treatment, including decreased memory, attention, and processing speed. Though CRCC negatively impacts everyday functioning and reduces overall quality of life in women diagnosed with breast cancer, effective interventions to prevent and/or manage CRCC are elusive. Consequently, women seldom receive advice on how to prevent or manage CRCC. Aerobic exercise is associated with improved cognitive functioning in healthy older adults and adults with cognitive impairments. Accordingly, it holds promise as an intervention to prevent and/or manage CRCC. However, evidence from randomized controlled trials (RCTs) supporting a beneficial effect of aerobic exercise on CRCC is limited. The primary aim of the ACTIVATE trial is to evaluate the impact of supervised aerobic exercise on CRCC in women receiving chemotherapy for breast cancer.Methods: The ACTIVATE trial is a two-arm, two-centre RCT. Women diagnosed with stage I-III breast cancer and awaiting neo-adjuvant or adjuvant chemotherapy are recruited from hospitals in Ottawa (Ontario) and Vancouver (British Columbia), Canada. Recruits are randomized to the intervention group (aerobic exercise during chemotherapy) or the wait-list control group (usual care during chemotherapy and aerobic exercise post-chemotherapy). The primary outcome is cognitive functioning as measured by a composite cognitive summary score (COGSUM) of several neuropsychological tests. Secondary outcomes are self-reported cognitive functioning, quality of life, and brain structure and functioning (measured by magnetic resonance imaging (MRI)/functional MRI and electroencephalography). Assessments take place pre-chemotherapy (pre-intervention), mid-way through chemotherapy (mid-intervention/mid-wait period), end of chemotherapy (post-intervention/post-wait period; primary endpoint), 16-weeks post-chemotherapy, and at 1-year post-baseline.Discussion: Aerobic exercise is a promising intervention for preventing and/or managing CRCC and enhancing quality of life among women diagnosed with breast cancer. The ACTIVATE trial tests several novel hypotheses, including that aerobic exercise can prevent and/or mitigate CRCC and that this effect is mediated by the timing of intervention delivery (i.e., during versus post-chemotherapy). Findings may support prescribing exercise during (or post-) chemotherapy for breast cancer and elucidate the potential role of aerobic exercise as a management strategy for CRCC in women with early-stage breast cancer.Trial Registration: The trial was registered with the ClinicalTrials.gov database ( NCT03277898 ) on September 11, 2017. [ABSTRACT FROM AUTHOR]

Purpose: Kilovoltage intrafraction monitoring (KIM) is a novel software platform implemented on standard radiation therapy systems and enabling real-time image guided radiation therapy (IGRT). In a multi-institutional prospective trial, we investigated whether real-time IGRT improved the accuracy of the dose patients with prostate cancer received during radiation therapy.Methods and Materials: Forty-eight patients with prostate cancer were treated with KIM-guided SABR with 36.25 Gy in 5 fractions. During KIM-guided treatment, the prostate motion was corrected for by either beam gating with couch shifts or multileaf collimator tracking. A dose reconstruction method was used to evaluate the dose delivered to the target and organs at risk with and without real-time IGRT. Primary outcome was the effect of real-time IGRT on dose distributions. Secondary outcomes included patient-reported outcomes and toxicity.Results: Motion correction occurred in ≥1 treatment for 88% of patients (42 of 48) and 51% of treatments (121 of 235). With real-time IGRT, no treatments had prostate clinical target volume (CTV) D98% dose 5% less than planned. Without real-time IGRT, 13 treatments (5.5%) had prostate CTV D98% doses 5% less than planned. The prostate CTV D98% dose with real-time IGRT was closer to the plan by an average of 1.0% (range, -2.8% to 20.3%). Patient outcomes showed no change in the 12-month patient-reported outcomes compared with baseline and no grade ≥3 genitourinary or gastrointestinal toxicities.Conclusions: Real-time IGRT is clinically effective for prostate cancer SABR. [ABSTRACT FROM AUTHOR]

Objectives: To test whether providing psychological self-help materials would significantly lower the incidence of post-traumatic stress disorder (PTSD) at 6-12 weeks postnatally.Design: Open-label randomised controlled trial, with blinded outcome assessment.Setting: Community midwifery services in two National Health Service (NHS) trusts in the North West.Sample: A cohort of 2419 women receiving normal NHS postnatal care.Methods: Midwives screened women for traumatic birth experience; 678 women who screened positively (28.1%) were randomly allocated to self-help with usual care (n = 336) or to usual care alone (n = 342). The self-help materials were a leaflet and online film designed to prevent the development of PTSD after trauma exposure through explaining how to manage early psychological responses.Main Outcome Measure: The primary outcome was a composite of diagnostic and subdiagnostic PTSD at 6-12 weeks postnatally using the gold-standard Clinician-Administered PTSD Scale (CAPS-5) interview.Results: Of the 678 women correctly randomised plus the nine women randomised in error, 478 (70.5%) were followed up. Diagnostic or subdiagnostic PTSD rates at follow-up did not differ between groups who received self-help (26.7%, 65/243) or usual care alone (26.2%, 64/244) (intention-to-treat analysis: RR 1.02, 95% CI 0.68-1.53). Findings remained consistent in the per-protocol analysis (RR 1.04, 95% CI 0.85-1.27). Women viewed the materials very positively. There were no adverse effects. Health economic micro-costing indicated implementation would be very low cost.Conclusions: Many women experience a traumatic birth and risk developing PTSD, but self-help strategies without professional support are insufficient and should not be routinely introduced.Tweetable Abstract: Self-help information alone does not reduce the number of women developing PTSD after a traumatic childbirth. [ABSTRACT FROM AUTHOR]

Purpose: For brain metastases, surgical resection with postoperative stereotactic radiosurgery is an emerging standard of care. Postoperative cavity stereotactic radiosurgery is associated with a specific, underrecognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease. We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve interrater reliability (IRR) and validity in diagnosing LMD.Methods and Materials: Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system expertise, completed a 2-phase survey that included magnetic resonance imaging and treatment information for 30 patients. In the "pretraining" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "posttraining" phase and relabeled the 30 cases using the 4 following labels: LR, DR, classical leptomeningeal disease, and nLMD.Results: IRR increased 34% after training (Fleiss' Kappa K = 0.41 to K = 0.55, P < .001). IRR increased most among non-central nervous system specialists (+58%, P < .001). Before training, IRR was lowest for LMD (K = 0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD.Conclusions: This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training. [ABSTRACT FROM AUTHOR]

Introduction: This study examined the effects of simulated and actual vessel motion at high seas on task load and surgical performance.Methods: This project was performed in phases. Phase I was a feasibility study. Phase II utilized a motion base simulator to replicate vessel motion. Phase III was conducted aboard the U.S. Naval Ship Brunswick. After performing surgical tasks on a surgical simulation mannequin, participants completed the Surgical Task Load Index (TLX) designed to collect workload data. Simulated surgeries were evaluated by subject matter experts.Results: TLX scores were higher in Phase III than Phase II, particularly at higher sea states. Surgical performance was not significantly different between Phase II (84%) and Phase III (89%). Simulated motions were comparable in both phases.Conclusions: Simulated motion was not associated with a significant difference in surgical performance or deck motion, suggesting that this simulator replicates the conditions experienced during surgery at sea on the U.S. Naval Ship Brunswick. However, Surgical TLX scores were dramatically different between the two phases, suggesting increased workload at sea, which may be the result of time at sea, the stress of travel, or other factors. Surgical performance was not affected by sea state in either phase. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetic kidney disease (DKD) often struggle with blood pressure control. In team-based models of care, pharmacists and primary care providers (PCPs) play important roles in supporting patients' blood pressure management.Objective: To describe whether PCPs' acceptance of pharmacists' recommendations impacts systolic blood pressure (SBP) at 36 months.Design: An observational analysis of a subset of participants randomized to the intervention arm of the Simultaneous risk factor control using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study.Participants: STOP-DKD participants for whom (1) the pharmacist made at least one recommendation to the PCP; (2) there were available data regarding the PCP's corresponding action; and (3) there were SBP measurements at baseline and 36 months.Intervention: Participants received monthly telephone calls with a pharmacist addressing health behaviors and medication management. Pharmacists made medication-related recommendations to PCPs.Main Measures: We fit an unadjusted generalized linear mixed model to assess the association between the number of pharmacists' recommendations for DKD and blood pressure management and PCPs' acceptance of such recommendations. We used a linear regression model to evaluate the association between PCP acceptance and SBP at 36 months, adjusted for baseline SBP.Key Results: Pharmacists made 176 treatment recommendations (among 59 participants), of which 107 (61%) were accepted by PCPs. SBP significantly declined by an average of 10.5 mmHg (p < 0.01) among 47 of 59 participants who had valid measurements at baseline and 36 months. There was a significant association between the number of pharmacist recommendations and the odds of PCP acceptance (OR 1.19; 95%CI 1.00, 1.42; p < 0.05), but no association between the number of accepted recommendations and SBP.Conclusions: Pharmacists provided actionable medication-related recommendations. We identified a significant decline in SBP at 36 months, but this reduction was not associated with recommendation acceptance.Trial Registration: NCT01829256. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.Methods: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.Results: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.Conclusions: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.). [ABSTRACT FROM AUTHOR]

Background: The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear.Methods: We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days.Results: The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months.Conclusions: Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.). [ABSTRACT FROM AUTHOR]

Background: Pridopidine, in development for Huntington's disease, may modulate aberrant l-dopa-induced effects including l-dopa-induced dyskinesia (LID).Objective: This study investigated whether pridopidine could reduce LID in the MPTP macaque model of Parkinson's disease and characterized the observed behavioral effects in terms of receptor occupancy.Methods: The pharmacokinetic profile and effects of pridopidine (15-30 mg/kg) on parkinsonism, dyskinesia, and quality of on-time, in combination with l-dopa, were assessed in MPTP macaques with LID. Pridopidine receptor occupancy was estimated using known in vitro binding affinities to σ1 and dopamine D2 receptors, in vivo PET imaging, and pharmacokinetic profiling across different species.Results: Pridopidine produced a dose-dependent reduction in dyskinesia (up to 71%, 30 mg/kg) and decreased the duration of on-time with disabling dyskinesia evoked by l-dopa by 37% (20 mg/kg) and 60% (30 mg/kg). Pridopidine did not compromise the anti-parkinsonian benefit of l-dopa. Plasma exposures following the ineffective dose (15 mg/kg) were associated with full σ1 occupancy (>80%), suggesting that σ1 engagement alone is unlikely to account for the antidyskinetic benefits of pridopidine. Exposures following effective doses (20-30 mg/kg), while providing full σ1 occupancy, provide only modest dopamine D2 occupancy (<40%). However, effective pridopidine doses clearly engage a range of receptors (including adrenergic-α2C , dopamine-D3 , and serotoninergic-5-HT1A sites) to a higher degree than D2 and might contribute to the antidyskinetic actions.Conclusions: In MPTP macaques, pridopidine produced a significant decrease in LID without compromising the antiparkinsonian benefit of l-dopa. Although the actions of pridopidine were associated with full σ1 occupancy, effective exposures are more likely associated with occupancy of additional, non-sigma receptors. This complex pharmacology may underlie the effectiveness of pridopidine against LID. © 2018 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Introduction: Obesity treatment is less successful for socioeconomically disadvantaged populations, particularly when delivered in primary care. Digital health strategies can extend the reach of clinical obesity treatments to care settings serving patients at highest risk.Methods: Track was an effectiveness RCT of a 12-month digital weight-loss intervention, embedded within a community health center system. Participants were 351 adult patients (aged 21-65 years) with obesity and hypertension, diabetes, and hyperlipidemia. Patients were randomized to usual care (n=175) or an intervention (n=176) comprising app-based self-monitoring of behavior change goals with tailored feedback, a smart scale, dietitian-delivered counseling calls, and clinician counseling informed by app-generated recommendations, delivered via electronic health record. The primary outcome was 12-month weight change. Randomization began on June 18, 2013, final assessments were completed on September 10, 2015. Data analysis was conducted in 2016 and 2017. The trial retained 92% of usual care and 96% of intervention participants at 12 months.Results: The Track intervention produced larger weight losses relative to usual care at 6 months (net effect: -4.4 kg, 95% CI= -5.5, -3.3, p<0.001) and 12 months (net effect: -3.8 kg, 95% CI= -5.0, -2.5, p<0.001). Intervention participants were more likely to lose ≥5% of their baseline weight at 6 months (43% vs 6%, p<0.001) and 12 months (40% vs 17%, p<0.001). Intervention participants completing ≥80% of expected self-monitoring episodes (-3.5 kg); counseling calls (-3.0 kg); or self-weighing days (-4.4 kg) lost significantly more weight than less engaged intervention participants (all p<0.01).Conclusions: A digital obesity treatment, integrated with health system resources, can produce clinically meaningful weight-loss outcomes among socioeconomically disadvantaged primary care patients with elevated cardiovascular disease risk.Trial Registration: This study is registered at www.clinicaltrials.gov NCT01827800. [ABSTRACT FROM AUTHOR]

Peripheral intravenous cannula (PIVC) insertion is one of the most common invasive procedures performed in neonates and is frequently associated with adverse events. There are no studies in the neonatal population looking at the possibility of reducing the risk of PIVC-related complications by elective replacement of PIVC. A randomised, non-blinded, control trial was conducted in a tertiary level neonatal unit in Melbourne, Australia, to examine rates of extravasation in neonates with elective replacement of PIVC as compared to standard practice. Neonates born at 32 weeks of gestation or more were randomly assigned to have their PIVC replaced electively (every 72-96 h) or when clinically indicated in a 1:1 allocation ratio after parental consent. Primary outcome studied was rate of extravasation. Secondary outcomes included rates of phlebitis, leakage or spontaneous dislodgement of PIVC. One hundred thirteen infants were enrolled. Extravasation was noted in 33 (60%) of standard practice group vs. 28 (48.3%) of elective replacement (RR 0.80, CI 0.57-1.13, p = 0.21) infants. Time to first extravasation was similar between the groups (hazard ratio 0.69, CI 0.42-1.15). Extravasation events per 1000 IV hours were also similar between groups. Similar results were seen by both intention to treat and per protocol analyses. There was an increase in leaking rates (HR1.98, CI 1.03-3.81, p = 0.04) in the elective group, while phlebitis and spontaneous dislodgement rates were similar to standard group.Conclusion: Elective replacement of PIVC in neonates is not associated with reduction in extravasation rates.Trial registration: This trial has been registered with the Australian and New Zealand Clinical Trials Register. Identifier: ACTRN12615000827538. What is Known: • The reported incidence of extravasation injury is as high as 70% in the neonatal and paediatric population and has an association with cannula dwell time. • Adult studies have done to look at the possibility of reducing intravenous cannula-related complications with routine replacement of the cannulas but no similar studies have been done in the neonatal population. What is New: • Routine replacement of intravenous cannula in neonates between 72 and 96 h of use does not reduce the rate of extravasation injuries. • There might be some added complications associated with such a practice. [ABSTRACT FROM AUTHOR]

Background: The province of Manitoba, Canada, with a population of approximately 1.3 million, has been experiencing increased incidence of syphilis cases since 2015. In this study, we examined the detection of Treponema pallidum DNA in 354 clinical samples from 2012 to 2016, and determined molecular types and mutations conferring resistance to azithromycin in the polymerase chain reaction (PCR)-positive samples.Methods: T. pallidum DNA detection was done by PCR amplification of tpp47, bmp, and polA genes. Syphilis serology results were reviewed for the PCR-positive cases. Molecular typing of syphilis strains was done by analysis of the T, pallidum arp, tpr, and tp0548 gene targets as well as partial sequencing of the 23S rRNA gene for azithromycin resistance.Results: Of the 354 samples tested, 74 individual cases were PCR positive. A result from the treponemal antibody chemiluminescent microparticle immunoassay test was positive in 72 of these cases and that from the Venereal Disease Research Laboratory testing was positive in 66. Mutations conferring resistance to azithromycin were found in all 74 PCR-positive samples. Molecular typing was completed on 57 PCR-positive samples, and 12 molecular types were identified with 14d/g found in 63.2%. Increased strain diversity was observed with 8 molecular types detected in 2016, whereas only 2 to 3 types were found in 2012 to 2014. A patient with 2 episodes of infection 9 months apart caused by different molecular strain types was also identified.Conclusions: The finding of an increase in genetic diversity in the strains in this study and an increase in macrolide resistance compared with previous Canadian reports highlighted the need for continued surveillance including strain characterization. [ABSTRACT FROM AUTHOR]

Background Context: There has been renewed interest in the pelvic vertebrae by spinal surgeons recently. Those involved in working with patients with adult spinal deformity focus on the position of the fused spine as it relates to the pelvis, and determine success or failure by specific numbers for given pelvic parameters. The pelvic parameters that are commonly measured for these patients are pelvic tilt, sacral slope, and pelvic incidence (PI). Out of the three, PI has always been considered to be the fixed measurement, whereas pelvic tilt and sacral slope have the capacity to change in relation to external forces. The assumption that the PI does not change has not been proven in a healthy, asymptomatic population.Purpose: This study aimed to investigate the differences in PI between three pelvic positions used in common functional activities: resting baseline pelvic posture, maximal anterior pelvic rotation, and maximal posterior pelvic rotation.Study Design/setting: This was a randomized, prospective study of 50 healthy, asymptomatic, individuals who were recruited from the vicinity of our institution.Patient Sample: Fifty patients (16 men with a mean age of 26.5±12.1 years; 34 women with a mean age of 27.2±10.8 years) were recruited for this study. Initial screening occurred by telephone. The inclusion criteria consisted of participants being between 18 and 79 years of age, no previous history of spine, pelvic, or lower extremity pain which had lasted longer than 48 hours, or history of any disorder in the spine, pelvis, or lower extremity that had required medical care. Female patients could not be pregnant at the time of participation.Outcome Measures: Changes in PI were assessed by examining the differences between the values of the PI with each change in pelvic position: resting to maximal anterior pelvic rotation and resting to maximal posterior pelvic rotation. Inter-rater reliability was assessed using Cronbach's alpha.Methods: This study was funded by a Small Exploratory Grant from the Scoliosis Research Society. All subjects had an initial posterior-anterior and lateral radiograph taken in their resting pelvic position. If no spinal deformity was noted, each subject was instructed to maximally rotate their pelvis anteriorly and an immediate lateral radiograph was taken. The subject was then instructed to maximally rotate their pelvis posteriorly and an immediate lateral radiograph was again taken. Radiographic measurements of PI were independently measured by a board-certified, fellowship trained orthopedic spine surgeon and a board-certified musculoskeletal radiologist after defining and agreeing to the specific manner of measurement.Results: Pelvic incidence values changed in 44 of 50 subjects (88%) when they maximally anteriorly rotated their pelvis from the resting pelvic position. The mean change was 2.9°, with 23 of 50 subjects (46%) changing ≥3°. Pelvic incidence values changed in 40 of 50 subjects (80%) when they maximally posteriorly rotated their pelvis from the resting position. The mean change was 2.82° with 27 of 50 subjects (54%) changing by ≥3°.Conclusions: This study demonstrated that for a high percentage of the healthy subjects who participated, the PI changed when the subjects varied their pelvic position. This questions the assumption that PI is a fixed parameter and suggests a potential functional motion at the sacroiliac joint. It also supports the idea that intentionally changing one's posture could lead to a change in PI, an idea that could have ramifications in surgical cases. [ABSTRACT FROM AUTHOR]