A New Device for Fine-Needle Aspiration Cytology Consisting of a Vibrating Linear Resonant Actuator.

OBJECTIVE: To evaluate the efficacy of a new device for fine-needle aspiration cytology (FNAC) consisting of a vibrating linear resonant actuator (LRA). STUDY DESIGN: Prospective clinical study. METHODS: The LRA frequency was optimized by visualization of the needle motion using a high-speed camera. The FNAC device consists of a vibrating motor fixed to the stopper of a 5-ml syringe and piston. Upon insertion of the syringe needle into a thyroid nodule (with the stopper attached to the syringe piston), sufficient negative pressure with 1-ml suction was maintained. Subsequently, samples were obtained using vibration generated by an LRA or an eccentric rotating mass (ERM). Surgically resected thyroid specimens from 10 patients were evaluated. The number of follicular groups required for adequate diagnosis and the number of larger follicular groups were counted. Next, 254 thyroid nodules from 187 patients were also evaluated by FNAC. The inadequacy rate was determined, and final cytology was classified according to thyroid Bethesda categories. RESULTS: The optimized LRA frequency was 155 Hz. Both the LRA and ERM devices resulted in sufficient amounts of diagnostic material and achieved low inadequacy rates. The number of large follicular groups obtained was significantly greater with the LRA device compared with the ERM device. CONCLUSIONS: The vibrating device using an LRA for thyroid FNAC resulted in sufficient amounts of thyroid follicular groups and achieved low inadequacy rates. In addition, the LRA device allowed for collection of larger follicular groups sufficient to diagnose appropriate thyroid Bethesda categories. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E1393-E1399, 2021.

Effectiveness of different treatments in obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity, defined as daytime hypoventilation, sleep disorder breathing and obesity; during the past few years the prevalence of extreme obesity has markedly increased worldwide consequently increasing the prevalence of OHS. Patients with OHS have a lower quality of life and a higher risk of unfavourable cardiometabolic consequences. Early diagnosis and effective treatment can lead to significant improvement in patient outcomes; therefore, such data has noticeably raised interest in the management and treatment of this sleep disorder. This paper will discuss the findings on the main current treatment modalities OHS will be discussed.

Comparative Clinical Effectiveness Research Focused on Community-Based Delivery of Palliative Care: Overview of the Patient-Centered Outcomes Research Institute's Funding Initiative.

Palliative care is a growing specialty that addresses the needs of individuals diagnosed with advanced illness and their caregivers. Although palliative care has been shown to improve a variety of patient- and caregiver-centered outcomes, access to comprehensive palliative care services for patients is often limited. There is a need to identify the most effective approaches to delivering palliative care to patients in community settings. In fiscal year 2017, based on extensive input from a diverse set of stakeholders, the Patient-Centered Outcomes Research Institute (PCORI) funded nine multisite comparative clinical effectiveness research (CER) trials focused on community-based delivery of palliative care for a total investment of $80 million. These studies, focusing on advance care planning and models of palliative care delivery, represent some of the largest most complex palliative care trials funded to date. Each study evaluates both patient and caregiver outcomes, and together, these trials include a broad range of health conditions, interventions, and settings of care. PCORI has also fostered a learning network of the funded awardees to facilitate the successful conduct of these CER studies and to support awardee efforts to develop collaborative products relevant to advancing the field of palliative care research and practice. The protocols of each of the nine trials, detailed in this issue, demonstrate the expansive reach of the investment PCORI has made in an effort to further the research agenda and provide substantive research evidence in stakeholder-identified areas of need in the field of palliative care.

A Comprehensive Review of Methods to Measure Oral Oncolytic Dose Intensity Using Retrospective Data.

BACKGROUND: Understanding the real-world use of oral oncolytics is essential to assess drug effectiveness. Retrospective analyses using medical and pharmacy claims data allow observation of drug use patterns and health outcomes. However, studies of medication adherence to oral oncolytics may not be sufficient in characterizing exposure because they typically measure refill frequency, not the administered dose or dose changes. Patients who appear fully adherent by traditional measures may be receiving different doses and experiencing differing effectiveness. Relative dose intensity (RDI) is a measure that has been used for intravenous drugs to capture the amount of a particular chemotherapeutic agent administered per unit of time (dose intensity), expressed as the fraction of the amount recommended in evidence-based guidelines. Such a measure would be useful for real-world studies of comparative effectiveness to characterize patient exposure to oral oncolytics. OBJECTIVE: To identify studies that used administrative claims data to measure real-world oral oncolytic dose intensity, RDI, or similar constructs. METHODS: Two health sciences librarians conducted a literature search (PubMed, January 1, 1809-February 6, 2018) including terms in each of the following concept areas: oncology drugs, dosage, and retrospective data sources. At least 2 reviewers scanned each title and abstract of publications retrieved from PubMed. Abstracts that indicated the study reported dose or related concepts and oral oncolytics using retrospective data sources were marked for full-text review. During full-text review, papers were excluded if they did not study oral oncolytics (i.e., only described intravenous chemotherapy); if they did not report drug dosage; or if the study was not retrospective. Resulting studies were included for full-text data extraction. RESULTS: Of the 1,640 publications returned from the search, 41 were marked for full-text review. Full-text review established that 17 studies addressed a concept related to dose of oral oncolytics using retrospective data. Twenty-four studies were excluded: 11 did not measure dose; 9 did not study oral oncolytics; and 4 were not retrospective studies. Among the 17 articles marked for extraction, 5 articles reported dose intensity or RDI using medical records or electronic health record (EHR) data. CONCLUSIONS: This study reveals not only the need for a claims-based measure of dose intensity for oral oncolytics, but also provides a basis for the development of such a measure based on previous EHR-based studies. While several claims data studies have characterized oral oncolytic dosing and duration, we found that no studies combined these dimensions into a single measure such as dose intensity. Methods using EHR data may be translatable to a claims data study. Future research is needed to develop and validate such measures. DISCLOSURES: Novartis Pharmaceuticals provided funding for this study and is a manufacturer of oral onalytics, which is under study in this article. Arcona and Zacker are employees of Novartis. Slejko reports grants from PhRMA, PhRMA Foundation, and Takeda Pharmaceuticals and consulting fees from Pfizer, outside the submitted work. Stuart reports consulting fees from the University of Maryland during the study. The other authors have nothing to disclose. The preliminary findings of this study were presented in a poster at AMCP Nexus 2018, October 22-25, 2018, in Orlando, FL.

Perceived Effectiveness of Anti-Marijuana Messages in Adult Users and Nonusers: An Examination of Responses to Messages About Marijuana's Effects on Cognitive Performance, Driving, and Health.

OBJECTIVE: Marijuana use is associated with negative cognitive and health outcomes and risky driving. Given the rapidly changing policies regarding legal recreational and medicinal marijuana use, it is important to examine what types of marijuana prevention messages may be effective in minimizing such outcomes. This study examined cognitive and affective responses to anti-marijuana public health messages in a sample of adult marijuana users and nonusers to determine the correlates of perceived message effectiveness. METHOD: Participants (N = 203; mean age = 37.7 years) were adult marijuana users and nonusers recruited via Amazon Mechanical Turk (August 2017). After completing self-report measures of marijuana use, they viewed six anti-marijuana messages presented in a random order, addressing marijuana's effects in each of three topic areas: cognitive performance, driving, and adverse health outcomes (e.g., two messages per topic). Participants completed assessments of cognitive and affective perceptions after viewing each message. For each message topic, a linear regression model was used to determine which cognitive and affective perceptions were most predictive of perceived message effectiveness. RESULTS: For all message topics, nonusers perceived the messages as more effective than did users (p < .001). In the majority of analyses, greater message effectiveness was associated with increased perceived harm of marijuana and increased liking of the message. For driving and health messages, greater message effectiveness was also significantly correlated with lower pleasant affect. CONCLUSIONS: The findings suggest that audience perceptions may be uniquely predictive of message effectiveness, depending on the topic.

US young adults' perceived effectiveness of draft pictorial e-cigarette warning labels.

SIGNIFICANCE: Research shows that pictorial warning labels for cigarettes are more effective than text-only warnings, and preliminary work suggests that pictorial warnings could also be considered for electronic cigarettes (e-cigarettes). Pictorial warnings may be important for maximising their effectiveness among young people and enhancing the salience of the single nicotine addiction warning required for e-cigarettes to date in the USA. This study collected pilot data about the perceived effectiveness of draft e-cigarette pictorial warnings. METHODS: Participants were 876 young adults (ages 18-29) recruited through Amazon Mechanical Turk who completed an online e-cigarette survey in 2018. Participants viewed and ranked five versions of the same e-cigarette nicotine addiction warning message-four pictorial and one text-only-on their perceived noticeability, likelihood of capturing young people's attention, memorability, relevance to the addiction warning text and overall effectiveness in warning people about e-cigarette risks. For each outcome, presentation of the five warning versions was randomised. Pictorials included symbolic images of risk and addiction, and of priority audiences for the warning (ie, young people). RESULTS: For all outcomes, pictorial warnings were ranked higher than the text-only warning, and the warning using a yellow triangle caution icon was ranked highest for all outcomes. The text-only warning was ranked as the least likely to be effective for all four outcomes in which it was assessed. Trends were similar for current e-cigarette users and non-users. CONCLUSIONS: Future research should assess perceptions and the appropriateness of pictorial imagery for e-cigarette warnings and test their efficacy against text-only warnings experimentally.

Alternative Conversion Methods for Transition Probabilities in State-Transition Models: Validity and Impact on Comparative Effectiveness and Cost-Effectiveness.

Background. In state-transition models (STMs), decision problems are conceptualized using health states and transitions among those health states after predefined time cycles. The naive, commonly applied method (C) for cycle length conversion transforms all transition probabilities separately. In STMs with more than 2 health states, this method is not accurate. Therefore, we aim to describe and compare the performance of method C with that of alternative matrix transformation methods. Design. We compare 2 alternative matrix transformation methods (Eigenvalue method [E], Schure-Padé method [SP]) to method C applied in an STM of 3 different treatment strategies for women with breast cancer. We convert the given annual transition matrix into a monthly-cycle matrix and evaluate induced transformation errors for the transition matrices and the long-term outcomes: life years, quality-adjusted life-years, costs and incremental cost-effectiveness ratios, and the performance related to the decisions. In addition, we applied these transformation methods to randomly generated annual transition matrices with 4, 7, 10, and 20 health states. Results. In theory, there is no generally applicable correct transformation method. Based on our simulations, SP resulted in the smallest transformation-induced discrepancies for generated annual transition matrices for 2 treatment strategies. E showed slightly smaller discrepancies than SP in the strategy, where one of the direct transitions between health states was excluded. For long-term outcomes, the largest discrepancy occurred for estimated costs applying method C. For higher dimensional models, E performs best. Conclusions. In our modeling examples, matrix transformations (E, SP) perform better than transforming all transition probabilities separately (C). Transition probabilities based on alternative conversion methods should therefore be applied in sensitivity analyses.

Two-stage residual inclusion for survival data and competing risks-An instrumental variable approach with application to SEER-Medicare linked data.

Instrumental variable is an essential tool for addressing unmeasured confounding in observational studies. Two-stage predictor substitution (2SPS) estimator and two-stage residual inclusion (2SRI) are two commonly used approaches in applying instrumental variables. Recently, 2SPS was studied under the additive hazards model in the presence of competing risks of time-to-events data, where linearity was assumed for the relationship between the treatment and the instrument variable. This assumption may not be the most appropriate when we have binary treatments. In this paper, we consider the 2SRI estimator under the additive hazards model for general survival data and in the presence of competing risks, which allows generalized linear models for the relation between the treatment and the instrumental variable. We derive the asymptotic properties including a closed-form asymptotic variance estimate for the 2SRI estimator. We carry out numerical studies in finite samples and apply our methodology to the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database comparing radical prostatectomy versus conservative treatment in early-stage prostate cancer patients.

Comparing drug effectiveness in children: A systematic review.

PURPOSE: The purpose of the study is to assess the current state of the art in pediatric comparative effectiveness research, potential gaps, and areas for improvement. METHODS: Relevant articles from inception to February 2015 were retrieved from Embase and Medline. We sequentially screened titles, abstracts, and full texts, with independent validation. Data regarding general information and study methods including statistical analysis were extracted. Study quality was assessed using Newcastle-Ottawa Scale (NOS). Investigated drugs were ranked and compared with data on the prevalence of pediatric drug use. RESULTS: Three thousand nine hundred twenty-six abstracts were screened for eligibility and inclusion, and 164 articles were included in the review. Most studies were from North America (46.7%). Only 78 studies (47.6%) reported the design: 90.8% were cohort studies. Neonates were least frequently investigated. The drugs that were most often studied included systemic antibacterials (11.4%), psycholeptics (7.9%), and antiepileptics (7.6%). Adjustment for confounding was made using propensity scores in 8.5% of the studies. Studies that did not report the design were of lower quality. Many effectiveness studies were done on antineoplastic agents, which are not frequently used and few studies on analgesics and drugs for obstructive airway diseases which are frequently prescribed. CONCLUSIONS: There is ample opportunity to improve comparative effectiveness research for drugs used in pediatrics. Routinely prescribed drugs were seldom investigated. Modern methods for confounding adjustment, such as propensity scores, were rarely used.

Outcomes research examining treatments, quality of life and costs in HER2-negative and triple-negative metastatic breast cancer: a systematic literature review.

AIM: With the aggregation of real-world data in healthcare, opportunities for outcomes research are growing. In this study, we summarize published literature examining comparative effectiveness research (CER), treatment patterns, quality of life (QoL) and costs in HER2-negative and triple-negative (TN) metastatic breast cancer (mBC). METHODS: PubMed (2010-January 2016) and four conferences (2013-January 2016) were searched using MeSH/keywords, including mBC, QoL, morbidity and therapeutics. Studies relating to CER, treatment patterns, QoL, costs or treatment appropriateness in US patients with HER2-negative/TN mBC were included in the review. RESULTS: Of 1782 identified records, 33 studies met full inclusion criteria: seven related to CER, 18 to treatment patterns, one to treatment appropriateness/navigation, two to QoL and five to costs. Studies varied in objectives, designs and outcomes. Study designs included retrospective chart reviews (52%), retrospective secondary database analyses (27%), economic models (12%), physician surveys (6%) and patient surveys (3%). 25 studies reported results on HER2-negative mBC, six on TN mBC and two on both subtypes. The most common end points examined were treatment patterns, overall survival and progression-free survival. CONCLUSION: Outcomes research in HER2-negative mBC in the USA was limited, specifically among TN patients, indicating an opportunity for further research in this high unmet need population. Endpoints and treatment options varied, thus, it is difficult to draw summary conclusions about these studies. Outcomes research examining real-world data in mBC has increased in recent years, and may continue to grow with the implementation of new policy programs.

The value of explicitly emulating a target trial when using real world evidence: an application to colorectal cancer screening.

Observational analyses for causal inference often rely on real world data collected for purposes other than research. A frequent goal of these observational analyses is to use the data to emulate a hypothetical randomized experiment, i.e., the target trial, that mimics the design features of a true experiment, including a clear definition of time zero with synchronization of treatment assignment and determination of eligibility. We review a recent observational analysis that explicitly emulated a target trial of screening colonoscopy using insurance claims from U.S. Medicare. We then compare this explicit emulation with alternative, simpler observational analyses that do not synchronize treatment assignment and eligibility determination at time zero and/or do not allow for repeated eligibility. This empirical comparison suggests that lack of an explicit emulation of the target trial leads to biased estimates, and shows that allowing for repeated eligibility increases the statistical efficiency of the estimates.

The economic value of rapid deployment aortic valve replacement via full sternotomy.

AIM: To compare the economic value of EDWARDS INTUITY Elite™ (EIE) valve system for rapid-deployment aortic valve replacement (RDAVR) in a full sternotomy (FS) approach (EIE-FS-RDAVR) versus FS-AVR using conventional stented bioprosthesis. DATA & METHODS: A simulation model to compare each treatment's 30-day inpatient utilization and complication rates utilized: clinical end points obtained from the TRANSFORM trial patient subset (EIE-FS-RDAVR) and a best evidence review of the published literature (FS-AVR); and costs from the Premier database and published literature. RESULTS: EIE-FS-RDAVR costs $800 less than FS-AVR per surgery episode attributable to lowered complication rates and utilization. Combined with the lower mortality, EIE-FS-RDAVR was a superior (dominant) technology versus FS-AVR. CONCLUSION: This preliminary investigation of EIE-FS-RDAVR versus conventional FS-AVR found the EIE valve offered superior economic value over a 30-day period. Real-world analyses with additional long-term follow-up are needed to evaluate if this result can be replicated over a longer timeframe.

Neuraxial vs general anaesthesia for total hip and total knee arthroplasty: a systematic review of comparative-effectiveness research.

BACKGROUND: This systematic review evaluated the evidence comparing patient-important outcomes in spinal or epidural vs general anaesthesia for total hip and total knee arthroplasty. METHODS: MEDLINE, Ovid EMBASE, EBSCO CINAHL, Thomson Reuters Web of Science, and the Cochrane Central Register of Controlled Trials from inception until March 2015 were searched. Eligible randomized controlled trials or prospective comparative studies investigating mortality, major morbidity, and patient-experience outcomes directly comparing neuraxial (spinal or epidural) with general anaesthesia for total hip arthroplasty, total knee arthroplasty, or both were included. Independent reviewers working in duplicate extracted study characteristics, validity, and outcomes data. Meta-analysis was conducted using the random-effects model. RESULTS: We included 29 studies involving 10 488 patients. Compared with general anaesthesia, neuraxial anaesthesia significantly reduced length of stay (weighted mean difference -0.40 days; 95% confidence interval -0.76 to -0.03; P=0.03; I2 73%; 12 studies). No statistically significant differences were found between neuraxial and general anaesthesia for mortality, surgical duration, surgical site or chest infections, nerve palsies, postoperative nausea and vomiting, or thromboembolic disease when antithrombotic prophylaxis was used. Subgroup analyses failed to find statistically significant interactions (P>0.05) based on risk of bias, type of surgery, or type of neuraxial anaesthesia. CONCLUSION: Neuraxial anaesthesia for total hip or total knee arthroplasty, or both appears equally effective without increased morbidity when compared with general anaesthesia. There is limited quantitative evidence to suggest that neuraxial anaesthesia is associated with improved perioperative outcomes. Future investigations should compare intermediate and long-term outcome differences to better inform anaesthesiologists, surgeons, and patients on importance of anaesthetic selection.

Emerging strategies to treat ruptured abdominal aortic aneurysms.

Population screening programmes and a falling population prevalence of smoking have led to a declining incidence of ruptured abdominal aortic aneurysms in men. However, ruptured abdominal aortic aneurysms remain a common vascular surgical emergency, with an increasing proportion of ruptures being in women. About one quarter of the ruptures have a juxta-renal aneurysm and are more challenging to repair using endovascular technologies. Endovascular technologies may not reduce the overall mortality, compared with open surgical repair, but appear to offer early benefits with respect to patient quality of life at acceptable cost. Challenges over the next 5 years include widening the access to repair, developing an accurate bedside risk scoring tool, as well as optimising strategies for pre-operative resuscitation, standardising peri-operative care and the management of post-operative complications.

The Evolution of Self-Reported Urinary and Sexual Dysfunction over the Last Two Decades: Implications for Comparative Effectiveness Research.

BACKGROUND: Despite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time. OBJECTIVE: To evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart. DESIGN, SETTING, AND PARTICIPANTS: Patients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies. RESULTS AND LIMITATIONS: The study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding. CONCLUSIONS: Reporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations. PATIENT SUMMARY: Patient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct high-quality, impactful comparative effectiveness research.

Comparative effectiveness of follow-up imaging approaches in pancreatic cancer.

AIM: Although PET imaging is sometimes used in follow-up of pancreatic cancer, evidence regarding comparative effectiveness of PET and older imaging modalities is limited. PATIENTS & METHODS: Linked cancer registry and Medicare claims data were analyzed to examine patterns of imaging and effects on treatment patterns and survival among newly diagnosed pancreatic cancer patients from 2003 to 2007. RESULTS: 12% of patients received PET during follow-up. In a time-varying exposure model, computed tomography/MRI was associated with lower mortality risk relative to PET in surgical patients (HR: 0.66; 95% CI: 0.52-0.83). In a subset analysis, type of follow-up imaging before 180 days was not associated with mortality after 180 days (computed tomography/MRI vs PET; hazard ratio: 0.98; 95% CI: 0.84-1.16). CONCLUSION: Follow-up PET is uncommon among Medicare beneficiaries with pancreatic cancer, and is generally used late in the disease course. This pattern of PET use was not associated with decreased mortality risk compared with conventional imaging.

Introducción al meta-análisis indirecto / Introduction to the indirect meta-analyses

Los meta-análisis son estudios que tienen la finalidad de compilar toda la información disponible, agrupándola según un tema específico y evaluándola a través de herramientas de calidad metodológica. Cuando existen comparaciones de dos tratamientos específicos basados en ensayos clínicos aleatorizados los meta-análisis tradicionales son la mejor opción, pero existen escenarios en donde no se dispone de suficientes estudios comparativos directos. En estos casos una opción a tomar en consideración son las comparaciones indirectas o meta-análisis indirectos. El objetivo de la presente revisión es comprender el fundamento conceptual, la necesidad, las aplicaciones y limitaciones de las comparaciones indirectas para el posterior entendimiento de los meta-análisis en red o network meta-análisis.

Meta-analyses are studies that aim to compile all available information, grouping them according to an specific theme and evaluating it through methodological quality tools. When there are two specific comparisons of treatments based on randomized clinical trials, standard meta-analyses are the best option, but there are scenarios in which there is no available literature for those direct comparisons. In these cases, an alternative method to consider is indirect comparison or indirect meta-analyses. The aim of this review is to understand the conceptual foundations, the need, applications and limitations of indirect comparisons for further understanding of network meta-analyses.

Establishment of an 11-year cohort of 8733 pediatric patients hospitalized at United States free-standing children's hospitals with de novo acute lymphoblastic leukemia from health care administrative data.

BACKGROUND: Acute lymphoblastic leukemia (ALL) accounts for almost one quarter of pediatric cancer in the United States. Despite cooperative group therapeutic trials, there remains a paucity of large cohort data on which to conduct epidemiology and comparative effectiveness research studies. RESEARCH DESIGN: We designed a 3-step process utilizing International Classification of Diseases-9 Clinical Modification (ICD-9) discharge diagnoses codes and chemotherapy exposure data contained in the Pediatric Health Information System administrative database to establish a cohort of children with de novo ALL. This process was validated by chart review at 1 of the pediatric centers. RESULTS: An ALL cohort of 8733 patients was identified with a sensitivity of 88% [95% confidence interval (CI), 83%-92%] and a positive predictive value of 93% (95% CI, 89%-96%). The 30-day all cause inpatient case fatality rate using this 3-step process was 0.80% (95% CI, 0.63%-1.01%), which was significantly different than the case fatality rate of 1.40% (95% CI, 1.23%-1.60%) when ICD-9 codes alone were used. CONCLUSIONS: This is the first report of assembly and validation of a cohort of de novo ALL patients from a database representative of free-standing children's hospitals across the United States. Our data demonstrate that the use of ICD-9 codes alone to establish cohorts will lead to substantial patient misclassification and result in biased outcome estimates. Systematic methods beyond the use of just ICD-9 codes must be used before analysis to establish accurate cohorts of patients with malignancy. A similar approach should be followed when establishing future cohorts from administrative data.

Avaliação clínica e microbiológica das técnicas de full mouth disinfection e raspagem e alisamento radicular associadas à azitromicina ou clorexidina no tratamento da periodontite crônica: ensaio clínico controlado randomizado / Clinical and microbiological analysis of full mouth disinfection and scaling and root planing per quadrant techniques associated with chlorhexidine or azithromycin in the treatment of chronic periodontitis: randomized controlled trial

O tratamento não cirúrgico da doença periodontal inclui a realização de procedimentos de instrução de higiene oral e a raspagem e alisamento radicular por quadrantes (RAR). Com a finalidade de prevenir a rápida recolonização das bolsas periodontais por bactérias presentes em outros sítios intraorais, foi proposta a técnica de one stage full-mouth disinfection (FMD). De acordo com essa técnica as raspagens de todos os hemi-arcos são realizadas em 24 horas associadas à realização da descontaminação de tonsilas, mucosas, bolsas e língua com diferentes concentrações e formas de apresentação da clorexidina. Estudos revelaram dados controversos sobre a efetividade da técnica FMD, questionaram a necessidade de uso da clorexidina e, em adição propuseram o uso adjuvante de antibióticos. Neste sentido, a justificativa deste é a necessidade de estudos controlados que comparem a técnica FMD com a RAR, com as diferentes variações que podem ser aplicadas a ambos, analisando o seu impacto nos parâmetros periodontais clínicos e microbiológicos. Assim, o objetivo deste estudo foi avaliar, por meio de ensaio clínico controlado randomizado, a efetividade da técnica FMD e sua associação com clorexidina ou azitromicina em relação à RAR associada à clorexidina e azitromicina sob uma perspectiva clínica (avaliação da profundidade de sondagem, nível clínico de inserção, índice gengival e índice de placa) e microbiana (quantificação da carga bacteriana total e das seguintes bactérias: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola e Streptococcus oralis, por meio de PCR em tempo real, nos períodos de 90 e 180 dias após o tratamento). No presente ensaio clínico controlado randomizado foram avaliados 77 indivíduos divididos em 6 grupos: FMD-CX (raspagem e alisamento radicular de todos os dentes em 24 h associada à clorexidina para desinfecção de bolsas, tonsilas e mucosa ­ n= 15), FMD (raspagem e alisamento radicular de todos os dentes em 24 h ­ n=10), FMD-AZ (raspagem e alisamento radicular de todos os dentes em 24 h + azitromicina ­ n=15), RAR-AZ (raspagem e alisamento radicular por quadrante em intervalos semanais + azitromicina ­ n=11), RAR-CX (raspagem e alisamento radicular por quadrante, em intervalos semanais + clorexidina ­ n=13), RAR (raspagem e alisamento radicular, por quadrantes, em intervalos semanais ­ n=13). Os parâmetros clínicos foram analisados estatisticamente pelo teste de análise de variância (ANOVA) baseado em um planejamento para medidas repetidas e teste de comparações múltiplas de médias. A carga bacteriana total e das bactérias foi avaliada intragrupo (Teste de Friedman) e intergrupos (Teste de Kruskal Wallis). O grupo FMD-CX mostrou maior redução da profundidade de sondagem e ganho do nível clínico de inserção que os demais. Além disso, esse grupo mostrou redução de carga para quatro das cinco bactérias avaliadas: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Streptococcus oralis, Treponema denticola, Tannerella forsythia. Os grupos que utilizaram azitromicina não mostraram melhores resultados clínicos e microbiológicos. Pode-se concluir que a utilização da clorexidina nos grupos FMD-CX e RAR-CX mostrou melhores resultados clínicos e microbiológicos. Por outro lado, a utilização da azitromicina não apresentou melhorias nesses parâmetros

The non-surgical treatment of periodontal disease involves performing procedures of oral hygiene instruction and scaling and root planing per quadrant (SRP). This therapeutic approach aims to prevent rapid recolonization of bacteria in periodontal pockets in other intraoral sites, the technique of one stage full -mouth disinfection (FMD) is proposed. According to this technique the scalings of all hemi - arches are made within 24 hours associated with performing the decontamination of tonsils, mucosa, periodontal pockets and tongue with different concentrations and forms of presentation of chlorhexidine. Studies over the years have revealed controversial data on the effectiveness of the technique FMD, questioned the need to use chlorhexidine, and proposed adding the adjuvant use of antibiotics. In this sense, the justification of this research is the need for further controlled studies comparing the FMD technique with conventional quadrant scaling with differnt variations that can be applied to both, analyzing their impact on clinical and microbiological periodontal parameters. The objective of this study was to evaluate through a randomized controlled trial the effectiveness of the technique one stage full -mouth disinfection and its association with chlorhexidine or azithromycin compared to scaling and root planing per quadrant associated with chlorhexidine and azithromycin under a clinical perspective (evaluation of probing depth, clinical attachment level , gingival index and plaque index ) and microbial (assessment of the total bacterial load and the following bacteria : Aggregatibacter actinomycetemcomitans , Porphyromonas gingivalis , Tannerella forsythia , Treponema denticola and Streptococcus oralis) through of real-time PCR , in periods of 90 and 180 days after treatment. In the present randomized controlled trial evaluated 77 individuals were divided into 6 groups : FMD-CX (scaling and root planing of all teeth in 24 associated with chlorhexidine for disinfection pockets, tonsils and mucosa - n = 15 ) , FMD ( scaling and root planing of all teeth in 24 hours- n = 10 ) , FMD- AZ (scaling and root planing of all teeth in 24 hours + azithromycin - n = 15 ) , RAR - AZ ( scaling and root planing per quadrant at weekly intervals + azithromycinn = 11 ) , RAR - CX ( scaling and root planing per quadrant at weekly intervals + chlorhexidine - n = 13 ) , RAR ( scaling and root planing per quadrants at weekly intervals - n = 13 ) . The clinical parameters were statistically analyzed by analysis of variance (ANOVA) based on a planning for repeated measures and multiple comparisons of means test. The total bacterial load and bacteria was evaluated intragroup (Friedman test) and between groups (Kruskal Wallis). The FMD- CX group showed greater reduction in probing depth and gain in clinical attachment level than the others. Moreover, this group showed reduced load for four of five surveyed bacterias: Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Streptococcus oralis, Treponema denticola, Tannerella forsythia. Groups using azithromycin did not show improved clinical and microbiological outcomes. It can be concluded that the use of chlorhexidine groups FMD-CX and RAR-CX showed the best clinical and microbiological results. On the other hand, the use of azithromycin did not show improvements in these parameters

Systematic review of comparative effectiveness data for oncology orphan drugs.

OBJECTIVES: To systematically assess clinical and economic evidence for oncology orphan drugs marketed in the United States and to highlight the challenges and opportunities for evidence development within this pharmaceutical category. STUDY DESIGN: Systematic review. METHODS: We conducted systematic literature searches of the Medline and Embase databases for clinical and cost-effectiveness studies published before June 2010 for all oncology orphan drugs marketed in the United States. We used the Grading of Recommendations Assessment, Development and Evaluation method and the Quality of Health Economic Studies criteria to assess the quality of the selected studies. RESULTS: We identified 60 randomized controlled trials and 21 cost-effectiveness analyses to support 47 oncology orphan drugs. A total of 21 drugs had moderate or high-quality bodies of clinical evidence, 11 had low-quality or very low quality clinical evidence, and 15 drugs could not be evaluated because we were unable to identify clinical evidence that met our inclusion criteria. The Spearman rank correlation coefficient for the level of evidence for oncology orphan drugs and disease prevalence was 0.3 (95% confidence interval, 0.0-0.5). The cost-effectiveness analyses received quality scores between 72 and 100 (range 0-100), with a mean score of 85. CONCLUSIONS: The results of our study show that oncology orphan drugs marketed in the United States have varying levels and quality of clinical evidence and a paucity of evidence regarding economic value. Innovative analytic and policy approaches are needed to develop and implement a decision-making framework for this pharmaceutical category that is consistent with evidence-based medicine and comparative effectiveness research.