Search

High placebo responses could significantly reduce the treatment effect in a parallel randomized trial. To combat that challenge, several approaches were developed, including the sequential parallel comparison design (SPCD) that was shown to increase the statistical power as compared to the traditional randomized trial. A linear combination of the response rate differences from two phases per the SPCD is commonly used to measure the overall treatment effect size. The traditional approach to calculate the confidence interval for the overall rate difference is based on the delta method using the variance–covariance matrix of all outcomes. As outcomes from a multinomial distribution are correlated, we suggest utilizing a constrained variance–covariance matrix in the delta method. In the observation of anti-conservative coverages from asymptotic intervals, we further propose using importance sampling to develop accurate intervals. Simulation studies show that accurate intervals have better coverage probabilities than others and the interval width of accurate intervals is similar to the interval width of others. Two real trials to treat major depressive disorder are used to illustrate the application of the proposed intervals. [ABSTRACT FROM AUTHOR]

Soft tissue lesions are commonly encountered and imaging is an important diagnostic step in the diagnosis and management of these lesions. While some of these lesions are true neoplasms, others are not. These soft tissue tumor mimickers can be due to a variety of conditions including traumatic, iatrogenic, inflammatory/reactive, infection, vascular, and variant anatomy. It is important for the radiologist and clinician to be aware of these common soft tissue tumor mimickers and their characteristic imaging features to avoid unnecessary workup and provide the best treatment outcome. [ABSTRACT FROM AUTHOR]

Background: Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor used to prevent neutropenia, is not indicated for administration within 24 h of completion of chemotherapy. The safety of administering pegfilgrastim in gastrointestinal cancer chemotherapy regimens containing continuous intravenous infusion of 5-fluorouracil (5-FUCI) on the day of completion of 5-fluorouracil has not been adequately studied. Methods: An institutional review board-approved retrospective analysis of patients with a gastrointestinal malignancy receiving pegfilgrastim on the final day of 5-FUCI was conducted. The primary end point was to determine the incidence of grade 3 and grade 4 neutropenia and febrile neutropenia when pegfilgrastim was administered on the final day of 5-FUCI. The secondary endpoint was to determine rate of dose reductions and treatment delays. Results: A total of 300 patients were reviewed from January 2010 to May 2017. The most common cancers were colorectal (25%) and pancreatic (60%), with 77% of patients having late stage disease. The risk of a patient developing grade 3 neutropenia was 0.010 (95% CI 0.002–0.029) and grade 4 neutropenia was 0.007 (95% CI 0.001–0.024). The risk of febrile neutropenia was 0.007 (95% CI 0.001–0.024). The risks of treatment delay and treatment reduction were 0.013 (95% CI 0.004–0.034) and 0.010 (95% CI 0.002–0.029), respectively. Conclusion: The low risk of grade 3 and grade 4 neutropenia, febrile neutropenia, as well as dose delays and/or reduction suggests that pegfilgrastim can be administered on the final day of 5-FUCI. Limitations of this study were that it was retrospective in nature and was conducted at a single institution. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia and inflammation have been associated with poor survival in patients with cancer. We explored the combined effects of these variables on survival in patients with cancer treated with immunotherapy. Methods: We performed a retrospective review of 90 patients enrolled on immunotherapy‐based phase I clinical trials at Emory University from 2009 to 2017. Baseline neutrophil‐to‐lymphocyte ratio, monocyte‐to‐lymphocyte ratio, and platelet‐to‐lymphocyte ratio (PLR) were used as surrogates of inflammation. The skeletal muscle index (SMI) was derived from the skeletal muscle density calculated from baseline abdominal computed tomography images. Optimal cutoffs for continuous inflammation biomarkers and SMI were determined by bias‐adjusted log‐rank test. A four‐level risk stratification was used to create low‐risk (PLR <242 and nonsarcopenic), intermediate‐risk (PLR <242 and sarcopenic), high‐risk (PLR ≥242 and nonsarcopenic), and very‐high‐risk (PLR ≥242 and sarcopenic) groups with subsequent association with survival. Results: Most patients (59%) were male, and the most common cancers were melanoma (33%) and gastrointestinal (22%). Very high‐risk, high‐risk, and intermediate‐risk patients had significantly shorter overall survival (hazard ratio [HR], 8.46; 95% confidence interval [CI], 2.65–27.01; p <.001; HR, 5.32; CI, 1.96–14.43; p =.001; and HR, 4.01; CI, 1.66–9.68; p =.002, respectively) and progression‐free survival (HR, 12.29; CI, 5.15–29.32; p <.001; HR, 3.51; CI, 1.37–9.02; p =.009; and HR, 2.14; CI, 1.12–4.10; p =.022, respectively) compared with low‐risk patients. Conclusion: Baseline sarcopenia and elevated inflammatory biomarkers may have a combined effect on decreasing survival in immunotherapy‐treated patients in phase I trials. These data may be immediately applicable for medical oncologists for the risk stratification of patients beginning immunotherapeutic agents. Implications for Practice: Sarcopenia and inflammation have been associated with poor survival in patients with cancer, but it is unclear how to apply this information to patient care. The authors created a risk‐stratification system that combined sarcopenia and platelet‐to‐lymphocyte ratio as a marker of systemic inflammation. The presence of sarcopenia and systemic inflammation decreased progression‐free survival and overall survival in our cohort of 90 patients who received immunotherapy in phase I clinical trials. The data presented in this study may be immediately applicable for medical oncologists as a way to risk‐stratify patients who are beginning treatment with immunotherapy. The interaction between chronic inflammation and body composition is particularly important in the era of immunotherapy, considering that immune checkpoint inhibitors rely on the host immune system for their efficacy. This article reports on the combined effects of inflammation and sarcopenia on clinical outcomes in patients with solid tumors treated with immunotherapy‐based regimens. [ABSTRACT FROM AUTHOR]

Background: Cancer cachexia (CC) is a significant contributor to mortality and morbidity in patients with gastrointestinal (GI) cancer. Treatment options to prevent or halt the progression of CC are limited. Targeted acupuncture (TA) was used in GI patients with CC to evaluate for a potential gender effect. Patients and methods: Participants (n = 30) were recruited from two outpatient clinics in the northern central part of Florida. All participants were diagnosed with CC and GI cancers. A randomized, single-blind, placebo-controlled clinical trial was used to compare TA to non-targeted acupuncture (NTA) over the course of 8 weeks. Primary endpoints were weight and body composition changes measured by bioelectrical impedance analysis (BIA) and biomarker analysis (tumor necrosis factor (TNF)-α and leptin). Herein, gender differences across and within TA and NTA groups were examined as a secondary analysis. Results: A significant (p = 0.026) interaction between weight and gender was noted, which manifested in a non-significant increase in the male intervention (MI) group, while TNF-α levels significantly increased by gender (p = 0.028) and group (p = 0.006) over the course of the study. All other groups either lost or did not change weight. The extracellular-to-intracellular water (ECW/ICW) ratio was significantly elevated for the TA group (p = 0.02) and for males (p = 0.009) at completion of the study. TNF-α and leptin levels were positively correlated within the MI group at the end of the study. Conclusion: A decrease in leptin in the MI group corresponded to higher appetite and weight gain. The elevated ECW/ICW ratio indicates an inflammatory response in the MI group. This gender-specific response may be based on hormone-specific regulation of food intake. Further studies with larger sample sizes are required to support the results. [ABSTRACT FROM AUTHOR]

This study examined the relationship between caregivers' and youths' treatment expectations and characteristics of exposure tasks (quantity, mastery, compliance) in cognitive-behavioral therapy (CBT) for childhood anxiety. Additionally, compliance with exposure tasks was tested as a mediator of the relationship between treatment expectations and symptom improvement. Data were from youth (N = 279; 7-17 years old) enrolled in the Child/Adolescent Anxiety Multimodal Study (CAMS) and randomized to cognitive-behavioral therapy (CBT) or the combination of CBT and sertraline for the treatment of separation anxiety disorder, generalized anxiety disorder, and social phobia. Caregivers and youth independently reported treatment expectations prior to randomization, anxiety was assessed pre- and post-treatment by independent evaluators blind to treatment condition, and exposure characteristics were recorded by the cognitive-behavioral therapists following each session. For both caregivers and youths, more positive expectations that anxiety would improve with treatment were associated with greater compliance with exposure tasks, and compliance mediated the relationship between treatment expectations and change in anxiety symptoms following treatment. Additionally, more positive parent treatment expectations were related to a greater number and percentage of sessions with exposure. More positive youth treatment expectations were associated with greater mastery during sessions focused on exposure. Findings underscore the importance of addressing parents' and youths' treatment expectations at the outset of therapy to facilitate engagement in exposure and maximize therapeutic gains. [ABSTRACT FROM AUTHOR]

Summary: Background Given the increasing number of available immunotherapeutic agents, more patients are presenting after failing immunotherapy in need of new treatment options. In this study, we investigated the clinical outcomes of patients treated with sequential immunotherapy. Methods We performed a retrospective review of 90 advanced stage cancer patients treated on immunotherapy-based phase 1 clinical trials at Winship Cancer Institute from 2009 to 2017. We included 49 patients with an immune checkpoint inhibitor (ICI)-indicated histology. Patients were analyzed based on whether they had received prior ICI. Clinical outcomes were overall survival (OS), progression-free survival (PFS), and clinical benefit (best response of complete response, partial response, or stable disease). Univariate analysis (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazard or logistic regression model. Covariates included age, liver metastases, number of prior lines of therapy, histology, and Royal Marsden Hospital (RMH) risk group. Results The most common histologies were melanoma (61%) and lung/head and neck cancers (37%). More than half of patients (n = 27, 55%) received at least one ICI prior to trial enrollment: ten received anti-PD-1, two received anti-CTLA-4, five received anti-PD-1/CTLA-4 combination, and ten received multiple ICI. In MVA, ICI-naïve patients had significantly longer OS (HR: 0.22, CI: 0.07–0.70, p = 0.010) and trended towards higher chance of CB (HR: 2.52, CI: 0.49–12.97, p = 0.268). Patients who received prior ICI had substantially shorter median OS (10.9 vs 24.3 months, p = 0.046) and PFS (2.8 vs. 5.1 months, p = 0.380) than ICI-naïve patients per Kaplan-Meier estimation. Within the ICI-naïve group, 78% (7 of 9) of patients who received prior interleukin (IL-2) or interferon gamma (IFNγ) experienced disease control for at least 6 months, compared to a disease control rate of 15% (2 of 13) in patients who had received chemotherapy, targeted therapy, or no prior treatment. Conclusions ICI-naïve patients may experience improved clinical outcomes on immunotherapy-based phase 1 clinical trials than patients who have received prior ICI. This may be particularly true for patients who received prior IL-2 or IFNγ. Further development of immunotherapy combination therapies is needed to improve clinical outcomes of these patients. These results should be validated in a larger study. [ABSTRACT FROM AUTHOR]

Background: Optimal prognostic and predictive biomarkers for patients with advanced-stage cancer patients who received immunotherapy (IO) are lacking. Inflammatory markers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR), are readily available. The authors investigated the association between these markers and clinical outcomes of patients with advanced-stage cancer who received IO.Methods: A retrospective review was conducted of 90 patients with advanced cancer who received treatment on phase 1 clinical trials of IO-based treatment regimens. NLR, MLR, and PLR values were log-transformed and treated as continuous variables for each patient. Overall survival (OS), progression-free survival (PFS), and clinical benefit were used to measure clinical outcomes. For univariate associations and multivariable analyses, Cox proportional-hazards models or logistic regression models were used.Results: The median patient age was 63 years, and most were men (59%). The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). High baseline NLR, MLR, and PLR values were associated significantly with worse OS and PFS (P < .05) and a lower chance of benefit (NLR and PLR; P < .05). Increased NLR, MLR, and PLR values 6 weeks after baseline were associated with shorter OS and PFS (P ≤ .052).Conclusions: Baseline and early changes in NLR, MLR, and PLR values were strongly associated with clinical outcomes in patients who received IO-based treatment regimens on phase 1 trials. Confirmation in a homogenous patient population treated on late-stage trials or outside of trial settings is warranted. These values may warrant consideration for inclusion when risk stratifying patients enrolled onto phase 1 clinical trials of IO agents. [ABSTRACT FROM AUTHOR]

Background. Musculoskeletal pain is a societal epidemic because it is highly prevalent and a leading contributor to disability; however, physical therapists are still challenged when predicting which patients are at high risk for persistent symptoms. Objective. The objectives of this study were to identify patient characteristics predictive of persistent musculoskeletal pain 12 months following physical therapist care and to determine the influence of anatomical region. Design. The design included a secondary analysis of a cohort study. Methods. Participants ranged in age from 18 to 65 years, had a primary report of knee, shoulder, back, or neck pain, were receiving physical therapy, and were enrolled in the Orthopedic Physical Therapy Investigative Network (OPT-IN) Optimal Screening for Prediction of Referral and Outcome (OSPRO) validation cohort study. Candidate predictor variables included demographic and clinical characteristics, comorbidities, and OSPRO Review of Systems (OSPRO-ROS) and OSPRO Yellow Flag (OSPRO-YF) tool scores. Persistent musculoskeletal pain was assessed by self-report responses to questions on the duration of pain and activity limitation. Logistic regression was used for completed cases to identify predictors of persistent pain at 12 months in full and parsimonious models. Results. Follow-up assessment at 12 months was performed for 63.4% of participants (279/440). Participants with persistent pain at 12 months (n = 101; 36.2%) had more comorbidities, higher numerical pain rating scale scores, and higher OSPRO-ROS and OSPRO-YF tool scores at baseline than those without persistent pain, and the findings were independent of anatomical region. The number of comorbidities (odds ratio [OR] range = 0.30-0.46), numerical pain rating scale scores (OR at baseline = 1.44-1.75; OR at 4 weeks = 1.37-1.39), and OSPRO-ROS (plus additional items) scores (OR = 1.33-1.54) were predictors in full and parsimonious models. Limitations. Convenience sampling was used, with a follow-up rate at 12 months (63.4%) that was lower than anticipated, and an operational definition for chronic low back pain was applied to persistent musculoskeletal pain in other body regions. Conclusions. The OSPRO-ROS tool may be used to improve the prediction of persistent musculoskeletal pain at 12 months in conjunction with comorbidities and pain intensity (baseline and 4 weeks). These are potentially important findings because persistent pain was not commonly evaluated in previous screening studies; however, it is a relevant outcome in an era of front-line nonpharmacological pain management. [ABSTRACT FROM AUTHOR]

Drop-the-losers designs have been discussed extensively in the past decades, mostly focusing on two-stage models. The designs with more than two stages have recently received increasing attention due to their improved efficiency over the corresponding two-stage designs. In this paper, we consider the problem of estimating and testing the effect of selected treatment under the setting of three-stage drop-the-losers designs. A conservative interval estimator is proposed, which is proved to have at least the specified coverage probability using a stochastic ordering approach. The proposed interval estimator is also demonstrated numerically to have narrower interval width but higher coverage rate than the bootstrap method proposed by Bowden and Glimm (Biometrical Journal, vol. 56, pp. 332-349) in most cases. It is also a straightforward derivation from the stochastic ordering result that the family-wise error rate is strongly controlled with the maximum achieved at the global null hypothesis. [ABSTRACT FROM AUTHOR]

Objective: To identify novel combinations of genetic and psychological factors that predicted 12-month postoperative pain and disability outcomes following arthroscopic shoulder surgery.Methods: A prospective presurgical cohort (n = 150) was recruited to complete validated psychological questionnaires and have their DNA collected from saliva. DNA was genotyped for a priori selected genes involved with pain modulation (ADRB2, OPRM1, AVPR1A, GCH1, and KCNS1) and inflammation (IL1B, TNF/LTA, and IL6). The outcome measures of interest were the Brief Pain Inventory and Disabilities of the Arm, Shoulder, and Hand questionnaire. Followup for the cohort was at 3, 6, and 12 months postoperatively. After controlling for age, sex, race, and preoperative status, genetic and psychological factors were entered as main effects and interaction terms in separate general linear models for predicting postoperative pain and disability outcomes.Results: Seven interactions involving pain-modulatory genes were identified. Three provided strong statistical evidence for different outcomes, including KCNS1 and kinesiophobia for preoperative pain intensity, ADRB2 and depressive symptoms for postoperative course, and GCH1 and anxiety symptoms for 12-month pain-intensity outcome. Ten interactions involving inflammatory genes were identified. Three provided strong statistical evidence for the 12-month postoperative course outcome, including 2 different IL6 single-nucleotide polymorphism and pain catastrophizing, and IL6 and depressive symptoms.Conclusion: The current study identified novel genetic and psychological interactions that can be used in future studies to further understand the development of persistent postoperative pain and investigate the effectiveness of tailored treatment. [ABSTRACT FROM AUTHOR]

Although there are efficacious, evidence-based treatments for anxiety disorders, youth often experience delays in seeking therapy. Myriad reasons may contribute to this lag in treatment initiation, with some youth possessing concerns about therapy. Treatment concerns are broadly characterized by worries/ambivalence about seeking treatment, including concerns about the negative reactions, consequences, and inconvenience of treatment. As no studies exist for youth with anxiety disorders, this study examined the phenomenology of treatment concerns in 119 treatment-seeking, anxious youth and utilized a structural equation model to examine the relationship between child anxiety, depressive symptoms, treatment concerns, and anxiety-related functional impairment. Over 90 % of the children positively endorsed some type of treatment-related fear, with the most frequently expressed concern being that therapy would take too much time (50.4 %). Based on the model, both child anxiety and depressive symptoms predicted functional impairment, and treatment concerns mediated the relationship between child anxiety and functional impairment. [ABSTRACT FROM AUTHOR]

Objective: To ascertain the existence of discordance between perceived and measured balance in persons with stroke and to examine the impact on walking speed and falls. Design: A secondary analysis of a phase three, multicentered randomized controlled trial examining walking recovery following stroke. Subjects: A total of 352 participants from the Locomotor Experience Applied Post-Stroke (LEAPS) trial. Methods: Participants were categorized into four groups: two concordant and two discordant groups in relation to measured and perceived balance. Number and percentage of individuals with concordance and discordance were evaluated at two and 12 months. Walking speed and fall incidence between groups were examined. Main measures: Perceived balance was measured by the Activities-Specific Balance Confidence scale, measured balance was determined by the Berg Balance Scale and gait speed was measured by the 10-meter walk test. Results: Discordance was present for 35.8% of participants at two months post stroke with no statistically significant change in proportion at 12 months. Discordant participants with high perceived balance and low measured balance walked 0.09 m/s faster at two months than participants with concordant low perceived and measured balance (p < 0.05). Discordant participants with low perceived balance and high measured balance walked 0.15 m/s slower than those that were concordant with high perceived and measured balance (p ⩽ 0.0001) at 12 months. Concordant participants with high perceived and measured balance walked fastest and had fewer falls. Conclusions: Discordance existed between perceived and measured balance in one-third of individuals at two and 12 months post-stroke. Perceived balance impacted gait speed but not fall incidence. [ABSTRACT FROM AUTHOR]

Background Whether 10-day or 14-day sequential therapy is superior to 14-day triple therapy in the first-line treatment of Helicobacter pylori remains controversial. Aim To compare the efficacy of 10-day or 14-day sequential therapy vs. 14-day triple therapy. Methods Randomised controlled trials ( RCTs) comparing 10-day or 14-day sequential therapy and 14-day triple therapy as first-line treatment in adults were searched from the PubMed and Cochrane databases from 2000 to October 2015. Abstracts from international annual conferences were also searched. The primary and secondary outcomes were the eradication rate according to the intention-to-treat analysis and adverse effects, respectively. Results Of the 109 articles identified, 13 RCTs including 2749 patients in the sequential therapy group and 2424 patients in the 14-day triple therapy group were eligible. Overall, sequential therapy for 10 or 14 days was not significantly superior to 14-day triple therapy [Risk ratio ( RR) 1.04, 95% confidence interval ( CI) 0.99-1.08, P = 0.145]. However, there was significant heterogeneity ( I2 = 57.6%, P = 0.005). In the subgroup analysis of four trials, we found that 14-day sequential therapy was significantly more effective than 14-day triple therapy ( RR: 1.09, 95% CI: 1.04-1.16, P = 0.002), and there was no significant heterogeneity ( I2 = 0%, P = 0.624) in this comparison. Sequential therapy given for 10 days was not superior to 14-day triple therapy ( RR: 1.03, 95% CI: 0.98-1.09, P = 0.207). There was no significant difference in the risk of adverse effects. Conclusion Sequential therapy given for 14 days, but not 10 days, was more effective than 14-day triple therapy as first-line treatment. [ABSTRACT FROM AUTHOR]

BackgroundWhile oral antidepressants reach efficacy after weeks, single-dose intravenous (i.v.) ketamine has rapid, yet time-limited antidepressant effects. We aimed to determine the efficacy and safety of single-dose i.v. ketamine augmentation of escitalopram in major depressive disorder (MDD).MethodThirty outpatients with severe MDD (17-item Hamilton Rating Scale for Depression total score ⩾24) were randomized to 4 weeks double-blind treatment with escitalopram 10 mg/day+single-dose i.v. ketamine (0.5 mg/kg over 40 min) or escitalopram 10 mg/day + placebo (0.9% i.v. saline). Depressive symptoms were measured using the Montgomery–Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology – Self-Report (QIDS-SR). Suicidal ideation was evaluated with the QIDS-SR item 12. Adverse psychopathological effects were measured with the Brief Psychiatric Rating Scale (BPRS)-positive symptoms, Young Mania Rating Scale (YMRS) and Clinician Administered Dissociative States Scale (CADSS). Patients were assessed at baseline, 1, 2, 4, 24 and 72 h and 7, 14, 21 and 28 days. Time to response (⩾50% MADRS score reduction) was the primary outcome.ResultsBy 4 weeks, more escitalopram + ketamine-treated than escitalopram + placebo-treated patients responded (92.3% v. 57.1%, p = 0.04) and remitted (76.9% v. 14.3%, p = 0.001), with significantly shorter time to response [hazard ratio (HR) 0.04, 95% confidence interval (CI) 0.01–0.22, p < 0.001] and remission (HR 0.11, 95% CI 0.02–0.63, p = 0.01). Compared to escitalopram + placebo, escitalopram + ketamine was associated with significantly lower MADRS scores from 2 h to 2 weeks [(peak = 3 days–2 weeks; effect size (ES) = 1.08–1.18)], QIDS-SR scores from 2 h to 2 weeks (maximum ES = 1.27), and QIDS-SR suicidality from 2 to 72 h (maximum ES = 2.24). Only YMRS scores increased significantly with ketamine augmentation (1 and 2 h), without significant BPRS or CADSS elevation.ConclusionsSingle-dose i.v. ketamine augmentation of escitalopram was safe and effective in severe MDD, holding promise for speeding up early oral antidepressant efficacy. [ABSTRACT FROM PUBLISHER]

What is known and objective Proton pump inhibitors ( PPIs) are one of the most widely used classes of drugs. However, the quantum clinical benefit of newer and more expensive PPIs over the older generation PPIs remains uncertain. This meta-analysis sought to assess the clinical and safety profiles of esomeprazole versus omeprazole at pharmacologically equivalent doses in healing gastroesophageal reflux disease ( GERD), peptic ulcer disease and eradicating Helicobacter pylori (H. pylori) infection. Methods PubMed and the Cochrane Library were searched for randomized controlled trials comparing esomeprazole with omeprazole at all doses up to February 2015. Trials were assessed by two reviewers for eligibility according to predefined study inclusion criteria. Meta-analysis was conducted using a random effects model, and heterogeneity in the estimated effects was investigated using meta-regression. Sensitivity analysis was performed to test the robustness of the findings. Results and Discussion Fifteen trials were included and none of which compared esomeprazole with omeprazole in peptic ulcer disease. The included studies had not evaluated esomeprazole 20 mg versus omeprazole 40 mg. In GERD, esomeprazole 40 mg (relative risk ( RR) = 1·07; 95% confidence interval ( CI) 1·02 to 1·12) and 20 mg ( RR=1·04; 95% CI 1·01 to 1·08) significantly improved esophagitis healing when compared with omeprazole 20 mg at week 8. The corresponding numbers needed to treat were 17 and 30, respectively. No significant difference was observed between esomeprazole 20 mg and omeprazole 20 mg at week 4. In H. pylori eradication, there was no difference in the treatment effects between esomeprazole 20 mg and omeprazole 20 mg ( RR = 1·01;95% CI 0·96 to 1·05). Their safety profiles were comparable. What is new and conclusion Esomeprazole demonstrated better esophagitis healing rate in patients with GERD than omeprazole at week 8. However, this clinical advantage diminished when both drugs were given at the same doses at week 4. Superiority of esomeprazole was not observed in the H. pylori eradication rates. [ABSTRACT FROM AUTHOR]

Aims: The standard of care for locally advanced head and neck squamous cell carcinoma (HNSCC) is radiation therapy (RT) with concurrent cisplatin (CIS). Patients with renal or cardiac dysfunction, hearing loss or poor performance status (PS) may receive RT and cetuximab (CET) at our institution. This study compares treatment toxicities and outcomes. Methods and Materials: All patients treated with curative intent RT and concurrent CIS (100 mg/m² Day 1, 22, 43) or CET (400 mg/m² Day -7, 250 mg/m² weekly during RT) between August 2007 and July 2010 were reviewed and toxicity and outcomes analyzed. Results: Among 349 subjects (262 RT-CIS, 87 RT-CET) characteristics were similar except in age, head and neck subsite and RT fractionation. RT-CIS required more dose reductions, delays, and unplanned admissions and received less intended systemic therapy (ST). Weight loss and gastrostomy-tube use were similar. RT-CIS caused more nausea/vomiting, while RT-CET was associated with more dermatitis and acneiform rash. With mean follow-up of 20 months and 16 months, RT-CIS subjects experienced improved 1-year locoregional control (LRC) (90% vs. 72%, P < 0.01), disease-free survival (DFS) (83% vs. 67%, P < 0.01) and overall survival (OS) (90% vs. 80%, P = 0.04). On multivariate analysis type of ST was associated with LRC and DFS, but not OS. Conclusions: In patients with locally advanced HNSCC, CIS and CET were associated with different toxicity profiles. RT-CIS was associated with improved LRC and DFS, but similar OS compared to RT-CET. [ABSTRACT FROM AUTHOR]

Background: A review of the literature pertaining to percutaneous transhepatic cholangioscopic lithotomy (PTCSL) showed that more than 50% of reported patients had undergone earlier biliary surgery.Methods: A retrospective study investigated 74 patients undergoing initial PTCSL for hepatolithiasis who had undergone no prior biliary surgery or manipulation. The patients were followed for 1 to 23 years after PTCSL for effective evaluation of the procedure outcome.Results: Complete clearance of hepatolithiasis was achieved for 61 (82%) patients. The incomplete clearance rate was higher for patients with intrahepatic duct stricture (11/37 [30%] vs 2/37 [5%]; p < 0.05), although it showed no relation to the actual lobar distribution of hepatolithiasis (left: 7/41 [17%] vs right: 2/11 [18%] vs bilateral: 4/22 [18%]; p < 0.05). The recurrence rate for hepatolithiasis also was higher for patients with intrahepatic duct stricture (18/26 [69%] vs 13/35 [37%]; p < 0.05), but the recurrence rate showed no relation to the lobar distribution of hepatolithiasis (left: 18/34 [53%] vs right: 4/9 [44%] vs bilateral: 9/18 [50%] p > 0.05) or the presence of gallbladder stones (5/12 [42%] vs 26/49 [53%]; p > 0.05). Patients showing the coexistence of retained or recurrent hepatolithiasis demonstrated a higher incidence of recurrent cholangitis (57% [13/23] vs 14% [7/51]; p < 0.01) or cholangiocarcinoma (17% [4/23]) vs 0% [0/51]; p < 0.01).Conclusions: The findings show that PTCSL is effective for treating primary hepatolithiasis, and that complete stone clearance is mandatory to diminish the sequelae of hepatolithiasis. Intrahepatic duct stricture was the main factor contributing to incomplete clearance and stone recurrence. [ABSTRACT FROM AUTHOR]

Background: Unlike sliding hiatal hernias, paraesophageal hiatal hernias (PEH) present a risk of catastrophic complications and should be repaired. To assess laparoscopic repair of PEH, we prospectively evaluated the outcome of 38 consecutive patients with type II (20 patients) or III (18 patients) PEH treated laparoscopically.Methods: With the use of 5 or 6 ports, laparoscopic PEH reduction and repair was attempted. One patient (3%) was converted to an open procedure. In the first 12 patients, the hiatus was closed using varying techniques including the placement of prothestic mesh in 6 patients, and the hernia sac was not routinely excised. In the next 25 patients, the hernia sac always was excised and the hiatus routinely sutured posteriorly to the esophagus. Twenty-nine patients also underwent either a Nissen (n = 27) or Toupet (n = 2) fundoplication, which is now performed routinely. Sutured anterior gastropexy was performed selectively in 10 of the first 20 patients, then routinely, using T-fasteners in the last 17 patients. Barium swallow studies were performed on all patients at 3 to 5 months postoperatively.Results: Mean +/- standard error of the mean (SEM) age was 67 +/- 2 year (range, 39-92 years; 11 men, 27 women), and the American Society of Anesthesia (ASA) score was 2.5 +/- 0.1. The operating time was 195 +/- 10 min: 244 +/- 15 min in the first 12 patients and 170 +/- 11 min in the last 25 patients (p < 0.001). There were three (8%) intraoperation complications, which were treated without sequelae, and four (11%) grade II postoperation morbidities. Median discharge was 3 days, and return to full activity was 14 days. Two patients (5%) died of cardiovascular disease after discharge. Barium swallow revealed 2/35 (6%) PEH recurrences (1 reoperated), 3 (9%) intrathoracic wraps, and 3 (9%) small sliding hiatal hernias. At follow-up of 1 year or more, 6/28 (21%) patients noted mild symptoms of reflux or bloating, but only 1 patient (4%) required medication for these symptoms.Conclusions: Laparoscopic PEH repair offers a reasonable alternative to traditional surgery, especially for high-risk patients. Rapid recovery is achieved with acceptable morbidity and early outcome. Barium x-rays revealed hiatal abnormalities in a significant fraction of patients, many of whom were asymptomatic. Longer follow-up will be required to determine the ideal strategy for management of these patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study examined the frequency and relation of death and/or suicidal ideation to treatment response in 101 adults with obsessive-compulsive disorder (OCD) presenting for intensive intervention. METHODS: Within 2 days of admission to an intensive treatment program, 101 adults with OCD completed the Yale-Brown Obsessive Compulsive Scale-Self Report, Quick Inventory of Depressive Symptomatology-Self Report, Intolerance of Uncertainty Scale, Obsessive-Compulsive Inventory-Revised, Penn State Worry Questionnaire, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form, and were administered the Columbia Suicide Scale by a trained clinician. RESULTS: A majority of patients reported death ideation within their lifetime (62.4%) and within the past month (67%). Approximately 12% of patients reported recent suicidal ideation. Patients with recent suicidal ideation reported significantly more depressive symptoms, more OCD symptoms, and less life satisfaction compared with patients not reporting suicidal ideation. Although prevalent, the presence of suicidal ideation was not associated with treatment response in the current sample. CONCLUSIONS: Suicidal ideation and history are prevalent among patients being treated intensively and are associated with OCD severity and depression, but they do not predict intensive multimodal treatment response. [ABSTRACT FROM AUTHOR]

Veterans with blast-related mild traumatic brain injury (TBI) experience cognitive deficits that interfere with functional activities. Goal Management Training (GMT), which is a metacognitive intervention, offers an executive function rehabilitation approach that draws upon theories concerning goal processing and sustained attention. GMT has received empirical support in studies of patients with TBI but has not been tested in Veterans with blast-related mild TBI. GMT was modified from 7 weekly to 10 biweekly sessions. Participants included six combat Veterans who reported multiple blast exposures resulting in symptoms consistent with mild TBI. Group analysis showed a significant improvement in measures of executive function derived from performance on the computerized Tower of London. There were no significant changes on self/informant questionnaires of executive function, indicating a lack of generalization of improvement from the clinic to everyday activities. Overall, while the data indicate efficacy of GMT in the rehabilitation of combat Veterans with executive function deficits because of blast-related mild TBI, enhancement of generalization is needed. [ABSTRACT FROM AUTHOR]

The Locomotor Experience Applied Post Stroke rehabilitation trial found equivalent walking outcomes for body weight-supported treadmill plus overground walking practice versus home-based exercise that did not emphasize walking. From this large database, we examined several clinically important questions that provide insights into recovery of walking that may affect future trial designs. Using logistic regression analyses, we examined predictors of response based on a variety of walking speed-related outcomes and measures that captured disability, physical impairment, and quality of life. The most robust predictor was being closer at baseline to the primary outcome measure, which was the functional walking speed thresholds of 0.4 m/s (household walking) and 0.8 m/s (community walking). Regardless of baseline walking speed, a younger age and higher Berg Balance Scale score were relative predictors of responding, whether operationally defined by transitioning beyond each speed boundary or by a continuous change or a greater than median increase in walking speed. Of note, the cutoff values of 0.4 and 0.8 m/s had no particular significance compared with other walking speed changes despite their general use as descriptors of functional levels of walking. No evidence was found for any difference in predictors based on treatment group. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) is a leading cause of late life pain and disability, and non-Hispanic black (NHB) adults experience greater OA-related pain and disability than non-Hispanic whites (NHWs). Recent evidence implicates psychosocial stress, cognitive-attentional processes, and altered central pain processing as contributors to greater OA-related pain and disability among NHBs. To address these ethnic/race disparities, this clinical trial will test whether a mindfulness intervention (Breathing and Attention Training, BAT) combined with transcranial direct current stimulation (tDCS) will enhance pain modulatory balance and pain-related brain function, reduce clinical pain, and attenuate ethnic differences therein, among NHBs and NHWs with knee OA. Participants will complete assessments of clinical pain, function, psychosocial measures, and quantitative sensory testing (QST), including mechanical temporal summation and conditioned pain modulation. Neuroimaging will be performed to examine pain-related brain structure and function. Then, participants will be randomized to one of four groups created by crossing two BAT conditions (Real vs. Sham) with two tDCS conditions (Real vs. Sham). Participants will then undergo five treatment sessions during which the assigned BAT and tDCS interventions will be delivered concurrently for 20 min over one week. After the fifth intervention session, participants will undergo assessments of clinical pain and function, QST and neuroimaging identical to the pretreatment measures, and monthly follow-up assessments of pain will be conducted for three months. This will be the first study to determine whether mindfulness and tDCS treatments will show additive or synergistic effects when combined, and whether treatment effects differ across ethnic/race groups. [ABSTRACT FROM AUTHOR]