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Objectives: Clinical trials in early diffuse cutaneous systemic sclerosis (SSc) using the modified Rodnan skin score (mRSS) as the primary outcome measure have most often been negative. We wanted to assess how the definition of disease onset (first SSc manifestation vs first non-Raynaud manifestation) and varying lengths of disease duration at trial entry as an inclusion criteria functioned. Our objective was to optimize trial inclusion criteria., Methods: We used the prospective, observational University of Pittsburgh Scleroderma Cohort to identify early diffuse SSc patients first evaluated between 1980 and 2015. All had <3 years from first SSc (n = 481) or first non-Raynaud manifestation (n = 514) and three or more mRSS scores. We used descriptive, survival and group-based trajectory analyses to compare the different definitions of disease onset and disease duration as inclusion criteria for clinical trials., Results: There was no appreciable difference between using first SSc manifestation compared with first non-Raynaud manifestation as the definition of disease onset. Compared with other disease durations, <18 months of disease had >70% of patients fitting into trajectories with worsening cutaneous disease over 6 months of follow-up. Longer disease durations demonstrated the majority of patients with trajectories showing an improvement in mRSS (regression to the mean) over 6 months., Conclusions: Regardless of whether the first SSc or first non-Raynaud manifestation is used to define disease onset, duration of <18 months at enrolment is preferable. A longer disease duration criterion more frequently results in regression to the mean of the mRSS score, and likely contributes to negative trial outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Ultrasound (US)-guided hip joint injections are commonly performed for patients with suspected or known intra-articular hip pain. Lidocaine is a well-established local anesthetic used prior to hip joint injections, but it is often associated with discomfort during infiltration. Bacteriostatic saline is an alternative local anesthetic that has been shown to be less painful during infiltration for superficial injections., Objective: To compare infiltrative pain and anesthetic efficacy of bacteriostatic saline (0.9% benzyl alcohol) with a standard local anesthetic (buffered 1% lidocaine) used for local anesthesia prior to US-guided intra-articular hip corticosteroid injections., Design: Double-blinded, randomized controlled trial., Setting: Tertiary care medical center., Participants: Sixty eight patients age 18-80 (mean 54.8) years referred for US-guided intra-articular hip corticosteroid injections., Intervention: Patients were randomized to receive a US-guided hip joint corticosteroid injection using either bacteriostatic saline or buffered 1% lidocaine for preinjection local anesthesia., Main Outcome Measures: Visual Analog Scale (VAS) for pain (0-100) during local anesthetic infiltration as well as during the intra-articular injection. Adverse events were also recorded., Results: There were no significant differences between bacteriostatic saline and buffered lidocaine with respect to pain during local anesthetic infiltration or during the subsequent intra-articular injection. Pain VAS during local anesthetic infiltration was 13.2 (95% confidence interval [CI] 7.8, 18.5) in the bacteriostatic saline group and 14.0 (95% CI 9.4, 18.5) in the buffered 1% lidocaine group (P = .82). Furthermore, pain VAS during the intra-articular injection was 20.7 (95% CI 14.1, 27.3) in the bacteriostatic saline group and 15.7 (95% CI 10.9, 20.3) in the buffered 1% lidocaine group (P = .57). No adverse events occurred., Conclusions: Bacteriostatic saline is a safe and comparably effective alternative to buffered 1% lidocaine for local anesthesia before US-guided hip joint injections and may be considered for subcutaneous/periarticular anesthesia during similar musculoskeletal procedures., (© 2020 American Academy of Physical Medicine and Rehabilitation.)

Background and Objectives: Filtering the deluge of new research to facilitate evidence synthesis has proven to be unmanageable using current paradigms of search and retrieval. Crowdsourcing, a way of harnessing the collective effort of a "crowd" of people, has the potential to support evidence synthesis by addressing this information overload created by the exponential growth in primary research outputs. Cochrane Crowd, Cochrane's citizen science platform, offers a range of tasks aimed at identifying studies related to health care. Accompanying each task are brief, interactive training modules, and agreement algorithms that help ensure accurate collective decision-making.The aims of the study were to evaluate the performance of Cochrane Crowd in terms of its accuracy, capacity, and autonomy and to examine contributor engagement across three tasks aimed at identifying randomized trials., Study Design and Setting: Crowd accuracy was evaluated by measuring the sensitivity and specificity of crowd screening decisions on a sample of titles and abstracts, compared with "quasi gold-standard" decisions about the same records using the conventional methods of dual screening. Crowd capacity, in the form of output volume, was evaluated by measuring the number of records processed by the crowd, compared with baseline. Crowd autonomy, the capability of the crowd to produce accurate collectively derived decisions without the need for expert resolution, was measured by the proportion of records that needed resolving by an expert., Results: The Cochrane Crowd community currently has 18,897 contributors from 163 countries. Collectively, the Crowd has processed 1,021,227 records, helping to identify 178,437 reports of randomized controlled trials (RCTs) for Cochrane's Central Register of Controlled Trials. The sensitivity for each task was 99.1% for the RCT identification task (RCT ID), 99.7% for the RCT identification task of trials from ClinicalTrials.gov (CT ID), and 97.7% for the identification of RCTs from the International Clinical Trials Registry Platform (ICTRP ID). The specificity for each task was 99% for RCT ID, 98.6% for CT ID, and 99.1% for CT ICTRP ID. The capacity of the combined Crowd and machine learning workflow has increased fivefold in 6 years, compared with baseline. The proportion of records requiring expert resolution across the tasks ranged from 16.6% to 19.7%., Conclusion: Cochrane Crowd is sufficiently accurate and scalable to keep pace with the current rate of publication (and registration) of new primary studies. It has also proved to be a popular, efficient, and accurate way for a large number of people to play an important voluntary role in health evidence production. Cochrane Crowd is now an established part of Cochrane's effort to manage the deluge of primary research being produced., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Mild traumatic brain injury (TBI) is experienced by 55.9 million people globally each year. The symptoms of mild TBI are diverse and sometimes long-lasting, requiring frequent use of pharmacological interventions to mitigate them. A thorough understanding of the data supporting pharmacological interventions is important for decision-making among clinicians treating this common injury., Objective: To systematically review studies of pharmacological interventions and their associations with symptom burden reduction among patients with mild TBI and to use an evidence-based model to identify potential directions for future research that may aid in clinical decision-making., Evidence Review: A systematic review was performed in PubMed, Scopus, and Web of Science. Search strings modified for the advanced search interfaces of each search engine were developed in consultation with a librarian and included combinations of search terms, such as brain concussion, post-concussion syndrome, mild traumatic brain injury, and pharmacological treatment. Articles published between January 1, 2000, and July 1, 2020, were analyzed. Studies were included if (1) they were clinical studies with discrete analyses of participants with mild TBI or complicated mild TBI, (2) they were assessments of a pharmacological intervention, (3) they included human participants, and (4) they were published in a peer-reviewed journal in the English language. Studies were excluded if the severity of TBI among participants could not be ascertained (ie, inadequate definition of mild TBI) and the inclusion criteria for the study required intracranial hemorrhage. A total of 23 studies examining 20 pharmacological interventions met the inclusion criteria. Risk of bias was assessed using the Cochrane Risk of Bias for Randomized Trials (for randomized clinical trials) and the Cochrane Risk of Bias in Non-Randomized Studies of Interventions (for all other studies). Data were analyzed from June to September 2020., Findings: A total of 1495 articles were identified; of those, 131 articles were excluded as duplicates. Titles and abstracts were screened for inclusion and exclusion criteria among the remaining 1364 articles, and 134 of those articles received a full-text review. After exclusions, 23 studies (11 randomized clinical trials, 7 prospective observational studies, 3 retrospective observational studies, and 2 case studies) examining 20 pharmacological interventions were identified for inclusion in the systematic review. Studies included 22 distinct participant populations comprising 8277 participants with mild TBI and 45 participants without TBI. Among 23 total studies, 8 studies specifically addressed the pediatric population, 9 studies had a low risk of bias, and 16 studies reported symptom burden reduction. Of the 20 pharmacological interventions examined in the studies, methylphenidate, sertraline hydrochloride, ondansetron, amitriptyline, and melatonin were the only medications included in multiple studies., Conclusions and Relevance: This systematic review found a limited number of high-quality, clinically meaningful studies, particularly among children and individuals in the acute stage of injury; therefore, performing an evidence-based analysis that would inform clinical decision-making was not possible. Future studies are needed to focus on standardizing measures and increasing sample sizes (including large multicenter clinical trials) to generate a body of research that may provide additional options for the treatment of patients with mild TBI.

Background and Objectives: The Cochrane Central Register of Controlled Trials (CENTRAL) is compiled from a number of sources, including PubMed and Embase. Since 2017, we have increased the number of sources feeding into CENTRAL and improved the efficiency of our processes through the use of application programming interfaces, machine learning, and crowdsourcing.Our objectives were twofold: (1) Assess the effectiveness of Cochrane's centralized search and screening processes to correctly identify references to published reports which are eligible for inclusion in Cochrane systematic reviews of randomized controlled trials (RCTs). (2) Identify opportunities to improve the performance of Cochrane's centralized search and screening processes to identify references to eligible trials., Methods: We identified all references to RCTs (either published journal articles or trial registration records) with a publication or registration date between 1st January 2017 and 31st December 2018 that had been included in a Cochrane intervention review. We then viewed an audit trail for each included reference to determine if it had been identified by our centralized search process and subsequently added to CENTRAL., Results: We identified 650 references to included studies with a publication year of 2017 or 2018. Of those, 634 (97.5%) had been captured by Cochrane's Centralised Search Service. Sixteen references had been missed by the Cochrane's Centralised Search Service: six had PubMed-not-MEDLINE status, four were missed by the centralized Embase search, three had been misclassified by Cochrane Crowd, one was from a journal not indexed in MEDLINE or Embase, one had only been added to Embase in 2019, and one reference had been rejected by the automated RCT machine learning classifier. Of the sixteen missed references, eight were the main or only publication to the trial in the review in which it had been included., Conclusion: This analysis has shown that Cochrane's centralized search and screening processes are highly sensitive. It has also helped us to understand better why some references to eligible RCTs have been missed. The CSS is playing a critical role in helping to populate CENTRAL and is moving us toward making CENTRAL a comprehensive repository of RCTs., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The use of tranexamic acid (TXA) has recently gained popularity as a treatment modality for epistaxis in the emergency department. Data are presented on the efficacy of the topical use of the intravenous formulation of TXA versus the vasoconstrictor oxymetazoline applied topically in achieving hemostasis in patient presenting to the emergency department with anterior epistaxis. The original article "Comparative Effectiveness of Topically Administered TXA Versus Topical Oxymetazoline Spray for Achieving Hemostasis in Epistaxis" [1] provides complete interpretation of the data. The dataset regarding these treatment modalities has clinical significance toward preventing an avoidable need for escalation of treatment that could potentially increase patient discomfort and prolong emergency department throughput time., (© 2020 The Authors.)

Background: The use of tranexamic acid (TXA) has recently gained popularity as a treatment modality for epistaxis in the emergency department. Previous studies have compared topical TXA to nasal packing. However, topical TXA has not yet been compared with topical oxymetazoline in the treatment of epistaxis., Objectives: This study compares the efficacy of the intravenous formulation of TXA applied topically vs. the vasoconstrictor oxymetazoline applied topically in achieving hemostasis in patients presenting to the emergency department with anterior epistaxis., Methods: In this prospective study, patients presenting to the emergency department with the chief complaint of epistaxis, and meeting inclusion criteria, were allocated into 2 treatment groups; topical oxymetazoline vs. topical application of the intravenous preparation of TXA. Patients were assessed for time to hemostasis in the emergency department as well as the occurrence of rebleeding within the next 48 h after discharge., Results: Hemostasis was achieved in 14 (78%) of the 18 patients in the TXA group compared with 7 (35%) of the 20 patients in the oxymetazoline group. While there were occurrences of rebleeding in the emergency department before discharge and at 48 h in both groups, 11 patients in the TXA group had no recurrence of bleeding compared with 5 in the oxymetazoline group., Conclusion: This study demonstrated that the topical application of the intravenous preparation of TXA is more effective than topical oxymetazoline for achievement of hemostasis in anterior epistaxis. This has clinical significance toward preventing an avoidable need for escalation of treatment that could include applying nasal packing or cautery as well as preventing avoidable return emergency department visits. These outcomes would increase cost, potentially increase patient discomfort, and prolong emergency department throughput time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Posttransplantation diabetes mellitus (PTDM) is a common and significant complication related to immunosuppressive agents required to prevent organ or cell transplant rejection. To elucidate the effects of 2 commonly used agents, the calcineurin inhibitor tacrolimus (TAC) and the mTOR inhibitor sirolimus (SIR), on islet function and test whether these effects could be reversed or prevented, we investigated human islets transplanted into immunodeficient mice treated with TAC or SIR at clinically relevant levels. Both TAC and SIR impaired insulin secretion in fasted and/or stimulated conditions. Treatment with TAC or SIR increased amyloid deposition and islet macrophages, disrupted insulin granule formation, and induced broad transcriptional dysregulation related to peptide processing, ion/calcium flux, and the extracellular matrix; however, it did not affect regulation of β cell mass. Interestingly, these β cell abnormalities reversed after withdrawal of drug treatment. Furthermore, cotreatment with a GLP-1 receptor agonist completely prevented TAC-induced β cell dysfunction and partially prevented SIR-induced β cell dysfunction. These results highlight the importance of both calcineurin and mTOR signaling in normal human β cell function in vivo and suggest that modulation of these pathways may prevent or ameliorate PTDM.

Given the lack of evidence regarding effective pharmacological and non-pharmacological interventions for pediatric mild traumatic brain injury (mTBI) and the resultant lack of treatment recommendations reflected in consensus guidelines, variation in the management of pediatric mTBI is to be expected. We therefore surveyed practitioners across 15 centers in the United States and Canada who care for children with pediatric mTBI to evaluate common-practice variation in the management of pediatric mTBI. The survey, developed by a panel of pediatric mTBI experts, consisted of a 10-item survey instrument regarding providers' perception of common pediatric mTBI symptoms and mTBI interventions. Surveys were distributed electronically to a convenience sample of local experts at each center. Frequencies and percentages (with confidence intervals [CI]) were determined for survey responses. One hundred and seven respondents (71% response rate) included specialists in pediatric Emergency Medicine, Sports Medicine, Neurology, Neurosurgery, Neuropsychology, Neuropsychiatry, Physical and Occupational Therapy, Physiatry/Rehabilitation, and General Pediatrics. Respondents rated headache as the most prevalently reported symptom after pediatric mTBI, followed by cognitive problems, dizziness, and irritability. Of the 65 (61%; [95% CI: 51,70]) respondents able to prescribe medications, non-steroidal anti-inflammatory medications (55%; [95% CI: 42,68]) and acetaminophen (59%; [95% CI: 46,71]) were most commonly recommended. One in five respondents reported prescribing amitriptyline for headache management after pediatric mTBI, whereas topiramate (8%; [95% CI: 3,17]) was less commonly reported. For cognitive problems, methylphenidate (11%; [95% CI: 4,21]) was used more commonly than amantadine (2%; [95% CI: 0,8]). The most common non-pharmacological interventions were rest ("always" or "often" recommended by 83% [95% CI: 63,92] of the 107 respondents), exercise (59%; [95%CI: 49,69]), vestibular therapy (42% [95%CI: 33,53]) and cervical spine exercises (29% [95%CI: 21,39]). Self-reported utilization for common pediatric mTBI interventions varied widely across our Canadian and United States consortium. Future effectiveness studies for pediatric mTBI are urgently needed to advance the evidence-based care.

Background: Information specialists frequently translate search filters from one interface to another. Publications advise that translation can be complex and should be undertaken carefully., Objectives: To investigate the issues arising when translating the Cochrane Embase RCT search filter from one interface (Ovid) to another (Embase.com)., Methods: We drafted a translation of the Cochrane Ovid RCT filter to run in Embase.com. We compared the line-by-line results of the Ovid filter with the results of the translation. We revised the filter. We identified differences between database versions including records with different publication years and subject headings. Some records were in Embase in one interface but not in the other. We encountered expected interface differences relating to proximity operators. We also encountered unexpected interface issues around truncation and the use of the original title or original abstract field., Discussion: Filter conversion is challenging and time consuming revealing unexpected differences in interfaces and databases. Careful planning can pre-empt some issues, but others may only emerge during testing. We identified interface anomalies that have led database publishers to review aspects of the way their interfaces work., Conclusions: Translators should be vigilant for known and unknown differences in both interfaces and database versions., (© 2019 Health Libraries Group.)

Background: Evidence synthesis reviews in health care rely on the efficient identification of research evidence, particularly evidence from randomised controlled trials (RCTs). There are no recently validated filters to identify RCTs in the Cumulative Index to Nursing and Allied Health Literature (CINAHL Plus)., Objectives: To develop, test and validate a search filter to identify reports of RCTs from CINAHL Plus., Methods: Nine sets of relevant and irrelevant records were identified to develop and test search filters iteratively. Two sets were used to validate the sensitivity and precision of the filters. The performance of two previously published filters and the filter built into EBSCOhost was evaluated., Results: We present a validated filter which offers sensitivity of 0.88 (95% CI: 0.77-0.95) and precision of 0.36 (95% CI: 0.31-0.41). This is comparable to the sensitivity of published filters, but has much better precision., Conclusions: A sensitive and precise filter, developed using records selected based on title and abstract information, is available for identifying reports of RCTs in the CINAHL Plus database via EBSCOhost. Using this filter is likely to reduce the number of results needing to be screened to a quarter of those retrieved by other published filters., (© 2019 Health Libraries Group.)

Objective: Medical devices innovations and associated procedures represent a large part of health facilities budget. The aim of this work was to evaluate the cost of medical devices used during different surgical procedures. This cost was compare with the revenue collected from hospital stay pricing., Method: A prospective analysis of the medical devices used in operating room was carried out for different types of programmed surgeries. For five weeks, references of sterile single-use medical devices used during the interventions were collected., Results: Expenditure on medical devices used during surgical procedures represented 5.7 % of the hospitalization value for an inguinal hernia repair, 12 % for a cholecystectomy, 9.35 % for a colectomy, 14.5 % for a hepatectomy and 7 % for pancreatectomy, any severity index combined. The most important correlations existed between act duration and patient's level of severity and between operating times and consumables expenditure., Conclusion: Cost optimization opportunities are equivalence of some medical devices ranges, purchases with national groupings and potential decreases in operating times related to the use of innovative medical devices., (Copyright © 2018 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Long-term daylight deprivation such as during the Antarctic winter has been shown to lead to delayed sleep timing and sleep fragmentation. We aimed at testing whether retinal sensitivity, sleep and circadian rest-activity will change during long-term daylight deprivation on two Antarctic bases (Concordia and Halley VI) in a total of 25 healthy crew members (mean age: 34 ± 11y; 7f). The pupil responses to different light stimuli were used to assess retinal sensitivity changes. Rest-activity cycles were continuously monitored by activity watches. Overall, our data showed increased pupil responses under scotopic (mainly rod-dependent), photopic (mainly L-/M-cone dependent) as well as bright-blue light (mainly melanopsin-dependent) conditions during the time without direct sunlight. Circadian rhythm analysis revealed a significant decay of intra-daily stability, indicating more fragmented rest-activity rhythms during the dark period. Sleep and wake times (as assessed from rest-activity recordings) were significantly delayed after the first month without sunlight (p < 0.05). Our results suggest that during long-term daylight deprivation, retinal sensitivity to blue light increases, whereas circadian rhythm stability decreases and sleep-wake timing is delayed.

Background: The circadian clock is a fundamental and pervasive biological program that coordinates 24-hour rhythms in physiology, metabolism, and behavior, and it is essential to health. Whereas therapy adapted to time of day is increasingly reported to be highly successful, it needs to be personalized, since internal circadian time is different for each individual. In addition, internal time is not a stable trait, but is influenced by many factors, including genetic predisposition, age, sex, environmental light levels, and season. An easy and convenient diagnostic tool is currently missing., Methods: To establish a validated test, we followed a 3-stage biomarker development strategy: (a) using circadian transcriptomics of blood monocytes from 12 individuals in a constant routine protocol combined with machine learning approaches, we identified biomarkers for internal time; and these biomarkers (b) were migrated to a clinically relevant gene expression profiling platform (NanoString) and (c) were externally validated using an independent study with 28 early or late chronotypes., Results: We developed a highly accurate and simple assay (BodyTime) to estimate the internal circadian time in humans from a single blood sample. Our assay needs only a small set of blood-based transcript biomarkers and is as accurate as the current gold standard method, dim-light melatonin onset, at smaller monetary, time, and sample-number cost., Conclusion: The BodyTime assay provides a new diagnostic tool for personalization of health care according to the patient's circadian clock., Funding: This study was supported by the Bundesministerium für Bildung und Forschung, Germany (FKZ: 13N13160 and 13N13162) and Intellux GmbH, Germany.

Under entrained conditions, the accumulation of homeostatic sleep pressure in the evening is opposed by a strong circadian arousal signal prior to the dim light melatonin onset, called the Wake Maintenance Zone (WMZ). This study aimed at investigating the impact of the WMZ on different cognitive performance tests, as well as on subjective and objective sleepiness. Twelve young male participants completed a constant routine protocol with 40 h of extended wakefulness that included two WMZs. Cognitive tests and saliva samples were assessed hourly, while the electroencephalogram (EEG) was recorded continuously. Participants improved in cognitive response inhibition during WMZ1 (13.5 h awake) and sustained attention during WMZ2 (37.5 h awake), but not in higher executive function tests. There were significant EEG power density reductions in the delta/theta frequency range during WMZ1 and in delta/theta, alpha, and sigma/beta ranges during WMZ2, with a greater change in the sigma/beta range during WMZ2 compared to WMZ1. EEG power reductions coincided during WMZ1 with stable subjective sleepiness and sustained attention. During WMZ2, EEG power reductions were more pronounced and coincided with improved sustained attention. Our results suggest the circadian arousal signal in the evening differently modulates cognitive functions and EEG power depending on the duration of prior wakefulness.

Squamous cell carcinoma (SCC) of the head and neck can be treated with a combination of modalities. There is an esthetic and functional compromise with midfacial defects secondary to ablative surgery and adjuvant therapies for SCC. Osteoradionecrosis, tissue contracture, and trismus, are all negative side effects of treatment and can impact a patient's function and possibly their nutrition. In this report, we describe a procedure for fabrication of a prosthesis that provides cosmetic improvement and labial competence to maintain caloric intake., (© 2018 by the American College of Prosthodontists.)

Refractory acute cellular rejection (rACR) is associated with death and bronchiolitis obliterans syndrome (BOS) post-lung transplantation. We report the largest cohort of lung transplant recipients (LTRs) treated with rescue alemtuzumab for rACR or BOS. RACR outcomes included burden of ACR 30 days before and 180 days after rescue assessed by a novel composite rejection standardized score (CRSS, range 0-6) and freedom from ≥A2 ACR. BOS outcomes included freedom from BOS progression and FEV1 decline >10%. Univariate parametric and nonparametric statistical approaches were used to assess treatment response. Kaplan-Meier method with log rank conversion was used to assess freedom from events. Fifty-seven alemtuzumab doses (ACR 40 and BOS 17) given to 51 patients were included. Median time to rescue was 722 (IQR 42-1403) days. CRSS declined significantly (3 vs 0.67, P<0.001) after rescue. Freedom from ≥A2 was 62.5% in rACR. Freedom from BOS progression was 52.9% at 180 days in the BOS cohort. Freedom from FEV1 decline >10% was 70% in BOS grade 1 and 14.3% in advanced BOS grades 2-3. Infections developed in 72.5% and 76.5% of rACR and BOS groups. Rescue alemtuzumab appears useful for rACR. Patients with BOS 1 may have transient benefit, and patients with advanced BOS seem not to respond to alemtuzumab., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Study Objectives: To determine if patients with childhood onsets (CO) of both major depression and insomnia disorder show blunted depression and insomnia treatment responses to concurrent interventions for both disorders compared to those with adult onsets (AO) of both conditions., Methods: This study was a secondary analysis of data obtained from a multisite randomized clinical trial designed to test the efficacy of combining a psychological/behavior insomnia therapy with antidepressant medication to enhance depression treatment outcomes in patients with comorbid major depression and insomnia. This study included 27 adults with CO of depression and insomnia and 77 adults with AO of both conditions. They underwent a 16-week treatment including: (1) a standardized two-step pharmacotherapy for depression algorithm, consisting of escitalopram, sertraline, and desvenlafaxine in a prescribed sequence; and (2) either cognitive behavioral insomnia therapy (CBT-I) or a quasi-desensitization control (CTRL) therapy. Main outcome measures were the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the Insomnia Severity Index (ISI) completed pre-treatment and every 2 weeks thereafter., Results: The AO and CO groups did not differ significantly in regard to their pre-treatment HRSD-17 and ISI scores. Mixed model analyses that adjusted for the number of insomnia treatment sessions attended showed that the AO group achieved significantly lower, subclinical scores on the HRSD-17 and ISI than did the CO group by the time of study exit. Moreover, a significant group by treatment arm interaction suggested that HRSD-17 scores at study exit remained significantly higher in the CO group receiving the CTRL therapy than was the case for the participants in the CO group receiving CBT-I. Greater proportions of the AO group achieved a priori criteria for remission of insomnia (49.3% vs. 29.2%, p = 0.04) and depression (45.5% vs. 29.6%, p = 0.07) than did those in the CO group., Conclusions: Patients with comorbid depression and insomnia who experienced the first onset of both disorders in childhood are less responsive to the treatments offered herein than are those with adult onsets of these comorbid disorders. Further research is needed to identify therapies that enhance the depression and insomnia treatment responses of those with childhood onsets of these two conditions., (© 2017 American Academy of Sleep Medicine)

The ions Na + , K + , Ca 2+ , Mg 2+ , Cl - , SO 4 2- , and HCO 3 - /CO 3 2- (referred to in the present study as "major ions") are present in all freshwaters and physiologically required by aquatic organisms but can increase to harmful levels from a variety of anthropogenic activities. It is also known that the toxicities of major ion salts can vary depending on the concentrations of other ions, and understanding these relationships is key to establishing appropriate environmental limits. The authors present a series of experiments with Ceriodaphnia dubia to evaluate the acute toxicity of 12 major ion salts and to determine how toxicity of these salts varies as a function of background water chemistry. All salts except CaSO 4 and CaCO 3 were acutely toxic below saturation, with the lowest median lethal concentrations found for K salts. All 10 salts that showed toxicity also showed some degree of reduced toxicity as the ionic content of the background water increased. Experiments that independently varied Ca:Mg ratio, Na:K ratio, Cl:SO 4 ratio, and alkalinity/pH demonstrated that Ca concentration was the primary factor influencing the toxicities of Na and Mg salts, whereas the toxicities of K salts were primarily influenced by the concentration of Na. These experiments also indicated multiple mechanisms of toxicity and suggested important aspects of dosimetry; the toxicities of K, Mg, and Ca salts were best related to the chemical activity of the cation, whereas the toxicities of Na salts also reflected an influence of the anions and were well correlated with osmolarity. Understanding these relationships between major ion toxicity and background water chemistry should aid in the development of sensible risk-assessments and regulatory standards. Environ Toxicol Chem 2016;35:3039-3057. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America., (Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.)

Background: Unipolar and bipolar depression identified in the postpartum period have a heterogeneous etiology. The objectives of this study are to examine the risk factors that distinguish the timing of onset for unipolar and bipolar depression and the associations between depression onset by diagnosis, and general and atypical depressive symptoms., Methods: Symptoms of depression were assessed at 4- to 6-weeks postpartum by the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Symptoms in an obstetrical sample of 727 women. Data were analyzed using ANOVA, Chi-square, and linear regression., Results: Mothers with postpartum onset of depression were more likely to be older, Caucasian, educated, married/cohabitating, have one or no previous child, and have private insurance in contrast to mothers with pre-pregnancy and prenatal onset of depression. Mothers with bipolar depression were more likely to have a pre-pregnancy onset. Three general and two atypical depressive symptoms distinguished pre-pregnancy, during pregnancy, and postpartum depression onset, and the presence of agitation distinguished between unipolar and bipolar depression., Limitations: The sample was urban, which may not be generalizable to other populations. The study was cross-sectional, which excludes potential late onset of depression (after 4-6 weeks) in the first postpartum year., Conclusions: A collective set of factors predicted the onset of depression identified in the postpartum for mothers distinguished by episodes of unipolar versus bipolar depression, which can inform clinical interventions. Future research on the onset of major depressive episodes could inform prophylactic and early psychiatric interventions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: The goal of the present study was to evaluate the potential advantages of a silicon ring tourniquet in comparison to the conventional pneumatic cuff tourniquet. The tested hypothesis was that the calculated blood loss will be decreased after use of the silicone ring tourniquet., Methods: The study was monocentric and mixed retrospective and prospective evaluation of prospectively collected data. Inclusion criterion was implantation of a total knee arthroplasty. The retrospective control group involved 39 patients operated on with a pneumatic cuff tourniquet. The prospective study group involved 33 patients operated on with a silicone ring tourniquet. All patients were followed for three months. Primary criterion was the calculated blood loss (OSTHEO formula). Secondary criteria were pain on third post-op day, need for allogenic transfusion, haemoglobin drop, delay of discharge, and occurrence of complications., Results: The mean calculated blood loss was 901 ml in the study group and 989 ml in the control group (NS). There was no significant difference in pain evaluation and haemoglobin drop between the two groups. There was a non significant decrease of allogeneic transfusion and length of stay in the study group. There was a significant decrease of complication rate in the study group, and especially for skin complications., Conclusions: The tested hypothesis was not confirmed: there was no significant change in the calculated blood loss. No bias was identified in complication analysis. The decreased rate of skin complication might be a positive influence of the silicone ring tourniquet.

Context: -Jejunoileal neuroendocrine tumors (JINETs) are slow-growing, malignant tumors that are often associated with protracted survival, despite their frequent presentation at an advanced stage. A subset of JINETs is complicated by intestinal ischemic necrosis (IIN), which leads to their initial clinical presentation., Objective: -To assess the effect of IIN on overall survival in patients with JINETs., Design: -Ten JINETs with IIN during a 14-year period and a control group of 52 JINETs without IIN were identified retrospectively. The hematoxylin-eosin slides and gross descriptions were reviewed, and pathologic features were assessed. Overall survival was compared between the 2 groups using the Kaplan Meier method and Cox proportional hazards model., Results: -At 1 year postresection, only 40% (4 of 10) of the patients with IIN were alive, whereas 94% (49 of 52) of those without IIN were alive (P < .001). Patients with IIN were significantly older than those without IIN (median, 83 years versus 65.5 years, P = .001). By univariate Cox proportional hazards regression, IIN was associated with a 4.30-fold increased risk of death (95% confidence interval 1.75-10.56; P = .001). When controlling for age, advanced stage (stage III or IV), tumor grade, and synchronous carcinoma in a multivariate analysis, IIN showed a trend toward prognostic significance (2.31-fold increased risk of death; 95% confidence interval, 0.85-6.27; P = .10)., Conclusions: -The pathologic identification of tumor-associated IIN portends a worse overall survival among patients with JINETs.

Background: The Mini Mental State Examination (MMSE) is a cognitive test that is commonly used as part of the evaluation for possible dementia., Objectives: To determine the diagnostic accuracy of the Mini-Mental State Examination (MMSE) at various cut points for dementia in people aged 65 years and over in community and primary care settings who had not undergone prior testing for dementia., Search Methods: We searched the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (OvidSP), EMBASE (OvidSP), PsycINFO (OvidSP), LILACS (BIREME), ALOIS, BIOSIS previews (Thomson Reuters Web of Science), and Web of Science Core Collection, including the Science Citation Index and the Conference Proceedings Citation Index (Thomson Reuters Web of Science). We also searched specialised sources of diagnostic test accuracy studies and reviews: MEDION (Universities of Maastricht and Leuven, www.mediondatabase.nl), DARE (Database of Abstracts of Reviews of Effects, via the Cochrane Library), HTA Database (Health Technology Assessment Database, via the Cochrane Library), and ARIF (University of Birmingham, UK, www.arif.bham.ac.uk). We attempted to locate possibly relevant but unpublished data by contacting researchers in this field. We first performed the searches in November 2012 and then fully updated them in May 2014. We did not apply any language or date restrictions to the electronic searches, and we did not use any methodological filters as a method to restrict the search overall., Selection Criteria: We included studies that compared the 11-item (maximum score 30) MMSE test (at any cut point) in people who had not undergone prior testing versus a commonly accepted clinical reference standard for all-cause dementia and subtypes (Alzheimer disease dementia, Lewy body dementia, vascular dementia, frontotemporal dementia). Clinical diagnosis included all-cause (unspecified) dementia, as defined by any version of the Diagnostic and Statistical Manual of Mental Disorders (DSM); International Classification of Diseases (ICD) and the Clinical Dementia Rating., Data Collection and Analysis: At least three authors screened all citations.Two authors handled data extraction and quality assessment. We performed meta-analysis using the hierarchical summary receiver-operator curves (HSROC) method and the bivariate method., Main Results: We retrieved 24,310 citations after removal of duplicates. We reviewed the full text of 317 full-text articles and finally included 70 records, referring to 48 studies, in our synthesis. We were able to perform meta-analysis on 28 studies in the community setting (44 articles) and on 6 studies in primary care (8 articles), but we could not extract usable 2 x 2 data for the remaining 14 community studies, which we did not include in the meta-analysis. All of the studies in the community were in asymptomatic people, whereas two of the six studies in primary care were conducted in people who had symptoms of possible dementia. We judged two studies to be at high risk of bias in the patient selection domain, three studies to be at high risk of bias in the index test domain and nine studies to be at high risk of bias regarding flow and timing. We assessed most studies as being applicable to the review question though we had concerns about selection of participants in six studies and target condition in one study.The accuracy of the MMSE for diagnosing dementia was reported at 18 cut points in the community (MMSE score 10, 14-30 inclusive) and 10 cut points in primary care (MMSE score 17-26 inclusive). The total number of participants in studies included in the meta-analyses ranged from 37 to 2727, median 314 (interquartile range (IQR) 160 to 647). In the community, the pooled accuracy at a cut point of 24 (15 studies) was sensitivity 0.85 (95% confidence interval (CI) 0.74 to 0.92), specificity 0.90 (95% CI 0.82 to 0.95); at a cut point of 25 (10 studies), sensitivity 0.87 (95% CI 0.78 to 0.93), specificity 0.82 (95% CI 0.65 to 0.92); and in seven studies that adjusted accuracy estimates for level of education, sensitivity 0.97 (95% CI 0.83 to 1.00), specificity 0.70 (95% CI 0.50 to 0.85). There was insufficient data to evaluate the accuracy of the MMSE for diagnosing dementia subtypes.We could not estimate summary diagnostic accuracy in primary care due to insufficient data., Authors' Conclusions: The MMSE contributes to a diagnosis of dementia in low prevalence settings, but should not be used in isolation to confirm or exclude disease. We recommend that future work evaluates the diagnostic accuracy of tests in the context of the diagnostic pathway experienced by the patient and that investigators report how undergoing the MMSE changes patient-relevant outcomes.

Background: Down's syndrome occurs when a person has three copies of chromosome 21, or the specific area of chromosome 21 implicated in causing Down's syndrome, rather than two. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life. The risk of a Down's syndrome affected pregnancy increases with advancing maternal age.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. Before agreeing to screening tests, parents need to be fully informed about the risks, benefits and possible consequences of such a test. This includes subsequent choices for further tests they may face, and the implications of both false positive and false negative screening tests (i.e. invasive diagnostic testing, and the possibility that a miscarried fetus may be chromosomally normal). The decisions that may be faced by expectant parents inevitably engender a high level of anxiety at all stages of the screening process, and the outcomes of screening can be associated with considerable physical and psychological morbidity. No screening test can predict the severity of problems a person with Down's syndrome will have., Objectives: To estimate and compare the accuracy of first and second trimester urine markers for the detection of Down's syndrome., Search Methods: We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), EMBASE (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2011, Issue 7), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (archived 2007), Health Services Research Projects in Progress database (25 August 2011). We studied reference lists and published review articles., Selection Criteria: Studies evaluating tests of maternal urine in women up to 24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection., Data Collection and Analysis: We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC (receiver operating characteristic) meta-analytical methods to analyse test performance and compare test accuracy. We performed analysis of studies allowing direct comparison between tests. We investigated the impact of maternal age on test performance in subgroup analyses., Main Results: We included 19 studies involving 18,013 pregnancies (including 527 with Down's syndrome). Studies were generally of high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Twenty-four test combinations were evaluated formed from combinations of the following seven different markers with and without maternal age: AFP (alpha-fetoprotein), ITA (invasive trophoblast antigen), ß-core fragment, free ßhCG (beta human chorionic gonadotrophin), total hCG, oestriol, gonadotropin peptide and various marker ratios. The strategies evaluated included three double tests and seven single tests in combination with maternal age, and one triple test, two double tests and 11 single tests without maternal age. Twelve of the 19 studies only evaluated the performance of a single test strategy while the remaining seven evaluated at least two test strategies. Two marker combinations were evaluated in more than four studies; second trimester ß-core fragment (six studies), and second trimester ß-core fragment with maternal age (five studies).In direct test comparisons, for a 5% false positive rate (FPR), the diagnostic accuracy of the double marker second trimester ß-core fragment and oestriol with maternal age test combination was significantly better (ratio of diagnostic odds ratio (RDOR): 2.2 (95% confidence interval (CI) 1.1 to 4.5), P = 0.02) (summary sensitivity of 73% (CI 57 to 85) at a cut-point of 5% FPR) than that of the single marker test strategy of second trimester ß-core fragment and maternal age (summary sensitivity of 56% (CI 45 to 66) at a cut-point of 5% FPR), but was not significantly better (RDOR: 1.5 (0.8 to 2.8), P = 0.21) than that of the second trimester ß-core fragment to oestriol ratio and maternal age test strategy (summary sensitivity of 71% (CI 51 to 86) at a cut-point of 5% FPR)., Authors' Conclusions: Tests involving second trimester ß-core fragment and oestriol with maternal age are significantly more sensitive than the single marker second trimester ß-core fragment and maternal age, however, there were few studies. There is a paucity of evidence available to support the use of urine testing for Down's syndrome screening in clinical practice where alternatives are available.

Background: Suicide is one of the leading causes of death in postpartum women. Identifying modifiable factors related to suicide risk in mothers after delivery is a public health priority. Our study aim was to examine associations between suicidal ideation (SI) and plausible risk factors (experience of abuse in childhood or as an adult, sleep disturbance, and anxiety symptoms) in depressed postpartum women., Methods: This secondary analysis included 628 depressed mothers at 4-6 weeks postpartum. Diagnosis was confirmed with the Structured Clinical Interview for DSM-IV. We examined SI from responses to the Edinburgh Postnatal Depression Scale-EPDS item 10; depression levels on the Structured Interview Guide for the Hamilton Depression Rating Scale, Atypical Depression Symptoms (SIGH-ADS); plus sleep disturbance and anxiety levels with subscales from the EPDS and SIGH-ADS items on sleep and anxiety symptoms., Results: Of the depressed mothers, 496 (79%) 'never' had thoughts of self-harm; 98 (15.6%) 'hardly ever'; and 34 (5.4%) 'sometimes' or 'quite often'. Logistic regression models indicated that having frequent thoughts of self-harm was related to childhood physical abuse (odds ratio-OR = 1.68, 95% CI = 1.00, 2.81); in mothers without childhood physical abuse, having frequent self-harm thoughts was related to sleep disturbance (OR = 1.15, 95% CI = 1.02, 1.29) and anxiety symptoms (OR = 1.11, 95% CI = 1.01, 1.23)., Discussion: Because women with postpartum depression can present with frequent thoughts of self-harm and a high level of clinical complexity, conducting a detailed safety assessment, that includes evaluation of childhood abuse history and current symptoms of sleep disturbance and anxiety, is a key component in the management of depressed mothers., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To determine the effects of symptoms and presence of confirmed influenza on intention to receive an influenza vaccine, specifically in patients recovering from a medically-attended acute (≤ 7 days' duration) respiratory illness (ARI)., Methods: During the 2013-14 influenza season individuals seeking outpatient care for an ARI that included cough were tested for influenza using reverse transcription polymerase chain reaction assays (PCR) and completed surveys. Children (6 months-18 years) and adults (≥ 18 years) were grouped by their combined current season's influenza vaccination status (vaccinated/not vaccinated) and their vaccination intentions for next season (intend/do not intend)., Results: Overall, 41% (323/786) were unvaccinated at enrollment; of those, nearly half (151/323) intended to be vaccinated next season. When adjusting for demographic, health, and other factors, unvaccinated individuals who intended to be vaccinated next season were approximately 1.5 times more likely to have PCR-confirmed influenza compared with vaccinated individuals who intended to be vaccinated next season., Conclusion: The combined experience of not being vaccinated against influenza and seeking medical attention for an ARI seemed to influence approximately one-half of unvaccinated participants to consider influenza vaccination for next season.

In order to get a marketing authorization, breast implants (BI) must meet a number of standard requirements. French and European standards ISO 14607 list a number of official tests to be performed before an implant can be used clinically. However, the BI material characteristics evolution over implantation time remains a research field which is unexplored. The goal of the present study is to compare the mechanical ageing of two breast implant generations and assess if the use of one generation rather than the other is advantageous in terms of durability. For that purpose, 21 explanted BI were analyzed in terms of biomechanical characteristics and compared. Twelve BI were textured anatomic specimens of 5th generation and 10 BI were round textured specimens of 4th generation. All the specimens were produced by the same manufacturer. Implantation time ranged from 3 to 130 months. Both the shell and the gel of every specimen were analyzed. Results show that the mechanical properties go down with the implantation time for all the implants. Moreover, the shell of round implants appear to be less resistant than the shell of anatomic specimens with 25% lower rupture forces. With regard to the gel, whatever the specimen, results show that the properties change with implantation time. The color changes from transparent to milky to finally become yellow, while the cohesion goes down especially for the round specimens. Globally, the study brings out that BI get degraded with implantation time and provides information which could help predicting the durability of the implant., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: While it is known that acute respiratory illness (ARI) is caused by an array of viruses, less is known about co-detections and the resultant comparative symptoms and illness burden. This study examined the co-detections, the distribution of viruses, symptoms, and illness burden associated with ARI between December 2012 and March 2013., Methods: Outpatients with ARI were assayed for presence of 18 viruses using multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) to simultaneously detect multiple viruses., Results: Among 935 patients, 60% tested positive for a single virus, 9% tested positive for ≥1 virus and 287 (31%) tested negative. Among children (<18 years), the respective distributions were 63%, 14%, and 23%; whereas for younger adults (18-49 years), the distributions were 58%, 8%, and 34% and for older adults (≥50 years) the distributions were 61%, 5%, and 32% (P < 0.001). Co-detections were more common in children than older adults (P = 0.01), and less frequent in households without children (P = 0.003). Most frequently co-detected viruses were coronavirus, respiratory syncytial virus, and influenza A virus. Compared with single viral infections, those with co-detections less frequently reported sore throat (P = 0.01), missed fewer days of school (1.1 vs. 2 days; P = 0.04), or work (2 vs. 3 days; P = 0.03); other measures of illness severity did not vary., Conclusions: Among outpatients with ARI, 69% of visits were associated with a viral etiology. Co-detections of specific clusters of viruses were observed in 9% of ARI cases particularly in children, were less frequent in households without children, and were less symptomatic (e.g., lower fever) than single infections.

Background: Respiratory tract infections are a major cause of outpatient visits, yet only a portion is tested to determine the etiologic organism. Multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) assays for detection of multiple viruses are being used increasingly in clinical settings., Methods: During January-April 2012, outpatients with acute respiratory illness (≤ 7 days) were tested for influenza using singleplex RT-PCR (SRT-PCR). A subset was assayed for 18 viruses using MRT-PCR to compare detection of influenza and examine the distribution of viruses and characteristics of patients using multinomial logistic regression., Results: Among 662 participants (6 months-82 years), detection of influenza was similar between the MRT-PCR and SRT-PCR (κ = 0.83). No virus was identified in 267 (40.3%) samples. Commonly detected viruses were human rhinovirus (HRV, 15.4%), coronavirus (CoV, 10.4%), respiratory syncytial virus (RSV, 8.4%), human metapneumovirus (hMPV, 8.3%), and influenza (6%). Co-detections were infrequent (6.9%) and most commonly occurred among those <18 years old. In regression analyses, compared with non-viral illnesses, RSV and hMPV were significantly more frequent in children and less frequent in 18- to 49-year-olds than in those ≥ 50 years (P = 0.01), fever was more common in hMPV and influenza infections (P = 0.008), nasal congestion was more frequent in CoV, HRV, hMPV, influenza and RSV infections (P = 0.001), and body mass index was higher among those with influenza (P = 0.036)., Conclusions: Using MRT-PCR, a viral etiology was found in three-fifths of patients with medically attended outpatient visits for acute respiratory illness during the influenza season; co-detected viruses were infrequent. Symptoms varied by viral etiology., (© 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Objective: Gestational diabetes mellitus (GDM) affects 7% of pregnant mothers, and those with GDM have increased rates of perinatal complications. Major depressive disorder (MDD) and its pharmacologic treatments are associated with obesity and adverse pregnancy outcomes. In this prospective study, we investigated the relationship between abnormal GDM screens, maternal mood disorders, and adverse outcomes., Methods: We examined mothers with MDD, those with bipolar disorder (BD), and healthy controls (HC) at 20, 30, and 36 weeks of gestation and delivery. We obtained demographic data and pre-pregnancy body mass index (BMI), and confirmed diagnoses with the Structured Clinical Interview for DSM-IV. We evaluated smoking, alcohol use, substance use, and medication treatments with the Longitudinal Interval Follow-up Evaluation interview. Mothers received the one-hour 50-g glucose challenge test (GCT) at 26-28 weeks of gestation. Outcome variables were preterm birth, birth weight (BW) and peripartum events., Results: We enrolled 62 HC, 50 BD, 41 past MDD, and 39 current MDD mother-infant pairs. Mean GCT levels and the frequency of abnormal GCT (>140 mg/dL) did not differ across groups. Rates of smoking (χ(2)  = 20.68, df = 3, p < 0.001), substance use (χ(2)  = 21.76, df = 3, p < 0.001), and pre-pregnancy obesity [BMI ≥ 30 (χ(2)  = 9.97, df = 3, p = 0.019)] differed significantly across groups. Mothers with BD received medications associated with weight gain significantly more often than others [13/45 (29%), p < 0.001). After adjusting for group differences, GCT levels were associated significantly with increased odds for preterm birth (odds ratio = 1.29, 95% confidence interval: 1.0-1.7, p = 0.05) and increased perinatal events (beta = 0.11, p = 0.04) but were not associated with BW., Conclusions: In mothers with or without mood disorders, having increased GCT levels contributes to a higher likelihood for adverse pregnancy outcomes. Mothers with BD or current MDD can have additional risks for adverse outcomes and may benefit from early referral for high-risk services and supportive management in pregnancy., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To assess the efficacy of collaborative care for behavior problems, attention-deficit/hyperactivity disorder (ADHD), and anxiety in pediatric primary care (Doctor Office Collaborative Care; DOCC)., Methods: Children and their caregivers participated from 8 pediatric practices that were cluster randomized to DOCC (n = 160) or enhanced usual care (EUC; n = 161). In DOCC, a care manager delivered a personalized, evidence-based intervention. EUC patients received psychoeducation and a facilitated specialty care referral. Care processes measures were collected after the 6-month intervention period. Family outcome measures included the Vanderbilt ADHD Diagnostic Parent Rating Scale, Parenting Stress Index-Short Form, Individualized Goal Attainment Ratings, and Clinical Global Impression-Improvement Scale. Most measures were collected at baseline, and 6-, 12-, and 18-month assessments. Provider outcome measures examined perceived treatment change, efficacy, and obstacles, and practice climate., Results: DOCC (versus EUC) was associated with higher rates of treatment initiation (99.4% vs 54.2%; P < .001) and completion (76.6% vs 11.6%, P < .001), improvement in behavior problems, hyperactivity, and internalizing problems (P < .05 to .01), and parental stress (P < .05-.001), remission in behavior and internalizing problems (P < .01, .05), goal improvement (P < .05 to .001), treatment response (P < .05), and consumer satisfaction (P < .05). DOCC pediatricians reported greater perceived practice change, efficacy, and skill use to treat ADHD (P < .05 to .01)., Conclusions: Implementing a collaborative care intervention for behavior problems in community pediatric practices is feasible and broadly effective, supporting the utility of integrated behavioral health care services.

Purpose: The collaboration between a drug information center (DIC) and an academic detailing program is described., Methods: An agreement was reached between the South Carolina Offering Prescribing Excellence (SCORxE) academic detailing program and the Medical University of South Carolina (MUSC) Drug Information Center (DIC) to provide responses to drug information (DI) questions pharmacists received on academic detailing visits. Questions received were analyzed to determine the impact that the collaboration had on MUSC DIC requests., Results: From May 2009 to October 2012, the MUSC DIC answered 2727 DI questions, 62 (2.3%) of which were generated by SCORxE. Compared with DIC questions received from other sources, academic detailing questions were more likely to be therapeutic consultations, reference searches, or dosage queries and less likely to be about formulation or drug interactions. When comparing the deadline for the 62 academic detailing requests with the deadline for all other requests, the academic detailing requests allowed for a longer median time to deadline per request (21.2 days versus 27.1 hours). The majority of SCORxE questions (68%) were completed by students or residents. Benefits of the collaboration for the DIC included advanced educational opportunities for learners, increased dissemination of provided information, external funding, and scholarship opportunities. SCORxE has benefited from increased access to information and efficiency., Conclusion: Collaboration between an academic detailing program and an academic medical center DIC has proven beneficial for both parties. Questions have been communicated by a simple and effective process and have required more research than queries received from other sources.

Rapid, accurate, and cost-effective methods to identify the cause of respiratory tract infections are needed to maximize clinical benefit. Outpatients with acute respiratory illness were tested for influenza using a singleplex reverse transcriptase polymerase chain reaction (SRT-PCR) method. A multiplex RT-PCR (MRT-PCR) method tested for influenza and 17 other viruses and was compared with SRT-PCR using chi-square tests. Among 935 patients, 335 (36%) tested positive for influenza A and influenza B using SRT-PCR. Using MRT-PCR, 320 (34.2%) tested positive for influenza A and influenza B. This study supports MRT-PCR as a comparable method for detecting influenza among patients seeking outpatient care for acute respiratory illnesses.

Background: Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD., Methods/design: The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n=102), test the findings in the second half, and then extend the analyses to the total sample., Trial Registration: International Study to Predict Optimized Treatment--in Depression (iSPOT-D). ClinicalTrials.gov, NCT00693849.

Cocaine addiction is characterized by a persistently heightened susceptibility to drug relapse. For this reason, the identification of medications that prevent drug relapse is a critical goal of drug abuse research. Drug re-exposure, the onset of stressful life events, and exposure to cues previously associated with drug use have been identified as determinants of relapse in humans and have been found to reinstate extinguished cocaine seeking in rats. This study examined the effects of acute oral (gavage) administration of levo-tetrahydropalmatine (l-THP), a tetrahydroprotoberberine isoquinoline with a pharmacological profile that includes antagonism of D1, D2 and D3 dopamine receptors, on the reinstatement of extinguished cocaine seeking by a cocaine challenge (10mg/kg, ip), a stressor (uncontrollable electric footshock [EFS]) or response-contingent exposure to a stimulus (tone and light complex) previously associated with drug delivery in male Sprague-Dawley rats. Extinguished drug seeking was reinstated by ip cocaine, EFS, or response-contingent presentation of drug-associated cues in vehicle-pretreated rats following extinction of iv cocaine self-adminisration. Oral administration of either 3.0 or 10.0mg/kg l-THP 1h prior to reinstatement testing significantly attenuated reinstatement by each of the stimuli. Food-reinforced responding and baseline post-extinction responding were significantly attenuated at the 10.0, but not the 3.0mg/kg, l-THP dose, indicating that the effects of 3mg/kg l-THP on reinstatement were likely independent of non-specific motor impairment. These findings further suggest that l-THP may have utility for the treatment of cocaine addiction., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: Maternal major depressive disorder is an established risk factor for child psychopathology. The authors previously reported that 1 year after initiation of treatment for maternal depression, children of mothers whose depression remitted had significantly improved functioning and psychiatric symptoms. This study extends these findings by examining changes in psychiatric symptoms, behavioral problems, and functioning among children of depressed mothers during the first year after the mothers' remission from depression., Method: Children were assessed at baseline and at 3-month intervals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, the Child Behavior Checklist, and the Children's Global Assessment Scale for 1 year after their mothers' remission or for 2 years if the mothers did not remit. The authors compared children of early remitters (0-3 months; N=36), late remitters (3-12 months; N=28), and nonremitters (N=16)., Results: During the postremission year, children of early-remitting mothers showed significant improvement on all outcomes. Externalizing behavioral problems decreased in children of early- and late-remitting mothers but increased in children of nonremitting mothers. Psychiatric symptoms decreased significantly only in children of mothers who remitted, and functioning improved only in children of early-remitting mothers., Conclusions: Remission of mothers' depression, regardless of its timing, appears to be related to decreases in problem behaviors and symptoms in their children over the year after remission. The favorable effect of mothers' remission on children's functioning was observed only in children of early-remitting mothers.

Background: Poor sleep quality, dysregulation of hormones and increased inflammatory cytokines are all associated with the risk for postpartum major depression (PPMD). We evaluated change over time in sleep quality and hormones during the first 17 weeks postpartum, as well as a single cytokine measure, and their association with PPMD recurrence., Methods: Participants were pregnant women (N=56), with past histories of MDD/PPMD but not depressed in their current pregnancy. The Pittsburgh Sleep Quality Index (PSQI) and blood samples were collected 8 times during the first 17 weeks postpartum. Estradiol, prolactin and cortisol, and a single measure of IL-6 were assayed. Recurrence was determined by two consecutive 21-item Hamilton Rating Scale for Depression (HRSD) scores≥15 and clinician interview., Results: In the analyses of time to PPMD recurrence, poor sleep quality, but none of the hormones, was associated with PPMD recurrence (p<.05) after controlling for medication assignment. With every one point increase in PSQI scores across time, a woman's risk for recurrence increased by approximately 25% There was no significant association between PSQI scores and IL-6 concentrations in early postpartum (χ(2)=0.98, p=.32)., Conclusions: Poor sleep quality across the first 17 weeks post-delivery increases the risk for recurrent PPMD among women with a history of MDD. Changes in the hormonal milieu were not associated with recurrence. Further exploration of the degree to which poor sleep contributes to hormonal and cytokine dysregulation and how they are involved in the pathophysiology of PPMD is warranted., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the short-term repeatability of diurnal intraocular pressure (IOP) patterns in eyes with primary open-angle glaucoma (POAG)., Design: Observational cohort study., Participants: Forty-seven subjects with treated POAG., Methods: Subjects underwent assessment of IOP using Goldmann tonometry every 2 hours from 0800 to 2000 on 2 visits 1 week apart. Intervisit agreement of IOP by time point and of IOP change between time points was assessed using intraclass correlation coefficients (ICCs)., Main Outcome Measures: Diurnal IOP patterns., Results: Between-visit agreement of IOP values at each time point was generally fair to good, with ICCs ranging from 0.45 to 0.71 in right eyes and from 0.51 to 0.71 in left eyes. Between-visit agreement of IOP change over time periods between time points was uniformly poor, with ICCs ranging from -0.08 to 0.38 in right eyes and from -0.11 to 0.36 in left eyes., Conclusions: Treated POAG patients do not manifest a repeatable diurnal IOP pattern from day to day when measured by Goldmann tonometry. Measurement of single-day IOP variation poorly characterized short-term IOP variation., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Levo-tetrahydropalmatine (l-THP) is an alkaloid found in many traditional Chinese herbal preparations and has a unique pharmacological profile that includes dopamine receptor antagonism. Previously we demonstrated that l-THP attenuates fixed-ratio (FR) cocaine self-administration (SA) and cocaine-induced reinstatement in rats at doses that do not alter food-reinforced responding. This study examined the effects of l-THP on cocaine and food SA under progressive-ratio (PR) schedules of reinforcement and the discriminative stimulus effects of cocaine. In adult male Sprague-Dawley rats self-administering cocaine (0.5 or 1.0mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and 7.5mg/kg doses. l-THP also reduced the breaking point and response rate for PR SA of sucrose-sweetened food pellets, although the decrease was significant only at the 7.5mg/kg l-THP dose. In rats trained to discriminate cocaine (10mg/kg, ip) from saline, l-THP (1.875, 3.75 and 7.5mg/kg) produced a rightward shift in the dose-response curve for cocaine generalization. During generalization testing, l-THP reduced response rate, but only at the 7.5mg/kg dose. l-THP also prevented substitution of the dopamine D2/D3 receptor agonist, (±) 7-OH-DPAT, for cocaine suggesting a potential role for antagonism of D2 and/or D3 receptors in the effects of l-THP. These data further demonstrate that l-THP attenuates the reinforcing and subjective effects of cocaine at doses that do not produce marked motor effects and provide additional evidence that l-THP may have utility for the management of cocaine addiction., (Copyright © 2010 Elsevier Inc. All rights reserved.)

This report describes the first assumed locally transmitted case of the eye worm Thelazia callipaeda in a dog living in southern Germany. A 4-year-old male golden retriever from the town of Bühl in north eastern Baden-Württemberg, about 10 km from the German-French border, showed one sided lacrimation for over 2 weeks. Despite the application of antibiotics, there was no improvement, and the dog additionally showed blepharospasmus, epiphora and red conjunctivas. A deepened eye inspection revealed five whitish filiform parasites that were morphologically identified as T. callipaeda. The partial sequence of the mitochondrial cytochrome c oxidase subunit 1 gene (cox1, 605 bp) from one specimen revealed a novel haplotype, which differs by 1.3% from the only one (haplotype 1) identified in Europe so far. Since the infected dog had never been abroad with the exception of two daytrips to the close Alsace region in France, the transmission of T. callipaeda most probably was domestic. With the presence of end hosts and Phortica flies nourishing on lachrymal secretions acting as intermediate hosts and an increasing number of dogs travelling to and coming from endemic regions in the South, the establishment of T. callipaeda in large parts of Europe cannot be excluded.

A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for cocaine-induced reinstatement. In this report, we examined whether drug-induced adaptations that are necessary to generate cocaine-induced reinstatement also determine relapse vulnerability. To do this, rats were assigned to self-administer cocaine under conditions resulting in low (2 h/d; 0.5 mg/kg/infusion, i.v.) or high (6 h/d; 1.0 mg/kg/infusion, i.v.) levels of drug intake since these manipulations produce groups of rats exhibiting differences in the magnitude of cocaine-induced reinstatement. Approximately 19 d after the last session, cocaine-induced drug seeking and extracellular levels of glutamate and dopamine in the NAcc were measured. Contrary to our hypothesis, high-intake rats exhibited a more robust cocaine-induced increase in extracellular levels of dopamine but not glutamate. Further, increased reinstatement in high-intake rats was no longer observed when the D(1) receptor antagonist SCH-23390 was infused into the NAcc. The sensitized dopamine response to cocaine in high-intake rats may involve blunted cystine-glutamate exchange by system x(c(-)). Reduced (14)C-cystine uptake through system x(c(-)) was evident in NAcc tissue slices obtained from high-intake rats, and the augmented dopamine response in these rats was no longer observed when subjects received the cysteine prodrug N-acetyl cysteine. These data reveal a role for drug-induced NAcc dopamine in heightened relapse vulnerability observed in rats with a history of high levels of drug intake.

Objectives: To explore whether the psychologic variables anxiety, depression, and fear-avoidance beliefs, and interactions between these variables, are associated with physical function in patients with knee osteoarthritis (OA). We hypothesized lower levels of function would be related to higher anxiety, higher depression, and higher fear-avoidance beliefs, and that high levels of 2 of these factors simultaneously might interact to have a greater adverse effect on physical function., Design: Cross-sectional, correlational design., Setting: Institutional practice., Participants: Subjects included patients with knee OA (N=182; age, mean +/- SD, 63.9+/-8.8y; 122 women)., Interventions: Not applicable., Main Outcome Measures: Self-report measures of function included the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, the Lower Extremity Function Scale (LEFS), and the Knee Outcome Survey-Activity of Daily Living Scale. The Get Up and Go test was used as a physical performance measure of function. Self-report measures for psychologic variables included the Beck Anxiety Inventory, the Center for Epidemiological Studies Depression Scale, and the Fear Avoidance Belief Questionnaire-Physical Activity Scale modified for the knee., Results: Higher anxiety was related to poorer function on the WOMAC physical function. Both high anxiety and fear-avoidance beliefs were related to poorer function on the LEFS and Knee Outcome Survey-Activity of Daily Living Scale. There was no association between the psychologic variables and the Get Up and Go test. The anxiety x depression interaction was associated with the LEFS., Conclusions: Anxiety and fear-avoidance beliefs are associated with self-report measures of function in patients with knee OA. Depression may influence scores on the LEFS under conditions of low anxiety.

Objective: To identify changes in impairments associated with functional and pain outcome in patients with patello-femoral pain syndrome following a standardized physiotherapy treatment., Design: One group pre-post design., Subjects: Seventy-four patients (median age 27 years, 52% female) diagnosed with patellofemoral pain syndrome and referred to physiotherapy treatment., Methods: Baseline measures included self-reported function and pain, which were the dependent variables, and measures of independent variables: strength of quadriceps, hip abduction and hip external rotation; length of hamstrings, quadriceps, plantar flexors, iliotibial band/tensor fascia lata complex, and lateral retinaculum; quality of movement, and fear-avoidance beliefs. Following the baseline measurements, subjects participated in a standardized physiotherapy program. Measurements were repeated at 2-month follow-up. Data were analyzed using 2 forward regression models, the first using function outcome, and the second using pain outcome as the criterion. Age, gender, height and weight were controlled in the regression models., Results: Change in fear-avoidance beliefs about physical activity and change in gastrocnemius length predicted function outcome. Change in fear-avoidance beliefs about physical activity and about work predicted outcome of pain., Conclusion: Change in fear-avoidance beliefs about physical activity was the strongest predictor of function and pain outcome. The fact that patients who decreased their fear-avoidance beliefs improved function and decreased pain indicates that perhaps fear-avoidance beliefs should be targeted during the treatment of patients with patellofemoral pain syndrome.

Objectives: To explore whether impairment of muscle strength, soft tissue length, movement control, postural and biomechanic alterations, and psychologic factors are associated with physical function and pain in patients with patellofemoral pain syndrome (PFPS)., Design: Cross-sectional study., Setting: Rehabilitation outpatient., Participants: Seventy-four patients diagnosed with PFPS., Interventions: Not applicable., Main Outcome Measures: Measurements were self-reported function and pain; strength of quadriceps, hip abduction, and hip external rotation; length of hamstrings, quadriceps, plantar flexors, iliotibial band/tensor fasciae latae complex, and lateral retinaculum; foot pronation; Q-angle; tibial torsion; visual observation of quality of movement during a lateral step-down task; anxiety; and fear-avoidance beliefs., Results: After controlling for age and sex, anxiety and fear-avoidance beliefs about work and physical activity were associated with function, while only fear-avoidance beliefs about work and physical activity were associated with pain., Conclusions: Psychologic factors were the only associates of function and pain in patients with PFPS. Factors related to physical impairments did not associate to function or pain. Our results should be validated in other samples of patients with PFPS. Further studies should determine the role of other psychologic factors, and how they relate to anxiety and fear-avoidance beliefs in these patients.

Objective: This secondary data analysis from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared clinical characteristics and outcome after citalopram treatment for Hispanic outpatients whose language preference was English (N=121) or Spanish (N=74)., Methods: Data for Hispanic outpatients with nonpsychotic major depression were gathered from two STAR*D regional centers. Participants received citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission with a measurement-based care approach, with adjustments symptoms and side effects., Results: Spanish speakers were older, were more likely to be women, were less educated, had lower income, had more medical burden, and were more likely than English speakers to be seen in primary care rather than in psychiatric clinics. Compared with Spanish speakers, English speakers had more previous suicide attempts and more family history of mood disorders. The groups did not differ in a clinically meaningful way in severity of depression. Before adjustment for baseline differences, Spanish-speaking participants had lower rates of and slower times to remission and response compared with English speakers. After adjustment for baseline variables, these differences were no longer significant. Relapse rates did not differ between groups., Conclusions: Compared with English-speaking Hispanic patients, Spanish-speaking Hispanic patients may have a less robust response to antidepressants. The reasons for this are not clear but may include more disadvantaged social status. The degree to which these results can be generalized to other Hispanic populations or to other non-English-speaking groups remains to be seen.

Objective: Maternal depression is a consistent and well-replicated risk factor for child psychopathology. The authors examined the changes in psychiatric symptoms and global functioning in children of depressed women 1 year following the initiation of treatment for maternal major depressive disorder., Method: Participants were 1) 151 women with maternal major depression who were enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 2) their eligible offspring who, along with the mother, participated in the child STAR*D (STAR*D-Child) study (mother-child pairs: N=151). The STAR*D study was a multisite study designed to determine the comparative effectiveness and acceptability of various treatment options for adult outpatients with nonpsychotic major depressive disorder. The STAR*D-Child study examined children of depressed women at baseline and involved periodic follow-ups for 1 year after the initiation of treatment for maternal major depressive disorder to ascertain the following data: 1) whether changes in children's psychiatric symptoms were associated with changes in the severity of maternal depression and 2) whether outcomes differed among the offspring of women who did and did not remit (mother-child pairs with follow-up data: N=123). Children's psychiatric symptoms in the STAR*D-Child study were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), and maternal depression severity in the STAR*D study was assessed by an independent clinician, using the 17-item Hamilton Depression Rating Scale (HAM-D)., Results: During the year following the initiation of treatment, maternal depression severity and children's psychiatric symptoms continued to decrease over time. Decreases in the number of children's psychiatric symptoms were significantly associated with decreases in maternal depression severity. When children's outcomes were examined separately, a statistically significant decrease in symptoms was evident in the offspring of women who remitted early (i.e., within the first 3 months after the initiation of treatment for maternal depression) or late (i.e., over the 1-year follow-up interval) but not in the offspring of nonremitting women., Conclusions: Continued efforts to treat maternal depression until remission is achieved are associated with decreased psychiatric symptoms and improved functioning in the offspring.

To identify caregivers at risk for adverse health effects associated with caregiving, the stress, coping, health and service use of 500 primary caregivers of patients with bipolar disorder were assessed at baseline, 6, and 12 months. K-means cluster analysis and ANOVA identified and characterized groups with differing baseline stress/coping profiles. Mixed effects models examined the effects of cluster, time, and covariates on health outcomes. Three groups were identified. Burdened caregivers had higher burden and avoidance coping levels, and lower mastery and social support than effective and stigmatized caregivers; stigmatized caregivers reported the highest perceived stigma (p < 0.05). Effective and stigmatized groups had better health outcomes and less service use than the burdened group over time; stigmatized caregivers had poorer self-care than effective caregivers. Cluster analysis is a promising method for identifying subgroups of caregivers with different stress and coping profiles associated with different health-related outcomes.