Surgical Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.

BACKGROUND AND OBJECTIVES: Early life epilepsies (epilepsies in children 1-36 months old) are common and may be refractory to antiseizure medications. We summarize findings of a systematic review commissioned by the American Epilepsy Society to assess evidence and identify evidence gaps for surgical treatments for epilepsy in children aged 1-36 months without infantile spasms. METHODS: EMBASE, MEDLINE, PubMed, and the Cochrane Library were searched for studies published from 1/1/1999 to 8/19/21. We included studies reporting data on children aged 1 month to ≤36 months undergoing surgical interventions or neurostimulation for epilepsy and enrolling ≥10 patients per procedure. We excluded studies of infants with infantile spasms or status epilepticus. For effectiveness outcomes (seizure freedom, seizure frequency), studies were required to report follow-up at ≥ 12 weeks. For harm outcomes, no minimum follow-up was required. Outcomes for all epilepsy types, regardless of etiology, were reported together. RESULTS: Eighteen studies (in 19 articles) met the inclusion criteria. Sixteen prestudies/poststudies reported on efficacy, and 12 studies addressed harms. Surgeries were performed from 1979 to 2020. Seizure freedom for infants undergoing hemispherectomy/hemispherotomy ranged from 7% to 76% at 1 year after surgery. For nonhemispheric surgeries, seizure freedom ranged from 40% to 70%. For efficacy, we concluded low strength of evidence (SOE) suggests some infants achieve seizure freedom after epilepsy surgery. Over half of infants undergoing hemispherectomy/hemispherotomy achieved a favorable outcome (Engel I or II, International League Against Epilepsy I to IV, or >50% seizure reduction) at follow-up of >1 year, although studies had key limitations. Surgical mortality was rare for functional hemispherectomy/hemispherotomy and nonhemispheric resections. Low SOE suggests postoperative hydrocephalus is uncommon for infants undergoing nonhemispheric procedures for epilepsy. DISCUSSION: Although existing evidence remains sparse and low quality, some infants achieve seizure freedom after surgery and ≥50% achieve favorable outcomes. Future prospective studies in this age group are needed. In addition to seizure outcomes, studies should evaluate other important outcomes (developmental outcomes, quality of life [QOL], sleep, functional performance, and caregiver QOL). TRIAL REGISTRATION INFORMATION: This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Pharmacologic and Dietary Treatments for Epilepsies in Children Aged 1-36 Months: A Systematic Review.

BACKGROUND AND OBJECTIVES: Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms. METHODS: We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months. RESULTS: Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported. DISCUSSION: Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life. TRIAL REGISTRATION INFORMATION: This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.

Interventions for malnutrition in hospitalized adults: A systematic review and meta-analysis.

BACKGROUND: Malnutrition is associated with poor outcomes in hospitalized adults. We aimed to assess the effectiveness of hospital-initiated interventions for patients with malnutrition. METHODS: Data sources included MEDLINE, Embase, Cochrane Library from January 1, 2000 to June 3, 2021. We included randomized controlled trials (RCTs) assessing interventions for hospitalized adults diagnosed or identified as at-risk for malnutrition using malnutrition screening and diagnostic assessment tools. Individual reviewers extracted study data and performed quality checks for accuracy. Meta-analysis was conducted using a random-effects model with variance correction. We assessed the overall strength of evidence at the outcome level. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. RESULTS: We found 11 RCTs that assessed two types of interventions: specialized nutrition care (8 RCTs) and increased protein provision (3 RCTs). The pooled findings of 11 RCTs found moderate strength of evidence that specialized nutrition care and increased protein provision reduced mortality by 21% (relative risk [RR]: 0.79, 95% confidence interval [CI]: 0.63-0.98; absolute risk reduction [ARR]: -0.02, 95% CI: -0.03 to -0.00). Pooled estimates indicated a nonsignificant decrease of 0.18 days in the length of stay (9 RCTs) and a 10% reduction in readmissions (7 RCTs). No eligible RCTs assessed parenteral or enteral nutrition. CONCLUSION: Certain malnutrition-focused hospital-initiated interventions (e.g., specialized nutrition care and increased protein provision) reduce mortality and may improve the quality of life among patients at risk for or diagnosed with malnutrition. Future trials are needed to assess the effectiveness of parenteral and enteral nutrition.

Interventions to Reduce Hospital Length of Stay in High-risk Populations: A Systematic Review.

Importance: Many strategies to reduce hospital length of stay (LOS) have been implemented, but few studies have evaluated hospital-led interventions focused on high-risk populations. The Agency for Healthcare Research and Quality (AHRQ) Learning Health System panel commissioned this study to further evaluate system-level interventions for LOS reduction. Objective: To identify and synthesize evidence regarding potential systems-level strategies to reduce LOS for patients at high risk for prolonged LOS. Evidence Review: Multiple databases, including MEDLINE and Embase, were searched for English-language systematic reviews from January 1, 2010, through September 30, 2020, with updated searches through January 19, 2021. The scope of the protocol was determined with input from AHRQ Key Informants. Systematic reviews were included if they reported on hospital-led interventions intended to decrease LOS for high-risk populations, defined as those with high-risk medical conditions or socioeconomically vulnerable populations (eg, patients with high levels of socioeconomic risk, who are medically uninsured or underinsured, with limited English proficiency, or who are hospitalized at a safety-net, tertiary, or quaternary care institution). Exclusion criteria included interventions that were conducted outside of the hospital setting, including community health programs. Data extraction was conducted independently, with extraction of strength of evidence (SOE) ratings provided by systematic reviews; if unavailable, SOE was assessed using the AHRQ Evidence-Based Practice Center methods guide. Findings: Our searches yielded 4432 potential studies. We included 19 systematic reviews reported in 20 articles. The reviews described 8 strategies for reducing LOS in high-risk populations: discharge planning, geriatric assessment, medication management, clinical pathways, interdisciplinary or multidisciplinary care, case management, hospitalist services, and telehealth. Interventions were most frequently designed for older patients, often those who were frail (9 studies), or patients with heart failure. There were notable evidence gaps, as there were no systematic reviews studying interventions for patients with socioeconomic risk. For patients with medically complex conditions, discharge planning, medication management, and interdisciplinary care teams were associated with inconsistent outcomes (LOS, readmissions, mortality) across populations. For patients with heart failure, clinical pathways and case management were associated with reduced length of stay (clinical pathways: mean difference reduction, 1.89 [95% CI, 1.33 to 2.44] days; case management: mean difference reduction, 1.28 [95% CI, 0.52 to 2.04] days). Conclusions and Relevance: This systematic review found inconsistent results across all high-risk populations on the effectiveness associated with interventions, such as discharge planning, that are often widely used by health systems. This systematic review highlights important evidence gaps, such as the lack of existing systematic reviews focused on patients with socioeconomic risk factors, and the need for further research.

Ethical Considerations in Dementia Diagnosis and Care: AAN Position Statement.

Alzheimer disease and other dementias present unique practical challenges for patients, their families, clinicians, and health systems. These challenges reflect not only the growing public health effect of dementia in an aging global population, but also more specific ethical complexities including early loss of patients' capacity to make decisions regarding their own care, the stigma often associated with a dementia diagnosis, the difficulty of balancing concern for patients' welfare with respect for patients' remaining independence, and the effect on the physical, emotional, and financial well-being of family caregivers. Caring for patients with dementia requires respecting patient autonomy while acknowledging progressively diminishing decisional capacity and continuing to provide care in accordance with other core ethical principles (beneficence, justice, and nonmaleficence). Whereas these ethical principles remain unchanged, neurologists must reconsider how to apply them given changes across multiple domains including our understanding of disease, clinical and legal tools for addressing manifestations of illness, our expanding awareness of the crucial role of family caregivers in providing care and maintaining patient quality of life, and societal conceptions of dementia and individuals' personal expectations for aging. This revision to the American Academy of Neurology's 1996 position statement summarizes ethical considerations that often arise in caring for patients with dementia; although it addresses how such considerations influence patient management, it is not a clinical practice guideline.

Improving the utility of evidence synthesis for decision makers in the face of insufficient evidence.

OBJECTIVE: To identify and suggest strategies to make insufficient evidence ratings in systematic reviews more actionable. STUDY DESIGN AND SETTING: A workgroup comprising members from the Evidence-Based Practice (EPC) Program of the Agency for Healthcare Research and Quality convened throughout 2020. We conducted iterative discussions considering information from three data sources: a literature review for relevant publications and frameworks, a review of a convenience sample of past systematic reviews conducted by the EPCs, and an audit of methods used in past EPC technical briefs. RESULTS: We identified five strategies for supplementing systematic review findings when evidence on benefits or harms is expected to be, or found to be, insufficient: 1) reconsider eligible study designs, 2) summarize indirect evidence, 3) summarize contextual and implementation evidence, 4) consider modelling, and 5) incorporate unpublished health system data in the evidence synthesis. While these strategies may not increase the strength of evidence, they may improve the utility of reports for decision makers. Adopting these strategies depends on feasibility, timeline, funding, and expertise of the systematic reviewers. CONCLUSION: Throughout the process of evidence synthesis of early scoping, protocol development, review conduct, and review presentation, authors can consider these five strategies to supplement evidence with insufficient rating to make it more actionable for end-users.

Ethical Perspectives on Costly Drugs and Health Care: AAN Position Statement.

High drug prices have created substantial challenges for patients, physicians, health systems, and payers. High drug prices can affect patient care in many ways, including limiting access to treatment, increasing the burden of administrative tasks, and contributing to physician burnout. Exorbitant drug pricing poses direct challenges for distributive justice, which is concerned with fairly distributing benefits and burdens across society. In this position statement, we discuss ethical concerns raised by high drug costs, primarily focusing on concerns around distributive justice. We consider forms of rationing, approaches to allocation, potential complexities in real-life application, and structural forces contributing to high drug costs. Finally, we consider potential policy solutions and ramifications for individual clinicians.

Translating an evidence-based clinical pathway into shareable CDS: developing a systematic process using publicly available tools.

OBJECTIVE: To develop a process for translating semi-structured clinical decision support (CDS) into shareable, computer-readable CDS. MATERIALS AND METHODS: We developed a systematic and transparent process using publicly available tools (eGLIA, GEM Cutter, VSAC, and the CDS Authoring Tool) to translate an evidence-based clinical pathway (CP) into a Clinical Quality Language (CQL)-encoded CDS artifact. RESULTS: We produced a 4-phase process for translating a CP into a CQL-based CDS artifact. CP content was extracted using GEM into discrete clinical concepts, encoded using standard terminologies into value sets on VSAC, evaluated against workflows using a wireframe, and finally structured as a computer readable CDS artifact using CQL. This process included a quality control step and intermediate products to support transparency and reuse by other CDS developers. DISCUSSION: Translating a CP into a shareable, computer-readable CDS artifact was accomplished through a systematic process. Our process identified areas of ambiguity and gaps in the CP, which generated improvements in the CP. Collaboration with clinical subject experts and the CP development team was essential for translation. Publicly available tools were sufficient to support most translation steps, but expression of certain complex concepts required manual encoding. CONCLUSION: Standardized development of CDS from a CP is feasible using a systematic 4-phase process. CPs represent a potential reservoir for developers of evidence-based CDS. Aspects of CP development simplified portions of the CDS translation process. Publicly available tools can facilitate CDS development; however, enhanced tool features are needed to model complex CDS statements.

Medical Care of Adults With Down Syndrome: A Clinical Guideline.

Importance: Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. Objective: To develop an evidence-based clinical practice guideline for adults with Down syndrome. Evidence Review: The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. Findings: From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. Conclusions and Relevance: These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

Machine learning for screening prioritization in systematic reviews: comparative performance of Abstrackr and EPPI-Reviewer.

BACKGROUND: Improving the speed of systematic review (SR) development is key to supporting evidence-based medicine. Machine learning tools which semi-automate citation screening might improve efficiency. Few studies have assessed use of screening prioritization functionality or compared two tools head to head. In this project, we compared performance of two machine-learning tools for potential use in citation screening. METHODS: Using 9 evidence reports previously completed by the ECRI Institute Evidence-based Practice Center team, we compared performance of Abstrackr and EPPI-Reviewer, two off-the-shelf citations screening tools, for identifying relevant citations. Screening prioritization functionality was tested for 3 large reports and 6 small reports on a range of clinical topics. Large report topics were imaging for pancreatic cancer, indoor allergen reduction, and inguinal hernia repair. We trained Abstrackr and EPPI-Reviewer and screened all citations in 10% increments. In Task 1, we inputted whether an abstract was ordered for full-text screening; in Task 2, we inputted whether an abstract was included in the final report. For both tasks, screening continued until all studies ordered and included for the actual reports were identified. We assessed potential reductions in hypothetical screening burden (proportion of citations screened to identify all included studies) offered by each tool for all 9 reports. RESULTS: For the 3 large reports, both EPPI-Reviewer and Abstrackr performed well with potential reductions in screening burden of 4 to 49% (Abstrackr) and 9 to 60% (EPPI-Reviewer). Both tools had markedly poorer performance for 1 large report (inguinal hernia), possibly due to its heterogeneous key questions. Based on McNemar's test for paired proportions in the 3 large reports, EPPI-Reviewer outperformed Abstrackr for identifying articles ordered for full-text review, but Abstrackr performed better in 2 of 3 reports for identifying articles included in the final report. For small reports, both tools provided benefits but EPPI-Reviewer generally outperformed Abstrackr in both tasks, although these results were often not statistically significant. CONCLUSIONS: Abstrackr and EPPI-Reviewer performed well, but prioritization accuracy varied greatly across reports. Our work suggests screening prioritization functionality is a promising modality offering efficiency gains without giving up human involvement in the screening process.

More Guidelines than states: variations in U.S. lead screening and management guidance and impacts on shareable CDS development.

BACKGROUND: Pediatric lead exposure in the United States (U.S.) remains a preventable public health crisis. Shareable electronic clinical decision support (CDS) could improve lead screening and management. However, discrepancies between federal, state and local recommendations could present significant challenges for implementation. METHODS: We identified publically available guidance on lead screening and management. We extracted definitions for elevated lead and recommendations for screening, follow-up, reporting, and management. We compared thresholds and level of obligation for management actions. Finally, we assessed the feasibility of development of shareable CDS. RESULTS: We identified 54 guidance sources. States offered different definitions of elevated lead, and recommendations for screening, reporting, follow-up and management. Only 37 of 48 states providing guidance used the Center for Disease Control (CDC) definition for elevated lead. There were 17 distinct management actions. Guidance sources indicated an average of 5.5 management actions, but offered different criteria and levels of obligation for these actions. Despite differences, the recommendations were well-structured, actionable, and encodable, indicating shareable CDS is feasible. CONCLUSION: Current variability across guidance poses challenges for clinicians. Developing shareable CDS is feasible and could improve pediatric lead screening and management. Shareable CDS would need to account for local variability in guidance.

Treatments for Poststroke Motor Deficits and Mood Disorders: A Systematic Review for the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense Guidelines for Stroke Rehabilitation.

Background: Early rehabilitation after stroke is essential to help reduce disability. Purpose: To summarize evidence on the benefits and harms of nonpharmacologic and pharmacologic treatments for motor deficits and mood disorders in adults who have had stroke. Data Sources: English-language searches of multiple electronic databases from April 2009 through July 2018; targeted searches to December 2018 for studies of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors. Study Selection: 19 systematic reviews and 37 randomized controlled trials addressing therapies for motor deficits or mood disorders in adults with stroke. Data Extraction: One investigator abstracted the data, and quality and GRADE assessment were checked by a second investigator. Data Synthesis: Most interventions (for example, SSRIs, mental practice, mirror therapy) did not improve motor function. High-quality evidence did not support use of fluoxetine to improve motor function. Moderate-quality evidence supported use of cardiorespiratory training to improve maximum walking speed and repetitive task training or transcranial direct current stimulation to improve activities of daily living (ADLs). Low-quality evidence supported use of robotic arm training to improve ADLs. Low-quality evidence indicated that antidepressants may reduce depression, whereas the frequency and severity of antidepressant-related adverse effects was unclear. Low-quality evidence suggested that cognitive behavioral therapy and exercise, including mind-body exercise, may reduce symptoms of depression and anxiety. Limitation: Studies were of poor quality, interventions and comparators were heterogeneous, and evidence on harms was scarce. Conclusion: Cardiorespiratory training, repetitive task training, and transcranial direct current stimulation may improve ADLs in adults with stroke. Cognitive behavioral therapy, exercise, and SSRIs may reduce symptoms of poststroke depression, but use of SSRIs to prevent depression or improve motor function was not supported. Primary Funding Source: U.S. Department of Veterans Affairs, Veterans Health Administration.

Safe Practices for Copy and Paste in the EHR. Systematic Review, Recommendations, and Novel Model for Health IT Collaboration.

BACKGROUND: Copy and paste functionality can support efficiency during clinical documentation, but may promote inaccurate documentation with risks for patient safety. The Partnership for Health IT Patient Safety was formed to gather data, conduct analysis, educate, and disseminate safe practices for safer care using health information technology (IT). OBJECTIVE: To characterize copy and paste events in clinical care, identify safety risks, describe existing evidence, and develop implementable practice recommendations for safe reuse of information via copy and paste. METHODS: The Partnership 1) reviewed 12 reported safety events, 2) solicited expert input, and 3) performed a systematic literature review (2010 to January 2015) to identify publications addressing frequency, perceptions/attitudes, patient safety risks, existing guidance, and potential interventions and mitigation practices. RESULTS: The literature review identified 51 publications that were included. Overall, 66% to 90% of clinicians routinely use copy and paste. One study of diagnostic errors found that copy and paste led to 2.6% of errors in which a missed diagnosis required patients to seek additional unplanned care. Copy and paste can promote note bloat, internal inconsistencies, error propagation, and documentation in the wrong patient chart. Existing guidance identified specific responsibilities for authors, organizations, and electronic health record (EHR) developers. Analysis of 12 reported copy and paste safety events was congruent with problems identified from the literature review. CONCLUSION: Despite regular copy and paste use, evidence regarding direct risk to patient safety remains sparse, with significant study limitations. Drawing on existing evidence, the Partnership developed four safe practice recommendations: 1) Provide a mechanism to make copy and paste material easily identifiable; 2) Ensure the provenance of copy and paste material is readily available; 3) Ensure adequate staff training and education; 4) Ensure copy and paste practices are regularly monitored, measured, and assessed.

Quality and clarity in systematic review abstracts: an empirical study.

BACKGROUND: Systematic review (SR) abstracts are important for disseminating evidence syntheses to inform medical decision making. We assess reporting quality in SR abstracts using PRISMA for Abstracts (PRISMA-A), Cochrane Handbook, and Agency for Healthcare Research & Quality guidance. METHODS: We evaluated a random sample of 200 SR abstracts (from 2014) comparing interventions in the general medical literature. We assessed adherence to PRISMA-A criteria, problematic wording in conclusions, and whether "positive" studies described clinical significance. RESULTS: On average, abstracts reported 60% of PRISMA-A checklist items (mean 8.9 ± 1.7, range 4 to 12). Eighty percent of meta-analyses reported quantitative measures with a confidence interval. Only 49% described effects in terms meaningful to patients and clinicians (e.g., absolute measures), and only 43% mentioned strengths/limitations of the evidence base. Average abstract word count was 274 (SD 89). Word count explained only 13% of score variability. PRISMA-A scores did not differ between Cochrane and non-Cochrane abstracts (mean difference 0.08, 95% confidence interval -1.16 to 1.00). Of 275 primary outcomes, 48% were statistically significant, 32% were not statistically significant, and 19% did not report significance or results. Only one abstract described clinical significance for positive findings. For "negative" outcomes, we identified problematic simple restatements (20%), vague "no evidence of effect" wording (9%), and wishful wording (8%). CONCLUSIONS: Improved SR abstract reporting is needed, particularly reporting of quantitative measures (for meta-analysis), easily interpretable units, strengths/limitations of evidence, clinical significance, and clarifying whether negative results reflect true equivalence between treatments. Copyright © 2016 John Wiley & Sons, Ltd.

Imaging for the Pretreatment Staging of Small cell Lung Cancer: A Systematic Review.

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive form of lung cancer. Accurate staging is essential to select the optimal treatment plan to maximize survival. No consensus exists on standard imaging modalities for pretreatment staging of SCLC. MATERIALS AND METHODS: We conducted a systematic review of the literature on imaging modalities in the pretreatment staging of SCLC. A systematic search of multiple databases identified relevant studies published from 2000 through June 2015. Outcomes of interest included test concordance, staging accuracy (sensitivity and specificity), choice of treatment, timeliness of treatment, and patient outcomes. RESULTS: The search identified 2880 citations; 7 studies met inclusion criteria, n = 408 patients. Six of the seven studies were deemed to have moderate risk of bias, and one was deemed to have high risk of bias. One of the studies reported test concordance, three studies reported comparative accuracy of testing strategies, and four studies reported the accuracy of a single imaging modality. Analysis from these studies revealed that fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is more sensitive than multidetector CT for detecting osseous metastases, more sensitive than bone scintigraphy for detecting osseous metastases, and more sensitive for detecting any distant metastases. CONCLUSIONS: Evidence is sparse on the use of imaging in the pretreatment staging of SCLC. There is a lack of evidence on patient-oriented outcomes and a lack of evidence on whether comparative accuracy or effectiveness is associated with patient factors. We found low-strength evidence suggesting that FDG-PET/CT is more sensitive than CT and bone scintigraphy for detecting osseous metastases.

Surgical checklists: a systematic review of impacts and implementation.

BACKGROUND: Surgical complications represent a significant cause of morbidity and mortality with the rate of major complications after inpatient surgery estimated at 3-17% in industrialised countries. The purpose of this review was to summarise experience with surgical checklist use and efficacy for improving patient safety. METHODS: A search of four databases (MEDLINE, CINAHL, EMBASE and the Cochrane Database of Controlled Trials) was conducted from 1 January 2000 to 26 October 2012. Articles describing actual use of the WHO checklist, the Surgical Patient Safety System (SURPASS) checklist, a wrong-site surgery checklist or an anaesthesia equipment checklist were eligible for inclusion (this manuscript summarises all but the anaesthesia equipment checklists, which are described in the Agency for Healthcare Research and Quality publication). RESULTS: We included a total of 33 studies. We report a variety of outcomes including avoidance of adverse events, facilitators and barriers to implementation. Checklists have been adopted in a wide variety of settings and represent a promising strategy for improving the culture of patient safety and perioperative care in a wide variety of settings. Surgical checklists were associated with increased detection of potential safety hazards, decreased surgical complications and improved communication among operating staff. Strategies for successful checklist implementation included enlisting institutional leaders as local champions, incorporating staff feedback for checklist adaptation and avoiding redundancies with existing systems for collecting information. CONCLUSIONS: Surgical checklists represent a relatively simple and promising strategy for addressing surgical patient safety worldwide. Further studies are needed to evaluate to what degree checklists improve clinical outcomes and whether improvements may be more pronounced in particular settings.

The good doctor: professionalism in the 21st century.

Medical professionalism faces distinctive challenges in the 21st century. In this chapter, we review the history of professionalism, address specific challenges physicians face today, and provide an overview of efforts to address these issues, including behavioral and virtue ethics approaches. First, we discuss core features professions share and the development of codes of medical ethics that guide the practice of western medicine. Second, we address challenges related to the doctor-patient relationship, continuity of care, cultural competence, conflicts of interest, and the regulation of quality of care through maintenance of certification. We then explore three cultural trajectories that have deeply influenced medical practice: the technologic imperative, physicians' collective neglect of structural factors impacting medicine, and the rise of commercialism. Finally, we describe efforts to address these challenges, focusing on the Physician Charter developed by the American Board of Internal Medicine and widely endorsed by medical boards and societies internationally.

Predictors of emergent feeding tubes and tracheostomies in amyotrophic lateral sclerosis (ALS).

Predictable decline in ALS makes unplanned gastrostomy and tracheostomy avoidable. We determined whether gastrostomy or tracheostomy insertion during emergent hospitalization is associated with patient or hospital characteristics, changed Medicare policy in 2001, or proximity to specialized ALS care. We performed a retrospective analysis of hospitalizations and procedures for ALS/MND patients in Pennsylvania between 1996 and 2009. We identified predictors of gastrostomy/tracheostomy during emergent hospitalization and trends over time. Patients underwent 1748 gastrostomies and 373 tracheostomies. Thirty-two percent of gastrostomies and 67% of tracheostomies were placed emergently. Emergent hospitalizations involving gastrostomy were more expensive with fewer home discharges. Black patients and Medicaid patients had higher odds of emergent gastrostomy placement. Conversely, academic hospital affiliation decreased odds of emergent gastrostomy or tracheostomy placement (AOR 0.49, AOR 0.37, p < 0.001). After Medicare policy changes, gastrostomy use increased, while emergent gastrostomies decreased. Surprisingly, proximity to specialized care was associated with increased emergent gastrostomy placement. In conclusion, black patients and Medicaid patients were more likely to undergo emergent gastrostomy insertion. Patients receiving gastrostomy during emergent admissions had fewer home discharges and higher costs. Academic hospital affiliation decreased odds of emergent gastrostomy or tracheostomy. After Medicare changes broadening access, while gastrostomy use increased, the proportion of emergent procedures decreased.

Mortality in Friedreich ataxia.

BACKGROUND: Although cardiac dysfunction is widely accepted as the most common cause of mortality in Friedreich ataxia (FRDA), no studies have evaluated this since the advent of specific clinical and genetic diagnostic criteria. METHODS: We performed a retrospective study of FRDA patients to determine cause of death followed by a case-control analysis comparing characteristics of deceased patients with living, age- and sex-matched FRDA controls. RESULTS: Causes of death were cardiac dysfunction (59%), probable cardiac dysfunction (3.3%), non-cardiac (27.9%) or unknown (9.8%). Compared to non-cardiac deaths, cardiac deaths occurred earlier in the disease course (median 29 vs. 17years respectively). Congestive heart failure and arrhythmia were common causes of cardiac-related death. Compared to living, matched FRDA controls, deceased patients had longer triplet repeat lengths and higher rates of arrhythmia and dilated cardiomyopathy. The presence of hypertrophic cardiomyopathy did not differ between deceased and living patients. CONCLUSION: Cardiac dysfunction was the most frequent cause of death (59%), most commonly from congestive heart failure or arrhythmia. Arrhythmia and dilated cardiomyopathy were significantly more common in deceased patients compared to matched FRDA controls, while in contrast, the presence of cardiac hypertrophy did not differ. More research is needed to establish the clinical significance of hypertrophy in FRDA.

Pharmacotherapy for Friedreich ataxia.

Friedreich ataxia (FA) is a progressive genetic neurological disorder associated with degeneration of the dorsal columns, spinocerebellar tracts and other regions of the nervous system. The disorder results from mutations in the gene referred to as FXN. Almost all mutations are expansions of an intronic GAA repeat in this gene, which gives rise to decreased transcription of the gene product (called frataxin). Following these discoveries, drug discovery has moved at a rapid pace. Therapeutic trials in the next 5 years are expected to address amelioration of the effects of frataxin deficiency and methods for increasing frataxin expression. These therapies are directed at all levels of biochemical dysfunction in FA. Agents such as idebenone potentially improve mitochondrial function and decrease production of reactive oxygen species. Idebenone is presently in a phase III trial in the US and in Europe, with the primary outcome measure being neurological function. Deferiprone, an atypical iron chelator, may decrease build-up of toxic iron in the mitochondria in patients. It has entered a phase II trial in Europe, Australia and Canada directed toward improvement of neurological abilities. Finally, targeted histone deacetylase (HDAC) inhibitors and erythropoietin increase levels of frataxin when used in vitro, suggesting that they may provide methods for increasing frataxin levels in patients. Erythropoietin has been tested in a small phase II trial in Austria, while HDAC inhibitors are still at a preclinical stage. Symptomatic therapies are also in use for specific symptoms such as spasticity (baclofen). Thus, there is substantial optimism for development of new therapies for FA in the near future, and we suggest that one or several may be available over the next few years. However, continued development of new therapies will require creation of new, more sensitive measures for neurological dysfunction in FA, and clinically relevant measures of cardiac dysfunction.